ID   ATM_HUMAN               Reviewed;        3056 AA.
AC   Q13315; B2RNX5; O15429; Q12758; Q16551; Q93007; Q9NP02; Q9UCX7;
DT   27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT   22-JAN-2014, sequence version 4.
DT   28-JAN-2026, entry version 269.
DE   RecName: Full=Serine-protein kinase ATM;
DE            EC=2.7.11.1 {ECO:0000269|PubMed:15448695, ECO:0000269|PubMed:15790808, ECO:0000269|PubMed:16858402, ECO:0000269|PubMed:28508083, ECO:0000269|PubMed:30886146, ECO:0000269|PubMed:8988033, ECO:0000269|PubMed:9843217};
DE   AltName: Full=Ataxia telangiectasia mutated;
DE            Short=A-T mutated;
GN   Name=ATM;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT AT ASP-3003.
RX   PubMed=8589678; DOI=10.1093/hmg/4.11.2025;
RA   Savitsky K., Sfez S., Tagle D.A., Ziv Y., Sartiel A., Collins F.S.,
RA   Shiloh Y., Rotman G.;
RT   "The complete sequence of the coding region of the ATM gene reveals
RT   similarity to cell cycle regulators in different species.";
RL   Hum. Mol. Genet. 4:2025-2032(1995).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], VARIANT AT ASP-3003, AND VARIANTS
RP   CYS-49; ARG-1054; PHE-1420; ILE-2079 AND ALA-2287.
RX   PubMed=8665503;
RA   Vorechovsky I., Rasio D., Luo L., Monaco C., Hammarstroem L.,
RA   Webster A.D.B., Zaloudik J., Barbanti-Brodano G., James M.R., Russo G.,
RA   Croce C.M., Negrini M.;
RT   "The ATM gene and susceptibility to breast cancer: analysis of 38 breast
RT   tumors reveals no evidence for mutation.";
RL   Cancer Res. 56:2726-2732(1996).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=9199932; DOI=10.1101/gr.7.6.592;
RA   Platzer M., Rotman G., Bauer D., Uziel T., Savitsky K., Bar-Shira A.,
RA   Gilad S., Shiloh Y., Rosenthal A.;
RT   "Ataxia-telangiectasia locus: sequence analysis of 184 kb of human genomic
RT   DNA containing the entire ATM gene.";
RL   Genome Res. 7:592-605(1997).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ASN-1983.
RX   PubMed=16554811; DOI=10.1038/nature04632;
RA   Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA   Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA   Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA   Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA   Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA   Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT   "Human chromosome 11 DNA sequence and analysis including novel gene
RT   identification.";
RL   Nature 440:497-500(2006).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-2756.
RG   NIEHS SNPs program;
RL   Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 1-1369, AND VARIANT AT 2546-SER--ILE-2548
RP   DEL.
RX   PubMed=8789452; DOI=10.1093/hmg/5.1.145;
RA   Byrd P.J., McConville C.M., Cooper P., Parkhill J., Stankovic T.,
RA   McGuire G.M., Thick J.A., Taylor A.M.R.;
RT   "Mutations revealed by sequencing the 5' half of the gene for ataxia
RT   telangiectasia.";
RL   Hum. Mol. Genet. 5:145-149(1996).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-24.
RX   PubMed=9108147; DOI=10.1093/nar/25.9.1678;
RA   Savitsky K., Platzer M., Uziel T., Gilad S., Sartiel A., Rosenthal A.,
RA   Elroy-Stein O., Shiloh Y., Rotman G.;
RT   "Ataxia-telangiectasia: structural diversity of untranslated sequences
RT   suggests complex post-transcriptional regulation of ATM gene expression.";
RL   Nucleic Acids Res. 25:1678-1684(1997).
RN   [9]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 1332-3056, AND VARIANTS 2427-LEU-ARG-2428
RP   DEL; 2546-SER--ILE-2548 DEL; SER-2860 DEL AND ASP-3003.
RC   TISSUE=Fibroblast;
RX   PubMed=7792600; DOI=10.1126/science.7792600;
RA   Savitsky K., Bar-Shira A., Gilad S., Rotman G., Ziv Y., Vanagaite L.,
RA   Tagle D.A., Smith S., Uziel T., Sfez S., Ashkenazi M., Pecker I.,
RA   Frydman M., Harnik R., Patanjali S.R., Simmons A., Clines G.A., Sartiel A.,
RA   Gatti R.A., Chessa L., Sanal O., Lavin M.F., Jaspers N.G.J., Taylor A.M.R.,
RA   Arlett C.F., Miki T., Weissman S.M., Lovett M., Collins F.S., Shiloh Y.;
RT   "A single ataxia telangiectasia gene with a product similar to PI-3
RT   kinase.";
RL   Science 268:1749-1753(1995).
RN   [10]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1332-3056.
RC   TISSUE=Brain;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [11]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1349-3056.
RX   PubMed=8521392;
RA   Rasio D., Negrini M., Croce C.M.;
RT   "Genomic organization of the ATM locus involved in ataxia-telangiectasia.";
RL   Cancer Res. 55:6053-6057(1995).
RN   [12]
RP   PHOSPHORYLATION.
RX   PubMed=8969240; DOI=10.1074/jbc.271.52.33693;
RA   Chen G., Lee E.Y.-H.P.;
RT   "The product of the ATM gene is a 370-kDa nuclear phosphoprotein.";
RL   J. Biol. Chem. 271:33693-33697(1996).
RN   [13]
RP   SUBCELLULAR LOCATION.
RX   PubMed=9050866; DOI=10.1073/pnas.94.5.1840;
RA   Brown K.D., Ziv Y., Sadanandan S.N., Chessa L., Collins F.S., Shiloh Y.,
RA   Tagle D.A.;
RT   "The ataxia-telangiectasia gene product, a constitutively expressed nuclear
RT   protein that is not up-regulated following genome damage.";
RL   Proc. Natl. Acad. Sci. U.S.A. 94:1840-1845(1997).
RN   [14]
RP   SUBCELLULAR LOCATION, AND VARIANTS 2546-SER--ILE-2548 DEL AND TYR-2824.
RX   PubMed=9150358; DOI=10.1038/sj.onc.1201037;
RA   Watters D., Khanna K.K., Beamish H., Birrell G., Spring K., Kedar P.,
RA   Gatei M., Stenzel D., Hobson K., Kozlov S., Zhang N., Farrell A.,
RA   Ramsay J., Gatti R.A., Lavin M.F.;
RT   "Cellular localisation of the ataxia-telangiectasia (ATM) gene product and
RT   discrimination between mutated and normal forms.";
RL   Oncogene 14:1911-1921(1997).
RN   [15]
RP   CATALYTIC ACTIVITY.
RX   PubMed=8988033;
RA   Jung M., Kondratyev A., Lee S.A., Dimtchev A., Dritschilo A.;
RT   "ATM gene product phosphorylates I kappa B-alpha.";
RL   Cancer Res. 57:24-27(1997).
RN   [16]
RP   INTERACTION WITH ABL1.
RX   PubMed=9168117; DOI=10.1038/387520a0;
RA   Shafman T., Khanna K.K., Kedar P., Spring K., Kozlov S., Yen T., Hobson K.,
RA   Gatei M., Zhang N., Watters D., Egerton M., Shiloh Y., Kharbanda S.,
RA   Kufe D., Lavin M.F.;
RT   "Interaction between ATM protein and c-Abl in response to DNA damage.";
RL   Nature 387:520-523(1997).
RN   [17]
RP   ACTIVITY REGULATION.
RX   PubMed=9766667;
RA   Sarkaria J.N., Tibbetts R.S., Busby E.C., Kennedy A.P., Hill D.E.,
RA   Abraham R.T.;
RT   "Inhibition of phosphoinositide 3-kinase related kinases by the
RT   radiosensitizing agent wortmannin.";
RL   Cancer Res. 58:4375-4382(1998).
RN   [18]
RP   FUNCTION, INTERACTION WITH TP53, AND CATALYTIC ACTIVITY.
RX   PubMed=9843217; DOI=10.1038/3882;
RA   Khanna K.K., Keating K.E., Kozlov S., Scott S., Gatei M., Hobson K.,
RA   Taya Y., Gabrielli B., Chan D., Lees-Miller S.P., Lavin M.F.;
RT   "ATM associates with and phosphorylates p53: mapping the region of
RT   interaction.";
RL   Nat. Genet. 20:398-400(1998).
RN   [19]
RP   SUBCELLULAR LOCATION.
RX   PubMed=9707615; DOI=10.1073/pnas.95.17.10146;
RA   Lim D.-S., Kirsch D.G., Canman C.E., Ahn J.-H., Ziv Y., Newman L.S.,
RA   Darnell R.B., Shiloh Y., Kastan M.B.;
RT   "ATM binds to beta-adaptin in cytoplasmic vesicles.";
RL   Proc. Natl. Acad. Sci. U.S.A. 95:10146-10151(1998).
RN   [20]
RP   FUNCTION IN PHOSPHORYLATION OF TP53.
RX   PubMed=9733514; DOI=10.1126/science.281.5383.1674;
RA   Banin S., Moyal L., Shieh S.-Y., Taya Y., Anderson C.W., Chessa L.,
RA   Smorodinsky N.I., Prives C., Reiss Y., Shiloh Y., Ziv Y.;
RT   "Enhanced phosphorylation of p53 by ATM in response to DNA damage.";
RL   Science 281:1674-1677(1998).
RN   [21]
RP   FUNCTION IN PHOSPHORYLATION OF TP53, AND MUTAGENESIS OF ASP-2870 AND
RP   ASN-2875.
RX   PubMed=9733515; DOI=10.1126/science.281.5383.1677;
RA   Canman C.E., Lim D.-S., Cimprich K.A., Taya Y., Tamai K., Sakaguchi K.,
RA   Appella E., Kastan M.B., Siliciano J.D.;
RT   "Activation of the ATM kinase by ionizing radiation and phosphorylation of
RT   p53.";
RL   Science 281:1677-1679(1998).
RN   [22]
RP   DNA-BINDING.
RX   PubMed=10500142; DOI=10.1073/pnas.96.20.11134;
RA   Smith G.C.M., Cary R.B., Lakin N.D., Hann B.C., Teo S.-H., Chen D.J.,
RA   Jackson S.P.;
RT   "Purification and DNA binding properties of the ataxia-telangiectasia gene
RT   product ATM.";
RL   Proc. Natl. Acad. Sci. U.S.A. 96:11134-11139(1999).
RN   [23]
RP   FUNCTION IN PHOSPHORYLATION OF BRCA1.
RX   PubMed=10550055; DOI=10.1126/science.286.5442.1162;
RA   Cortez D., Wang Y., Qin J., Elledge S.J.;
RT   "Requirement of ATM-dependent phosphorylation of brca1 in the DNA damage
RT   response to double-strand breaks.";
RL   Science 286:1162-1166(1999).
RN   [24]
RP   IDENTIFICATION OF ATM AS MEMBER OF BASC.
RX   PubMed=10783165;
RA   Wang Y., Cortez D., Yazdi P., Neff N., Elledge S.J., Qin J.;
RT   "BASC, a super complex of BRCA1-associated proteins involved in the
RT   recognition and repair of aberrant DNA structures.";
RL   Genes Dev. 14:927-939(2000).
RN   [25]
RP   FUNCTION IN PHOSPHORYLATION OF NBN.
RX   PubMed=10766245; DOI=10.1038/35007091;
RA   Lim D.-S., Kim S.-T., Xu B., Maser R.S., Lin J., Petrini J.H.J.,
RA   Kastan M.B.;
RT   "ATM phosphorylates p95/nbs1 in an S-phase checkpoint pathway.";
RL   Nature 404:613-617(2000).
RN   [26]
RP   FUNCTION IN PHOSPHORYLATION OF NBN.
RX   PubMed=10839545; DOI=10.1038/35013089;
RA   Wu X., Ranganathan V., Weisman D.S., Heine W.F., Ciccone D.N.,
RA   O'Neill T.B., Crick K.E., Pierce K.A., Lane W.S., Rathbun G.,
RA   Livingston D.M., Weaver D.T.;
RT   "ATM phosphorylation of Nijmegen breakage syndrome protein is required in a
RT   DNA damage response.";
RL   Nature 405:477-482(2000).
RN   [27]
RP   FUNCTION IN PHOSPHORYLATION OF CTIP.
RX   PubMed=10910365; DOI=10.1038/35018134;
RA   Li S., Ting N.S.Y., Zheng L., Chen P.-L., Ziv Y., Shiloh Y., Lee E.Y.-H.P.,
RA   Lee W.-H.;
RT   "Functional link of BRCA1 and ataxia telangiectasia gene product in DNA
RT   damage response.";
RL   Nature 406:210-215(2000).
RN   [28]
RP   FUNCTION IN PHOSPHORYLATION OF NBN.
RX   PubMed=10802669; DOI=10.1038/75508;
RA   Gatei M., Young D., Cerosaletti K.M., Desai-Mehta A., Spring K., Kozlov S.,
RA   Lavin M.F., Gatti R.A., Concannon P., Khanna K.K.;
RT   "ATM-dependent phosphorylation of nibrin in response to radiation
RT   exposure.";
RL   Nat. Genet. 25:115-119(2000).
RN   [29]
RP   FUNCTION IN PHOSPHORYLATION OF CHEK2.
RX   PubMed=10973490; DOI=10.1073/pnas.190030497;
RA   Matsuoka S., Rotman G., Ogawa A., Shiloh Y., Tamai K., Elledge S.J.;
RT   "Ataxia telangiectasia-mutated phosphorylates Chk2 in vivo and in vitro.";
RL   Proc. Natl. Acad. Sci. U.S.A. 97:10389-10394(2000).
RN   [30]
RP   FUNCTION IN PHOSPHORYLATION OF TERF1.
RX   PubMed=11375976; DOI=10.1074/jbc.m011534200;
RA   Kishi S., Zhou X.Z., Ziv Y., Khoo C., Hill D.E., Shiloh Y., Lu K.P.;
RT   "Telomeric protein Pin2/TRF1 as an important ATM target in response to
RT   double strand DNA breaks.";
RL   J. Biol. Chem. 276:29282-29291(2001).
RN   [31]
RP   INTERACTION WITH RAD17.
RX   PubMed=11418864; DOI=10.1038/35082110;
RA   Bao S., Tibbetts R.S., Brumbaugh K.M., Fang Y., Richardson D.A., Ali A.,
RA   Chen S.M., Abraham R.T., Wang X.-F.;
RT   "ATR/ATM-mediated phosphorylation of human Rad17 is required for genotoxic
RT   stress responses.";
RL   Nature 411:969-974(2001).
RN   [32]
RP   FUNCTION IN PHOSPHORYLATION OF FANCD2.
RX   PubMed=12086603; DOI=10.1016/s0092-8674(02)00747-x;
RA   Taniguchi T., Garcia-Higuera I., Xu B., Andreassen P.R., Gregory R.C.,
RA   Kim S.-T., Lane W.S., Kastan M.B., D'Andrea A.D.;
RT   "Convergence of the Fanconi anemia and ataxia telangiectasia signaling
RT   pathways.";
RL   Cell 109:459-472(2002).
RN   [33]
RP   PHOSPHORYLATION BY NUAK1.
RX   PubMed=12409306; DOI=10.1074/jbc.m206025200;
RA   Suzuki A., Kusakai G., Kishimoto A., Lu J., Ogura T., Lavin M.F., Esumi H.;
RT   "Identification of a novel protein kinase mediating Akt survival signaling
RT   to the ATM protein.";
RL   J. Biol. Chem. 278:48-53(2003).
RN   [34]
RP   PHOSPHORYLATION AT SER-1981, SUBUNIT, FUNCTION, AND MUTAGENESIS OF
RP   SER-1981.
RX   PubMed=12556884; DOI=10.1038/nature01368;
RA   Bakkenist C.J., Kastan M.B.;
RT   "DNA damage activates ATM through intermolecular autophosphorylation and
RT   dimer dissociation.";
RL   Nature 421:499-506(2003).
RN   [35]
RP   FUNCTION IN DNA DAMAGE RESPONSE.
RX   PubMed=14871926; DOI=10.1101/gad.1176004;
RA   Ali A., Zhang J., Bao S., Liu I., Otterness D., Dean N.M., Abraham R.T.,
RA   Wang X.F.;
RT   "Requirement of protein phosphatase 5 in DNA-damage-induced ATM
RT   activation.";
RL   Genes Dev. 18:249-254(2004).
RN   [36]
RP   FUNCTION IN PHOSPHORYLATION OF DCLRE1C.
RX   PubMed=15456891; DOI=10.1128/mcb.24.20.9207-9220.2004;
RA   Zhang X., Succi J., Feng Z., Prithivirajsingh S., Story M.D.,
RA   Legerski R.J.;
RT   "Artemis is a phosphorylation target of ATM and ATR and is involved in the
RT   G2/M DNA damage checkpoint response.";
RL   Mol. Cell. Biol. 24:9207-9220(2004).
RN   [37]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=15448695; DOI=10.1038/ncb1170;
RA   Demonacos C., Krstic-Demonacos M., Smith L., Xu D., O'Connor D.P.,
RA   Jansson M., La Thangue N.B.;
RT   "A new effector pathway links ATM kinase with the DNA damage response.";
RL   Nat. Cell Biol. 6:968-976(2004).
RN   [38]
RP   FUNCTION, AND ACTIVITY REGULATION.
RX   PubMed=15064416; DOI=10.1126/science.1091496;
RA   Lee J.-H., Paull T.T.;
RT   "Direct activation of the ATM protein kinase by the Mre11/Rad50/Nbs1
RT   complex.";
RL   Science 304:93-96(2004).
RN   [39]
RP   INTERACTION WITH EEF1E1.
RX   PubMed=15680327; DOI=10.1016/j.cell.2004.11.054;
RA   Park B.-J., Kang J.W., Lee S.W., Choi S.-J., Shin Y.K., Ahn Y.H.,
RA   Choi Y.H., Choi D., Lee K.S., Kim S.;
RT   "The haploinsufficient tumor suppressor p18 upregulates p53 via
RT   interactions with ATM/ATR.";
RL   Cell 120:209-221(2005).
RN   [40]
RP   FUNCTION.
RX   PubMed=15916964; DOI=10.1016/j.molcel.2005.04.015;
RA   Bhoumik A., Takahashi S., Breitweiser W., Shiloh Y., Jones N., Ronai Z.;
RT   "ATM-dependent phosphorylation of ATF2 is required for the DNA damage
RT   response.";
RL   Mol. Cell 18:577-587(2005).
RN   [41]
RP   INTERACTION WITH KAT8.
RX   PubMed=15923642; DOI=10.1128/mcb.25.12.5292-5305.2005;
RA   Gupta A., Sharma G.G., Young C.S.H., Agarwal M., Smith E.R., Paull T.T.,
RA   Lucchesi J.C., Khanna K.K., Ludwig T., Pandita T.K.;
RT   "Involvement of human MOF in ATM function.";
RL   Mol. Cell. Biol. 25:5292-5305(2005).
RN   [42]
RP   FUNCTION IN HISTONE MRNA DEGRADATION ACTIVITY.
RX   PubMed=16086026; DOI=10.1038/nsmb972;
RA   Kaygun H., Marzluff W.F.;
RT   "Regulated degradation of replication-dependent histone mRNAs requires both
RT   ATR and Upf1.";
RL   Nat. Struct. Mol. Biol. 12:794-800(2005).
RN   [43]
RP   PHOSPHORYLATION AT SER-1981, AND ACETYLATION.
RX   PubMed=16141325; DOI=10.1073/pnas.0504211102;
RA   Sun Y., Jiang X., Chen S., Fernandes N., Price B.D.;
RT   "A role for the Tip60 histone acetyltransferase in the acetylation and
RT   activation of ATM.";
RL   Proc. Natl. Acad. Sci. U.S.A. 102:13182-13187(2005).
RN   [44]
RP   FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBUNIT, AND
RP   PHOSPHORYLATION AT SER-1981.
RX   PubMed=15790808; DOI=10.1126/science.1108297;
RA   Lee J.H., Paull T.T.;
RT   "ATM activation by DNA double-strand breaks through the Mre11-Rad50-Nbs1
RT   complex.";
RL   Science 308:551-554(2005).
RN   [45]
RP   PHOSPHORYLATION AT SER-367; SER-1893 AND SER-1981, FUNCTION, CATALYTIC
RP   ACTIVITY, MUTAGENESIS OF SER-367; SER-1893 AND SER-1981, AND IDENTIFICATION
RP   BY MASS SPECTROMETRY.
RX   PubMed=16858402; DOI=10.1038/sj.emboj.7601231;
RA   Kozlov S.V., Graham M.E., Peng C., Chen P., Robinson P.J., Lavin M.F.;
RT   "Involvement of novel autophosphorylation sites in ATM activation.";
RL   EMBO J. 25:3504-3514(2006).
RN   [46]
RP   INTERACTION WITH ATMIN.
RX   PubMed=17525732; DOI=10.1038/sj.emboj.7601733;
RA   Kanu N., Behrens A.;
RT   "ATMIN defines an NBS1-independent pathway of ATM signalling.";
RL   EMBO J. 26:2933-2941(2007).
RN   [47]
RP   ACETYLATION AT LYS-3016, FUNCTION, AND MUTAGENESIS OF LYS-3016 AND
RP   LYS-3018.
RX   PubMed=17923702; DOI=10.1128/mcb.01382-07;
RA   Sun Y., Xu Y., Roy K., Price B.D.;
RT   "DNA damage-induced acetylation of lysine 3016 of ATM activates ATM kinase
RT   activity.";
RL   Mol. Cell. Biol. 27:8502-8509(2007).
RN   [48]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1981 AND SER-1983, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Embryonic kidney;
RX   PubMed=17525332; DOI=10.1126/science.1140321;
RA   Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA   Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA   Gygi S.P., Elledge S.J.;
RT   "ATM and ATR substrate analysis reveals extensive protein networks
RT   responsive to DNA damage.";
RL   Science 316:1160-1166(2007).
RN   [49]
RP   INTERACTION WITH CEP164.
RX   PubMed=18283122; DOI=10.1101/gad.1627708;
RA   Sivasubramaniam S., Sun X., Pan Y.R., Wang S., Lee E.Y.;
RT   "Cep164 is a mediator protein required for the maintenance of genomic
RT   stability through modulation of MDC1, RPA, and CHK1.";
RL   Genes Dev. 22:587-600(2008).
RN   [50]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2996, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA   Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA   Greff Z., Keri G., Stemmann O., Mann M.;
RT   "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT   kinome across the cell cycle.";
RL   Mol. Cell 31:438-448(2008).
RN   [51]
RP   INTERACTION WITH NABP2.
RX   PubMed=18449195; DOI=10.1038/nature06883;
RA   Richard D.J., Bolderson E., Cubeddu L., Wadsworth R.I.M., Savage K.,
RA   Sharma G.G., Nicolette M.L., Tsvetanov S., McIlwraith M.J., Pandita R.K.,
RA   Takeda S., Hay R.T., Gautier J., West S.C., Paull T.T., Pandita T.K.,
RA   White M.F., Khanna K.K.;
RT   "Single-stranded DNA-binding protein hSSB1 is critical for genomic
RT   stability.";
RL   Nature 453:677-681(2008).
RN   [52]
RP   INTERACTION WITH DDX1.
RX   PubMed=18710941; DOI=10.1128/mcb.01053-08;
RA   Li L., Monckton E.A., Godbout R.;
RT   "A role for DEAD box 1 at DNA double-strand breaks.";
RL   Mol. Cell. Biol. 28:6413-6425(2008).
RN   [53]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2996, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA   Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA   Mann M., Daub H.;
RT   "Large-scale proteomics analysis of the human kinome.";
RL   Mol. Cell. Proteomics 8:1751-1764(2009).
RN   [54]
RP   FUNCTION AS DYRK2 KINASE.
RX   PubMed=19965871; DOI=10.1074/jbc.m109.042341;
RA   Taira N., Yamamoto H., Yamaguchi T., Miki Y., Yoshida K.;
RT   "ATM augments nuclear stabilization of DYRK2 by inhibiting MDM2 in the
RT   apoptotic response to DNA damage.";
RL   J. Biol. Chem. 285:4909-4919(2010).
RN   [55]
RP   INTERACTION WITH TTI1.
RX   PubMed=20810650; DOI=10.1101/gad.1934210;
RA   Hurov K.E., Cotta-Ramusino C., Elledge S.J.;
RT   "A genetic screen identifies the Triple T complex required for DNA damage
RT   signaling and ATM and ATR stability.";
RL   Genes Dev. 24:1939-1950(2010).
RN   [56]
RP   INTERACTION WITH TELO2.
RX   PubMed=20801936; DOI=10.1101/gad.1956410;
RA   Takai H., Xie Y., de Lange T., Pavletich N.P.;
RT   "Tel2 structure and function in the Hsp90-dependent maturation of mTOR and
RT   ATR complexes.";
RL   Genes Dev. 24:2019-2030(2010).
RN   [57]
RP   INTERACTION WITH TELO2 AND TTI1.
RX   PubMed=20427287; DOI=10.1074/jbc.m110.121699;
RA   Kaizuka T., Hara T., Oshiro N., Kikkawa U., Yonezawa K., Takehana K.,
RA   Iemura S., Natsume T., Mizushima N.;
RT   "Tti1 and Tel2 are critical factors in mammalian target of rapamycin
RT   complex assembly.";
RL   J. Biol. Chem. 285:20109-20116(2010).
RN   [58]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [59]
RP   PHOSPHORYLATION AT SER-1981.
RX   PubMed=21144835; DOI=10.1016/j.bbrc.2010.12.005;
RA   Kang Y., Cheong H.M., Lee J.H., Song P.I., Lee K.H., Kim S.Y., Jun J.Y.,
RA   You H.J.;
RT   "Protein phosphatase 5 is necessary for ATR-mediated DNA repair.";
RL   Biochem. Biophys. Res. Commun. 404:476-481(2011).
RN   [60]
RP   INTERACTION WITH BRAT1.
RX   PubMed=22977523; DOI=10.3892/etm.2011.232;
RA   So E.Y., Ouchi T.;
RT   "Functional interaction of BRCA1/ATM-associated BAAT1 with the DNA-PK
RT   catalytic subunit.";
RL   Exp. Ther. Med. 2:443-447(2011).
RN   [61]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=21757780; DOI=10.1074/jbc.m111.258152;
RA   Gatei M., Jakob B., Chen P., Kijas A.W., Becherel O.J., Gueven N.,
RA   Birrell G., Lee J.H., Paull T.T., Lerenthal Y., Fazry S.,
RA   Taucher-Scholz G., Kalb R., Schindler D., Waltes R., Doerk T., Lavin M.F.;
RT   "ATM protein-dependent phosphorylation of Rad50 protein regulates DNA
RT   repair and cell cycle control.";
RL   J. Biol. Chem. 286:31542-31556(2011).
RN   [62]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP   METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP   [LARGE SCALE ANALYSIS].
RX   PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA   Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA   Giglione C.;
RT   "Comparative large-scale characterisation of plant vs. mammal proteins
RT   reveals similar and idiosyncratic N-alpha acetylation features.";
RL   Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN   [63]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma, and Erythroleukemia;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [64]
RP   FUNCTION.
RX   PubMed=24534091; DOI=10.1002/embj.201386064;
RA   Wang Q., Goldstein M., Alexander P., Wakeman T.P., Sun T., Feng J., Lou Z.,
RA   Kastan M.B., Wang X.F.;
RT   "Rad17 recruits the MRE11-RAD50-NBS1 complex to regulate the cellular
RT   response to DNA double-strand breaks.";
RL   EMBO J. 33:862-877(2014).
RN   [65]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [66]
RP   FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, INTERACTION WITH PEX5,
RP   AND MUTAGENESIS OF ARG-3047.
RX   PubMed=26344566; DOI=10.1038/ncb3230;
RA   Zhang J., Tripathi D.N., Jing J., Alexander A., Kim J., Powell R.T.,
RA   Dere R., Tait-Mulder J., Lee J.H., Paull T.T., Pandita R.K., Charaka V.K.,
RA   Pandita T.K., Kastan M.B., Walker C.L.;
RT   "ATM functions at the peroxisome to induce pexophagy in response to ROS.";
RL   Nat. Cell Biol. 17:1259-1269(2015).
RN   [67]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=26240375; DOI=10.1093/nar/gkv754;
RA   Kijas A.W., Lim Y.C., Bolderson E., Cerosaletti K., Gatei M., Jakob B.,
RA   Tobias F., Taucher-Scholz G., Gueven N., Oakley G., Concannon P.,
RA   Wolvetang E., Khanna K.K., Wiesmueller L., Lavin M.F.;
RT   "ATM-dependent phosphorylation of MRE11 controls extent of resection during
RT   homology directed repair by signalling through Exonuclease 1.";
RL   Nucleic Acids Res. 43:8352-8367(2015).
RN   [68]
RP   FUNCTION IN PHOSPHORYLATION OF FBXW7.
RX   PubMed=26774286; DOI=10.1016/j.molcel.2015.12.010;
RA   Zhang Q., Karnak D., Tan M., Lawrence T.S., Morgan M.A., Sun Y.;
RT   "FBXW7 facilitates nonhomologous end-joining via K63-linked
RT   polyubiquitylation of XRCC4.";
RL   Mol. Cell 61:419-433(2016).
RN   [69]
RP   FUNCTION.
RX   PubMed=29203878; DOI=10.1038/s41467-017-02114-x;
RA   Batenburg N.L., Walker J.R., Noordermeer S.M., Moatti N., Durocher D.,
RA   Zhu X.D.;
RT   "ATM and CDK2 control chromatin remodeler CSB to inhibit RIF1 in DSB repair
RT   pathway choice.";
RL   Nat. Commun. 8:1921-1921(2017).
RN   [70]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=30171069; DOI=10.1074/jbc.ra118.005354;
RA   Choppara S., Ganga S., Manne R., Dutta P., Singh S., Santra M.K.;
RT   "The SCFFBXO46 ubiquitin ligase complex mediates degradation of the tumor
RT   suppressor FBXO31 and thereby prevents premature cellular senescence.";
RL   J. Biol. Chem. 293:16291-16306(2018).
RN   [71]
RP   FUNCTION.
RX   PubMed=30612738; DOI=10.1016/j.cell.2018.11.024;
RA   Jachimowicz R.D., Beleggia F., Isensee J., Velpula B.B., Goergens J.,
RA   Bustos M.A., Doll M.A., Shenoy A., Checa-Rodriguez C., Wiederstein J.L.,
RA   Baranes-Bachar K., Bartenhagen C., Hertwig F., Teper N., Nishi T.,
RA   Schmitt A., Distelmaier F., Luedecke H.J., Albrecht B., Krueger M.,
RA   Schumacher B., Geiger T., Hoon D.S.B., Huertas P., Fischer M., Hucho T.,
RA   Peifer M., Ziv Y., Reinhardt H.C., Wieczorek D., Shiloh Y.;
RT   "UBQLN4 represses homologous recombination and is overexpressed in
RT   aggressive tumors.";
RL   Cell 0:0-0(2019).
RN   [72]
RP   FUNCTION IN PHOSPHORYLATION OF UFL1, AND CATALYTIC ACTIVITY.
RX   PubMed=30886146; DOI=10.1038/s41467-019-09175-0;
RA   Qin B., Yu J., Nowsheen S., Wang M., Tu X., Liu T., Li H., Wang L., Lou Z.;
RT   "UFL1 promotes histone H4 ufmylation and ATM activation.";
RL   Nat. Commun. 10:1242-1242(2019).
RN   [73]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=30952868; DOI=10.1038/s41467-019-09641-9;
RA   Ha G.H., Ji J.H., Chae S., Park J., Kim S., Lee J.K., Kim Y., Min S.,
RA   Park J.M., Kang T.H., Lee H., Cho H., Lee C.W.;
RT   "Pellino1 regulates reversible ATM activation via NBS1 ubiquitination at
RT   DNA double-strand breaks.";
RL   Nat. Commun. 10:1577-1577(2019).
RN   [74]
RP   ACETYLATION AT LYS-3016, PHOSPHORYLATION AT SER-1981, AND MUTAGENESIS OF
RP   LYS-3016.
RX   PubMed=30944854; DOI=10.1126/sciadv.aav1118;
RA   Tang M., Li Z., Zhang C., Lu X., Tu B., Cao Z., Li Y., Chen Y., Jiang L.,
RA   Wang H., Wang L., Wang J., Liu B., Xu X., Wang H., Zhu W.G.;
RT   "SIRT7-mediated ATM deacetylation is essential for its deactivation and DNA
RT   damage repair.";
RL   Sci. Adv. 5:EAAV1118-EAAV1118(2019).
RN   [75]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=38128537; DOI=10.1016/j.cell.2023.11.022;
RA   Chen Y., Wu J., Zhai L., Zhang T., Yin H., Gao H., Zhao F., Wang Z.,
RA   Yang X., Jin M., Huang B., Ding X., Li R., Yang J., He Y., Wang Q.,
RA   Wang W., Kloeber J.A., Li Y., Hao B., Zhang Y., Wang J., Tan M., Li K.,
RA   Wang P., Lou Z., Yuan J.;
RT   "Metabolic regulation of homologous recombination repair by MRE11
RT   lactylation.";
RL   Cell 187:294-311(2024).
RN   [76] {ECO:0007744|PDB:5NP0, ECO:0007744|PDB:5NP1}
RP   STRUCTURE BY ELECTRON MICROSCOPY (5.70 ANGSTROMS), CATALYTIC ACTIVITY, AND
RP   SUBUNIT.
RX   PubMed=28508083; DOI=10.1126/sciadv.1700933;
RA   Baretic D., Pollard H.K., Fisher D.I., Johnson C.M., Santhanam B.,
RA   Truman C.M., Kouba T., Fersht A.R., Phillips C., Williams R.L.;
RT   "Structures of closed and open conformations of dimeric human ATM.";
RL   Sci. Adv. 3:E1700933-E1700933(2017).
RN   [77] {ECO:0007744|PDB:7SIC, ECO:0007744|PDB:7SID}
RP   STRUCTURE BY ELECTRON MICROSCOPY (2.51 ANGSTROMS) IN COMPLEX WITH NBN,
RP   FUNCTION, INTERACTION WITH NBN, AND ACTIVITY REGULATION.
RX   PubMed=35076389; DOI=10.7554/elife.74218;
RA   Warren C., Pavletich N.P.;
RT   "Structure of the human ATM kinase and mechanism of Nbs1 binding.";
RL   Elife 11:0-0(2022).
RN   [78]
RP   VARIANTS GLY-2424; 2546-SER--ILE-2548 DEL AND CYS-2827.
RX   PubMed=8755918;
RA   McConville C.M., Stankovic T., Byrd P.J., McGuire G.M., Yao Q.-Y.,
RA   Lennox G.G., Taylor A.M.R.;
RT   "Mutations associated with variant phenotypes in ataxia-telangiectasia.";
RL   Am. J. Hum. Genet. 59:320-330(1996).
RN   [79]
RP   VARIANT AT 2546-SER--ILE-2548 DEL, AND VARIANT ILE-2438.
RX   PubMed=8808599;
RA   Wright J., Teraoka S., Onengut S., Tolun A., Gatti R.A., Ochs H.D.,
RA   Concannon P.;
RT   "A high frequency of distinct ATM gene mutations in ataxia-
RT   telangiectasia.";
RL   Am. J. Hum. Genet. 59:839-846(1996).
RN   [80]
RP   VARIANTS 705-TYR--SER-707 DELINS PHE-ILE-PRO AND 2546-SER--ILE-2548 DEL,
RP   AND VARIANTS CYS-49; LEU-858; ARG-1054; PHE-1420 AND ARG-1691.
RX   PubMed=8797579;
RA   Vorechovsky I., Luo L., Lindblom A., Negrini M., Webster A.D.B.,
RA   Croce C.M., Hammarstroem L.;
RT   "ATM mutations in cancer families.";
RL   Cancer Res. 56:4130-4133(1996).
RN   [81]
RP   VARIANT AT 705-TYR--SER-707 DELINS PHE-ILE-PRO, AND VARIANTS LEU-858 AND
RP   ARG-1054.
RX   PubMed=9043869; DOI=10.1159/000472231;
RA   Vorechovsky I., Luo L., Prudente S., Chessa L., Russo G., Kanariou M.,
RA   James M.R., Negrini M., Webster A.D.B., Hammarstroem L.;
RT   "Exon-scanning mutation analysis of the ATM gene in patients with ataxia-
RT   telangiectasia.";
RL   Eur. J. Hum. Genet. 4:352-355(1996).
RN   [82]
RP   VARIANT AT ARG-2867.
RX   PubMed=8698354; DOI=10.1007/s004390050202;
RA   Baumer A., Bernthaler U., Wolz W., Hoehn H., Schindler D.;
RT   "New mutations in the ataxia telangiectasia gene.";
RL   Hum. Genet. 98:246-249(1996).
RN   [83]
RP   VARIANTS 2427-LEU-ARG-2428 DEL; 2546-SER--ILE-2548 DEL; SER-2860 DEL AND
RP   GLY-2904.
RX   PubMed=8845835; DOI=10.1093/hmg/5.4.433;
RA   Gilad S., Khosravi R., Shkedy D., Uziel T., Ziv Y., Savitsky K., Rotman G.,
RA   Smith S., Chessa L., Jorgensen T.J., Harnik R., Frydman M., Sanal O.,
RA   Portnoi S., Goldwicz Z., Jaspers N.G.J., Gatti R.A., Lenoir G., Lavin M.F.,
RA   Tatsumi K., Wegner R.-D., Shiloh Y., Bar-Shira A.;
RT   "Predominance of null mutations in ataxia-telangiectasia.";
RL   Hum. Mol. Genet. 5:433-439(1996).
RN   [84]
RP   POSSIBLE INVOLVEMENT IN TPLL AND BNHL, AND VARIANTS VAL-1040; THR-1407;
RP   SER-1463; HIS-1682; HIS-1910; LYS-2164; SER-2396; GLY-2424; PRO-2442;
RP   2546-SER--ILE-2548 DEL; ALA-2695; ARG-2722; VAL-2725; LEU-2732; LYS-2810
RP   DEL; CYS-2832 AND 2871-ARG-HIS-2872 DELINS SER AND VAL-2890.
RX   PubMed=9288106; DOI=10.1038/ng0997-96;
RA   Vorechovsky I., Luo L., Dyer M.J.S., Catovsky D., Amlot P.L., Yaxley J.C.,
RA   Foroni L., Hammarstroem L., Webster A.D.B., Yuille M.A.R.;
RT   "Clustering of missense mutations in the ataxia-telangiectasia gene in a
RT   sporadic T-cell leukaemia.";
RL   Nat. Genet. 17:96-99(1997).
RN   [85]
RP   POSSIBLE INVOLVEMENT IN TPLL, AND VARIANTS GLY-2725; PRO-3006 AND CYS-3008.
RX   PubMed=9334731; DOI=10.1038/nm1097-1155;
RA   Stilgenbauer S., Schaffner C., Litterst A., Liebisch P., Gilad S.,
RA   Bar-Shira A., James M.R., Lichter P., Doehner H.;
RT   "Biallelic mutations in the ATM gene in T-prolymphocytic leukemia.";
RL   Nat. Med. 3:1155-1159(1997).
RN   [86]
RP   VARIANT AT CYS-2832.
RX   PubMed=9443866; DOI=10.1086/301673;
RA   Telatar M., Teraoka S., Wang Z., Chun H.H., Liang T., Castellvi-Bel S.,
RA   Udar N., Boerresen-Dale A.-L., Chessa L., Bernatowska-Matuszkiewicz E.,
RA   Porras O., Watanabe M., Junker A., Concannon P., Gatti R.A.;
RT   "Ataxia-telangiectasia: identification and detection of founder-effect
RT   mutations in the ATM gene in ethnic populations.";
RL   Am. J. Hum. Genet. 62:86-97(1998).
RN   [87]
RP   POSSIBLE INVOLVEMENT IN TALL, AND VARIANTS AT LEU-292; ASP-768; GLN-1001;
RP   ARG-1691; ILE-1743; GLY-2424; 2427-LEU-ARG-2428 DEL; 2546-SER--ILE-2548
RP   DEL; ASP-2554; GLY-2668 AND CYS-2827.
RX   PubMed=9463314; DOI=10.1086/301706;
RA   Stankovic T., Kidd A.M.J., Sutcliffe A., McGuire G.M., Robinson P.,
RA   Weber P., Bedenham T., Bradwell A.R., Easton D.F., Lennox G.G., Haites N.,
RA   Byrd P.J., Taylor A.M.R.;
RT   "ATM mutations and phenotypes in ataxia-telangiectasia families in the
RT   British Isles: expression of mutant ATM and the risk of leukemia, lymphoma,
RT   and breast cancer.";
RL   Am. J. Hum. Genet. 62:334-345(1998).
RN   [88]
RP   VARIANT AT 1812-ALA-PHE-1813 DELINS VAL.
RX   PubMed=9497252; DOI=10.1086/301755;
RA   Gilad S., Chessa L., Khosravi R., Russell P., Galanty Y., Piane M.,
RA   Gatti R.A., Jorgensen T.J., Shiloh Y., Bar-Shira A.;
RT   "Genotype-phenotype relationships in ataxia-telangiectasia and variants.";
RL   Am. J. Hum. Genet. 62:551-561(1998).
RN   [89]
RP   VARIANT AT PRO-2656.
RX   PubMed=9450874;
RX   DOI=10.1002/(sici)1096-8628(19980113)75:2<141::aid-ajmg4>3.3.co;2-8;
RA   Toyoshima M., Hara T., Zhang H., Yamamoto T., Akaboshi S., Nanba E.,
RA   Ohno K., Hori N., Sato K., Takeshita K.;
RT   "Ataxia-telangiectasia without immunodeficiency: novel point mutations
RT   within and adjacent to the phosphatidylinositol 3-kinase-like domain.";
RL   Am. J. Med. Genet. 75:141-144(1998).
RN   [90]
RP   VARIANT TPLL GLY-2486.
RX   PubMed=9573030;
RA   Stoppa-Lyonnet D., Soulier J., Lauge A., Dastot H., Garand R., Sigaux F.,
RA   Stern M.-H.;
RT   "Inactivation of the ATM gene in T-cell prolymphocytic leukemias.";
RL   Blood 91:3920-3926(1998).
RN   [91]
RP   VARIANTS 2855-SER-VAL-2856 DELINS ARG-ILE AND CYS-3008, AND VARIANT
RP   VAL-1853.
RX   PubMed=9872980; DOI=10.1101/gr.8.12.1245;
RA   Hacia J.G., Sun B., Hunt N., Edgemon K., Mosbrook D., Robbins C.,
RA   Fodor S.P.A., Tagle D.A., Collins F.S.;
RT   "Strategies for mutational analysis of the large multiexon ATM gene using
RT   high-density oligonucleotide arrays.";
RL   Genome Res. 8:1245-1258(1998).
RN   [92]
RP   VARIANT AT 2625-ASP-ALA-2626 DELINS GLU-PRO.
RX   PubMed=9521587; DOI=10.1007/s004390050675;
RA   van Belzen M.J., Hiel J.A.P., Weemaes C.M.R., Gabreeels F.J.M.,
RA   van Engelen B.G.M., Smeets D.F.C.M., van den Heuvel L.P.W.J.;
RT   "A double missense mutation in the ATM gene of a Dutch family with ataxia
RT   telangiectasia.";
RL   Hum. Genet. 102:187-191(1998).
RN   [93]
RP   VARIANT AT LEU-2829, AND VARIANTS GLU-126; ASP-514 AND ASN-1853.
RX   PubMed=9711876;
RX   DOI=10.1002/(sici)1098-1004(1998)12:3<186::aid-humu6>3.0.co;2-f;
RA   Sasaki T., Tian H., Kukita Y., Inazuka M., Tahira T., Imai T., Yamauchi M.,
RA   Saito T., Hori T., Hashimoto-Tamaoki T., Komatsu K., Nikaido O.,
RA   Hayashi K.;
RT   "ATM mutations in patients with ataxia telangiectasia screened by a
RT   hierarchical strategy.";
RL   Hum. Mutat. 12:186-195(1998).
RN   [94]
RP   VARIANTS AT LEU-858; ARG-1054; ASP-1091 AND ARG-1566.
RX   PubMed=9792409;
RX   DOI=10.1002/(sici)1098-1004(1998)12:5<330::aid-humu6>3.0.co;2-h;
RA   Broeks A., de Klein A., Floore A.N., Muijtjens M., Kleijer W.J.,
RA   Jaspers N.G.J., van 't Veer L.J.;
RT   "ATM germline mutations in classical ataxia-telangiectasia patients in the
RT   Dutch population.";
RL   Hum. Mutat. 12:330-337(1998).
RN   [95]
RP   VARIANTS AT ARG-2491 AND GLY-2909.
RX   PubMed=9792410;
RX   DOI=10.1002/(sici)1098-1004(1998)12:5<338::aid-humu7>3.0.co;2-9;
RA   Fukao T., Song X.-Q., Yoshida T., Tashita H., Kaneko H., Teramoto T.,
RA   Inoue R., Katamura K., Mayumi M., Hiratani M., Taniguchi N., Arai J.,
RA   Wakiguchi H., Bar-Shira A., Shiloh Y., Kondo N.;
RT   "Ataxia-telangiectasia in the Japanese population: identification of
RT   R1917X, W2491R, R2909G, IVS33+2T-->A, and 7883del5, the latter two being
RT   relatively common mutations.";
RL   Hum. Mutat. 12:338-343(1998).
RN   [96]
RP   VARIANTS TPLL GLY-2139; VAL-2890 AND CYS-3008.
RX   PubMed=9488043; DOI=10.1038/sj.onc.1201603;
RA   Yuille M.A.R., Coignet L.J.A., Abraham S.M., Yaqub F., Luo L., Matutes E.,
RA   Brito-Babapulle V., Vorechovsky I., Dyer M.J.S., Catovsky D.;
RT   "ATM is usually rearranged in T-cell prolymphocytic leukaemia.";
RL   Oncogene 16:789-796(1998).
RN   [97]
RP   ERRATUM OF PUBMED:9488043.
RA   Yuille M.A.R., Coignet L.J.A., Abraham S.M., Yaqub F., Luo L., Matutes E.,
RA   Brito-Babapulle V., Vorechovsky I., Dyer M.J.S., Catovsky D.;
RL   Oncogene 16:2955-2955(1998).
RN   [98]
RP   POSSIBLE INVOLVEMENT IN BCLL AND MCL, AND VARIANTS ASN-1853; VAL-1853;
RP   ARG-1953; LYS-2418 INS; PRO-2420; GLY-2423; HIS-3008 AND ASN-3018.
RX   PubMed=10397742;
RA   Schaffner C., Stilgenbauer S., Rappold G.A., Doehner H., Lichter P.;
RT   "Somatic ATM mutations indicate a pathogenic role of ATM in B-cell chronic
RT   lymphocytic leukemia.";
RL   Blood 94:748-753(1999).
RN   [99]
RP   POSSIBLE INVOLVEMENT IN BCLL, AND VARIANTS CYS-332; ARG-1691 AND GLY-2424.
RX   PubMed=9892178;
RA   Bullrich F., Rasio D., Kitada S., Starostik P., Kipps T., Keating M.,
RA   Albitar M., Reed J.C., Croce C.M.;
RT   "ATM mutations in B-cell chronic lymphocytic leukemia.";
RL   Cancer Res. 59:24-27(1999).
RN   [100]
RP   VARIANT AT PRO-1465.
RX   PubMed=10234507; DOI=10.1038/sj.ejhg.5200288;
RA   Izatt L., Vessey C., Hodgson S.V., Solomon E.;
RT   "Rapid and efficient ATM mutation detection by fluorescent chemical
RT   cleavage of mismatch: identification of four novel mutations.";
RL   Eur. J. Hum. Genet. 7:310-320(1999).
RN   [101]
RP   VARIANTS CYS-49; LEU-182; PRO-707; LEU-858; PHE-1420; ALA-1570; ASN-1853
RP   AND SER-2765.
RX   PubMed=10534763;
RX   DOI=10.1002/(sici)1098-2264(199912)26:4<286::aid-gcc2>3.3.co;2-o;
RA   Izatt L., Greenman J., Hodgson S.V., Ellis D., Watts S., Scott G.,
RA   Jacobs C., Liebmann R., Zvelebil M.J., Mathew C., Solomon E.;
RT   "Identification of germline missense mutations and rare allelic variants in
RT   the ATM gene in early-onset breast cancer.";
RL   Genes Chromosomes Cancer 26:286-294(1999).
RN   [102]
RP   VARIANTS AT SER-570; CYS-785; GLY-1913; GLY-2016; ASP-2067; CYS-2227;
RP   ASP-2470; VAL-2662 DEL; PRO-2849 AND ARG-2867, AND VARIANTS CYS-49;
RP   LEU-858; ARG-1054; ASN-1853 AND VAL-1853.
RX   PubMed=9887333; DOI=10.1093/hmg/8.1.69;
RA   Sandoval N., Platzer M., Rosenthal A., Doerk T., Bendix R., Skawran B.,
RA   Stuhrmann M., Wegner R.-D., Sperling K., Banin S., Shiloh Y., Baumer A.,
RA   Bernthaler U., Sennefelder H., Brohm M., Weber B.H.F., Schindler D.;
RT   "Characterization of ATM gene mutations in 66 ataxia telangiectasia
RT   families.";
RL   Hum. Mol. Genet. 8:69-79(1999).
RN   [103]
RP   VARIANTS AT 375-GLN--VAL-3056 DEL; 1466-ARG--VAL-3056 DEL;
RP   1730-ARG--VAL-3056 DEL; GLY-2016; 2224-MET--ARG-2227 DELINS ILE-SER;
RP   2246-CYS--THR-2252 DELINS HIS; VAL-2664 DEL; VAL-2726; 2849-ARG--VAL-3056
RP   DEL AND ARG-2855, AND VARIANT CYS-49.
RX   PubMed=10425038;
RX   DOI=10.1002/(sici)1098-1004(1999)14:2<156::aid-humu7>3.0.co;2-e;
RA   Castellvi-Bel S., Sheikhavandi S., Telatar M., Tai L.-Q., Hwang M.J.,
RA   Wang Z., Yang Z., Cheng R., Gatti R.A.;
RT   "New mutations, polymorphisms, and rare variants in the ATM gene detected
RT   by a novel SSCP strategy.";
RL   Hum. Mutat. 14:156-162(1999).
RN   [104]
RP   POSSIBLE INVOLVEMENT IN BCLL, AND VARIANTS THR-350; THR-352; ARG-1054;
RP   THR-2274 AND ALA-2695.
RX   PubMed=10023947; DOI=10.1016/s0140-6736(98)10117-4;
RA   Stankovic T., Weber P., Stewart G., Bedenham T., Murray J., Byrd P.J.,
RA   Moss P.A.H., Taylor A.M.R.;
RT   "Inactivation of ataxia telangiectasia mutated gene in B-cell chronic
RT   lymphocytic leukaemia.";
RL   Lancet 353:26-29(1999).
RN   [105]
RP   VARIANT ARG-1054.
RX   PubMed=10217116; DOI=10.1016/s0140-6736(05)75199-0;
RA   Vorechovsky I., Luo L., Ortmann E., Steinmann D., Doerk T.;
RT   "Missense mutations at ATM gene and cancer risk.";
RL   Lancet 353:1276-1276(1999).
RN   [106]
RP   ERRATUM OF PUBMED:10217116.
RA   Vorechovsky I., Luo L., Ortmann E., Steinmann D., Doerk T.;
RL   Lancet 354:780-780(1999).
RN   [107]
RP   VARIANTS AT GLU-224; VAL-323; PRO-1420; CYS-2218; 2546-SER--ILE-2548 DEL;
RP   GLN-2625; CYS-2832; 2855-SER-VAL-2856 DELINS ARG-ILE AND CYS-3008, AND
RP   VARIANTS VAL-1853 AND ILE-2438.
RX   PubMed=10817650;
RX   DOI=10.1002/(sici)1096-8628(20000529)92:3<170::aid-ajmg3>3.0.co;2-#;
RA   Li A., Swift M.;
RT   "Mutations at the ataxia-telangiectasia locus and clinical phenotypes of A-
RT   T patients.";
RL   Am. J. Med. Genet. 92:170-177(2000).
RN   [108]
RP   VARIANTS AT 35-ARG--VAL-3056 DEL; LEU-292; 393-TRP--VAL-3056 DEL; ARG-950;
RP   LEU-1082; 1171-GLN--VAL-3056 DEL; 1839-GLN--VAL-3056 DEL; GLU-2063;
RP   CYS-2227; 2246-CYS--THR-2252 DELINS HIS; 2547-ARG--SER-2549 DEL; GLU-2625;
RP   PRO-2626 AND ARG-2702, AND VARIANT CYS-49.
RX   PubMed=10873394; DOI=10.1006/mgme.2000.2998;
RA   Becker-Catania S.G., Chen G., Hwang M.J., Wang Z., Sun X., Sanal O.,
RA   Bernatowska-Matuszkiewicz E., Chessa L., Lee E.Y.-H.P., Gatti R.A.;
RT   "Ataxia-telangiectasia: phenotype/genotype studies of ATM protein
RT   expression, mutations, and radiosensitivity.";
RL   Mol. Genet. Metab. 70:122-133(2000).
RN   [109]
RP   VARIANTS MCL LYS-2418 INS; GLY-2423 AND CYS-3008.
RX   PubMed=10706620; DOI=10.1073/pnas.050400997;
RA   Schaffner C., Idler I., Stilgenbauer S., Doehner H., Lichter P.;
RT   "Mantle cell lymphoma is characterized by inactivation of the ATM gene.";
RL   Proc. Natl. Acad. Sci. U.S.A. 97:2773-2778(2000).
RN   [110]
RP   VARIANTS TRP-45 AND CYS-49.
RX   PubMed=11897822; DOI=10.1136/jmg.39.3.192;
RA   Allinen M., Launonen V., Laake K., Jansen L., Huusko P., Kaeaeriaeinen H.,
RA   Boerresen-Dale A.L., Winqvist R.;
RT   "ATM mutations in Finnish breast cancer patients.";
RL   J. Med. Genet. 39:192-196(2002).
RN   [111]
RP   VARIANTS [LARGE SCALE ANALYSIS] GLN-23; CYS-49; GLU-126; HIS-140; GLN-250;
RP   PHE-333; CYS-337; HIS-337; ALA-410; SER-504; ASP-514; TYR-540; VAL-546;
RP   LEU-582; PRO-707; GLN-848; LEU-858; SER-872; TRP-924; ALA-935; ARG-1054;
RP   PHE-1179; ILE-1321; TYR-1380; SER-1382; PHE-1420; MET-1469; CYS-1475;
RP   SER-1650; THR-1739; ASN-1853; VAL-1853; ILE-1916; THR-1945; CYS-1961;
RP   ASP-1991; PHE-2307; PRO-2332; PHE-2356; LEU-2408; PRO-2442; GLN-2443;
RP   ARG-2464; ARG-2492; ALA-2666; HIS-2719; ARG-2842 AND ASN-2870.
RX   PubMed=17344846; DOI=10.1038/nature05610;
RA   Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA   Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA   Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA   Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA   Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA   Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA   Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA   Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA   Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA   Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA   Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA   Futreal P.A., Stratton M.R.;
RT   "Patterns of somatic mutation in human cancer genomes.";
RL   Nature 446:153-158(2007).
RN   [112]
RP   VARIANTS CYS-49; LEU-858; ARG-1054; VAL-1255; ASN-1853; THR-2105; SER-2396
RP   AND HIS-2719.
RX   PubMed=18384426; DOI=10.1111/j.1399-0004.2008.00987.x;
RA   Brunet J., Gutierrez-Enriquez S., Torres A., Berez V., Sanjose S.,
RA   Galceran J., Izquierdo A., Menendez J.A., Guma J., Borras J.;
RT   "ATM germline mutations in Spanish early-onset breast cancer patients
RT   negative for BRCA1/BRCA2 mutations.";
RL   Clin. Genet. 73:465-473(2008).
RN   [113]
RP   FUNCTION, CHARACTERIZATION OF VARIANTS AT LEU-292; PRO-1465; ILE-1743;
RP   THR-2274; GLY-2424; 2427-LEU-ARG-2428 DEL; 2546-SER--ILE-2548 DEL;
RP   ASP-2554; GLY-2668; CYS-2827; 2855-SER-VAL-2856 DELINS ARG-ILE AND
RP   CYS-3008, CHARACTERIZATION OF VARIANTS VAL-546; ARG-1054; ILE-1322;
RP   ARG-1691; CYS-1961 AND SER-2765, VARIANT ILE-1322, AND MUTAGENESIS OF
RP   LYS-1807; VAL-1941; TYR-2019; GLU-2039; LEU-2338; SER-2394; LEU-2452;
RP   SER-2685; PRO-2699; ASP-2708 AND GLN-2730.
RX   PubMed=19431188; DOI=10.1002/humu.21034;
RA   Barone G., Groom A., Reiman A., Srinivasan V., Byrd P.J., Taylor A.M.;
RT   "Modeling ATM mutant proteins from missense changes confirms retained
RT   kinase activity.";
RL   Hum. Mutat. 30:1222-1230(2009).
RN   [114]
RP   VARIANTS ALA-661; PRO-707; LEU-858; TRP-924; ARG-1054; ARG-1691 AND
RP   VAL-1853.
RX   PubMed=28202063; DOI=10.1186/s12920-017-0244-7;
RA   Jalkh N., Chouery E., Haidar Z., Khater C., Atallah D., Ali H.,
RA   Marafie M.J., Al-Mulla M.R., Al-Mulla F., Megarbane A.;
RT   "Next-generation sequencing in familial breast cancer patients from
RT   Lebanon.";
RL   BMC Med. Genomics 10:8-8(2017).
RN   [115]
RP   VARIANTS AT VAL-323; PRO-1046; ARG-2023; SER-2068; ASP-2080; HIS-2627;
RP   LEU-2834 AND ASP-3003, CHARACTERIZATION OF VARIANTS AT VAL-323; PRO-1046;
RP   ARG-2023; SER-2068; ASP-2080; HIS-2627; LEU-2834 AND ASP-3003, AND
RP   PHOSPHORYLATION.
RX   PubMed=27664052; DOI=10.1007/s12017-016-8440-8;
RA   Carranza D., Vega A.K., Torres-Rusillo S., Montero E., Martinez L.J.,
RA   Santamaria M., Santos J.L., Molina I.J.;
RT   "Molecular and functional characterization of a cohort of Spanish patients
RT   with ataxia-telangiectasia.";
RL   NeuroMolecular Med. 19:161-174(2017).
RN   [116]
RP   VARIANTS VAL-68; ILE-341; LEU-597; GLY-699; GLY-759; SER-813; GLY-869;
RP   ILE-897; ASP-1474; VAL-1488; CYS-1961; ALA-2287; PHE-2307; ARG-2464;
RP   PRO-2524; THR-2531; GLN-2810; HIS-2832; LEU-2974; ASP-3029 AND LEU-3056.
RX   PubMed=28726808; DOI=10.1038/gim.2017.85;
RA   Chaffee K.G., Oberg A.L., McWilliams R.R., Majithia N., Allen B.A.,
RA   Kidd J., Singh N., Hartman A.R., Wenstrup R.J., Petersen G.M.;
RT   "Prevalence of germ-line mutations in cancer genes among pancreatic cancer
RT   patients with a positive family history.";
RL   Genet. Med. 20:119-127(2018).
CC   -!- FUNCTION: Serine/threonine protein kinase which activates checkpoint
CC       signaling upon double strand breaks (DSBs), apoptosis and genotoxic
CC       stresses such as ionizing ultraviolet A light (UVA), thereby acting as
CC       a DNA damage sensor (PubMed:10550055, PubMed:10839545, PubMed:10910365,
CC       PubMed:12556884, PubMed:14871926, PubMed:15064416, PubMed:15448695,
CC       PubMed:15456891, PubMed:15790808, PubMed:15916964, PubMed:17923702,
CC       PubMed:21757780, PubMed:24534091, PubMed:35076389, PubMed:9733514).
CC       Recognizes the substrate consensus sequence [ST]-Q (PubMed:10550055,
CC       PubMed:10839545, PubMed:10910365, PubMed:12556884, PubMed:14871926,
CC       PubMed:15448695, PubMed:15456891, PubMed:15916964, PubMed:17923702,
CC       PubMed:24534091, PubMed:9733514). Phosphorylates 'Ser-139' of histone
CC       variant H2AX at double strand breaks (DSBs), thereby regulating DNA
CC       damage response mechanism (By similarity). Also plays a role in pre-B
CC       cell allelic exclusion, a process leading to expression of a single
CC       immunoglobulin heavy chain allele to enforce clonality and monospecific
CC       recognition by the B-cell antigen receptor (BCR) expressed on
CC       individual B-lymphocytes. After the introduction of DNA breaks by the
CC       RAG complex on one immunoglobulin allele, acts by mediating a
CC       repositioning of the second allele to pericentromeric heterochromatin,
CC       preventing accessibility to the RAG complex and recombination of the
CC       second allele. Also involved in signal transduction and cell cycle
CC       control. May function as a tumor suppressor. Necessary for activation
CC       of ABL1 and SAPK. Phosphorylates DYRK2, CHEK2, p53/TP53, FBXW7, FANCD2,
CC       NFKBIA, BRCA1, CREBBP/CBP, RBBP8/CTIP, FBXO46, MRE11, nibrin (NBN),
CC       RAD50, RAD17, PELI1, TERF1, UFL1, RAD9, UBQLN4 and DCLRE1C
CC       (PubMed:10550055, PubMed:10766245, PubMed:10802669, PubMed:10839545,
CC       PubMed:10910365, PubMed:10973490, PubMed:11375976, PubMed:12086603,
CC       PubMed:15456891, PubMed:19965871, PubMed:21757780, PubMed:24534091,
CC       PubMed:26240375, PubMed:26774286, PubMed:30171069, PubMed:30612738,
CC       PubMed:30886146, PubMed:30952868, PubMed:38128537, PubMed:9733515,
CC       PubMed:9843217). May play a role in vesicle and/or protein transport.
CC       Could play a role in T-cell development, gonad and neurological
CC       function. Plays a role in replication-dependent histone mRNA
CC       degradation. Binds DNA ends. Phosphorylation of DYRK2 in nucleus in
CC       response to genotoxic stress prevents its MDM2-mediated ubiquitination
CC       and subsequent proteasome degradation (PubMed:19965871). Phosphorylates
CC       ATF2 which stimulates its function in DNA damage response
CC       (PubMed:15916964). Phosphorylates ERCC6 which is essential for its
CC       chromatin remodeling activity at DNA double-strand breaks
CC       (PubMed:29203878). Phosphorylates TTC5/STRAP at 'Ser-203' in the
CC       cytoplasm in response to DNA damage, which promotes TTC5/STRAP nuclear
CC       localization (PubMed:15448695). Also involved in pexophagy by mediating
CC       phosphorylation of PEX5: translocated to peroxisomes in response to
CC       reactive oxygen species (ROS), and catalyzes phosphorylation of PEX5,
CC       promoting PEX5 ubiquitination and induction of pexophagy
CC       (PubMed:26344566). {ECO:0000250|UniProtKB:Q62388,
CC       ECO:0000269|PubMed:10550055, ECO:0000269|PubMed:10766245,
CC       ECO:0000269|PubMed:10802669, ECO:0000269|PubMed:10839545,
CC       ECO:0000269|PubMed:10910365, ECO:0000269|PubMed:10973490,
CC       ECO:0000269|PubMed:11375976, ECO:0000269|PubMed:12086603,
CC       ECO:0000269|PubMed:12556884, ECO:0000269|PubMed:14871926,
CC       ECO:0000269|PubMed:15448695, ECO:0000269|PubMed:15456891,
CC       ECO:0000269|PubMed:15916964, ECO:0000269|PubMed:16086026,
CC       ECO:0000269|PubMed:16858402, ECO:0000269|PubMed:17923702,
CC       ECO:0000269|PubMed:19431188, ECO:0000269|PubMed:19965871,
CC       ECO:0000269|PubMed:21757780, ECO:0000269|PubMed:24534091,
CC       ECO:0000269|PubMed:26240375, ECO:0000269|PubMed:26344566,
CC       ECO:0000269|PubMed:26774286, ECO:0000269|PubMed:29203878,
CC       ECO:0000269|PubMed:30171069, ECO:0000269|PubMed:30612738,
CC       ECO:0000269|PubMed:30886146, ECO:0000269|PubMed:30952868,
CC       ECO:0000269|PubMed:35076389, ECO:0000269|PubMed:38128537,
CC       ECO:0000269|PubMed:9733514, ECO:0000269|PubMed:9733515,
CC       ECO:0000269|PubMed:9843217}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP +
CC         H(+); Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC         COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC         Evidence={ECO:0000269|PubMed:15448695, ECO:0000269|PubMed:15790808,
CC         ECO:0000269|PubMed:16858402, ECO:0000269|PubMed:26240375,
CC         ECO:0000269|PubMed:26344566, ECO:0000269|PubMed:28508083,
CC         ECO:0000269|PubMed:30171069, ECO:0000269|PubMed:30886146,
CC         ECO:0000269|PubMed:30952868, ECO:0000269|PubMed:38128537,
CC         ECO:0000269|PubMed:8988033, ECO:0000269|PubMed:9843217};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990;
CC         Evidence={ECO:0000269|PubMed:15790808, ECO:0000269|PubMed:21757780,
CC         ECO:0000269|PubMed:26240375, ECO:0000269|PubMed:30952868,
CC         ECO:0000269|PubMed:9843217, ECO:0000305|PubMed:15448695};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] +
CC         ADP + H(+); Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-
CC         COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC         Evidence={ECO:0000269|PubMed:24534091, ECO:0000269|PubMed:28508083,
CC         ECO:0000269|PubMed:30952868, ECO:0000269|PubMed:8988033,
CC         ECO:0000269|PubMed:9843217};
CC   -!- ACTIVITY REGULATION: Activated by the MRN (MRE11-RAD50-NBS1) complex in
CC       response to DNA double strand breaks (DSBs), which recruits ATM to DSBs
CC       and promotes its activation (PubMed:15064416, PubMed:15790808,
CC       PubMed:35076389). Inhibited by wortmannin (PubMed:9766667).
CC       {ECO:0000269|PubMed:15064416, ECO:0000269|PubMed:15790808,
CC       ECO:0000269|PubMed:35076389, ECO:0000269|PubMed:9766667}.
CC   -!- SUBUNIT: Homodimer (PubMed:12556884, PubMed:15790808, PubMed:28508083).
CC       Dimers or tetramers in inactive state (PubMed:12556884,
CC       PubMed:15790808, PubMed:28508083). On DNA damage, autophosphorylation
CC       dissociates ATM into monomers rendering them catalytically active
CC       (PubMed:12556884, PubMed:28508083). Binds p53/TP53, ABL1, BRCA1 and
CC       TERF1 (PubMed:15790808, PubMed:9168117, PubMed:9843217). Interacts with
CC       NBN (via FxF/Y motif) (PubMed:35076389). Part of the BRCA1-associated
CC       genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6,
CC       MLH1, ATM, BLM, PMS2 and the RAD50-MRE11-NBN protein complex
CC       (PubMed:10783165). This association could be a dynamic process changing
CC       throughout the cell cycle and within subnuclear domains
CC       (PubMed:10783165). Interacts with RAD17; DNA damage promotes the
CC       association (PubMed:11418864). Interacts with EEF1E1; the interaction,
CC       induced on DNA damage, up-regulates TP53 (PubMed:15680327). Interacts
CC       with KAT8, NABP2, ATMIN and CEP164 (PubMed:15923642, PubMed:17525732,
CC       PubMed:18283122, PubMed:18449195). Interacts with AP2B1 and AP3B2; the
CC       interaction occurs in cytoplasmic vesicles (By similarity). Interacts
CC       with TELO2 and TTI1 (PubMed:20427287, PubMed:20801936,
CC       PubMed:20810650). Interacts with DDX1 (PubMed:18710941). Interacts with
CC       BRAT1 (PubMed:22977523). Interacts with CYREN (via XLF motif) (By
CC       similarity). Interacts (via microbody targeting signal) with PEX5;
CC       promoting translocation to peroxisomes in response to reactive oxygen
CC       species (ROS) (PubMed:26344566). {ECO:0000250|UniProtKB:Q62388,
CC       ECO:0000269|PubMed:10783165, ECO:0000269|PubMed:11418864,
CC       ECO:0000269|PubMed:12556884, ECO:0000269|PubMed:15680327,
CC       ECO:0000269|PubMed:15790808, ECO:0000269|PubMed:15923642,
CC       ECO:0000269|PubMed:17525732, ECO:0000269|PubMed:18283122,
CC       ECO:0000269|PubMed:18449195, ECO:0000269|PubMed:18710941,
CC       ECO:0000269|PubMed:20427287, ECO:0000269|PubMed:20801936,
CC       ECO:0000269|PubMed:20810650, ECO:0000269|PubMed:22977523,
CC       ECO:0000269|PubMed:26344566, ECO:0000269|PubMed:28508083,
CC       ECO:0000269|PubMed:35076389, ECO:0000269|PubMed:9168117,
CC       ECO:0000269|PubMed:9843217}.
CC   -!- INTERACTION:
CC       Q13315; Q9NY61: AATF; NbExp=3; IntAct=EBI-495465, EBI-372428;
CC       Q13315; P00519: ABL1; NbExp=4; IntAct=EBI-495465, EBI-375543;
CC       Q13315; P31749: AKT1; NbExp=5; IntAct=EBI-495465, EBI-296087;
CC       Q13315; O43313: ATMIN; NbExp=5; IntAct=EBI-495465, EBI-7422202;
CC       Q13315; Q6PJG6: BRAT1; NbExp=3; IntAct=EBI-495465, EBI-10826195;
CC       Q13315; P62508-3: ESRRG; NbExp=3; IntAct=EBI-495465, EBI-12001340;
CC       Q13315; Q5XUX0: FBXO31; NbExp=2; IntAct=EBI-495465, EBI-6162477;
CC       Q13315; Q9Y6K9: IKBKG; NbExp=4; IntAct=EBI-495465, EBI-81279;
CC       Q13315; Q13007: IL24; NbExp=2; IntAct=EBI-495465, EBI-3915542;
CC       Q13315; Q14676: MDC1; NbExp=3; IntAct=EBI-495465, EBI-495644;
CC       Q13315; Q9BQ15: NABP2; NbExp=4; IntAct=EBI-495465, EBI-2120336;
CC       Q13315; P11245: NAT2; NbExp=2; IntAct=EBI-495465, EBI-9057228;
CC       Q13315; O60934: NBN; NbExp=2; IntAct=EBI-495465, EBI-494844;
CC       Q13315; P46531: NOTCH1; NbExp=8; IntAct=EBI-495465, EBI-636374;
CC       Q13315; Q9BZ95: NSD3; NbExp=3; IntAct=EBI-495465, EBI-3390132;
CC       Q13315; Q7LG56: RRM2B; NbExp=3; IntAct=EBI-495465, EBI-9009083;
CC       Q13315; Q9Y4R8: TELO2; NbExp=4; IntAct=EBI-495465, EBI-1043674;
CC       Q13315; P54274: TERF1; NbExp=3; IntAct=EBI-495465, EBI-710997;
CC       Q13315; P54274-2: TERF1; NbExp=5; IntAct=EBI-495465, EBI-711018;
CC       Q13315; Q15554: TERF2; NbExp=2; IntAct=EBI-495465, EBI-706637;
CC       Q13315; Q12888: TP53BP1; NbExp=2; IntAct=EBI-495465, EBI-396540;
CC       Q13315; O43156: TTI1; NbExp=5; IntAct=EBI-495465, EBI-1055680;
CC       Q13315; PRO_0000037577 [P27958]; Xeno; NbExp=3; IntAct=EBI-495465, EBI-6904388;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:9050866,
CC       ECO:0000269|PubMed:9150358}. Cytoplasmic vesicle
CC       {ECO:0000269|PubMed:9050866, ECO:0000269|PubMed:9150358}. Cytoplasm,
CC       cytoskeleton, microtubule organizing center, centrosome
CC       {ECO:0000250|UniProtKB:Q62388}. Peroxisome matrix
CC       {ECO:0000269|PubMed:26344566}. Note=Primarily nuclear (PubMed:9050866,
CC       PubMed:9150358). Found also in endocytic vesicles in association with
CC       beta-adaptin (PubMed:9707615). Translocated to peroxisomes in response
CC       to reactive oxygen species (ROS) by PEX5 (PubMed:26344566).
CC       {ECO:0000269|PubMed:26344566, ECO:0000269|PubMed:9050866,
CC       ECO:0000269|PubMed:9150358, ECO:0000269|PubMed:9707615}.
CC   -!- TISSUE SPECIFICITY: Found in pancreas, kidney, skeletal muscle, liver,
CC       lung, placenta, brain, heart, spleen, thymus, testis, ovary, small
CC       intestine, colon and leukocytes.
CC   -!- INDUCTION: By ionizing radiation.
CC   -!- DOMAIN: The FATC domain is required for interaction with KAT5.
CC       {ECO:0000269|PubMed:16141325}.
CC   -!- PTM: Phosphorylated by NUAK1/ARK5 (PubMed:12409306).
CC       Autophosphorylation on Ser-367, Ser-1893, Ser-1981 correlates with DNA
CC       damage-mediated activation of the kinase (PubMed:12556884,
CC       PubMed:15790808, PubMed:16141325, PubMed:16858402, PubMed:21144835,
CC       PubMed:27664052). During the late stages of DNA damage response,
CC       dephosphorylated following deacetylation by SIRT7, leading to ATM
CC       deactivation (PubMed:30944854). {ECO:0000269|PubMed:12409306,
CC       ECO:0000269|PubMed:12556884, ECO:0000269|PubMed:15790808,
CC       ECO:0000269|PubMed:16141325, ECO:0000269|PubMed:16858402,
CC       ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:27664052,
CC       ECO:0000269|PubMed:30944854}.
CC   -!- PTM: Acetylation, on DNA damage, is required for activation of the
CC       kinase activity, dimer-monomer transition, and subsequent
CC       autophosphorylation on Ser-1981 (PubMed:12556884, PubMed:16141325,
CC       PubMed:16858402, PubMed:17923702, PubMed:21144835). Acetylated in vitro
CC       by KAT5/TIP60 (PubMed:16141325). Deacetylated by SIRT7 during the late
CC       stages of DNA damage response, promoting ATM dephosphorylation and
CC       subsequent deactivation (PubMed:30944854).
CC       {ECO:0000269|PubMed:12556884, ECO:0000269|PubMed:16141325,
CC       ECO:0000269|PubMed:16858402, ECO:0000269|PubMed:17923702,
CC       ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:30944854}.
CC   -!- DISEASE: Ataxia telangiectasia (AT) [MIM:208900]: A rare recessive
CC       disorder characterized by progressive cerebellar ataxia, dilation of
CC       the blood vessels in the conjunctiva and eyeballs, immunodeficiency,
CC       growth retardation and sexual immaturity. Patients have a strong
CC       predisposition to cancer; about 30% of patients develop tumors,
CC       particularly lymphomas and leukemias. Cells from affected individuals
CC       are highly sensitive to damage by ionizing radiation and resistant to
CC       inhibition of DNA synthesis following irradiation.
CC       {ECO:0000269|PubMed:10234507, ECO:0000269|PubMed:10425038,
CC       ECO:0000269|PubMed:10817650, ECO:0000269|PubMed:10873394,
CC       ECO:0000269|PubMed:19431188, ECO:0000269|PubMed:27664052,
CC       ECO:0000269|PubMed:7792600, ECO:0000269|PubMed:8589678,
CC       ECO:0000269|PubMed:8665503, ECO:0000269|PubMed:8698354,
CC       ECO:0000269|PubMed:8755918, ECO:0000269|PubMed:8789452,
CC       ECO:0000269|PubMed:8797579, ECO:0000269|PubMed:8808599,
CC       ECO:0000269|PubMed:8845835, ECO:0000269|PubMed:9043869,
CC       ECO:0000269|PubMed:9150358, ECO:0000269|PubMed:9443866,
CC       ECO:0000269|PubMed:9450874, ECO:0000269|PubMed:9463314,
CC       ECO:0000269|PubMed:9497252, ECO:0000269|PubMed:9521587,
CC       ECO:0000269|PubMed:9711876, ECO:0000269|PubMed:9792409,
CC       ECO:0000269|PubMed:9792410, ECO:0000269|PubMed:9872980,
CC       ECO:0000269|PubMed:9887333}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- DISEASE: Note=Defects in ATM may contribute to T-cell acute
CC       lymphoblastic leukemia (TALL) and T-prolymphocytic leukemia (TPLL).
CC       TPLL is characterized by a high white blood cell count, with a
CC       predominance of prolymphocytes, marked splenomegaly, lymphadenopathy,
CC       skin lesions and serous effusion. The clinical course is highly
CC       aggressive, with poor response to chemotherapy and short survival time.
CC       TPLL occurs both in adults as a sporadic disease and in younger AT
CC       patients. {ECO:0000269|PubMed:9288106, ECO:0000269|PubMed:9334731,
CC       ECO:0000269|PubMed:9463314, ECO:0000269|PubMed:9488043,
CC       ECO:0000269|PubMed:9573030}.
CC   -!- DISEASE: Note=Defects in ATM may contribute to B-cell non-Hodgkin
CC       lymphomas (BNHL), including mantle cell lymphoma (MCL).
CC       {ECO:0000269|PubMed:10397742, ECO:0000269|PubMed:10706620,
CC       ECO:0000269|PubMed:9288106}.
CC   -!- DISEASE: Note=Defects in ATM may contribute to B-cell chronic
CC       lymphocytic leukemia (BCLL). BCLL is the commonest form of leukemia in
CC       the elderly. It is characterized by the accumulation of mature CD5+ B-
CC       lymphocytes, lymphadenopathy, immunodeficiency and bone marrow failure.
CC       {ECO:0000269|PubMed:10023947, ECO:0000269|PubMed:10397742,
CC       ECO:0000269|PubMed:9892178}.
CC   -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. ATM subfamily.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAA86520.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC       Sequence=AAA86520.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};
CC       Sequence=AAI37170.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC       Sequence=AAI37170.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};
CC       Sequence=EAW67111.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC       Haematology;
CC       URL="https://atlasgeneticsoncology.org/gene/123/ATM";
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Ataxia telangiectasia mutated entry;
CC       URL="https://en.wikipedia.org/wiki/Ataxia_telangiectasia_mutated";
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DR   EMBL; U33841; AAC50289.1; -; mRNA.
DR   EMBL; U55757; AAB38309.1; -; Genomic_DNA.
DR   EMBL; U55704; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55705; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55707; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55708; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55709; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55710; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55711; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55712; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55713; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55714; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55715; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55716; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55717; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55718; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55719; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55720; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55721; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55722; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55723; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55724; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55725; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55726; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55727; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55728; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55729; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55730; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55731; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55732; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55733; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55734; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55735; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55736; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55737; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55738; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55739; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55740; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55741; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55742; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55743; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55744; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55745; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55746; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55747; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55748; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55749; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55750; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55751; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55752; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55753; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55754; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55755; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55756; AAB38309.1; JOINED; Genomic_DNA.
DR   EMBL; U55757; AAB38310.1; -; Genomic_DNA.
DR   EMBL; U55726; AAB38310.1; JOINED; Genomic_DNA.
DR   EMBL; U55727; AAB38310.1; JOINED; Genomic_DNA.
DR   EMBL; U55728; AAB38310.1; JOINED; Genomic_DNA.
DR   EMBL; U55729; AAB38310.1; JOINED; Genomic_DNA.
DR   EMBL; U55730; AAB38310.1; JOINED; Genomic_DNA.
DR   EMBL; U55731; AAB38310.1; JOINED; Genomic_DNA.
DR   EMBL; U55732; AAB38310.1; JOINED; Genomic_DNA.
DR   EMBL; U55733; AAB38310.1; JOINED; Genomic_DNA.
DR   EMBL; U55734; AAB38310.1; JOINED; Genomic_DNA.
DR   EMBL; U55735; AAB38310.1; JOINED; Genomic_DNA.
DR   EMBL; U55736; AAB38310.1; JOINED; Genomic_DNA.
DR   EMBL; U55737; AAB38310.1; JOINED; Genomic_DNA.
DR   EMBL; U55738; AAB38310.1; JOINED; Genomic_DNA.
DR   EMBL; U55739; AAB38310.1; JOINED; Genomic_DNA.
DR   EMBL; U55740; AAB38310.1; JOINED; Genomic_DNA.
DR   EMBL; U55741; AAB38310.1; JOINED; Genomic_DNA.
DR   EMBL; U55742; AAB38310.1; JOINED; Genomic_DNA.
DR   EMBL; U55743; AAB38310.1; JOINED; Genomic_DNA.
DR   EMBL; U55744; AAB38310.1; JOINED; Genomic_DNA.
DR   EMBL; U55745; AAB38310.1; JOINED; Genomic_DNA.
DR   EMBL; U55746; AAB38310.1; JOINED; Genomic_DNA.
DR   EMBL; U55747; AAB38310.1; JOINED; Genomic_DNA.
DR   EMBL; U55748; AAB38310.1; JOINED; Genomic_DNA.
DR   EMBL; U55749; AAB38310.1; JOINED; Genomic_DNA.
DR   EMBL; U55750; AAB38310.1; JOINED; Genomic_DNA.
DR   EMBL; U55751; AAB38310.1; JOINED; Genomic_DNA.
DR   EMBL; U55752; AAB38310.1; JOINED; Genomic_DNA.
DR   EMBL; U55753; AAB38310.1; JOINED; Genomic_DNA.
DR   EMBL; U55754; AAB38310.1; JOINED; Genomic_DNA.
DR   EMBL; U55755; AAB38310.1; JOINED; Genomic_DNA.
DR   EMBL; U55756; AAB38310.1; JOINED; Genomic_DNA.
DR   EMBL; U82828; AAB65827.1; -; Genomic_DNA.
DR   EMBL; AP001925; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AP005718; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; KF455499; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471065; EAW67111.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; X91196; CAA62603.1; -; mRNA.
DR   EMBL; U67092; AAC51298.1; -; Genomic_DNA.
DR   EMBL; AY220758; AAO26044.1; -; Genomic_DNA.
DR   EMBL; U26455; AAA86520.1; ALT_SEQ; mRNA.
DR   EMBL; BC137169; AAI37170.1; ALT_SEQ; mRNA.
DR   CCDS; CCDS31669.1; -.
DR   PIR; A43100; A43100.
DR   RefSeq; NP_000042.3; NM_000051.3.
DR   RefSeq; NP_001338763.1; NM_001351834.2.
DR   RefSeq; XP_005271619.2; XM_005271562.6.
DR   RefSeq; XP_006718906.1; XM_006718843.5.
DR   RefSeq; XP_006718908.1; XM_006718845.1.
DR   RefSeq; XP_011541142.1; XM_011542840.4.
DR   RefSeq; XP_016873279.1; XM_017017790.3.
DR   RefSeq; XP_047282931.1; XM_047426975.1.
DR   RefSeq; XP_047282932.1; XM_047426976.1.
DR   RefSeq; XP_054224846.1; XM_054368871.1.
DR   RefSeq; XP_054224847.1; XM_054368872.1.
DR   RefSeq; XP_054224848.1; XM_054368873.1.
DR   RefSeq; XP_054224849.1; XM_054368874.1.
DR   RefSeq; XP_054224850.1; XM_054368875.1.
DR   RefSeq; XP_054224851.1; XM_054368876.1.
DR   PDB; 5NP0; EM; 5.70 A; A/B=1-3056.
DR   PDB; 5NP1; EM; 5.70 A; A=1-3056.
DR   PDB; 6HKA; NMR; -; A=3024-3056.
DR   PDB; 6K9K; EM; 7.82 A; A=1-3056.
DR   PDB; 6K9L; EM; 4.27 A; A/B=1-3056.
DR   PDB; 7NI4; EM; 3.00 A; A/B=1-3056.
DR   PDB; 7NI5; EM; 2.78 A; A/B=1-3056.
DR   PDB; 7NI6; EM; 2.80 A; A/B=1-3056.
DR   PDB; 7SIC; EM; 2.51 A; A/B=1-3056.
DR   PDB; 7SID; EM; 2.53 A; A/C=1-3056.
DR   PDB; 8OXM; EM; 3.30 A; A/B=1-3056.
DR   PDB; 8OXO; EM; 3.00 A; A/B=1-3056.
DR   PDB; 8OXP; EM; 2.60 A; A/B=1-3056.
DR   PDB; 8OXQ; EM; 2.50 A; A/B=1-3056.
DR   PDBsum; 5NP0; -.
DR   PDBsum; 5NP1; -.
DR   PDBsum; 6HKA; -.
DR   PDBsum; 6K9K; -.
DR   PDBsum; 6K9L; -.
DR   PDBsum; 7NI4; -.
DR   PDBsum; 7NI5; -.
DR   PDBsum; 7NI6; -.
DR   PDBsum; 7SIC; -.
DR   PDBsum; 7SID; -.
DR   PDBsum; 8OXM; -.
DR   PDBsum; 8OXO; -.
DR   PDBsum; 8OXP; -.
DR   PDBsum; 8OXQ; -.
DR   EMDB; EMD-12350; -.
DR   EMDB; EMD-12351; -.
DR   EMDB; EMD-12352; -.
DR   EMDB; EMD-17265; -.
DR   EMDB; EMD-17266; -.
DR   EMDB; EMD-17267; -.
DR   EMDB; EMD-17268; -.
DR   EMDB; EMD-25140; -.
DR   EMDB; EMD-25141; -.
DR   EMDB; EMD-3669; -.
DR   EMDB; EMD-3672; -.
DR   EMDB; EMD-9949; -.
DR   EMDB; EMD-9950; -.
DR   SMR; Q13315; -.
DR   BioGRID; 106962; 345.
DR   CORUM; Q13315; -.
DR   DIP; DIP-182N; -.
DR   FunCoup; Q13315; 3527.
DR   IntAct; Q13315; 175.
DR   MINT; Q13315; -.
DR   STRING; 9606.ENSP00000278616; -.
DR   BindingDB; Q13315; -.
DR   ChEMBL; CHEMBL3797; -.
DR   DrugBank; DB02289; 2-Aminopropanedioic Acid.
DR   DrugBank; DB00201; Caffeine.
DR   GuidetoPHARMACOLOGY; 1934; -.
DR   GlyCosmos; Q13315; 4 sites, 2 glycans.
DR   GlyGen; Q13315; 7 sites, 2 O-linked glycans (6 sites).
DR   iPTMnet; Q13315; -.
DR   PhosphoSitePlus; Q13315; -.
DR   BioMuta; ATM; -.
DR   DMDM; 317373479; -.
DR   CPTAC; CPTAC-2874; -.
DR   CPTAC; CPTAC-2875; -.
DR   CPTAC; CPTAC-2876; -.
DR   CPTAC; CPTAC-3210; -.
DR   CPTAC; CPTAC-3211; -.
DR   CPTAC; CPTAC-3212; -.
DR   CPTAC; CPTAC-3213; -.
DR   CPTAC; CPTAC-5976; -.
DR   CPTAC; CPTAC-5977; -.
DR   CPTAC; CPTAC-5978; -.
DR   CPTAC; CPTAC-5979; -.
DR   CPTAC; CPTAC-912; -.
DR   CPTAC; CPTAC-913; -.
DR   jPOST; Q13315; -.
DR   MassIVE; Q13315; -.
DR   PaxDb; 9606-ENSP00000278616; -.
DR   PeptideAtlas; Q13315; -.
DR   ProteomicsDB; 59303; -.
DR   Pumba; Q13315; -.
DR   Antibodypedia; 3596; 1462 antibodies from 49 providers.
DR   CPTC; Q13315; 4 antibodies.
DR   DNASU; 472; -.
DR   Ensembl; ENST00000278616.10; ENSP00000278616.4; ENSG00000149311.23.
DR   Ensembl; ENST00000452508.7; ENSP00000388058.2; ENSG00000149311.23.
DR   Ensembl; ENST00000601453.3; ENSP00000469471.2; ENSG00000149311.23.
DR   Ensembl; ENST00000675843.1; ENSP00000501606.1; ENSG00000149311.23.
DR   Ensembl; ENST00000713844.1; ENSP00000519149.1; ENSG00000149311.23.
DR   GeneID; 472; -.
DR   KEGG; hsa:472; -.
DR   MANE-Select; ENST00000675843.1; ENSP00000501606.1; NM_000051.4; NP_000042.3.
DR   UCSC; uc001pkb.1; human.
DR   AGR; HGNC:795; -.
DR   CIViC; 472; 50 evidence items across 37 molecular profiles.
DR   ClinPGx; PA61; -.
DR   CTD; 472; -.
DR   DisGeNET; 472; -.
DR   GeneCards; ATM; -.
DR   GeneReviews; ATM; -.
DR   HGNC; HGNC:795; ATM.
DR   HPA; ENSG00000149311; Low tissue specificity.
DR   MalaCards; ATM; -.
DR   MIM; 208900; phenotype.
DR   MIM; 607585; gene.
DR   OpenTargets; ENSG00000149311; -.
DR   Orphanet; 100; Ataxia-telangiectasia.
DR   Orphanet; 370109; Ataxia-telangiectasia variant.
DR   Orphanet; 67038; B-cell chronic lymphocytic leukemia.
DR   Orphanet; 440437; Familial colorectal cancer Type X.
DR   Orphanet; 1331; Familial prostate cancer.
DR   Orphanet; 145; Hereditary breast and/or ovarian cancer syndrome.
DR   Orphanet; 227535; Hereditary breast cancer.
DR   Orphanet; 52416; Mantle cell lymphoma.
DR   VEuPathDB; HostDB:ENSG00000149311; -.
DR   eggNOG; KOG0892; Eukaryota.
DR   GeneTree; ENSGT00670000098061; -.
DR   HOGENOM; CLU_000178_3_1_1; -.
DR   InParanoid; Q13315; -.
DR   OMA; SEVYMKW; -.
DR   OrthoDB; 381190at2759; -.
DR   PAN-GO; Q13315; 7 GO annotations based on evolutionary models.
DR   PhylomeDB; Q13315; -.
DR   BRENDA; 2.7.11.1; 2681.
DR   PathwayCommons; Q13315; -.
DR   Reactome; R-HSA-2559586; DNA Damage/Telomere Stress Induced Senescence.
DR   Reactome; R-HSA-3371453; Regulation of HSF1-mediated heat shock response.
DR   Reactome; R-HSA-349425; Autodegradation of the E3 ubiquitin ligase COP1.
DR   Reactome; R-HSA-5685938; HDR through Single Strand Annealing (SSA).
DR   Reactome; R-HSA-5685942; HDR through Homologous Recombination (HRR).
DR   Reactome; R-HSA-5693548; Sensing of DNA Double Strand Breaks.
DR   Reactome; R-HSA-5693554; Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA).
DR   Reactome; R-HSA-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
DR   Reactome; R-HSA-5693568; Resolution of D-loop Structures through Holliday Junction Intermediates.
DR   Reactome; R-HSA-5693571; Nonhomologous End-Joining (NHEJ).
DR   Reactome; R-HSA-5693579; Homologous DNA Pairing and Strand Exchange.
DR   Reactome; R-HSA-5693607; Processing of DNA double-strand break ends.
DR   Reactome; R-HSA-5693616; Presynaptic phase of homologous DNA pairing and strand exchange.
DR   Reactome; R-HSA-6796648; TP53 Regulates Transcription of DNA Repair Genes.
DR   Reactome; R-HSA-6803204; TP53 Regulates Transcription of Genes Involved in Cytochrome C Release.
DR   Reactome; R-HSA-6803207; TP53 Regulates Transcription of Caspase Activators and Caspases.
DR   Reactome; R-HSA-6804756; Regulation of TP53 Activity through Phosphorylation.
DR   Reactome; R-HSA-6804757; Regulation of TP53 Degradation.
DR   Reactome; R-HSA-6804760; Regulation of TP53 Activity through Methylation.
DR   Reactome; R-HSA-69473; G2/M DNA damage checkpoint.
DR   Reactome; R-HSA-69541; Stabilization of p53.
DR   Reactome; R-HSA-912446; Meiotic recombination.
DR   Reactome; R-HSA-9664873; Pexophagy.
DR   Reactome; R-HSA-9701192; Defective homologous recombination repair (HRR) due to BRCA1 loss of function.
DR   Reactome; R-HSA-9704331; Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function.
DR   Reactome; R-HSA-9704646; Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function.
DR   Reactome; R-HSA-9709570; Impaired BRCA2 binding to RAD51.
DR   Reactome; R-HSA-9709603; Impaired BRCA2 binding to PALB2.
DR   SignaLink; Q13315; -.
DR   SIGNOR; Q13315; -.
DR   Agora; ENSG00000149311; -.
DR   BioGRID-ORCS; 472; 54 hits in 1215 CRISPR screens.
DR   CD-CODE; 8C2F96ED; Centrosome.
DR   CD-CODE; 91857CE7; Nucleolus.
DR   CD-CODE; A0DCDA94; DNA damage foci.
DR   ChiTaRS; ATM; human.
DR   GeneWiki; Ataxia_telangiectasia_mutated; -.
DR   GenomeRNAi; 472; -.
DR   Pharos; Q13315; Tchem.
DR   PRO; PR:Q13315; -.
DR   Proteomes; UP000005640; Chromosome 11.
DR   RNAct; Q13315; protein.
DR   Bgee; ENSG00000149311; Expressed in calcaneal tendon and 207 other cell types or tissues.
DR   ExpressionAtlas; Q13315; baseline and differential.
DR   GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR   GO; GO:0005694; C:chromosome; IBA:GO_Central.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:1990391; C:DNA repair complex; IDA:MGI.
DR   GO; GO:0098850; C:extrinsic component of synaptic vesicle membrane; IEA:Ensembl.
DR   GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0005634; C:nucleus; IDA:ParkinsonsUK-UCL.
DR   GO; GO:0005782; C:peroxisomal matrix; IDA:UniProtKB.
DR   GO; GO:0035861; C:site of double-strand break; IDA:UniProtKB.
DR   GO; GO:0005819; C:spindle; IEA:Ensembl.
DR   GO; GO:0016303; F:1-phosphatidylinositol-3-kinase activity; IMP:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR   GO; GO:0004677; F:DNA-dependent protein kinase activity; IDA:BHF-UCL.
DR   GO; GO:0035979; F:histone H2AXS139 kinase activity; ISS:UniProtKB.
DR   GO; GO:0042802; F:identical protein binding; IPI:BHF-UCL.
DR   GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR   GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR   GO; GO:0044877; F:protein-containing complex binding; IDA:BHF-UCL.
DR   GO; GO:0007420; P:brain development; IEA:Ensembl.
DR   GO; GO:0071480; P:cellular response to gamma radiation; IDA:CAFA.
DR   GO; GO:0071500; P:cellular response to nitrosative stress; IDA:ParkinsonsUK-UCL.
DR   GO; GO:0034614; P:cellular response to reactive oxygen species; IDA:UniProt.
DR   GO; GO:0071300; P:cellular response to retinoic acid; ISS:ARUK-UCL.
DR   GO; GO:0033554; P:cellular response to stress; IDA:UniProt.
DR   GO; GO:0071481; P:cellular response to X-ray; IDA:ParkinsonsUK-UCL.
DR   GO; GO:0090398; P:cellular senescence; TAS:Reactome.
DR   GO; GO:0008340; P:determination of adult lifespan; IEA:Ensembl.
DR   GO; GO:0000077; P:DNA damage checkpoint signaling; IDA:UniProtKB.
DR   GO; GO:0006974; P:DNA damage response; IDA:CAFA.
DR   GO; GO:0030330; P:DNA damage response, signal transduction by p53 class mediator; TAS:Reactome.
DR   GO; GO:0000729; P:DNA double-strand break processing; IDA:UniProt.
DR   GO; GO:0006302; P:double-strand break repair; IDA:UniProtKB.
DR   GO; GO:0000724; P:double-strand break repair via homologous recombination; IDA:UniProt.
DR   GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; TAS:Reactome.
DR   GO; GO:0097695; P:establishment of protein-containing complex localization to telomere; IMP:BHF-UCL.
DR   GO; GO:0097694; P:establishment of RNA localization to telomere; IMP:BHF-UCL.
DR   GO; GO:0007143; P:female meiotic nuclear division; IEA:Ensembl.
DR   GO; GO:0007507; P:heart development; IEA:Ensembl.
DR   GO; GO:0071044; P:histone mRNA catabolic process; IDA:UniProtKB.
DR   GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IBA:GO_Central.
DR   GO; GO:0042159; P:lipoprotein catabolic process; IEA:Ensembl.
DR   GO; GO:0007140; P:male meiotic nuclear division; IEA:Ensembl.
DR   GO; GO:0045141; P:meiotic telomere clustering; IEA:Ensembl.
DR   GO; GO:0007095; P:mitotic G2 DNA damage checkpoint signaling; IMP:BHF-UCL.
DR   GO; GO:0007094; P:mitotic spindle assembly checkpoint signaling; IMP:UniProtKB.
DR   GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl.
DR   GO; GO:0030889; P:negative regulation of B cell proliferation; IMP:UniProtKB.
DR   GO; GO:1904354; P:negative regulation of telomere capping; IMP:BHF-UCL.
DR   GO; GO:1904262; P:negative regulation of TORC1 signaling; IMP:ParkinsonsUK-UCL.
DR   GO; GO:0051402; P:neuron apoptotic process; IEA:Ensembl.
DR   GO; GO:0048599; P:oocyte development; IEA:Ensembl.
DR   GO; GO:0001541; P:ovarian follicle development; IEA:Ensembl.
DR   GO; GO:0036289; P:peptidyl-serine autophosphorylation; IMP:MGI.
DR   GO; GO:0000425; P:pexophagy; IDA:UniProtKB.
DR   GO; GO:0043065; P:positive regulation of apoptotic process; IMP:UniProtKB.
DR   GO; GO:0045785; P:positive regulation of cell adhesion; ISS:ARUK-UCL.
DR   GO; GO:0030335; P:positive regulation of cell migration; IMP:BHF-UCL.
DR   GO; GO:0043517; P:positive regulation of DNA damage response, signal transduction by p53 class mediator; IMP:BHF-UCL.
DR   GO; GO:2000781; P:positive regulation of double-strand break repair; IMP:BHF-UCL.
DR   GO; GO:0010628; P:positive regulation of gene expression; IMP:BHF-UCL.
DR   GO; GO:0043525; P:positive regulation of neuron apoptotic process; IEA:Ensembl.
DR   GO; GO:1904884; P:positive regulation of telomerase catalytic core complex assembly; IMP:BHF-UCL.
DR   GO; GO:0032212; P:positive regulation of telomere maintenance via telomerase; ISS:BHF-UCL.
DR   GO; GO:1904358; P:positive regulation of telomere maintenance via telomere lengthening; IMP:BHF-UCL.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:ARUK-UCL.
DR   GO; GO:0009791; P:post-embryonic development; IEA:Ensembl.
DR   GO; GO:0002331; P:pre-B cell allelic exclusion; ISS:UniProtKB.
DR   GO; GO:0046777; P:protein autophosphorylation; IMP:UniProtKB.
DR   GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR   GO; GO:0050821; P:protein stabilization; IDA:UniProt.
DR   GO; GO:0007131; P:reciprocal meiotic recombination; TAS:ProtInc.
DR   GO; GO:0042981; P:regulation of apoptotic process; TAS:Reactome.
DR   GO; GO:2000785; P:regulation of autophagosome assembly; IC:UniProt.
DR   GO; GO:0010506; P:regulation of autophagy; IMP:ParkinsonsUK-UCL.
DR   GO; GO:0051726; P:regulation of cell cycle; IMP:BHF-UCL.
DR   GO; GO:1900034; P:regulation of cellular response to heat; TAS:Reactome.
DR   GO; GO:1901796; P:regulation of signal transduction by p53 class mediator; TAS:Reactome.
DR   GO; GO:0032210; P:regulation of telomere maintenance via telomerase; IGI:BHF-UCL.
DR   GO; GO:0090399; P:replicative senescence; IMP:BHF-UCL.
DR   GO; GO:0010212; P:response to ionizing radiation; IDA:UniProtKB.
DR   GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR   GO; GO:0042770; P:signal transduction in response to DNA damage; IDA:UniProtKB.
DR   GO; GO:0001756; P:somitogenesis; IEA:Ensembl.
DR   GO; GO:0000723; P:telomere maintenance; IBA:GO_Central.
DR   GO; GO:0048538; P:thymus development; IEA:Ensembl.
DR   GO; GO:0033151; P:V(D)J recombination; IEA:Ensembl.
DR   CDD; cd05171; PIKKc_ATM; 1.
DR   FunFam; 1.10.1070.11:FF:000011; Serine-protein kinase ATM; 1.
DR   FunFam; 3.30.1010.10:FF:000015; Serine-protein kinase ATM; 1.
DR   Gene3D; 1.10.1070.11; Phosphatidylinositol 3-/4-kinase, catalytic domain; 1.
DR   Gene3D; 3.30.1010.10; Phosphatidylinositol 3-kinase Catalytic Subunit, Chain A, domain 4; 1.
DR   InterPro; IPR016024; ARM-type_fold.
DR   InterPro; IPR038980; ATM_plant.
DR   InterPro; IPR003152; FATC_dom.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR000403; PI3/4_kinase_cat_dom.
DR   InterPro; IPR036940; PI3/4_kinase_cat_sf.
DR   InterPro; IPR018936; PI3/4_kinase_CS.
DR   InterPro; IPR003151; PIK-rel_kinase_FAT.
DR   InterPro; IPR014009; PIK_FAT.
DR   InterPro; IPR044107; PIKKc_ATM.
DR   InterPro; IPR021668; TAN.
DR   PANTHER; PTHR37079; SERINE/THREONINE-PROTEIN KINASE ATM; 1.
DR   PANTHER; PTHR37079:SF4; SERINE_THREONINE-PROTEIN KINASE ATM; 1.
DR   Pfam; PF02259; FAT; 1.
DR   Pfam; PF02260; FATC; 1.
DR   Pfam; PF00454; PI3_PI4_kinase; 1.
DR   Pfam; PF11640; TAN; 1.
DR   SMART; SM01343; FATC; 1.
DR   SMART; SM00146; PI3Kc; 1.
DR   SMART; SM01342; TAN; 1.
DR   SUPFAM; SSF48371; ARM repeat; 1.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR   PROSITE; PS51189; FAT; 1.
DR   PROSITE; PS51190; FATC; 1.
DR   PROSITE; PS00915; PI3_4_KINASE_1; 1.
DR   PROSITE; PS00916; PI3_4_KINASE_2; 1.
DR   PROSITE; PS50290; PI3_4_KINASE_3; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; ATP-binding; Cell cycle; Cytoplasm;
KW   Cytoplasmic vesicle; Cytoskeleton; Disease variant; DNA damage;
KW   DNA-binding; Kinase; Neurodegeneration; Nucleotide-binding; Nucleus;
KW   Peroxisome; Phosphoprotein; Proteomics identification; Reference proteome;
KW   Serine/threonine-protein kinase; Transferase; Tumor suppressor.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0007744|PubMed:22223895"
FT   CHAIN           2..3056
FT                   /note="Serine-protein kinase ATM"
FT                   /id="PRO_0000088840"
FT   DOMAIN          1940..2566
FT                   /note="FAT"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00534"
FT   DOMAIN          2686..2998
FT                   /note="PI3K/PI4K catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT   DOMAIN          3024..3056
FT                   /note="FATC"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00534,
FT                   ECO:0000255|PROSITE-ProRule:PRU00535"
FT   REGION          1373..1382
FT                   /note="Interaction with ABL1"
FT                   /evidence="ECO:0000269|PubMed:9168117"
FT   REGION          2692..2698
FT                   /note="G-loop"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT   REGION          2867..2875
FT                   /note="Catalytic loop"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT   REGION          2887..2911
FT                   /note="Activation loop"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT   MOTIF           3046..3048
FT                   /note="Microbody targeting signal; atypical"
FT                   /evidence="ECO:0000269|PubMed:26344566"
FT   MOD_RES         2
FT                   /note="N-acetylserine"
FT                   /evidence="ECO:0007744|PubMed:22223895"
FT   MOD_RES         367
FT                   /note="Phosphoserine; by autocatalysis"
FT                   /evidence="ECO:0000269|PubMed:16858402"
FT   MOD_RES         1893
FT                   /note="Phosphoserine; by autocatalysis"
FT                   /evidence="ECO:0000269|PubMed:16858402"
FT   MOD_RES         1981
FT                   /note="Phosphoserine; by autocatalysis"
FT                   /evidence="ECO:0000269|PubMed:12556884,
FT                   ECO:0000269|PubMed:15790808, ECO:0000269|PubMed:16141325,
FT                   ECO:0000269|PubMed:16858402, ECO:0000269|PubMed:21144835,
FT                   ECO:0000269|PubMed:30944854, ECO:0007744|PubMed:17525332"
FT   MOD_RES         1983
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:17525332"
FT   MOD_RES         2996
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18691976,
FT                   ECO:0007744|PubMed:19369195"
FT   MOD_RES         3016
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000269|PubMed:17923702,
FT                   ECO:0000269|PubMed:30944854"
FT   VARIANT         23
FT                   /note="R -> Q (in a colorectal adenocarcinoma sample;
FT                   somatic mutation; dbSNP:rs587779858)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041545"
FT   VARIANT         35..3056
FT                   /note="Missing (in AT; dbSNP:rs55861249)"
FT                   /evidence="ECO:0000269|PubMed:10873394"
FT                   /id="VAR_085060"
FT   VARIANT         45
FT                   /note="R -> W (found in a patient with breast cancer;
FT                   uncertain significance; dbSNP:rs3218684)"
FT                   /evidence="ECO:0000269|PubMed:11897822"
FT                   /id="VAR_056678"
FT   VARIANT         49
FT                   /note="S -> C (in dbSNP:rs1800054)"
FT                   /evidence="ECO:0000269|PubMed:10425038,
FT                   ECO:0000269|PubMed:10534763, ECO:0000269|PubMed:10873394,
FT                   ECO:0000269|PubMed:11897822, ECO:0000269|PubMed:17344846,
FT                   ECO:0000269|PubMed:18384426, ECO:0000269|PubMed:8665503,
FT                   ECO:0000269|PubMed:8797579, ECO:0000269|PubMed:9887333"
FT                   /id="VAR_010798"
FT   VARIANT         68
FT                   /note="I -> V (found in a patient with familial pancreatic
FT                   cancer; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:28726808"
FT                   /id="VAR_083373"
FT   VARIANT         126
FT                   /note="D -> E (in dbSNP:rs2234997)"
FT                   /evidence="ECO:0000269|PubMed:17344846,
FT                   ECO:0000269|PubMed:9711876"
FT                   /id="VAR_010799"
FT   VARIANT         140
FT                   /note="D -> H (in dbSNP:rs55633650)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041546"
FT   VARIANT         182
FT                   /note="V -> L (in dbSNP:rs3218707)"
FT                   /evidence="ECO:0000269|PubMed:10534763"
FT                   /id="VAR_010800"
FT   VARIANT         224
FT                   /note="K -> E (in AT; uncertain significance;
FT                   dbSNP:rs145053092)"
FT                   /evidence="ECO:0000269|PubMed:10817650"
FT                   /id="VAR_010801"
FT   VARIANT         250
FT                   /note="R -> Q (in dbSNP:rs56123940)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041547"
FT   VARIANT         292
FT                   /note="P -> L (in AT; decrease phosphorylation of target
FT                   proteins; increases protein abundance; dbSNP:rs747727055)"
FT                   /evidence="ECO:0000269|PubMed:10873394,
FT                   ECO:0000269|PubMed:19431188, ECO:0000269|PubMed:9463314"
FT                   /id="VAR_010802"
FT   VARIANT         323
FT                   /note="I -> V (in AT; loss of protein expression;
FT                   dbSNP:rs587781511)"
FT                   /evidence="ECO:0000269|PubMed:10817650,
FT                   ECO:0000269|PubMed:27664052"
FT                   /id="VAR_010803"
FT   VARIANT         332
FT                   /note="Y -> C (in B-cell chronic lymphocytic leukemia)"
FT                   /evidence="ECO:0000269|PubMed:9892178"
FT                   /id="VAR_010804"
FT   VARIANT         333
FT                   /note="S -> F (in dbSNP:rs28904919)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041548"
FT   VARIANT         337
FT                   /note="R -> C (in a colorectal adenocarcinoma sample;
FT                   somatic mutation; dbSNP:rs138398778)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041549"
FT   VARIANT         337
FT                   /note="R -> H (in a colorectal adenocarcinoma sample;
FT                   somatic mutation; dbSNP:rs202160435)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041550"
FT   VARIANT         341
FT                   /note="V -> I (found in a patient with familial pancreatic
FT                   cancer; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:28726808"
FT                   /id="VAR_083374"
FT   VARIANT         350
FT                   /note="A -> T (in B-cell chronic lymphocytic leukemia;
FT                   dbSNP:rs371713984)"
FT                   /evidence="ECO:0000269|PubMed:10023947"
FT                   /id="VAR_010805"
FT   VARIANT         352
FT                   /note="I -> T (in B-cell chronic lymphocytic leukemia;
FT                   dbSNP:rs369203092)"
FT                   /evidence="ECO:0000269|PubMed:10023947"
FT                   /id="VAR_010806"
FT   VARIANT         374..3056
FT                   /note="Missing (in AT; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:10425038"
FT                   /id="VAR_085061"
FT   VARIANT         393..3056
FT                   /note="Missing (in AT; uncertain significance;
FT                   dbSNP:rs587776547)"
FT                   /evidence="ECO:0000269|PubMed:10873394"
FT                   /id="VAR_085062"
FT   VARIANT         410
FT                   /note="V -> A (in dbSNP:rs56128736)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041551"
FT   VARIANT         504
FT                   /note="N -> S (in dbSNP:rs56365018)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041552"
FT   VARIANT         514
FT                   /note="G -> D (in dbSNP:rs2235000)"
FT                   /evidence="ECO:0000269|PubMed:17344846,
FT                   ECO:0000269|PubMed:9711876"
FT                   /id="VAR_010807"
FT   VARIANT         540
FT                   /note="C -> Y (in a colorectal adenocarcinoma sample;
FT                   somatic mutation)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041553"
FT   VARIANT         546
FT                   /note="L -> V (no effect on phosphorylation of target
FT                   proteins; dbSNP:rs2227924)"
FT                   /evidence="ECO:0000269|PubMed:17344846,
FT                   ECO:0000269|PubMed:19431188"
FT                   /id="VAR_041554"
FT   VARIANT         570
FT                   /note="F -> S (in AT; dbSNP:rs777301065)"
FT                   /evidence="ECO:0000269|PubMed:9887333"
FT                   /id="VAR_010808"
FT   VARIANT         582
FT                   /note="F -> L (in dbSNP:rs2235006)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041555"
FT   VARIANT         597
FT                   /note="P -> L (found in a patient with familial pancreatic
FT                   cancer; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:28726808"
FT                   /id="VAR_083375"
FT   VARIANT         661
FT                   /note="D -> A (found in a patient with familial breast
FT                   cancer; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:28202063"
FT                   /id="VAR_083376"
FT   VARIANT         699
FT                   /note="E -> G (found in a patient with familial pancreatic
FT                   cancer; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:28726808"
FT                   /id="VAR_083377"
FT   VARIANT         705..707
FT                   /note="YSS -> FIP (in AT)"
FT                   /evidence="ECO:0000269|PubMed:8797579,
FT                   ECO:0000269|PubMed:9043869"
FT                   /id="VAR_010809"
FT   VARIANT         707
FT                   /note="S -> P (in dbSNP:rs4986761)"
FT                   /evidence="ECO:0000269|PubMed:10534763,
FT                   ECO:0000269|PubMed:17344846, ECO:0000269|PubMed:28202063"
FT                   /id="VAR_010810"
FT   VARIANT         759
FT                   /note="S -> G (found in a patient with familial pancreatic
FT                   cancer; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:28726808"
FT                   /id="VAR_083378"
FT   VARIANT         761
FT                   /note="T -> S (in dbSNP:rs2235011)"
FT                   /id="VAR_056679"
FT   VARIANT         768
FT                   /note="N -> D (in AT)"
FT                   /evidence="ECO:0000269|PubMed:9463314"
FT                   /id="VAR_010812"
FT   VARIANT         785
FT                   /note="R -> C (in AT; dbSNP:rs587778065)"
FT                   /evidence="ECO:0000269|PubMed:9887333"
FT                   /id="VAR_010813"
FT   VARIANT         788
FT                   /note="S -> R (in dbSNP:rs641252)"
FT                   /id="VAR_056680"
FT   VARIANT         813
FT                   /note="N -> S (found in a patient with familial pancreatic
FT                   cancer; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:28726808"
FT                   /id="VAR_083379"
FT   VARIANT         814
FT                   /note="D -> E (in dbSNP:rs3218695)"
FT                   /id="VAR_056681"
FT   VARIANT         848
FT                   /note="E -> Q (in a lung adenocarcinoma sample; somatic
FT                   mutation; dbSNP:rs879254046)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041556"
FT   VARIANT         858
FT                   /note="F -> L (in dbSNP:rs1800056)"
FT                   /evidence="ECO:0000269|PubMed:10534763,
FT                   ECO:0000269|PubMed:17344846, ECO:0000269|PubMed:18384426,
FT                   ECO:0000269|PubMed:28202063, ECO:0000269|PubMed:8797579,
FT                   ECO:0000269|PubMed:9043869, ECO:0000269|PubMed:9792409,
FT                   ECO:0000269|PubMed:9887333"
FT                   /id="VAR_010814"
FT   VARIANT         869
FT                   /note="A -> G (found in a patient with familial pancreatic
FT                   cancer; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:28726808"
FT                   /id="VAR_083380"
FT   VARIANT         872
FT                   /note="P -> S (in dbSNP:rs3218673)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041557"
FT   VARIANT         897
FT                   /note="F -> I (found in a patient with familial pancreatic
FT                   cancer; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:28726808"
FT                   /id="VAR_083381"
FT   VARIANT         924
FT                   /note="R -> W (found in a patient with familial breast
FT                   cancer; uncertain significance; dbSNP:rs55723361)"
FT                   /evidence="ECO:0000269|PubMed:17344846,
FT                   ECO:0000269|PubMed:28202063"
FT                   /id="VAR_041558"
FT   VARIANT         935
FT                   /note="T -> A (in dbSNP:rs35813135)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041559"
FT   VARIANT         935
FT                   /note="T -> M (in dbSNP:rs3218708)"
FT                   /id="VAR_056682"
FT   VARIANT         942
FT                   /note="L -> F (in dbSNP:rs3218688)"
FT                   /id="VAR_056683"
FT   VARIANT         950
FT                   /note="L -> R (in AT; dbSNP:rs786203054)"
FT                   /evidence="ECO:0000269|PubMed:10873394"
FT                   /id="VAR_010815"
FT   VARIANT         1001
FT                   /note="L -> Q (in AT; risk factor for T-cell acute
FT                   lymphoblastic leukemia)"
FT                   /evidence="ECO:0000269|PubMed:9463314"
FT                   /id="VAR_010816"
FT   VARIANT         1040
FT                   /note="M -> V (in dbSNP:rs3092857)"
FT                   /evidence="ECO:0000269|PubMed:9288106"
FT                   /id="VAR_010817"
FT   VARIANT         1046
FT                   /note="L -> P (in AT; loss of protein expression;
FT                   dbSNP:rs568461905)"
FT                   /evidence="ECO:0000269|PubMed:27664052"
FT                   /id="VAR_077237"
FT   VARIANT         1054
FT                   /note="P -> R (in AT; likely benign; no effect on
FT                   phosphorylation of target proteins; dbSNP:rs1800057)"
FT                   /evidence="ECO:0000269|PubMed:10023947,
FT                   ECO:0000269|PubMed:10217116, ECO:0000269|PubMed:17344846,
FT                   ECO:0000269|PubMed:18384426, ECO:0000269|PubMed:19431188,
FT                   ECO:0000269|PubMed:28202063, ECO:0000269|PubMed:8665503,
FT                   ECO:0000269|PubMed:8797579, ECO:0000269|PubMed:9043869,
FT                   ECO:0000269|PubMed:9792409, ECO:0000269|PubMed:9887333"
FT                   /id="VAR_010818"
FT   VARIANT         1082
FT                   /note="H -> L (in AT; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:10873394"
FT                   /id="VAR_010819"
FT   VARIANT         1091
FT                   /note="E -> D (in AT)"
FT                   /evidence="ECO:0000269|PubMed:9792409"
FT                   /id="VAR_010820"
FT   VARIANT         1171..3056
FT                   /note="Missing (in AT; uncertain significance; increases
FT                   protein abundance)"
FT                   /evidence="ECO:0000269|PubMed:10873394"
FT                   /id="VAR_085063"
FT   VARIANT         1179
FT                   /note="S -> F (in a gastric adenocarcinoma sample; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041560"
FT   VARIANT         1255
FT                   /note="L -> V (found in a patient with early-onset breast
FT                   cancer; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:18384426"
FT                   /id="VAR_083382"
FT   VARIANT         1313
FT                   /note="E -> Q (in dbSNP:rs3092841)"
FT                   /id="VAR_056684"
FT   VARIANT         1321
FT                   /note="M -> I (in dbSNP:rs35184530)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041561"
FT   VARIANT         1322
FT                   /note="L -> I (no effect on phosphorylation of target
FT                   proteins; dbSNP:rs144535256)"
FT                   /evidence="ECO:0000269|PubMed:19431188"
FT                   /id="VAR_080300"
FT   VARIANT         1380
FT                   /note="H -> Y (in dbSNP:rs3092856)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041562"
FT   VARIANT         1382
FT                   /note="P -> S (in dbSNP:rs55859590)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041563"
FT   VARIANT         1407
FT                   /note="I -> T (in T-prolymphocytic leukemia;
FT                   dbSNP:rs1234250980)"
FT                   /evidence="ECO:0000269|PubMed:9288106"
FT                   /id="VAR_010821"
FT   VARIANT         1420
FT                   /note="L -> F (in dbSNP:rs1800058)"
FT                   /evidence="ECO:0000269|PubMed:10534763,
FT                   ECO:0000269|PubMed:17344846, ECO:0000269|PubMed:8665503,
FT                   ECO:0000269|PubMed:8797579"
FT                   /id="VAR_010822"
FT   VARIANT         1420
FT                   /note="L -> P (in AT)"
FT                   /evidence="ECO:0000269|PubMed:10817650"
FT                   /id="VAR_010823"
FT   VARIANT         1427
FT                   /note="A -> T (in dbSNP:rs2229021)"
FT                   /id="VAR_056685"
FT   VARIANT         1463
FT                   /note="F -> S (found in B-cell non-Hodgkin lymphoma;
FT                   uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:9288106"
FT                   /id="VAR_010825"
FT   VARIANT         1465
FT                   /note="L -> P (in AT; decreased phosphorylation of target
FT                   proteins; dbSNP:rs730881391)"
FT                   /evidence="ECO:0000269|PubMed:10234507,
FT                   ECO:0000269|PubMed:19431188"
FT                   /id="VAR_010826"
FT   VARIANT         1466..3056
FT                   /note="Missing (in AT; uncertain significance;
FT                   dbSNP:rs730881369)"
FT                   /evidence="ECO:0000269|PubMed:10425038"
FT                   /id="VAR_085064"
FT   VARIANT         1469
FT                   /note="I -> M (in a renal papillary cancer sample; somatic
FT                   mutation; dbSNP:rs775047783)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041564"
FT   VARIANT         1474
FT                   /note="H -> D (found in a patient with familial pancreatic
FT                   cancer; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:28726808"
FT                   /id="VAR_083383"
FT   VARIANT         1475
FT                   /note="Y -> C (in dbSNP:rs34640941)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041565"
FT   VARIANT         1488
FT                   /note="L -> V (found in a patient with familial pancreatic
FT                   cancer; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:28726808"
FT                   /id="VAR_083384"
FT   VARIANT         1541
FT                   /note="L -> F (in dbSNP:rs3092849)"
FT                   /id="VAR_056686"
FT   VARIANT         1566
FT                   /note="P -> R (in AT)"
FT                   /evidence="ECO:0000269|PubMed:9792409"
FT                   /id="VAR_010827"
FT   VARIANT         1570
FT                   /note="V -> A (in dbSNP:rs140856217)"
FT                   /evidence="ECO:0000269|PubMed:10534763"
FT                   /id="VAR_010828"
FT   VARIANT         1650
FT                   /note="N -> S (in dbSNP:rs55870064)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041566"
FT   VARIANT         1682
FT                   /note="D -> H (in T-prolymphocytic leukemia;
FT                   dbSNP:rs121434217)"
FT                   /evidence="ECO:0000269|PubMed:9288106"
FT                   /id="VAR_010829"
FT   VARIANT         1691
FT                   /note="S -> R (in AT, B-cell chronic lymphocytic leukemia
FT                   and familial cancer patients; no effect on phosphorylation
FT                   of target proteins; dbSNP:rs1800059)"
FT                   /evidence="ECO:0000269|PubMed:19431188,
FT                   ECO:0000269|PubMed:28202063, ECO:0000269|PubMed:8797579,
FT                   ECO:0000269|PubMed:9463314, ECO:0000269|PubMed:9892178"
FT                   /id="VAR_010830"
FT   VARIANT         1729
FT                   /note="V -> L (in dbSNP:rs3092907)"
FT                   /id="VAR_056687"
FT   VARIANT         1730..3056
FT                   /note="Missing (in AT; uncertain significance;
FT                   dbSNP:rs764389018)"
FT                   /evidence="ECO:0000269|PubMed:10425038"
FT                   /id="VAR_085065"
FT   VARIANT         1739
FT                   /note="N -> T (in a colorectal adenocarcinoma sample;
FT                   somatic mutation)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041567"
FT   VARIANT         1743
FT                   /note="T -> I (in AT; decreased phosphorylation of target
FT                   proteins; dbSNP:rs587779844)"
FT                   /evidence="ECO:0000269|PubMed:19431188,
FT                   ECO:0000269|PubMed:9463314"
FT                   /id="VAR_010831"
FT   VARIANT         1812..1813
FT                   /note="AF -> V (in AT)"
FT                   /evidence="ECO:0000269|PubMed:9497252"
FT                   /id="VAR_010832"
FT   VARIANT         1839..3056
FT                   /note="Missing (in AT; uncertain significance; reduces
FT                   protein abundance)"
FT                   /evidence="ECO:0000269|PubMed:10873394"
FT                   /id="VAR_085066"
FT   VARIANT         1853
FT                   /note="D -> N (in dbSNP:rs1801516)"
FT                   /evidence="ECO:0000269|PubMed:10397742,
FT                   ECO:0000269|PubMed:10425038, ECO:0000269|PubMed:10534763,
FT                   ECO:0000269|PubMed:17344846, ECO:0000269|PubMed:18384426,
FT                   ECO:0000269|PubMed:9711876, ECO:0000269|PubMed:9887333"
FT                   /id="VAR_010833"
FT   VARIANT         1853
FT                   /note="D -> V (might contribute to B-cell chronic
FT                   lymphocytic leukemia; dbSNP:rs1801673)"
FT                   /evidence="ECO:0000269|PubMed:10397742,
FT                   ECO:0000269|PubMed:10817650, ECO:0000269|PubMed:17344846,
FT                   ECO:0000269|PubMed:28202063, ECO:0000269|PubMed:9872980,
FT                   ECO:0000269|PubMed:9887333"
FT                   /id="VAR_010834"
FT   VARIANT         1910
FT                   /note="L -> H (in T-prolymphocytic leukemia)"
FT                   /evidence="ECO:0000269|PubMed:9288106"
FT                   /id="VAR_010835"
FT   VARIANT         1913
FT                   /note="V -> G (in AT; dbSNP:rs1060501688)"
FT                   /evidence="ECO:0000269|PubMed:9887333"
FT                   /id="VAR_010836"
FT   VARIANT         1916
FT                   /note="M -> I (in a breast pleomorphic lobular carcinoma
FT                   sample; somatic mutation)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041568"
FT   VARIANT         1945
FT                   /note="A -> T (in a colorectal adenocarcinoma sample;
FT                   somatic mutation)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041569"
FT   VARIANT         1953
FT                   /note="T -> R (in B-cell chronic lymphocytic leukemia)"
FT                   /evidence="ECO:0000269|PubMed:10397742"
FT                   /id="VAR_010837"
FT   VARIANT         1961
FT                   /note="Y -> C (found in a patient with familial pancreatic
FT                   cancer; uncertain significance; also found in a lung
FT                   adenocarcinoma sample; uncertain significance; decreased
FT                   phosphorylation of target proteins; dbSNP:rs56399311)"
FT                   /evidence="ECO:0000269|PubMed:17344846,
FT                   ECO:0000269|PubMed:19431188, ECO:0000269|PubMed:28726808"
FT                   /id="VAR_041570"
FT   VARIANT         1983
FT                   /note="S -> N (in dbSNP:rs659243)"
FT                   /evidence="ECO:0000269|PubMed:16554811"
FT                   /id="VAR_041571"
FT   VARIANT         1991
FT                   /note="E -> D (in a renal clear cell carcinoma sample;
FT                   somatic mutation; dbSNP:rs587782274)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041572"
FT   VARIANT         2016
FT                   /note="D -> G (in AT; uncertain significance;
FT                   dbSNP:rs587781302)"
FT                   /evidence="ECO:0000269|PubMed:10425038,
FT                   ECO:0000269|PubMed:9887333"
FT                   /id="VAR_010838"
FT   VARIANT         2023
FT                   /note="G -> R (in AT; loss of protein expression;
FT                   dbSNP:rs11212587)"
FT                   /evidence="ECO:0000269|PubMed:27664052"
FT                   /id="VAR_077238"
FT   VARIANT         2034
FT                   /note="R -> Q (in dbSNP:rs3218670)"
FT                   /id="VAR_056688"
FT   VARIANT         2063
FT                   /note="G -> E (in AT; uncertain significance; reduces
FT                   protein abundance; dbSNP:rs866290641)"
FT                   /evidence="ECO:0000269|PubMed:10873394"
FT                   /id="VAR_010839"
FT   VARIANT         2067
FT                   /note="A -> D (in AT; dbSNP:rs397514577)"
FT                   /evidence="ECO:0000269|PubMed:9887333"
FT                   /id="VAR_010840"
FT   VARIANT         2068
FT                   /note="L -> S (in AT; decreased protein abundance; loss of
FT                   DNA damage induced protein autophosphorylation;
FT                   dbSNP:rs1555114558)"
FT                   /evidence="ECO:0000269|PubMed:27664052"
FT                   /id="VAR_077239"
FT   VARIANT         2079
FT                   /note="V -> I (in dbSNP:rs1800060)"
FT                   /evidence="ECO:0000269|PubMed:8665503"
FT                   /id="VAR_010841"
FT   VARIANT         2080
FT                   /note="Y -> D (in AT; loss of DNA damage induced protein
FT                   autophosphorylation; dbSNP:rs1064795467)"
FT                   /evidence="ECO:0000269|PubMed:27664052"
FT                   /id="VAR_077240"
FT   VARIANT         2105
FT                   /note="R -> T (found in a patient with early-onset breast
FT                   cancer; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:18384426"
FT                   /id="VAR_083385"
FT   VARIANT         2139
FT                   /note="E -> G (in T-prolymphocytic leukemia; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:9488043"
FT                   /id="VAR_010842"
FT   VARIANT         2164
FT                   /note="E -> K (in T-prolymphocytic leukemia;
FT                   dbSNP:rs1317619286)"
FT                   /evidence="ECO:0000269|PubMed:9288106"
FT                   /id="VAR_010843"
FT   VARIANT         2218
FT                   /note="S -> C (in AT)"
FT                   /evidence="ECO:0000269|PubMed:10817650"
FT                   /id="VAR_010844"
FT   VARIANT         2224..2227
FT                   /note="MALR -> IS (in AT; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:10425038"
FT                   /id="VAR_010845"
FT   VARIANT         2227
FT                   /note="R -> C (in AT; uncertain significance; reduces
FT                   protein abundance; dbSNP:rs564652222)"
FT                   /evidence="ECO:0000269|PubMed:10873394,
FT                   ECO:0000269|PubMed:9887333"
FT                   /id="VAR_010846"
FT   VARIANT         2246..2252
FT                   /note="CIKDILT -> H (in AT; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:10425038,
FT                   ECO:0000269|PubMed:10873394"
FT                   /id="VAR_010847"
FT   VARIANT         2274
FT                   /note="A -> T (in B-cell chronic lymphocytic leukemia;
FT                   uncertain significance; no effect on phosphorylation of
FT                   target proteins; dbSNP:rs567060474)"
FT                   /evidence="ECO:0000269|PubMed:10023947,
FT                   ECO:0000269|PubMed:19431188"
FT                   /id="VAR_010848"
FT   VARIANT         2287
FT                   /note="G -> A (found in a patient with familial pancreatic
FT                   cancer; uncertain significance; dbSNP:rs1800061)"
FT                   /evidence="ECO:0000269|PubMed:28726808,
FT                   ECO:0000269|PubMed:8665503"
FT                   /id="VAR_010849"
FT   VARIANT         2307
FT                   /note="L -> F (found in patients with familial pancreatic
FT                   cancer; uncertain significance; also found in a lung
FT                   adenocarcinoma sample; uncertain significance;
FT                   dbSNP:rs56009889)"
FT                   /evidence="ECO:0000269|PubMed:17344846,
FT                   ECO:0000269|PubMed:28726808"
FT                   /id="VAR_041573"
FT   VARIANT         2332
FT                   /note="L -> P (in dbSNP:rs4988111)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041574"
FT   VARIANT         2335
FT                   /note="T -> K (in dbSNP:rs3092831)"
FT                   /id="VAR_056689"
FT   VARIANT         2356
FT                   /note="I -> F (in a renal clear cell carcinoma sample;
FT                   somatic mutation; dbSNP:rs876658517)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041575"
FT   VARIANT         2396
FT                   /note="T -> S (found in a patient with T-prolymphocytic
FT                   leukemia; uncertain significance; also found in a patient
FT                   with early-onset breast cancer; uncertain significance;
FT                   dbSNP:rs370559102)"
FT                   /evidence="ECO:0000269|PubMed:18384426,
FT                   ECO:0000269|PubMed:9288106"
FT                   /id="VAR_010850"
FT   VARIANT         2408
FT                   /note="S -> L (in a colorectal adenocarcinoma sample;
FT                   somatic mutation; dbSNP:rs730881315)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041576"
FT   VARIANT         2418
FT                   /note="K -> KK (in mantle cell lymphoma)"
FT                   /evidence="ECO:0000269|PubMed:10397742,
FT                   ECO:0000269|PubMed:10706620"
FT                   /id="VAR_010851"
FT   VARIANT         2420
FT                   /note="A -> P (in B-cell chronic lymphocytic leukemia)"
FT                   /evidence="ECO:0000269|PubMed:10397742"
FT                   /id="VAR_010852"
FT   VARIANT         2423
FT                   /note="E -> G (in mantle cell lymphoma; dbSNP:rs121434221)"
FT                   /evidence="ECO:0000269|PubMed:10397742,
FT                   ECO:0000269|PubMed:10706620"
FT                   /id="VAR_010853"
FT   VARIANT         2424
FT                   /note="V -> G (in AT; also found in B-cell chronic
FT                   lymphocytic leukemia and T-prolymphocytic leukemia; risk
FT                   factor for breast cancer; decreased phosphorylation of
FT                   target proteins; dbSNP:rs28904921)"
FT                   /evidence="ECO:0000269|PubMed:19431188,
FT                   ECO:0000269|PubMed:8755918, ECO:0000269|PubMed:9288106,
FT                   ECO:0000269|PubMed:9463314, ECO:0000269|PubMed:9892178"
FT                   /id="VAR_010854"
FT   VARIANT         2427..2428
FT                   /note="Missing (in AT; also found in T-prolymphocytic
FT                   leukemia; lack of phosphorylation of target proteins)"
FT                   /evidence="ECO:0000269|PubMed:19431188,
FT                   ECO:0000269|PubMed:7792600, ECO:0000269|PubMed:8845835,
FT                   ECO:0000269|PubMed:9463314"
FT                   /id="VAR_010855"
FT   VARIANT         2438
FT                   /note="T -> I (in dbSNP:rs147604227)"
FT                   /evidence="ECO:0000269|PubMed:10817650,
FT                   ECO:0000269|PubMed:8808599"
FT                   /id="VAR_010856"
FT   VARIANT         2442
FT                   /note="Q -> P (in T-prolymphocytic leukemia; also in a lung
FT                   adenocarcinoma sample; somatic mutation)"
FT                   /evidence="ECO:0000269|PubMed:17344846,
FT                   ECO:0000269|PubMed:9288106"
FT                   /id="VAR_010857"
FT   VARIANT         2443
FT                   /note="R -> Q (in a colorectal adenocarcinoma sample;
FT                   somatic mutation; dbSNP:rs587782310)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041577"
FT   VARIANT         2464
FT                   /note="C -> R (found in patients with familial pancreatic
FT                   cancer; uncertain significance; also found in a small cell
FT                   lung cancer sample; uncertain significance;
FT                   dbSNP:rs55801750)"
FT                   /evidence="ECO:0000269|PubMed:17344846,
FT                   ECO:0000269|PubMed:28726808"
FT                   /id="VAR_041578"
FT   VARIANT         2470
FT                   /note="Y -> D (in AT; dbSNP:rs876659365)"
FT                   /evidence="ECO:0000269|PubMed:9887333"
FT                   /id="VAR_010858"
FT   VARIANT         2486
FT                   /note="R -> G (in T-prolymphocytic leukemia)"
FT                   /evidence="ECO:0000269|PubMed:9573030"
FT                   /id="VAR_010859"
FT   VARIANT         2491
FT                   /note="W -> R (in AT)"
FT                   /evidence="ECO:0000269|PubMed:9792410"
FT                   /id="VAR_010860"
FT   VARIANT         2492
FT                   /note="L -> R (in dbSNP:rs56399857)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041579"
FT   VARIANT         2524
FT                   /note="A -> P (found in a patient with familial pancreatic
FT                   cancer; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:28726808"
FT                   /id="VAR_083386"
FT   VARIANT         2531
FT                   /note="M -> T (found in patients with familial pancreatic
FT                   cancer; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:28726808"
FT                   /id="VAR_083387"
FT   VARIANT         2546..2548
FT                   /note="Missing (in AT; also found in T-prolymphocytic
FT                   leukemia and T-cell acute lymphoblastic leukemia; lack of
FT                   phosphorylation of target proteins)"
FT                   /evidence="ECO:0000269|PubMed:10817650,
FT                   ECO:0000269|PubMed:19431188, ECO:0000269|PubMed:7792600,
FT                   ECO:0000269|PubMed:8755918, ECO:0000269|PubMed:8789452,
FT                   ECO:0000269|PubMed:8797579, ECO:0000269|PubMed:8808599,
FT                   ECO:0000269|PubMed:8845835, ECO:0000269|PubMed:9150358,
FT                   ECO:0000269|PubMed:9288106, ECO:0000269|PubMed:9463314"
FT                   /id="VAR_010861"
FT   VARIANT         2547..2549
FT                   /note="Missing (in AT; dbSNP:rs587776547)"
FT                   /evidence="ECO:0000269|PubMed:10873394"
FT                   /id="VAR_085067"
FT   VARIANT         2554
FT                   /note="H -> D (in AT; lack of phosphorylation of target
FT                   proteins)"
FT                   /evidence="ECO:0000269|PubMed:19431188,
FT                   ECO:0000269|PubMed:9463314"
FT                   /id="VAR_010862"
FT   VARIANT         2570
FT                   /note="E -> G (in dbSNP:rs28904920)"
FT                   /id="VAR_056690"
FT   VARIANT         2625..2626
FT                   /note="DA -> EP (in AT; dbSNP:rs267606668)"
FT                   /evidence="ECO:0000269|PubMed:9521587"
FT                   /id="VAR_010864"
FT   VARIANT         2625
FT                   /note="D -> E (in AT; uncertain significance;
FT                   dbSNP:rs1196903858)"
FT                   /evidence="ECO:0000269|PubMed:10873394"
FT                   /id="VAR_085068"
FT   VARIANT         2625
FT                   /note="D -> Q (in AT; requires 2 nucleotide substitutions)"
FT                   /evidence="ECO:0000269|PubMed:10817650"
FT                   /id="VAR_010863"
FT   VARIANT         2626
FT                   /note="A -> P (in AT; uncertain significance;
FT                   dbSNP:rs267606669)"
FT                   /evidence="ECO:0000269|PubMed:10873394"
FT                   /id="VAR_085069"
FT   VARIANT         2627
FT                   /note="Y -> H (in AT; loss of protein expression)"
FT                   /evidence="ECO:0000269|PubMed:27664052"
FT                   /id="VAR_077241"
FT   VARIANT         2640
FT                   /note="T -> I (in dbSNP:rs4988125)"
FT                   /id="VAR_056691"
FT   VARIANT         2656
FT                   /note="L -> P (in AT; dbSNP:rs121434218)"
FT                   /evidence="ECO:0000269|PubMed:9450874"
FT                   /id="VAR_010865"
FT   VARIANT         2662
FT                   /note="Missing (in AT)"
FT                   /evidence="ECO:0000269|PubMed:9887333"
FT                   /id="VAR_010866"
FT   VARIANT         2664
FT                   /note="Missing (in AT; uncertain significance;
FT                   dbSNP:rs1471563800)"
FT                   /evidence="ECO:0000269|PubMed:10425038"
FT                   /id="VAR_085070"
FT   VARIANT         2666
FT                   /note="T -> A (in a lung adenocarcinoma sample; somatic
FT                   mutation; dbSNP:rs745775382)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041580"
FT   VARIANT         2668
FT                   /note="E -> G (in AT; uncertain significance; no effect on
FT                   phosphorylation of target proteins)"
FT                   /evidence="ECO:0000269|PubMed:19431188,
FT                   ECO:0000269|PubMed:9463314"
FT                   /id="VAR_010868"
FT   VARIANT         2695
FT                   /note="G -> A (in T-prolymphocytic leukemia and B-cell
FT                   chronic lymphocytic leukemia)"
FT                   /evidence="ECO:0000269|PubMed:10023947,
FT                   ECO:0000269|PubMed:9288106"
FT                   /id="VAR_010869"
FT   VARIANT         2702
FT                   /note="I -> R (in AT; dbSNP:rs876659735)"
FT                   /evidence="ECO:0000269|PubMed:10873394"
FT                   /id="VAR_010870"
FT   VARIANT         2709
FT                   /note="G -> S (in dbSNP:rs3218680)"
FT                   /id="VAR_056692"
FT   VARIANT         2719
FT                   /note="R -> H (found in a patient with early-onset breast
FT                   cancer; uncertain significance; dbSNP:rs55982963)"
FT                   /evidence="ECO:0000269|PubMed:17344846,
FT                   ECO:0000269|PubMed:18384426"
FT                   /id="VAR_041581"
FT   VARIANT         2722
FT                   /note="L -> R (in T-prolymphocytic leukemia)"
FT                   /evidence="ECO:0000269|PubMed:9288106"
FT                   /id="VAR_010871"
FT   VARIANT         2725
FT                   /note="D -> G (found in T-prolymphocytic leukemia;
FT                   uncertain significance; dbSNP:rs1555128314)"
FT                   /evidence="ECO:0000269|PubMed:9334731"
FT                   /id="VAR_010872"
FT   VARIANT         2725
FT                   /note="D -> V (in T-prolymphocytic leukemia)"
FT                   /evidence="ECO:0000269|PubMed:9288106"
FT                   /id="VAR_010873"
FT   VARIANT         2726
FT                   /note="A -> V (in AT; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:10425038"
FT                   /id="VAR_010874"
FT   VARIANT         2732
FT                   /note="F -> L (in T-prolymphocytic leukemia;
FT                   dbSNP:rs876659619)"
FT                   /evidence="ECO:0000269|PubMed:9288106"
FT                   /id="VAR_010875"
FT   VARIANT         2765
FT                   /note="G -> S (may contribute to breast cancer; lack of
FT                   phosphorylation of target proteins; dbSNP:rs748634900)"
FT                   /evidence="ECO:0000269|PubMed:10534763,
FT                   ECO:0000269|PubMed:19431188"
FT                   /id="VAR_010876"
FT   VARIANT         2810
FT                   /note="K -> Q (found in a patient with familial pancreatic
FT                   cancer; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:28726808"
FT                   /id="VAR_083388"
FT   VARIANT         2810
FT                   /note="Missing (in T-prolymphocytic leukemia)"
FT                   /evidence="ECO:0000269|PubMed:9288106"
FT                   /id="VAR_010877"
FT   VARIANT         2824
FT                   /note="C -> Y (in AT; dbSNP:rs876660927)"
FT                   /evidence="ECO:0000269|PubMed:9150358"
FT                   /id="VAR_010878"
FT   VARIANT         2827
FT                   /note="F -> C (in AT; mild; decreased phosphorylation of
FT                   target proteins; dbSNP:rs121434216)"
FT                   /evidence="ECO:0000269|PubMed:19431188,
FT                   ECO:0000269|PubMed:8755918, ECO:0000269|PubMed:9463314"
FT                   /id="VAR_010879"
FT   VARIANT         2829
FT                   /note="P -> L (in AT; dbSNP:rs938431501)"
FT                   /evidence="ECO:0000269|PubMed:9711876"
FT                   /id="VAR_010880"
FT   VARIANT         2832
FT                   /note="R -> C (in AT; also found in B-cell non-Hodgkin
FT                   lymphoma; increases protein abundance; dbSNP:rs587779872)"
FT                   /evidence="ECO:0000269|PubMed:10817650,
FT                   ECO:0000269|PubMed:10873394, ECO:0000269|PubMed:9288106,
FT                   ECO:0000269|PubMed:9443866"
FT                   /id="VAR_010881"
FT   VARIANT         2832
FT                   /note="R -> H (found in a patient with familial pancreatic
FT                   cancer; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:28726808"
FT                   /id="VAR_083389"
FT   VARIANT         2834
FT                   /note="F -> L (in AT; decreased protein abundance)"
FT                   /evidence="ECO:0000269|PubMed:27664052"
FT                   /id="VAR_077242"
FT   VARIANT         2842
FT                   /note="P -> R (in a lung adenocarcinoma sample; somatic
FT                   mutation; dbSNP:rs879254065)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041582"
FT   VARIANT         2849..3056
FT                   /note="Missing (in AT; uncertain significance;
FT                   dbSNP:rs587778080)"
FT                   /evidence="ECO:0000269|PubMed:10425038"
FT                   /id="VAR_085071"
FT   VARIANT         2849
FT                   /note="R -> P (in AT; dbSNP:rs587782202)"
FT                   /evidence="ECO:0000269|PubMed:9887333"
FT                   /id="VAR_010882"
FT   VARIANT         2855..2856
FT                   /note="SV -> RI (in AT; lack of phosphorylation of target
FT                   proteins; dbSNP:rs587781353)"
FT                   /evidence="ECO:0000269|PubMed:10817650,
FT                   ECO:0000269|PubMed:19431188, ECO:0000269|PubMed:9872980"
FT                   /id="VAR_010884"
FT   VARIANT         2855
FT                   /note="S -> R (in AT; uncertain significance;
FT                   dbSNP:rs780905851)"
FT                   /evidence="ECO:0000269|PubMed:10425038"
FT                   /id="VAR_010883"
FT   VARIANT         2860
FT                   /note="Missing (in AT)"
FT                   /evidence="ECO:0000269|PubMed:7792600,
FT                   ECO:0000269|PubMed:8845835"
FT                   /id="VAR_010885"
FT   VARIANT         2867
FT                   /note="G -> R (in AT)"
FT                   /evidence="ECO:0000269|PubMed:8698354,
FT                   ECO:0000269|PubMed:9887333"
FT                   /id="VAR_010886"
FT   VARIANT         2870
FT                   /note="D -> N (in dbSNP:rs55798854)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041583"
FT   VARIANT         2871..2872
FT                   /note="RH -> S (in T-prolymphocytic leukemia)"
FT                   /evidence="ECO:0000269|PubMed:9288106"
FT                   /id="VAR_010887"
FT   VARIANT         2890
FT                   /note="L -> V (in T-prolymphocytic leukemia;
FT                   dbSNP:rs587779874)"
FT                   /evidence="ECO:0000269|PubMed:9288106,
FT                   ECO:0000269|PubMed:9488043"
FT                   /id="VAR_010888"
FT   VARIANT         2904
FT                   /note="E -> G (in AT; dbSNP:rs786202826)"
FT                   /evidence="ECO:0000269|PubMed:8845835"
FT                   /id="VAR_010889"
FT   VARIANT         2909
FT                   /note="R -> G (in AT)"
FT                   /evidence="ECO:0000269|PubMed:9792410"
FT                   /id="VAR_010890"
FT   VARIANT         2974
FT                   /note="P -> L (found in a patient with familial pancreatic
FT                   cancer; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:28726808"
FT                   /id="VAR_083390"
FT   VARIANT         3003
FT                   /note="N -> D (in AT; decreased protein abundance;
FT                   dbSNP:rs1137889)"
FT                   /evidence="ECO:0000269|PubMed:27664052,
FT                   ECO:0000269|PubMed:7792600, ECO:0000269|PubMed:8589678,
FT                   ECO:0000269|PubMed:8665503"
FT                   /id="VAR_077243"
FT   VARIANT         3006
FT                   /note="A -> P (found in T-prolymphocytic leukemia;
FT                   uncertain significance; dbSNP:rs876658767)"
FT                   /evidence="ECO:0000269|PubMed:9334731"
FT                   /id="VAR_010892"
FT   VARIANT         3008
FT                   /note="R -> C (in AT; also found in T-prolymphocytic
FT                   leukemia and mantle cell lymphoma; lack of phosphorylation
FT                   of target proteins; dbSNP:rs587782292)"
FT                   /evidence="ECO:0000269|PubMed:10706620,
FT                   ECO:0000269|PubMed:10817650, ECO:0000269|PubMed:19431188,
FT                   ECO:0000269|PubMed:9334731, ECO:0000269|PubMed:9488043,
FT                   ECO:0000269|PubMed:9872980"
FT                   /id="VAR_010893"
FT   VARIANT         3008
FT                   /note="R -> H (in B-cell chronic lymphocytic leukemia;
FT                   dbSNP:rs587781894)"
FT                   /evidence="ECO:0000269|PubMed:10397742"
FT                   /id="VAR_010894"
FT   VARIANT         3018
FT                   /note="K -> N (in B-cell chronic lymphocytic leukemia)"
FT                   /evidence="ECO:0000269|PubMed:10397742"
FT                   /id="VAR_010895"
FT   VARIANT         3029
FT                   /note="G -> D (found in a patient with familial pancreatic
FT                   cancer; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:28726808"
FT                   /id="VAR_083391"
FT   VARIANT         3056
FT                   /note="V -> L (found in a patient with familial pancreatic
FT                   cancer; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:28726808"
FT                   /id="VAR_083392"
FT   MUTAGEN         367
FT                   /note="S->A: Loss of IR-induced S-367 autophosphorylation.
FT                   Reduced correction of cell cycle checkpoint defects and
FT                   DNA-repair activity. No effect on S-1893 nor S-1981
FT                   autophosphorylation."
FT                   /evidence="ECO:0000269|PubMed:16858402"
FT   MUTAGEN         1807
FT                   /note="K->E: Decreased phosphorylation of target proteins."
FT                   /evidence="ECO:0000269|PubMed:19431188"
FT   MUTAGEN         1893
FT                   /note="S->A: Loss of IR-induced S-1893 autophosphorylation.
FT                   Reduced correction of cell cycle checkpoint defects and
FT                   DNA-repair activity. No effect on S-367 nor S-1981
FT                   autophosphorylation."
FT                   /evidence="ECO:0000269|PubMed:16858402"
FT   MUTAGEN         1941
FT                   /note="V->L: Decreased phosphorylation of target proteins."
FT                   /evidence="ECO:0000269|PubMed:19431188"
FT   MUTAGEN         1981
FT                   /note="S->A: Loss of IR-induced S-1981 autophosphorylation.
FT                   Reduced correction of cell cycle checkpoint defects and
FT                   DNA-repair activity. No effect on S-367 nor S-1893
FT                   autophosphorylation. No dimer disruption."
FT                   /evidence="ECO:0000269|PubMed:12556884,
FT                   ECO:0000269|PubMed:16858402"
FT   MUTAGEN         1981
FT                   /note="S->D,E: Disrupts the dimer."
FT                   /evidence="ECO:0000269|PubMed:12556884,
FT                   ECO:0000269|PubMed:16858402"
FT   MUTAGEN         2019
FT                   /note="Y->C: Loss of phosphorylation of target proteins."
FT                   /evidence="ECO:0000269|PubMed:19431188"
FT   MUTAGEN         2039
FT                   /note="E->K: Decreased phosphorylation of target proteins."
FT                   /evidence="ECO:0000269|PubMed:19431188"
FT   MUTAGEN         2338
FT                   /note="L->P: Loss of phosphorylation of target proteins."
FT                   /evidence="ECO:0000269|PubMed:19431188"
FT   MUTAGEN         2394
FT                   /note="S->L: Loss of phosphorylation of target proteins."
FT                   /evidence="ECO:0000269|PubMed:19431188"
FT   MUTAGEN         2452
FT                   /note="L->P: Loss of phosphorylation of target proteins."
FT                   /evidence="ECO:0000269|PubMed:19431188"
FT   MUTAGEN         2685
FT                   /note="S->T: No effect on phosphorylation of target
FT                   proteins."
FT                   /evidence="ECO:0000269|PubMed:19431188"
FT   MUTAGEN         2699
FT                   /note="P->L: Loss of phosphorylation of target proteins."
FT                   /evidence="ECO:0000269|PubMed:19431188"
FT   MUTAGEN         2708
FT                   /note="D->N: Decreased phosphorylation of target proteins."
FT                   /evidence="ECO:0000269|PubMed:19431188"
FT   MUTAGEN         2730
FT                   /note="Q->P: Loss of phosphorylation of target proteins."
FT                   /evidence="ECO:0000269|PubMed:19431188"
FT   MUTAGEN         2870
FT                   /note="D->A: Loss of kinase activity."
FT                   /evidence="ECO:0000269|PubMed:9733515"
FT   MUTAGEN         2875
FT                   /note="N->K: Loss of kinase activity."
FT                   /evidence="ECO:0000269|PubMed:9733515"
FT   MUTAGEN         3016
FT                   /note="K->Q: Mimics acetylation, preventing
FT                   dephosphorylation and subsequent ATM deactivation during
FT                   the late stage of DNA damage response."
FT                   /evidence="ECO:0000269|PubMed:30944854"
FT   MUTAGEN         3016
FT                   /note="K->R: Loss of DNA damage-inducible acetylation.
FT                   Retains constitutive kinase activity, but blocks DNA
FT                   damage-induced kinase activation. Disrupts dimer and
FT                   abolishes S-1981 autophosphorylation."
FT                   /evidence="ECO:0000269|PubMed:17923702"
FT   MUTAGEN         3018
FT                   /note="K->R: Retains DNA damage-inducible acetylation and
FT                   S-1981 autophosphorylation."
FT                   /evidence="ECO:0000269|PubMed:17923702"
FT   MUTAGEN         3047
FT                   /note="R->Q: Abolished interaction with PEX5 and
FT                   translocation to peroxisomes in response to reactive oxygen
FT                   species (ROS)."
FT                   /evidence="ECO:0000269|PubMed:26344566"
FT   CONFLICT        46
FT                   /note="H -> N (in Ref. 7; CAA62603)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        56
FT                   /note="N -> I (in Ref. 7; CAA62603)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        313
FT                   /note="Y -> N (in Ref. 7; CAA62603)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        488
FT                   /note="W -> G (in Ref. 7; CAA62603)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        554
FT                   /note="T -> A (in Ref. 1; AAC50289)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        750
FT                   /note="K -> N (in Ref. 1; AAC50289)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        754
FT                   /note="Q -> K (in Ref. 7; CAA62603)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        887
FT                   /note="E -> G (in Ref. 7; CAA62603)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1003
FT                   /note="Q -> L (in Ref. 7; CAA62603)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1049
FT                   /note="L -> W (in Ref. 7; CAA62603)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1089
FT                   /note="A -> V (in Ref. 7; CAA62603)"
FT                   /evidence="ECO:0000305"
FT   HELIX           6..17
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           20..33
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           36..41
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           57..73
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           90..108
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   STRAND          109..112
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           117..129
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   STRAND          130..133
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           135..148
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   TURN            149..151
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           153..158
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           161..176
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           183..201
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           207..209
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           210..222
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   STRAND          223..225
FT                   /evidence="ECO:0007829|PDB:7NI5"
FT   HELIX           229..242
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   STRAND          244..246
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           248..268
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           273..290
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           292..294
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           298..300
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           306..323
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   STRAND          324..326
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           343..356
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           393..402
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   TURN            407..409
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           410..422
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           424..426
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           429..431
FT                   /evidence="ECO:0007829|PDB:7SID"
FT   HELIX           432..442
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   STRAND          445..447
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           452..466
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           474..492
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   TURN            493..496
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           498..500
FT                   /evidence="ECO:0007829|PDB:7SID"
FT   HELIX           501..513
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           521..524
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   TURN            525..527
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           528..530
FT                   /evidence="ECO:0007829|PDB:7NI5"
FT   HELIX           536..548
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           572..580
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           597..600
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   TURN            605..607
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           608..615
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   STRAND          617..619
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           620..628
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   TURN            634..636
FT                   /evidence="ECO:0007829|PDB:7NI5"
FT   HELIX           646..655
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           684..704
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   TURN            707..709
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           713..731
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   STRAND          732..735
FT                   /evidence="ECO:0007829|PDB:8OXP"
FT   HELIX           737..741
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           744..765
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           771..786
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   STRAND          792..794
FT                   /evidence="ECO:0007829|PDB:7NI5"
FT   HELIX           795..806
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           809..822
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           887..889
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           892..911
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           920..930
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   TURN            933..935
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           941..953
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   STRAND          957..959
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           963..970
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           973..979
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   TURN            980..982
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           984..994
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           995..997
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           998..1002
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           1009..1030
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   TURN            1031..1033
FT                   /evidence="ECO:0007829|PDB:7NI5"
FT   HELIX           1036..1052
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   STRAND          1060..1063
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   STRAND          1066..1069
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           1070..1076
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           1077..1079
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           1083..1092
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           1093..1096
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           1113..1132
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   STRAND          1136..1138
FT                   /evidence="ECO:0007829|PDB:7NI5"
FT   HELIX           1144..1164
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           1169..1181
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           1187..1201
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           1206..1212
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           1214..1223
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           1227..1229
FT                   /evidence="ECO:0007829|PDB:7NI5"
FT   TURN            1231..1233
FT                   /evidence="ECO:0007829|PDB:7SID"
FT   HELIX           1236..1238
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           1244..1261
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           1265..1275
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           1279..1285
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           1287..1294
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           1295..1297
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   TURN            1299..1303
FT                   /evidence="ECO:0007829|PDB:8OXM"
FT   HELIX           1306..1322
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   TURN            1325..1327
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           1328..1330
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           1332..1338
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           1340..1348
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           1383..1396
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   STRAND          1397..1399
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           1404..1408
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           1413..1428
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           1432..1450
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           1453..1455
FT                   /evidence="ECO:0007829|PDB:7SID"
FT   TURN            1456..1460
FT                   /evidence="ECO:0007829|PDB:7NI5"
FT   HELIX           1461..1477
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           1485..1508
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           1513..1515
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           1517..1527
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   TURN            1528..1530
FT                   /evidence="ECO:0007829|PDB:7SID"
FT   HELIX           1532..1545
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   TURN            1546..1551
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           1553..1560
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   STRAND          1567..1569
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           1572..1582
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   TURN            1583..1585
FT                   /evidence="ECO:0007829|PDB:7NI6"
FT   HELIX           1590..1601
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           1607..1610
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           1611..1623
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           1625..1634
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   STRAND          1635..1637
FT                   /evidence="ECO:0007829|PDB:8OXP"
FT   HELIX           1639..1641
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           1643..1658
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   STRAND          1661..1663
FT                   /evidence="ECO:0007829|PDB:8OXM"
FT   HELIX           1664..1677
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           1694..1702
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           1706..1721
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   STRAND          1723..1725
FT                   /evidence="ECO:0007829|PDB:8OXO"
FT   HELIX           1727..1742
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           1744..1753
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   STRAND          1754..1756
FT                   /evidence="ECO:0007829|PDB:7NI4"
FT   HELIX           1759..1763
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   TURN            1764..1767
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   TURN            1785..1789
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           1792..1795
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           1802..1815
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           1822..1825
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           1828..1831
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           1835..1851
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           1857..1874
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           1903..1917
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   STRAND          1922..1924
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           1927..1930
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           1938..1947
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           1951..1973
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           1986..1997
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2001..2012
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2016..2019
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   STRAND          2023..2028
FT                   /evidence="ECO:0007829|PDB:7SIC"
FT   HELIX           2029..2038
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2042..2051
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2057..2070
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2074..2087
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2093..2105
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2124..2136
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2140..2159
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2166..2168
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2170..2190
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2195..2210
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   TURN            2211..2214
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2217..2236
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   STRAND          2240..2242
FT                   /evidence="ECO:0007829|PDB:8OXP"
FT   HELIX           2245..2264
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2269..2281
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2290..2301
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2305..2322
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2328..2348
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2353..2359
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2361..2370
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2377..2406
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2408..2421
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2437..2475
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2481..2483
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2484..2493
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   TURN            2494..2496
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2498..2507
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2508..2510
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2513..2516
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2520..2525
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   STRAND          2529..2531
FT                   /evidence="ECO:0007829|PDB:7SID"
FT   STRAND          2533..2535
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2537..2551
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2553..2564
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   TURN            2565..2567
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2568..2572
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2593..2612
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2614..2632
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2637..2640
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   TURN            2652..2655
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   STRAND          2659..2663
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   STRAND          2665..2667
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   STRAND          2673..2675
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   STRAND          2682..2686
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   STRAND          2688..2692
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   STRAND          2695..2697
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   STRAND          2700..2706
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   STRAND          2707..2709
FT                   /evidence="ECO:0007829|PDB:7NI4"
FT   STRAND          2711..2717
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2723..2740
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2743..2748
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   STRAND          2757..2759
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   STRAND          2761..2763
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   STRAND          2765..2768
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   STRAND          2773..2775
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2776..2780
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   TURN            2783..2785
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2787..2791
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2798..2807
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2808..2810
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2813..2825
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2833..2838
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2842..2866
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2873..2875
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   STRAND          2876..2879
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   TURN            2880..2882
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   STRAND          2885..2887
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   TURN            2894..2899
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   STRAND          2900..2902
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   STRAND          2906..2908
FT                   /evidence="ECO:0007829|PDB:8OXP"
FT   HELIX           2912..2916
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   TURN            2920..2925
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2926..2940
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2942..2953
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           2964..2970
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           3002..3017
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   STRAND          3020..3025
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           3028..3040
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           3042..3047
FT                   /evidence="ECO:0007829|PDB:8OXQ"
FT   HELIX           3050..3052
FT                   /evidence="ECO:0007829|PDB:8OXQ"
SQ   SEQUENCE   3056 AA;  350687 MW;  C0B4866E1E3199E2 CRC64;
     MSLVLNDLLI CCRQLEHDRA TERKKEVEKF KRLIRDPETI KHLDRHSDSK QGKYLNWDAV
     FRFLQKYIQK ETECLRIAKP NVSASTQASR QKKMQEISSL VKYFIKCANR RAPRLKCQEL
     LNYIMDTVKD SSNGAIYGAD CSNILLKDIL SVRKYWCEIS QQQWLELFSV YFRLYLKPSQ
     DVHRVLVARI IHAVTKGCCS QTDGLNSKFL DFFSKAIQCA RQEKSSSGLN HILAALTIFL
     KTLAVNFRIR VCELGDEILP TLLYIWTQHR LNDSLKEVII ELFQLQIYIH HPKGAKTQEK
     GAYESTKWRS ILYNLYDLLV NEISHIGSRG KYSSGFRNIA VKENLIELMA DICHQVFNED
     TRSLEISQSY TTTQRESSDY SVPCKRKKIE LGWEVIKDHL QKSQNDFDLV PWLQIATQLI
     SKYPASLPNC ELSPLLMILS QLLPQQRHGE RTPYVLRCLT EVALCQDKRS NLESSQKSDL
     LKLWNKIWCI TFRGISSEQI QAENFGLLGA IIQGSLVEVD REFWKLFTGS ACRPSCPAVC
     CLTLALTTSI VPGTVKMGIE QNMCEVNRSF SLKESIMKWL LFYQLEGDLE NSTEVPPILH
     SNFPHLVLEK ILVSLTMKNC KAAMNFFQSV PECEHHQKDK EELSFSEVEE LFLQTTFDKM
     DFLTIVRECG IEKHQSSIGF SVHQNLKESL DRCLLGLSEQ LLNNYSSEIT NSETLVRCSR
     LLVGVLGCYC YMGVIAEEEA YKSELFQKAK SLMQCAGESI TLFKNKTNEE FRIGSLRNMM
     QLCTRCLSNC TKKSPNKIAS GFFLRLLTSK LMNDIADICK SLASFIKKPF DRGEVESMED
     DTNGNLMEVE DQSSMNLFND YPDSSVSDAN EPGESQSTIG AINPLAEEYL SKQDLLFLDM
     LKFLCLCVTT AQTNTVSFRA ADIRRKLLML IDSSTLEPTK SLHLHMYLML LKELPGEEYP
     LPMEDVLELL KPLSNVCSLY RRDQDVCKTI LNHVLHVVKN LGQSNMDSEN TRDAQGQFLT
     VIGAFWHLTK ERKYIFSVRM ALVNCLKTLL EADPYSKWAI LNVMGKDFPV NEVFTQFLAD
     NHHQVRMLAA ESINRLFQDT KGDSSRLLKA LPLKLQQTAF ENAYLKAQEG MREMSHSAEN
     PETLDEIYNR KSVLLTLIAV VLSCSPICEK QALFALCKSV KENGLEPHLV KKVLEKVSET
     FGYRRLEDFM ASHLDYLVLE WLNLQDTEYN LSSFPFILLN YTNIEDFYRS CYKVLIPHLV
     IRSHFDEVKS IANQIQEDWK SLLTDCFPKI LVNILPYFAY EGTRDSGMAQ QRETATKVYD
     MLKSENLLGK QIDHLFISNL PEIVVELLMT LHEPANSSAS QSTDLCDFSG DLDPAPNPPH
     FPSHVIKATF AYISNCHKTK LKSILEILSK SPDSYQKILL AICEQAAETN NVYKKHRILK
     IYHLFVSLLL KDIKSGLGGA WAFVLRDVIY TLIHYINQRP SCIMDVSLRS FSLCCDLLSQ
     VCQTAVTYCK DALENHLHVI VGTLIPLVYE QVEVQKQVLD LLKYLVIDNK DNENLYITIK
     LLDPFPDHVV FKDLRITQQK IKYSRGPFSL LEEINHFLSV SVYDALPLTR LEGLKDLRRQ
     LELHKDQMVD IMRASQDNPQ DGIMVKLVVN LLQLSKMAIN HTGEKEVLEA VGSCLGEVGP
     IDFSTIAIQH SKDASYTKAL KLFEDKELQW TFIMLTYLNN TLVEDCVKVR SAAVTCLKNI
     LATKTGHSFW EIYKMTTDPM LAYLQPFRTS RKKFLEVPRF DKENPFEGLD DINLWIPLSE
     NHDIWIKTLT CAFLDSGGTK CEILQLLKPM CEVKTDFCQT VLPYLIHDIL LQDTNESWRN
     LLSTHVQGFF TSCLRHFSQT SRSTTPANLD SESEHFFRCC LDKKSQRTML AVVDYMRRQK
     RPSSGTIFND AFWLDLNYLE VAKVAQSCAA HFTALLYAEI YADKKSMDDQ EKRSLAFEEG
     SQSTTISSLS EKSKEETGIS LQDLLLEIYR SIGEPDSLYG CGGGKMLQPI TRLRTYEHEA
     MWGKALVTYD LETAIPSSTR QAGIIQALQN LGLCHILSVY LKGLDYENKD WCPELEELHY
     QAAWRNMQWD HCTSVSKEVE GTSYHESLYN ALQSLRDREF STFYESLKYA RVKEVEEMCK
     RSLESVYSLY PTLSRLQAIG ELESIGELFS RSVTHRQLSE VYIKWQKHSQ LLKDSDFSFQ
     EPIMALRTVI LEILMEKEMD NSQRECIKDI LTKHLVELSI LARTFKNTQL PERAIFQIKQ
     YNSVSCGVSE WQLEEAQVFW AKKEQSLALS ILKQMIKKLD ASCAANNPSL KLTYTECLRV
     CGNWLAETCL ENPAVIMQTY LEKAVEVAGN YDGESSDELR NGKMKAFLSL ARFSDTQYQR
     IENYMKSSEF ENKQALLKRA KEEVGLLREH KIQTNRYTVK VQRELELDEL ALRALKEDRK
     RFLCKAVENY INCLLSGEEH DMWVFRLCSL WLENSGVSEV NGMMKRDGMK IPTYKFLPLM
     YQLAARMGTK MMGGLGFHEV LNNLISRISM DHPHHTLFII LALANANRDE FLTKPEVARR
     SRITKNVPKQ SSQLDEDRTE AANRIICTIR SRRPQMVRSV EALCDAYIIL ANLDATQWKT
     QRKGINIPAD QPITKLKNLE DVVVPTMEIK VDHTGEYGNL VTIQSFKAEF RLAGGVNLPK
     IIDCVGSDGK ERRQLVKGRD DLRQDAVMQQ VFQMCNTLLQ RNTETRKRKL TICTYKVVPL
     SQRSGVLEWC TGTVPIGEFL VNNEDGAHKR YRPNDFSAFQ CQKKMMEVQK KSFEEKYEVF
     MDVCQNFQPV FRYFCMEKFL DPAIWFEKRL AYTRSVATSS IVGYILGLGD RHVQNILINE
     QSAELVHIDL GVAFEQGKIL PTPETVPFRL TRDIVDGMGI TGVEGVFRRC CEKTMEVMRN
     SQETLLTIVE VLLYDPLFDW TMNPLKALYL QQRPEDETEL HPTLNADDQE CKRNLSDIDQ
     SFNKVAERVL MRLQEKLKGV EEGTVLSVGG QVNLLIQQAI DPKNLSRLFP GWKAWV
//
ID   KIT_HUMAN               Reviewed;         976 AA.
AC   P10721; B5A956; D5LXN2; D5M931; F5H8F8; Q6IQ28; Q99662; Q9UM99;
DT   01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT   01-JUL-1989, sequence version 1.
DT   28-JAN-2026, entry version 265.
DE   RecName: Full=Mast/stem cell growth factor receptor Kit;
DE            Short=SCFR;
DE            EC=2.7.10.1;
DE   AltName: Full=Piebald trait protein;
DE            Short=PBT;
DE   AltName: Full=Proto-oncogene c-Kit;
DE   AltName: Full=Tyrosine-protein kinase Kit;
DE   AltName: Full=p145 c-kit;
DE   AltName: Full=v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog;
DE   AltName: CD_antigen=CD117;
DE   Flags: Precursor;
GN   Name=KIT; Synonyms=SCFR;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CATALYTIC ACTIVITY,
RP   AUTOPHOSPHORYLATION, AND SUBCELLULAR LOCATION.
RC   TISSUE=Fetal brain, and Term placenta;
RX   PubMed=2448137; DOI=10.1002/j.1460-2075.1987.tb02655.x;
RA   Yarden Y., Kuang W.-J., Yang-Feng T., Coussens L., Munemitsu S., Dull T.J.,
RA   Chen E., Schlessinger J., Francke U., Ullrich A.;
RT   "Human proto-oncogene c-kit: a new cell surface receptor tyrosine kinase
RT   for an unidentified ligand.";
RL   EMBO J. 6:3341-3351(1987).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING (ISOFORMS 1 AND
RP   2).
RX   PubMed=1279499;
RA   Giebel L.B., Strunk K.M., Holmes S.A., Spritz R.A.;
RT   "Organization and nucleotide sequence of the human KIT (mast/stem cell
RT   growth factor receptor) proto-oncogene.";
RL   Oncogene 7:2207-2217(1992).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RC   TISSUE=Colon carcinoma;
RX   PubMed=7505199;
RA   Toyota M., Hinoda Y., Itoh F., Takaoka A., Imai K., Yachi A.;
RT   "Complementary DNA cloning and characterization of truncated form of c-kit
RT   in human colon carcinoma cells.";
RL   Cancer Res. 54:272-275(1994).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=9027509; DOI=10.1006/geno.1996.4482;
RA   Andre C., Hampe A., Lachaume P., Martin E., Wang X.P., Manus V., Hu W.X.,
RA   Galibert F.;
RT   "Sequence analysis of two genomic regions containing the KIT and the FMS
RT   receptor tyrosine kinase genes.";
RL   Genomics 39:216-226(1997).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RC   TISSUE=Prostate cancer;
RX   PubMed=15039213; DOI=10.1016/s0002-9440(10)63212-9;
RA   Paronetto M.P., Farini D., Sammarco I., Maturo G., Vespasiani G.,
RA   Geremia R., Rossi P., Sette C.;
RT   "Expression of a truncated form of the c-Kit tyrosine kinase receptor and
RT   activation of Src kinase in human prostatic cancer.";
RL   Am. J. Pathol. 164:1243-1251(2004).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), SUBCELLULAR LOCATION, AND
RP   INDUCTION.
RX   PubMed=20658618; DOI=10.1002/pbc.22603;
RA   Neumann I., Foell J.L., Bremer M., Volkmer I., Korholz D., Burdach S.,
RA   Staege M.S.;
RT   "Retinoic acid enhances sensitivity of neuroblastoma cells for imatinib
RT   mesylate.";
RL   Pediatr. Blood Cancer 55:464-470(2010).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA   Staege M.S., Neumann I., Volkmer I.;
RT   "Sequence of KIT mRNA from all-trans retinoic acid treated neuroblastoma
RT   cell lines.";
RL   Submitted (MAR-2010) to the EMBL/GenBank/DDBJ databases.
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Trachea;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [9]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15815621; DOI=10.1038/nature03466;
RA   Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA   Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA   Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA   Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA   Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA   Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA   Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA   Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA   Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA   McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA   Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA   Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA   Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA   Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA   Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA   Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA   Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA   Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA   Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA   Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA   Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT   4.";
RL   Nature 434:724-731(2005).
RN   [10]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Brain;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [11]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 1-411 (ISOFORMS 1/2).
RX   PubMed=18593464; DOI=10.1186/ar2447;
RA   Jin P., Zhang J., Sumariwalla P.F., Ni I., Jorgensen B., Crawford D.,
RA   Phillips S., Feldmann M., Shepard H.M., Paleolog E.M.;
RT   "Novel splice variants derived from the receptor tyrosine kinase
RT   superfamily are potential therapeutics for rheumatoid arthritis.";
RL   Arthritis Res. Ther. 10:R73-R73(2008).
RN   [12]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-22.
RX   PubMed=7506248; DOI=10.1111/j.1349-7006.1993.tb02813.x;
RA   Yamamoto K., Tojo A., Aoki N., Shibuya M.;
RT   "Characterization of the promoter region of the human c-kit proto-
RT   oncogene.";
RL   Jpn. J. Cancer Res. 84:1136-1144(1993).
RN   [13]
RP   FUNCTION IN PHOSPHORYLATION OF PIK3R1; RAF1 AND MAPK1, INTERACTION WITH
RP   GRB2; PIK3R1 AND PIK3 CATALYTIC SUBUNIT, ACTIVITY REGULATION, AND
RP   PHOSPHORYLATION.
RX   PubMed=7520444; DOI=10.1016/s0021-9258(17)31874-4;
RA   Blume-Jensen P., Ronnstrand L., Gout I., Waterfield M.D., Heldin C.H.;
RT   "Modulation of Kit/stem cell factor receptor-induced signaling by protein
RT   kinase C.";
RL   J. Biol. Chem. 269:21793-21802(1994).
RN   [14]
RP   PHOSPHORYLATION AT SER-741; SER-746; SER-821 AND SER-959, ACTIVITY
RP   REGULATION, PARTIAL PROTEIN SEQUENCE, AND MUTAGENESIS OF SER-741 AND
RP   SER-746.
RX   PubMed=7539802; DOI=10.1074/jbc.270.23.14192;
RA   Blume-Jensen P., Wernstedt C., Heldin C.H., Ronnstrand L.;
RT   "Identification of the major phosphorylation sites for protein kinase C in
RT   kit/stem cell factor receptor in vitro and in intact cells.";
RL   J. Biol. Chem. 270:14192-14200(1995).
RN   [15]
RP   INTERACTION WITH PIK3R1; MATK/CHK; FYN AND SHC1, AND PHOSPHORYLATION AT
RP   TYR-568; TYR-570 AND TYR-721.
RX   PubMed=9038210; DOI=10.1074/jbc.272.9.5915;
RA   Price D.J., Rivnay B., Fu Y., Jiang S., Avraham S., Avraham H.;
RT   "Direct association of Csk homologous kinase (CHK) with the
RT   diphosphorylated site Tyr568/570 of the activated c-KIT in
RT   megakaryocytes.";
RL   J. Biol. Chem. 272:5915-5920(1997).
RN   [16]
RP   INTERACTION WITH LYN.
RX   PubMed=9341198; DOI=10.1074/jbc.272.43.27450;
RA   Linnekin D., DeBerry C.S., Mou S.;
RT   "Lyn associates with the juxtamembrane region of c-Kit and is activated by
RT   stem cell factor in hematopoietic cell lines and normal progenitor cells.";
RL   J. Biol. Chem. 272:27450-27455(1997).
RN   [17]
RP   INTERACTION WITH PTPN6, AUTOPHOSPHORYLATION, AND FUNCTION IN
RP   PHOSPHORYLATION OF PTPN6.
RX   PubMed=9528781; DOI=10.1128/mcb.18.4.2089;
RA   Kozlowski M., Larose L., Lee F., Le D.M., Rottapel R., Siminovitch K.A.;
RT   "SHP-1 binds and negatively modulates the c-Kit receptor by interaction
RT   with tyrosine 569 in the c-Kit juxtamembrane domain.";
RL   Mol. Cell. Biol. 18:2089-2099(1998).
RN   [18]
RP   INTERACTION WITH GRB2 AND GRB7, PARTIAL PROTEIN SEQUENCE,
RP   AUTOPHOSPHORYLATION, AND PHOSPHORYLATION AT TYR-703 AND TYR-936.
RX   PubMed=10377264; DOI=10.1042/bj3410211;
RA   Thommes K., Lennartsson J., Carlberg M., Ronnstrand L.;
RT   "Identification of Tyr-703 and Tyr-936 as the primary association sites for
RT   Grb2 and Grb7 in the c-Kit/stem cell factor receptor.";
RL   Biochem. J. 341:211-216(1999).
RN   [19]
RP   INTERACTION WITH PTPRU, AND FUNCTION IN PHOSPHORYLATION OF PTPRU.
RX   PubMed=10397721;
RA   Taniguchi Y., London R., Schinkmann K., Jiang S., Avraham H.;
RT   "The receptor protein tyrosine phosphatase, PTP-RO, is upregulated during
RT   megakaryocyte differentiation and is associated with the c-Kit receptor.";
RL   Blood 94:539-549(1999).
RN   [20]
RP   INTERACTION WITH MPDZ, CHARACTERIZATION OF VARIANT VAL-816, AND MUTAGENESIS
RP   OF LYS-623.
RX   PubMed=11018522; DOI=10.1016/s0014-5793(00)02036-6;
RA   Mancini A., Koch A., Stefan M., Niemann H., Tamura T.;
RT   "The direct association of the multiple PDZ domain containing proteins
RT   (MUPP-1) with the human c-Kit C-terminus is regulated by tyrosine kinase
RT   activity.";
RL   FEBS Lett. 482:54-58(2000).
RN   [21]
RP   INTERACTION WITH LYN; TEC AND DOK1.
RX   PubMed=11825908; DOI=10.1074/jbc.m200277200;
RA   Liang X., Wisniewski D., Strife A., Shivakrupa R., Clarkson B., Resh M.D.;
RT   "Phosphatidylinositol 3-kinase and Src family kinases are required for
RT   phosphorylation and membrane recruitment of Dok-1 in c-Kit signaling.";
RL   J. Biol. Chem. 277:13732-13738(2002).
RN   [22]
RP   INTERACTION WITH SH2B2/APS, FUNCTION IN PHOSPHORYLATION OF SH2B2/APS, AND
RP   MUTAGENESIS OF ILE-571 AND LEU-939.
RX   PubMed=12444928; DOI=10.1042/bj20020716;
RA   Wollberg P., Lennartsson J., Gottfridsson E., Yoshimura A., Ronnstrand L.;
RT   "The adapter protein APS associates with the multifunctional docking sites
RT   Tyr-568 and Tyr-936 in c-Kit.";
RL   Biochem. J. 370:1033-1038(2003).
RN   [23]
RP   PHOSPHORYLATION AT SER-891 AND TYR-900, PARTIAL PROTEIN SEQUENCE,
RP   INTERACTION WITH CRK AND PIK3R1, FUNCTION IN PHOSPHORYLATION OF CRK; AKT1
RP   AND MAP KINASES, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX   PubMed=12878163; DOI=10.1016/s0014-4827(03)00206-4;
RA   Lennartsson J., Wernstedt C., Engstrom U., Hellman U., Ronnstrand L.;
RT   "Identification of Tyr900 in the kinase domain of c-Kit as a Src-dependent
RT   phosphorylation site mediating interaction with c-Crk.";
RL   Exp. Cell Res. 288:110-118(2003).
RN   [24]
RP   FUNCTION, AND ALTERNATIVE SPLICING.
RX   PubMed=12511554; DOI=10.1074/jbc.m211726200;
RA   Voytyuk O., Lennartsson J., Mogi A., Caruana G., Courtneidge S.,
RA   Ashman L.K., Ronnstrand L.;
RT   "Src family kinases are involved in the differential signaling from two
RT   splice forms of c-Kit.";
RL   J. Biol. Chem. 278:9159-9166(2003).
RN   [25]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-130.
RC   TISSUE=Plasma;
RX   PubMed=16335952; DOI=10.1021/pr0502065;
RA   Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA   Smith R.D.;
RT   "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT   hydrazide chemistry, and mass spectrometry.";
RL   J. Proteome Res. 4:2070-2080(2005).
RN   [26]
RP   INTERACTION WITH FES/FPS, AND CHARACTERIZATION OF VARIANT VAL-816.
RX   PubMed=17595334; DOI=10.1182/blood-2007-02-076471;
RA   Voisset E., Lopez S., Dubreuil P., De Sepulveda P.;
RT   "The tyrosine kinase FES is an essential effector of KITD816V proliferation
RT   signal.";
RL   Blood 110:2593-2599(2007).
RN   [27]
RP   INTERACTION WITH GRB2 AND CBL, UBIQUITINATION, AND FUNCTION IN
RP   PHOSPHORYLATION OF CBL.
RX   PubMed=17904548; DOI=10.1016/j.yexcr.2007.08.021;
RA   Sun J., Pedersen M., Bengtsson S., Ronnstrand L.;
RT   "Grb2 mediates negative regulation of stem cell factor receptor/c-Kit
RT   signaling by recruitment of Cbl.";
RL   Exp. Cell Res. 313:3935-3942(2007).
RN   [28]
RP   FUNCTION IN ACTIVATION OF SIGNALING PATHWAYS AND CELL SURVIVAL, FUNCTION IN
RP   PHOSPHORYLATION OF CBL, PHOSPHORYLATION AT TYR-568; TYR-703; TYR-721 AND
RP   TYR-936, UBIQUITINATION, SUBCELLULAR LOCATION, AND CHARACTERIZATION OF
RP   VARIANT VAL-816.
RX   PubMed=19265199; DOI=10.1074/jbc.m808058200;
RA   Sun J., Pedersen M., Ronnstrand L.;
RT   "The D816V mutation of c-Kit circumvents a requirement for Src family
RT   kinases in c-Kit signal transduction.";
RL   J. Biol. Chem. 284:11039-11047(2009).
RN   [29]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-959, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA   Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA   Mann M., Daub H.;
RT   "Large-scale proteomics analysis of the human kinome.";
RL   Mol. Cell. Proteomics 8:1751-1764(2009).
RN   [30]
RP   SUBCELLULAR LOCATION, ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY.
RX   PubMed=20601678; DOI=10.1093/humrep/deq168;
RA   Muciaccia B., Sette C., Paronetto M.P., Barchi M., Pensini S.,
RA   D'Agostino A., Gandini L., Geremia R., Stefanini M., Rossi P.;
RT   "Expression of a truncated form of KIT tyrosine kinase in human spermatozoa
RT   correlates with sperm DNA integrity.";
RL   Hum. Reprod. 25:2188-2202(2010).
RN   [31]
RP   PHOSPHORYLATION AT TYR-547; TYR-553; TYR-703; TYR-721; TYR-730; TYR-823 AND
RP   TYR-900, IDENTIFICATION BY MASS SPECTROMETRY, MUTAGENESIS OF TYR-823, AND
RP   CHARACTERIZATION OF VARIANT HIS-816.
RX   PubMed=20147452; DOI=10.1093/jb/mvq015;
RA   DiNitto J.P., Deshmukh G.D., Zhang Y., Jacques S.L., Coli R., Worrall J.W.,
RA   Diehl W., English J.M., Wu J.C.;
RT   "Function of activation loop tyrosine phosphorylation in the mechanism of
RT   c-Kit auto-activation and its implication in sunitinib resistance.";
RL   J. Biochem. 147:601-609(2010).
RN   [32]
RP   FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AUTOPHOSPHORYLATION,
RP   SUBUNIT, AND CHARACTERIZATION OF VARIANT VAL-816.
RX   PubMed=21640708; DOI=10.1016/j.bbrc.2011.05.111;
RA   Kim S.Y., Kang J.J., Lee H.H., Kang J.J., Kim B., Kim C.G., Park T.K.,
RA   Kang H.;
RT   "Mechanism of activation of human c-KIT kinase by internal tandem
RT   duplications of the juxtamembrane domain and point mutations at aspartic
RT   acid 816.";
RL   Biochem. Biophys. Res. Commun. 410:224-228(2011).
RN   [33]
RP   FUNCTION IN ACTIVATION AND PHOSPHORYLATION OF STAT1; STAT3; STAT5A AND
RP   STAT5B.
RX   PubMed=21135090; DOI=10.1074/jbc.m110.182642;
RA   Chaix A., Lopez S., Voisset E., Gros L., Dubreuil P., De Sepulveda P.;
RT   "Mechanisms of STAT protein activation by oncogenic KIT mutants in
RT   neoplastic mast cells.";
RL   J. Biol. Chem. 286:5956-5966(2011).
RN   [34]
RP   REVIEW.
RX   PubMed=15526160; DOI=10.1007/s00018-004-4189-6;
RA   Ronnstrand L.;
RT   "Signal transduction via the stem cell factor receptor/c-Kit.";
RL   Cell. Mol. Life Sci. 61:2535-2548(2004).
RN   [35]
RP   REVIEW ON KIT SIGNALING.
RX   PubMed=16129412; DOI=10.1016/j.bbrc.2005.08.055;
RA   Roskoski R. Jr.;
RT   "Signaling by Kit protein-tyrosine kinase--the stem cell factor receptor.";
RL   Biochem. Biophys. Res. Commun. 337:1-13(2005).
RN   [36]
RP   REVIEW.
RX   PubMed=15625120; DOI=10.1634/stemcells.2004-0117;
RA   Lennartsson J., Jelacic T., Linnekin D., Shivakrupa R.;
RT   "Normal and oncogenic forms of the receptor tyrosine kinase kit.";
RL   Stem Cells 23:16-43(2005).
RN   [37]
RP   REVIEW.
RX   PubMed=18381929; DOI=10.1158/1078-0432.ccr-07-5134;
RA   Kent D., Copley M., Benz C., Dykstra B., Bowie M., Eaves C.;
RT   "Regulation of hematopoietic stem cells by the steel factor/KIT signaling
RT   pathway.";
RL   Clin. Cancer Res. 14:1926-1930(2008).
RN   [38]
RP   REVIEW.
RX   PubMed=21057534; DOI=10.1038/onc.2010.494;
RA   Pittoni P., Piconese S., Tripodo C., Colombo M.P.;
RT   "Tumor-intrinsic and -extrinsic roles of c-Kit: mast cells as the primary
RT   off-target of tyrosine kinase inhibitors.";
RL   Oncogene 30:757-769(2011).
RN   [39]
RP   X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 549-931 IN COMPLEX WITH ADP AND
RP   MAGNESIUM IONS, SUBUNIT, PHOSPHORYLATION AT TYR-568 AND TYR-570, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY.
RX   PubMed=12824176; DOI=10.1074/jbc.c300186200;
RA   Mol C.D., Lim K.B., Sridhar V., Zou H., Chien E.Y., Sang B.C.,
RA   Nowakowski J., Kassel D.B., Cronin C.N., McRee D.E.;
RT   "Structure of a c-kit product complex reveals the basis for kinase
RT   transactivation.";
RL   J. Biol. Chem. 278:31461-31464(2003).
RN   [40]
RP   X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 565-935 IN COMPLEXES WITH
RP   INHIBITOR IMATINIB AND PHOSPHATE, AND ACTIVITY REGULATION.
RX   PubMed=15123710; DOI=10.1074/jbc.m403319200;
RA   Mol C.D., Dougan D.R., Schneider T.R., Skene R.J., Kraus M.L.,
RA   Scheibe D.N., Snell G.P., Zou H., Sang B.C., Wilson K.P.;
RT   "Structural basis for the autoinhibition and STI-571 inhibition of c-Kit
RT   tyrosine kinase.";
RL   J. Biol. Chem. 279:31655-31663(2004).
RN   [41]
RP   X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 1-519 IN COMPLEX WITH KITLG/SCF,
RP   INTERACTION WITH KITLG/SCF, SUBUNIT, DISULFIDE BONDS, CATALYTIC ACTIVITY,
RP   AUTOPHOSPHORYLATION, MUTAGENESIS OF ARG-381 AND GLU-386, AND GLYCOSYLATION
RP   AT ASN-130; ASN-283; ASN-293; ASN-300; ASN-320; ASN-352 AND ASN-367.
RX   PubMed=17662946; DOI=10.1016/j.cell.2007.05.055;
RA   Yuzawa S., Opatowsky Y., Zhang Z., Mandiyan V., Lax I., Schlessinger J.;
RT   "Structural basis for activation of the receptor tyrosine kinase KIT by
RT   stem cell factor.";
RL   Cell 130:323-334(2007).
RN   [42]
RP   X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 544-935 IN COMPLEX WITH SUNITINIB,
RP   CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, CHARACTERIZATION OF VARIANTS
RP   HIS-816 AND VAL-816, AND ACTIVITY REGULATION.
RX   PubMed=19164557; DOI=10.1073/pnas.0812413106;
RA   Gajiwala K.S., Wu J.C., Christensen J., Deshmukh G.D., Diehl W.,
RA   DiNitto J.P., English J.M., Greig M.J., He Y.A., Jacques S.L., Lunney E.A.,
RA   McTigue M., Molina D., Quenzer T., Wells P.A., Yu X., Zhang Y., Zou A.,
RA   Emmett M.R., Marshall A.G., Zhang H.M., Demetri G.D.;
RT   "KIT kinase mutants show unique mechanisms of drug resistance to imatinib
RT   and sunitinib in gastrointestinal stromal tumor patients.";
RL   Proc. Natl. Acad. Sci. U.S.A. 106:1542-1547(2009).
RN   [43]
RP   X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 564-574 IN COMPLEX WITH SOCS6,
RP   AND PHOSPHORYLATION AT TYR-568.
RX   PubMed=21030588; DOI=10.1074/jbc.m110.173526;
RA   Zadjali F., Pike A.C., Vesterlund M., Sun J., Wu C., Li S.S.,
RA   Ronnstrand L., Knapp S., Bullock A.N., Flores-Morales A.;
RT   "Structural basis for c-KIT inhibition by the suppressor of cytokine
RT   signaling 6 (SOCS6) ubiquitin ligase.";
RL   J. Biol. Chem. 286:480-490(2011).
RN   [44]
RP   VARIANT PBT LYS-583.
RX   PubMed=1376329; DOI=10.1172/jci115772;
RA   Fleischman R.A.;
RT   "Human piebald trait resulting from a dominant negative mutant allele of
RT   the c-kit membrane receptor gene.";
RL   J. Clin. Invest. 89:1713-1717(1992).
RN   [45]
RP   VARIANT PBT LEU-584.
RX   PubMed=1370874;
RA   Spritz R.A., Giebel L.B., Holmes S.A.;
RT   "Dominant negative and loss of function mutations of the c-kit (mast/stem
RT   cell growth factor receptor) proto-oncogene in human piebaldism.";
RL   Am. J. Hum. Genet. 50:261-269(1992).
RN   [46]
RP   VARIANT PBT ARG-664.
RX   PubMed=1717985; DOI=10.1073/pnas.88.19.8696;
RA   Giebel L.B., Spritz R.A.;
RT   "Mutation of the KIT (mast/stem cell growth factor receptor) protooncogene
RT   in human piebaldism.";
RL   Proc. Natl. Acad. Sci. U.S.A. 88:8696-8699(1991).
RN   [47]
RP   VARIANT MAST CELL LEUKEMIA VAL-816.
RX   PubMed=7691885; DOI=10.1172/jci116761;
RA   Furitsu T., Tsujimura T., Tono T., Ikeda H., Kitayama H., Koshimizu U.,
RA   Sugahara H., Butterfield J.H., Ashman L.K., Kanayama Y., Matsuzawa Y.,
RA   Kitamura Y., Kanakura Y.;
RT   "Identification of mutations in the coding sequence of the proto-oncogene
RT   c-kit in a human mast cell leukemia cell line causing ligand-independent
RT   activation of c-kit product.";
RL   J. Clin. Invest. 92:1736-1744(1993).
RN   [48]
RP   VARIANTS PBT GLY-791 AND VAL-812.
RX   PubMed=7687267; DOI=10.1111/1523-1747.ep12358440;
RA   Spritz R.A., Holmes S.A., Itin P., Kuester W.;
RT   "Novel mutations of the KIT (mast/stem cell growth factor receptor) proto-
RT   oncogene in human piebaldism.";
RL   J. Invest. Dermatol. 101:22-25(1993).
RN   [49]
RP   VARIANT PBT 893-GLU--PRO-896 DEL.
RX   PubMed=8680409; DOI=10.1002/humu.1380060409;
RA   Riva P., Milani N., Gandolfi P., Larizza L.;
RT   "A 12-bp deletion (7818del12) in the c-kit protooncogene in a large Italian
RT   kindred with piebaldism.";
RL   Hum. Mutat. 6:343-345(1995).
RN   [50]
RP   VARIANT MAST CELL DISEASE GLY-820.
RX   PubMed=9029028; DOI=10.1046/j.1365-2141.1997.d01-2042.x;
RA   Pignon J.-M., Giraudier S., Duquesnoy P., Jouault H., Imbert M.,
RA   Vainchenker W., Vernant J.-P., Tulliez M.;
RT   "A new c-kit mutation in a case of aggressive mast cell disease.";
RL   Br. J. Haematol. 96:374-376(1997).
RN   [51]
RP   VARIANT PBT GLY-796.
RX   PubMed=9450866;
RX   DOI=10.1002/(sici)1096-8628(19980106)75:1<101::aid-ajmg20>3.0.co;2-p;
RA   Spritz R.A., Beighton P.;
RT   "Piebaldism with deafness: molecular evidence for an expanded syndrome.";
RL   Am. J. Med. Genet. 75:101-103(1998).
RN   [52]
RP   VARIANT ACUTE MYELOID LEUKEMIA TYR-816.
RX   PubMed=9657776;
RA   Beghini A., Larizza L., Cairoli R., Morra E.;
RT   "c-kit activating mutations and mast cell proliferation in human
RT   leukemia.";
RL   Blood 92:701-702(1998).
RN   [53]
RP   VARIANT PBT PRO-847.
RX   PubMed=9699740; DOI=10.1046/j.1523-1747.1998.00269.x;
RA   Nomura K., Hatayama I., Narita T., Kaneko T., Shiraishi M.;
RT   "A novel KIT gene missense mutation in a Japanese family with piebaldism.";
RL   J. Invest. Dermatol. 111:337-338(1998).
RN   [54]
RP   VARIANT GIST VAL-559 DEL.
RX   PubMed=9697690; DOI=10.1038/1209;
RA   Nishida T., Hirota S., Taniguchi M., Hashimoto K., Isozaki K., Nakamura H.,
RA   Kanakura Y., Tanaka T., Takabayashi A., Matsuda H., Kitamura Y.;
RT   "Familial gastrointestinal stromal tumours with germline mutation of the
RT   KIT gene.";
RL   Nat. Genet. 19:323-324(1998).
RN   [55]
RP   VARIANTS GIST ILE-550; 550-LYS--LYS-558 DEL; 551-PRO--VAL-555 DEL; ASP-559
RP   AND 559-VAL-VAL-560 DEL.
RX   PubMed=9438854; DOI=10.1126/science.279.5350.577;
RA   Hirota S., Isozaki K., Moriyama Y., Hashimoto K., Nishida T., Ishiguro S.,
RA   Kawano K., Hanada M., Kurata A., Takeda M., Muhammad Tunio G.,
RA   Matsuzawa Y., Kanakura Y., Shinomura Y., Kitamura Y.;
RT   "Gain-of-function mutations of c-kit in human gastrointestinal stromal
RT   tumors.";
RL   Science 279:577-580(1998).
RN   [56]
RP   VARIANT HIS-816, AND CHARACTERIZATION OF VARIANT HIS-816.
RX   PubMed=10362788; DOI=10.1016/s0002-9440(10)65419-3;
RA   Tian Q., Frierson H.F. Jr., Krystal G.W., Moskaluk C.A.;
RT   "Activating c-kit gene mutations in human germ cell tumors.";
RL   Am. J. Pathol. 154:1643-1647(1999).
RN   [57]
RP   VARIANTS MASTSYS VAL-816 AND TYR-816, VARIANTS MASTC PHE-816 AND LYS-839,
RP   CHARACTERIZATION OF VARIANTS MASTSYS VAL-816 AND TYR-816, CHARACTERIZATION
RP   OF VARIANTS MASTC PHE-816 AND LYS-839, AND INVOLVEMENT IN MASTSYS AND
RP   MASTC.
RX   PubMed=9990072; DOI=10.1073/pnas.96.4.1609;
RA   Longley B.J. Jr., Metcalfe D.D., Tharp M., Wang X., Tyrrell L., Lu S.-Z.,
RA   Heitjan D., Ma Y.;
RT   "Activating and dominant inactivating c-KIT catalytic domain mutations in
RT   distinct clinical forms of human mastocytosis.";
RL   Proc. Natl. Acad. Sci. U.S.A. 96:1609-1614(1999).
RN   [58]
RP   VARIANTS PBT CYS-584; ARG-601 AND PRO-656.
RX   PubMed=11074500;
RX   DOI=10.1002/1096-8628(20001106)95:1<79::aid-ajmg16>3.0.co;2-4;
RA   Syrris P., Malik N.M., Murday V.A., Patton M.A., Carter N.D., Hughes H.E.,
RA   Metcalfe K.;
RT   "Three novel mutations of the proto-oncogene KIT cause human piebaldism.";
RL   Am. J. Med. Genet. 95:79-81(2000).
RN   [59]
RP   VARIANT GIST ALA-559.
RX   PubMed=11505412;
RX   DOI=10.1002/1097-0142(20010801)92:3<657::aid-cncr1367>3.0.co;2-d;
RA   Beghini A., Tibiletti M.G., Roversi G., Chiaravalli A.M., Serio G.,
RA   Capella C., Larizza L.;
RT   "Germline mutation in the juxtamembrane domain of the kit gene in a family
RT   with gastrointestinal stromal tumors and urticaria pigmentosa.";
RL   Cancer 92:657-662(2001).
RN   [60]
RP   VARIANT MASTC ASP-533, AND INVOLVEMENT IN MASTC.
RX   PubMed=15173254; DOI=10.1136/jmg.2003.015156;
RA   Tang X., Boxer M., Drummond A., Ogston P., Hodgins M., Burden A.D.;
RT   "A germline mutation in KIT in familial diffuse cutaneous mastocytosis.";
RL   J. Med. Genet. 41:E88-E88(2004).
RN   [61]
RP   VARIANT GIST 550-LYS--LYS-558 DEL.
RX   PubMed=15824741; DOI=10.1038/sj.onc.1208587;
RA   Chen L.L., Sabripour M., Wu E.F., Prieto V.G., Fuller G.N., Frazier M.L.;
RT   "A mutation-created novel intra-exonic pre-mRNA splice site causes
RT   constitutive activation of KIT in human gastrointestinal stromal tumors.";
RL   Oncogene 24:4271-4280(2005).
RN   [62]
RP   VARIANTS TYR-816; LYS-822 AND PRO-829.
RX   PubMed=16175573; DOI=10.1002/gcc.20265;
RA   Bignell G., Smith R., Hunter C., Stephens P., Davies H., Greenman C.,
RA   Teague J., Butler A., Edkins S., Stevens C., O'meara S., Parker A.,
RA   Avis T., Barthorpe S., Brackenbury L., Buck G., Clements J., Cole J.,
RA   Dicks E., Edwards K., Forbes S., Gorton M., Gray K., Halliday K.,
RA   Harrison R., Hills K., Hinton J., Jones D., Kosmidou V., Laman R., Lugg R.,
RA   Menzies A., Perry J., Petty R., Raine K., Shepherd R., Small A.,
RA   Solomon H., Stephens Y., Tofts C., Varian J., Webb A., West S., Widaa S.,
RA   Yates A., Gillis A.J.M., Stoop H.J., van Gurp R.J.H.L.M., Oosterhuis J.W.,
RA   Looijenga L.H.J., Futreal P.A., Wooster R., Stratton M.R.;
RT   "Sequence analysis of the protein kinase gene family in human testicular
RT   germ-cell tumors of adolescents and adults.";
RL   Genes Chromosomes Cancer 45:42-46(2006).
RN   [63]
RP   VARIANTS [LARGE SCALE ANALYSIS] ILE-532; LEU-541; SER-691; ASN-715;
RP   ASN-737; TRP-804; TYR-816; LYS-822 AND PRO-829.
RX   PubMed=17344846; DOI=10.1038/nature05610;
RA   Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA   Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA   Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA   Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA   Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA   Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA   Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA   Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA   Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA   Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA   Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA   Futreal P.A., Stratton M.R.;
RT   "Patterns of somatic mutation in human cancer genomes.";
RL   Nature 446:153-158(2007).
RN   [64]
RP   VARIANT LEU-541, VARIANTS MASTC ILE-816; TYR-816 AND VAL-816, AND
RP   CHARACTERIZATION OF VARIANTS MASTC ILE-816; TYR-816 AND VAL-816.
RX   PubMed=19865100; DOI=10.1038/jid.2009.281;
RA   Bodemer C., Hermine O., Palmerini F., Yang Y., Grandpeix-Guyodo C.,
RA   Leventhal P.S., Hadj-Rabia S., Nasca L., Georgin-Lavialle S.,
RA   Cohen-Akenine A., Launay J.M., Barete S., Feger F., Arock M., Catteau B.,
RA   Sans B., Stalder J.F., Skowron F., Thomas L., Lorette G., Plantin P.,
RA   Bordigoni P., Lortholary O., de Prost Y., Moussy A., Sobol H., Dubreuil P.;
RT   "Pediatric mastocytosis is a clonal disease associated with D816V and other
RT   activating c-KIT mutations.";
RL   J. Invest. Dermatol. 130:804-815(2010).
RN   [65]
RP   VARIANT MASTC ILE-822, CHARACTERIZATION OF VARIANT MASTC ILE-822, AND
RP   INVOLVEMENT IN MASTC.
RX   PubMed=21689725; DOI=10.1016/j.exphem.2011.05.009;
RA   Wasag B., Niedoszytko M., Piskorz A., Lange M., Renke J., Jassem E.,
RA   Biernat W., Debiec-Rychter M., Limon J.;
RT   "Novel, activating KIT-N822I mutation in familial cutaneous mastocytosis.";
RL   Exp. Hematol. 39:859-865(2011).
RN   [66]
RP   VARIANT MASTC CYS-451, AND INVOLVEMENT IN MASTC.
RX   PubMed=24289326; DOI=10.1111/ced.12225;
RA   Wang H.J., Lin Z.M., Zhang J., Yin J.H., Yang Y.;
RT   "A new germline mutation in KIT associated with diffuse cutaneous
RT   mastocytosis in a Chinese family.";
RL   Clin. Exp. Dermatol. 39:146-149(2014).
CC   -!- FUNCTION: Tyrosine-protein kinase that acts as a cell-surface receptor
CC       for the cytokine KITLG/SCF and plays an essential role in the
CC       regulation of cell survival and proliferation, hematopoiesis, stem cell
CC       maintenance, gametogenesis, mast cell development, migration and
CC       function, and in melanogenesis. In response to KITLG/SCF binding, KIT
CC       can activate several signaling pathways. Phosphorylates PIK3R1, PLCG1,
CC       SH2B2/APS and CBL. Activates the AKT1 signaling pathway by
CC       phosphorylation of PIK3R1, the regulatory subunit of
CC       phosphatidylinositol 3-kinase. Activated KIT also transmits signals via
CC       GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or
CC       MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3,
CC       STAT5A and STAT5B. Activation of PLCG1 leads to the production of the
CC       cellular signaling molecules diacylglycerol and inositol 1,4,5-
CC       trisphosphate. KIT signaling is modulated by protein phosphatases, and
CC       by rapid internalization and degradation of the receptor. Activated KIT
CC       promotes phosphorylation of the protein phosphatases PTPN6/SHP-1 and
CC       PTPRU, and of the transcription factors STAT1, STAT3, STAT5A and
CC       STAT5B. Promotes phosphorylation of PIK3R1, CBL, CRK (isoform Crk-II),
CC       LYN, MAPK1/ERK2 and/or MAPK3/ERK1, PLCG1, SRC and SHC1.
CC       {ECO:0000269|PubMed:10397721, ECO:0000269|PubMed:12444928,
CC       ECO:0000269|PubMed:12511554, ECO:0000269|PubMed:12878163,
CC       ECO:0000269|PubMed:17904548, ECO:0000269|PubMed:19265199,
CC       ECO:0000269|PubMed:21135090, ECO:0000269|PubMed:21640708,
CC       ECO:0000269|PubMed:7520444, ECO:0000269|PubMed:9528781}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] +
CC         ADP + H(+); Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC         COMP:20101, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC         ChEBI:CHEBI:61978, ChEBI:CHEBI:456216; EC=2.7.10.1;
CC         Evidence={ECO:0000255|PROSITE-ProRule:PRU10028,
CC         ECO:0000269|PubMed:17662946, ECO:0000269|PubMed:19164557,
CC         ECO:0000269|PubMed:21640708, ECO:0000269|PubMed:2448137};
CC   -!- ACTIVITY REGULATION: Present in an inactive conformation in the absence
CC       of bound ligand. KITLG/SCF binding leads to dimerization and activation
CC       by autophosphorylation on tyrosine residues. Activity is down-regulated
CC       by PRKCA-mediated phosphorylation on serine residues. Inhibited by
CC       imatinib/STI-571 (Gleevec) and sunitinib; these compounds maintain the
CC       kinase in an inactive conformation. {ECO:0000269|PubMed:15123710,
CC       ECO:0000269|PubMed:19164557, ECO:0000269|PubMed:21640708,
CC       ECO:0000269|PubMed:7520444, ECO:0000269|PubMed:7539802}.
CC   -!- SUBUNIT: Monomer in the absence of bound KITLG/SCF. Homodimer in the
CC       presence of bound KITLG/SCF, forming a heterotetramer with two
CC       KITLG/SCF molecules. Interacts (via phosphorylated tyrosine residues)
CC       with the adapter proteins GRB2 and GRB7 (via SH2 domain), and
CC       SH2B2/APS. Interacts (via C-terminus) with MPDZ (via the tenth PDZ
CC       domain). Interacts (via phosphorylated tyrosine residues) with PIK3R1
CC       and PIK3 catalytic subunit. Interacts (via phosphorylated tyrosine)
CC       with CRK (isoform Crk-II), FYN, SHC1 and MATK/CHK (via SH2 domain).
CC       Interacts with LYN and FES/FPS. Interacts (via phosphorylated tyrosine
CC       residues) with the protein phosphatases PTPN6/SHP-1 (via SH2 domain),
CC       PTPN11/SHP-2 (via SH2 domain) and PTPRU. Interacts with PLCG1.
CC       Interacts with DOK1 and TEC. Interacts (KITLG/SCF-bound) with IL1RL1.
CC       Interacts with IL1RAP (independent of stimulation with KITLG/SCF). A
CC       mast cell-specific KITLG/SCF-induced interleukin-33 signaling complex
CC       contains IL1RL1, IL1RAP, KIT and MYD88. {ECO:0000250|UniProtKB:P05532,
CC       ECO:0000269|PubMed:10377264, ECO:0000269|PubMed:10397721,
CC       ECO:0000269|PubMed:11018522, ECO:0000269|PubMed:11825908,
CC       ECO:0000269|PubMed:12444928, ECO:0000269|PubMed:12824176,
CC       ECO:0000269|PubMed:12878163, ECO:0000269|PubMed:17595334,
CC       ECO:0000269|PubMed:17662946, ECO:0000269|PubMed:17904548,
CC       ECO:0000269|PubMed:19164557, ECO:0000269|PubMed:21030588,
CC       ECO:0000269|PubMed:21640708, ECO:0000269|PubMed:7520444,
CC       ECO:0000269|PubMed:9038210, ECO:0000269|PubMed:9341198,
CC       ECO:0000269|PubMed:9528781}.
CC   -!- INTERACTION:
CC       P10721; P00519: ABL1; NbExp=2; IntAct=EBI-1379503, EBI-375543;
CC       P10721; P42684: ABL2; NbExp=2; IntAct=EBI-1379503, EBI-1102694;
CC       P10721; O75815: BCAR3; NbExp=3; IntAct=EBI-1379503, EBI-702336;
CC       P10721; P51451: BLK; NbExp=5; IntAct=EBI-1379503, EBI-2105445;
CC       P10721; Q8WV28: BLNK; NbExp=2; IntAct=EBI-1379503, EBI-2623522;
CC       P10721; P46108: CRK; NbExp=4; IntAct=EBI-1379503, EBI-886;
CC       P10721; P07332: FES; NbExp=2; IntAct=EBI-1379503, EBI-1055635;
CC       P10721; P09769: FGR; NbExp=2; IntAct=EBI-1379503, EBI-1383732;
CC       P10721; O75791: GRAP2; NbExp=2; IntAct=EBI-1379503, EBI-740418;
CC       P10721; P62993: GRB2; NbExp=6; IntAct=EBI-1379503, EBI-401755;
CC       P10721; Q14451: GRB7; NbExp=4; IntAct=EBI-1379503, EBI-970191;
CC       P10721; P08631: HCK; NbExp=2; IntAct=EBI-1379503, EBI-346340;
CC       P10721; Q96JZ2: HSH2D; NbExp=5; IntAct=EBI-1379503, EBI-3919324;
CC       P10721; P21583: KITLG; NbExp=2; IntAct=EBI-1379503, EBI-1379527;
CC       P10721; P06239: LCK; NbExp=8; IntAct=EBI-1379503, EBI-1348;
CC       P10721; P07948: LYN; NbExp=7; IntAct=EBI-1379503, EBI-79452;
CC       P10721; P16333: NCK1; NbExp=3; IntAct=EBI-1379503, EBI-389883;
CC       P10721; O43639: NCK2; NbExp=2; IntAct=EBI-1379503, EBI-713635;
CC       P10721; P27986: PIK3R1; NbExp=19; IntAct=EBI-1379503, EBI-79464;
CC       P10721; O00459: PIK3R2; NbExp=19; IntAct=EBI-1379503, EBI-346930;
CC       P10721; Q92569: PIK3R3; NbExp=31; IntAct=EBI-1379503, EBI-79893;
CC       P10721; P19174: PLCG1; NbExp=31; IntAct=EBI-1379503, EBI-79387;
CC       P10721; P16885: PLCG2; NbExp=8; IntAct=EBI-1379503, EBI-617403;
CC       P10721; Q13882: PTK6; NbExp=4; IntAct=EBI-1379503, EBI-1383632;
CC       P10721; Q06124: PTPN11; NbExp=29; IntAct=EBI-1379503, EBI-297779;
CC       P10721; Q92729: PTPRU; NbExp=2; IntAct=EBI-1379503, EBI-7052301;
CC       P10721; P20936: RASA1; NbExp=16; IntAct=EBI-1379503, EBI-1026476;
CC       P10721; Q9UQQ2: SH2B3; NbExp=2; IntAct=EBI-1379503, EBI-7879749;
CC       P10721; O14796: SH2D1B; NbExp=8; IntAct=EBI-1379503, EBI-3923013;
CC       P10721; Q9NP31: SH2D2A; NbExp=10; IntAct=EBI-1379503, EBI-490630;
CC       P10721; Q8N5H7: SH2D3C; NbExp=4; IntAct=EBI-1379503, EBI-745980;
CC       P10721; P78314: SH3BP2; NbExp=3; IntAct=EBI-1379503, EBI-727062;
CC       P10721; Q15464: SHB; NbExp=2; IntAct=EBI-1379503, EBI-4402156;
CC       P10721; P29353: SHC1; NbExp=8; IntAct=EBI-1379503, EBI-78835;
CC       P10721; P98077: SHC2; NbExp=5; IntAct=EBI-1379503, EBI-7256023;
CC       P10721; Q92529: SHC3; NbExp=3; IntAct=EBI-1379503, EBI-79084;
CC       P10721; Q9H6Q3: SLA2; NbExp=2; IntAct=EBI-1379503, EBI-1222854;
CC       P10721; O14508: SOCS2; NbExp=4; IntAct=EBI-1379503, EBI-617737;
CC       P10721; O14543: SOCS3; NbExp=3; IntAct=EBI-1379503, EBI-714146;
CC       P10721; O14544: SOCS6; NbExp=12; IntAct=EBI-1379503, EBI-3929549;
CC       P10721; P12931: SRC; NbExp=5; IntAct=EBI-1379503, EBI-621482;
CC       P10721; Q9ULZ2: STAP1; NbExp=3; IntAct=EBI-1379503, EBI-6083058;
CC       P10721; Q9HBL0: TNS1; NbExp=2; IntAct=EBI-1379503, EBI-3389814;
CC       P10721; Q63HR2: TNS2; NbExp=2; IntAct=EBI-1379503, EBI-949753;
CC       P10721; Q68CZ2: TNS3; NbExp=5; IntAct=EBI-1379503, EBI-1220488;
CC       P10721; P42681: TXK; NbExp=3; IntAct=EBI-1379503, EBI-7877438;
CC       P10721; P07947: YES1; NbExp=7; IntAct=EBI-1379503, EBI-515331;
CC       P10721; P43403: ZAP70; NbExp=2; IntAct=EBI-1379503, EBI-1211276;
CC       P10721; Q8VBX6: Mpdz; Xeno; NbExp=4; IntAct=EBI-1379503, EBI-8026435;
CC       P10721; P35235: Ptpn11; Xeno; NbExp=2; IntAct=EBI-1379503, EBI-397236;
CC   -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane; Single-pass type I
CC       membrane protein.
CC   -!- SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane; Single-pass type I
CC       membrane protein.
CC   -!- SUBCELLULAR LOCATION: [Isoform 3]: Cytoplasm
CC       {ECO:0000269|PubMed:20601678}. Note=Detected in the cytoplasm of
CC       spermatozoa, especially in the equatorial and subacrosomal region of
CC       the sperm head. {ECO:0000269|PubMed:20601678}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1; Synonyms=GNNK(+), KitA(+);
CC         IsoId=P10721-1; Sequence=Displayed;
CC       Name=2; Synonyms=GNNK(-), Kit(+);
CC         IsoId=P10721-2; Sequence=VSP_038385;
CC       Name=3; Synonyms=TR-KIT {ECO:0000303|PubMed:20601678};
CC         IsoId=P10721-4; Sequence=VSP_060976;
CC   -!- TISSUE SPECIFICITY: [Isoform 3]: In testis, detected in spermatogonia
CC       in the basal layer and in interstitial Leydig cells but not in Sertoli
CC       cells or spermatocytes inside the seminiferous tubules (at protein
CC       level) (PubMed:20601678). Expression is maintained in ejaculated
CC       spermatozoa (at protein level) (PubMed:20601678).
CC       {ECO:0000269|PubMed:20601678}.
CC   -!- INDUCTION: Up-regulated by cis-retinoic acid in neuroblastoma cell
CC       lines. {ECO:0000269|PubMed:20658618}.
CC   -!- PTM: Ubiquitinated by SOCS6. KIT is rapidly ubiquitinated after
CC       autophosphorylation induced by KITLG/SCF binding, leading to
CC       internalization and degradation. {ECO:0000269|PubMed:17904548,
CC       ECO:0000269|PubMed:19265199}.
CC   -!- PTM: Autophosphorylated on tyrosine residues. KITLG/SCF binding
CC       enhances autophosphorylation. Isoform 1 shows low levels of tyrosine
CC       phosphorylation in the absence of added KITLG/SCF (in vitro). Kinase
CC       activity is down-regulated by phosphorylation on serine residues by
CC       protein kinase C family members. Phosphorylation at Tyr-568 is required
CC       for interaction with PTPN11/SHP-2, CRK (isoform Crk-II) and members of
CC       the SRC tyrosine-protein kinase family. Phosphorylation at Tyr-570 is
CC       required for interaction with PTPN6/SHP-1. Phosphorylation at Tyr-703,
CC       Tyr-823 and Tyr-936 is important for interaction with GRB2.
CC       Phosphorylation at Tyr-721 is important for interaction with PIK3R1.
CC       Phosphorylation at Tyr-823 and Tyr-936 is important for interaction
CC       with GRB7. {ECO:0000269|PubMed:10377264, ECO:0000269|PubMed:12824176,
CC       ECO:0000269|PubMed:19265199, ECO:0000269|PubMed:20147452,
CC       ECO:0000269|PubMed:21030588, ECO:0000269|PubMed:9038210}.
CC   -!- DISEASE: Piebald trait (PBT) [MIM:172800]: Autosomal dominant genetic
CC       developmental abnormality of pigmentation characterized by congenital
CC       patches of white skin and hair that lack melanocytes.
CC       {ECO:0000269|PubMed:11074500, ECO:0000269|PubMed:1370874,
CC       ECO:0000269|PubMed:1376329, ECO:0000269|PubMed:1717985,
CC       ECO:0000269|PubMed:7687267, ECO:0000269|PubMed:8680409,
CC       ECO:0000269|PubMed:9450866, ECO:0000269|PubMed:9699740}. Note=The
CC       disease is caused by variants affecting the gene represented in this
CC       entry.
CC   -!- DISEASE: Gastrointestinal stromal tumor (GIST) [MIM:606764]: Common
CC       mesenchymal neoplasms arising in the gastrointestinal tract, most often
CC       in the stomach. They are histologically, immunohistochemically, and
CC       genetically different from typical leiomyomas, leiomyosarcomas, and
CC       schwannomas. Most GISTs are composed of a fairly uniform population of
CC       spindle-shaped cells. Some tumors are dominated by epithelioid cells or
CC       contain a mixture of spindle and epithelioid morphologies. Primary
CC       GISTs in the gastrointestinal tract commonly metastasize in the omentum
CC       and mesenteries, often as multiple nodules. However, primary tumors may
CC       also occur outside of the gastrointestinal tract, in other intra-
CC       abdominal locations, especially in the omentum and mesentery.
CC       {ECO:0000269|PubMed:11505412, ECO:0000269|PubMed:15824741,
CC       ECO:0000269|PubMed:9438854, ECO:0000269|PubMed:9697690}. Note=The gene
CC       represented in this entry is involved in disease pathogenesis.
CC   -!- DISEASE: Testicular germ cell tumor (TGCT) [MIM:273300]: A common
CC       malignancy in males representing 95% of all testicular neoplasms. TGCTs
CC       have various pathologic subtypes including: unclassified intratubular
CC       germ cell neoplasia, seminoma (including cases with
CC       syncytiotrophoblastic cells), spermatocytic seminoma, embryonal
CC       carcinoma, yolk sac tumor, choriocarcinoma, and teratoma. Note=The gene
CC       represented in this entry may be involved in disease pathogenesis.
CC   -!- DISEASE: Leukemia, acute myelogenous (AML) [MIM:601626]: A subtype of
CC       acute leukemia, a cancer of the white blood cells. AML is a malignant
CC       disease of bone marrow characterized by maturational arrest of
CC       hematopoietic precursors at an early stage of development. Clonal
CC       expansion of myeloid blasts occurs in bone marrow, blood, and other
CC       tissue. Myelogenous leukemias develop from changes in cells that
CC       normally produce neutrophils, basophils, eosinophils and monocytes.
CC       Note=The gene represented in this entry is involved in disease
CC       pathogenesis. Somatic mutations that lead to constitutive activation of
CC       KIT are detected in AML patients. These mutations fall into two
CC       classes, the most common being in-frame internal tandem duplications of
CC       variable length in the juxtamembrane region that disrupt the normal
CC       regulation of the kinase activity. Likewise, point mutations in the
CC       kinase domain can result in a constitutively activated kinase.
CC   -!- DISEASE: Mastocytosis, cutaneous (MASTC) [MIM:154800]: A form of
CC       mastocytosis, a heterogeneous group of disorders associated with
CC       abnormal proliferation and accumulation of mast cells in various
CC       tissues, especially in the skin and hematopoietic organs. MASTC is an
CC       autosomal dominant form characterized by macules, papules, nodules, or
CC       diffuse infiltration of the skin, often associated with localized
CC       hyperpigmentation. Gentle rubbing of the lesions induces histamine
CC       release from mechanically activated mast cells, causing local wheals,
CC       erythema, and often pruritus, a phenomenon termed Darier sign.
CC       {ECO:0000269|PubMed:15173254, ECO:0000269|PubMed:19865100,
CC       ECO:0000269|PubMed:21689725, ECO:0000269|PubMed:24289326,
CC       ECO:0000269|PubMed:9990072}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- DISEASE: Mastocytosis, systemic (MASTSYS) [MIM:154800]: A severe form
CC       of mastocytosis characterized by abnormal proliferation and
CC       accumulation of mast cells in several organs, resulting in a systemic
CC       disease that may affect bone, gastrointestinal tract, lymphatics,
CC       spleen, and liver. In some cases, it is associated with a clonal
CC       hematologic non-mast-cell lineage disease, such as a myelodysplastic or
CC       myeloproliferative disorder. It can also lead to mast cell leukemia,
CC       which carries a high risk of mortality. {ECO:0000269|PubMed:9990072}.
CC       Note=The disease is caused by variants affecting the gene represented
CC       in this entry.
CC   -!- MISCELLANEOUS: Numerous proteins are phosphorylated in response to KIT
CC       signaling, but it is not evident to determine which are directly
CC       phosphorylated by KIT under in vivo conditions.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC       kinase family. CSF-1/PDGF receptor subfamily. {ECO:0000255|PROSITE-
CC       ProRule:PRU00159}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=ACF47630.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC       Haematology;
CC       URL="https://atlasgeneticsoncology.org/gene/127/KIT";
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=CD117 entry;
CC       URL="https://en.wikipedia.org/wiki/CD117";
CC   -!- WEB RESOURCE: Name=Protein Spotlight; Note=two's company - Issue 163 of
CC       August 2014;
CC       URL="https://www.proteinspotlight.org/back_issues/163/";
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DR   EMBL; X06182; CAA29548.1; -; mRNA.
DR   EMBL; X69301; CAA49159.1; -; Genomic_DNA.
DR   EMBL; X69302; CAA49159.1; JOINED; Genomic_DNA.
DR   EMBL; X69303; CAA49159.1; JOINED; Genomic_DNA.
DR   EMBL; X69304; CAA49159.1; JOINED; Genomic_DNA.
DR   EMBL; X69305; CAA49159.1; JOINED; Genomic_DNA.
DR   EMBL; X69306; CAA49159.1; JOINED; Genomic_DNA.
DR   EMBL; X69307; CAA49159.1; JOINED; Genomic_DNA.
DR   EMBL; X69308; CAA49159.1; JOINED; Genomic_DNA.
DR   EMBL; X69309; CAA49159.1; JOINED; Genomic_DNA.
DR   EMBL; X69310; CAA49159.1; JOINED; Genomic_DNA.
DR   EMBL; X69311; CAA49159.1; JOINED; Genomic_DNA.
DR   EMBL; X69312; CAA49159.1; JOINED; Genomic_DNA.
DR   EMBL; X69313; CAA49159.1; JOINED; Genomic_DNA.
DR   EMBL; X69314; CAA49159.1; JOINED; Genomic_DNA.
DR   EMBL; X69315; CAA49159.1; JOINED; Genomic_DNA.
DR   EMBL; X69316; CAA49159.1; JOINED; Genomic_DNA.
DR   EMBL; U63834; AAC50968.1; -; Genomic_DNA.
DR   EMBL; U63834; AAC50969.1; -; Genomic_DNA.
DR   EMBL; GU983671; ADF36702.1; -; mRNA.
DR   EMBL; HM015525; ADF50068.1; -; mRNA.
DR   EMBL; HM015526; ADF50069.1; -; mRNA.
DR   EMBL; AK304031; BAG64945.1; -; mRNA.
DR   EMBL; AC006552; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC092545; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC071593; AAH71593.1; -; mRNA.
DR   EMBL; EU826594; ACF47630.1; ALT_SEQ; mRNA.
DR   EMBL; S67773; AAB29529.1; -; Genomic_DNA.
DR   CCDS; CCDS3496.1; -. [P10721-1]
DR   CCDS; CCDS47058.1; -. [P10721-2]
DR   PIR; S01426; TVHUKT.
DR   RefSeq; NP_000213.1; NM_000222.3. [P10721-1]
DR   RefSeq; NP_001087241.1; NM_001093772.2. [P10721-2]
DR   PDB; 1PKG; X-ray; 2.90 A; A/B=549-935.
DR   PDB; 1T45; X-ray; 1.90 A; A=547-693, A=754-935.
DR   PDB; 1T46; X-ray; 1.60 A; A=565-693, A=754-935.
DR   PDB; 2E9W; X-ray; 3.50 A; A/B=26-514.
DR   PDB; 2EC8; X-ray; 3.00 A; A=1-519.
DR   PDB; 2IUH; X-ray; 2.00 A; B=718-728.
DR   PDB; 2VIF; X-ray; 1.45 A; P=564-574.
DR   PDB; 3G0E; X-ray; 1.60 A; A=544-693, A=754-935.
DR   PDB; 3G0F; X-ray; 2.60 A; A/B=544-693, A/B=754-935.
DR   PDB; 4HVS; X-ray; 1.90 A; A=551-934.
DR   PDB; 4K94; X-ray; 2.40 A; C=308-518.
DR   PDB; 4K9E; X-ray; 2.70 A; C=308-518.
DR   PDB; 4PGZ; X-ray; 2.40 A; A/B/C=308-518.
DR   PDB; 4U0I; X-ray; 2.00 A; A=563-693, A=754-935.
DR   PDB; 6GQJ; X-ray; 2.33 A; A/B=551-933.
DR   PDB; 6GQK; X-ray; 2.31 A; A/B=551-687, A/B=771-934.
DR   PDB; 6GQL; X-ray; 2.01 A; A/B=551-934.
DR   PDB; 6GQM; X-ray; 2.00 A; A/B=551-934.
DR   PDB; 6HH1; X-ray; 2.25 A; A=565-702, A=802-929.
DR   PDB; 6ITT; X-ray; 2.10 A; A/B=547-693, A/B=754-935.
DR   PDB; 6ITV; X-ray; 1.88 A; A=547-693, A=754-935.
DR   PDB; 6KLA; X-ray; 2.11 A; A=547-693, A=754-935.
DR   PDB; 6MOB; X-ray; 1.80 A; A=566-693, A=754-935.
DR   PDB; 6XV9; X-ray; 3.38 A; A/B=551-687, A/B=766-934.
DR   PDB; 6XVA; X-ray; 2.30 A; A/B=551-687, A/B=766-934.
DR   PDB; 6XVB; X-ray; 2.15 A; A/B=551-687, A/B=766-934.
DR   PDB; 7KHG; X-ray; 2.15 A; A=545-934.
DR   PDB; 7KHJ; X-ray; 2.80 A; A/B=545-934.
DR   PDB; 7KHK; X-ray; 2.34 A; A/B=545-934.
DR   PDB; 7ZW8; X-ray; 2.12 A; A=551-935.
DR   PDB; 7ZY6; X-ray; 3.09 A; A=551-935.
DR   PDB; 8DFM; EM; 3.45 A; A/B=32-976.
DR   PDB; 8DFP; EM; 3.17 A; A/B=32-976.
DR   PDB; 8DFQ; EM; 3.96 A; A/B=32-976.
DR   PDB; 8PQ9; X-ray; 1.70 A; A/C=551-687, A/C=766-934.
DR   PDB; 8PQA; X-ray; 1.65 A; A/C=551-687, A/C=766-934.
DR   PDB; 8PQB; X-ray; 1.87 A; A=551-687, A=766-934.
DR   PDB; 8PQC; X-ray; 1.77 A; A/B=551-687, A/B=766-934.
DR   PDB; 8PQD; X-ray; 1.50 A; A/B=551-687, A/B=766-934.
DR   PDB; 8PQE; X-ray; 2.00 A; A/B=551-687, A/B=766-934.
DR   PDB; 8PQF; X-ray; 1.90 A; A/C=551-687, A/C=766-934.
DR   PDB; 8PQG; X-ray; 2.40 A; A/C=551-687, A/C=766-934.
DR   PDB; 8S13; X-ray; 2.00 A; A=551-687, A=766-934.
DR   PDB; 8S14; X-ray; 1.50 A; A=551-687, A=766-934.
DR   PDB; 8S15; X-ray; 2.40 A; A=551-687, A=766-934.
DR   PDB; 8S16; X-ray; 1.85 A; A/B=551-687, A/B=766-934.
DR   PDB; 8S17; X-ray; 2.20 A; A/B=551-687, A/B=766-934.
DR   PDB; 8S18; X-ray; 2.10 A; A/B=551-687, A/B=766-934.
DR   PDB; 8S19; X-ray; 2.30 A; A/B=551-687, A/B=766-934.
DR   PDB; 8S1A; X-ray; 1.85 A; A/B=551-687, A/B=766-934.
DR   PDB; 8S1B; X-ray; 2.00 A; A/B=551-687, A/B=766-934.
DR   PDBsum; 1PKG; -.
DR   PDBsum; 1T45; -.
DR   PDBsum; 1T46; -.
DR   PDBsum; 2E9W; -.
DR   PDBsum; 2EC8; -.
DR   PDBsum; 2IUH; -.
DR   PDBsum; 2VIF; -.
DR   PDBsum; 3G0E; -.
DR   PDBsum; 3G0F; -.
DR   PDBsum; 4HVS; -.
DR   PDBsum; 4K94; -.
DR   PDBsum; 4K9E; -.
DR   PDBsum; 4PGZ; -.
DR   PDBsum; 4U0I; -.
DR   PDBsum; 6GQJ; -.
DR   PDBsum; 6GQK; -.
DR   PDBsum; 6GQL; -.
DR   PDBsum; 6GQM; -.
DR   PDBsum; 6HH1; -.
DR   PDBsum; 6ITT; -.
DR   PDBsum; 6ITV; -.
DR   PDBsum; 6KLA; -.
DR   PDBsum; 6MOB; -.
DR   PDBsum; 6XV9; -.
DR   PDBsum; 6XVA; -.
DR   PDBsum; 6XVB; -.
DR   PDBsum; 7KHG; -.
DR   PDBsum; 7KHJ; -.
DR   PDBsum; 7KHK; -.
DR   PDBsum; 7ZW8; -.
DR   PDBsum; 7ZY6; -.
DR   PDBsum; 8DFM; -.
DR   PDBsum; 8DFP; -.
DR   PDBsum; 8DFQ; -.
DR   PDBsum; 8PQ9; -.
DR   PDBsum; 8PQA; -.
DR   PDBsum; 8PQB; -.
DR   PDBsum; 8PQC; -.
DR   PDBsum; 8PQD; -.
DR   PDBsum; 8PQE; -.
DR   PDBsum; 8PQF; -.
DR   PDBsum; 8PQG; -.
DR   PDBsum; 8S13; -.
DR   PDBsum; 8S14; -.
DR   PDBsum; 8S15; -.
DR   PDBsum; 8S16; -.
DR   PDBsum; 8S17; -.
DR   PDBsum; 8S18; -.
DR   PDBsum; 8S19; -.
DR   PDBsum; 8S1A; -.
DR   PDBsum; 8S1B; -.
DR   AlphaFoldDB; P10721; -.
DR   EMDB; EMD-27408; -.
DR   EMDB; EMD-27410; -.
DR   EMDB; EMD-27411; -.
DR   SMR; P10721; -.
DR   BioGRID; 110015; 108.
DR   CORUM; P10721; -.
DR   DIP; DIP-1055N; -.
DR   FunCoup; P10721; 1086.
DR   IntAct; P10721; 106.
DR   MINT; P10721; -.
DR   STRING; 9606.ENSP00000288135; -.
DR   BindingDB; P10721; -.
DR   ChEMBL; CHEMBL1936; -.
DR   DrugBank; DB12742; Amuvatinib.
DR   DrugBank; DB09103; Ancestim.
DR   DrugBank; DB15233; Avapritinib.
DR   DrugBank; DB18041; Bezuclastinib.
DR   DrugBank; DB01254; Dasatinib.
DR   DrugBank; DB12147; Erdafitinib.
DR   DrugBank; DB11741; Famitinib.
DR   DrugBank; DB12010; Fostamatinib.
DR   DrugBank; DB00619; Imatinib.
DR   DrugBank; DB17140; JNJ-28312141.
DR   DrugBank; DB09078; Lenvatinib.
DR   DrugBank; DB06080; Linifanib.
DR   DrugBank; DB06595; Midostaurin.
DR   DrugBank; DB05575; Motesanib.
DR   DrugBank; DB04868; Nilotinib.
DR   DrugBank; DB05913; OSI-930.
DR   DrugBank; DB06589; Pazopanib.
DR   DrugBank; DB08339; PD-166326.
DR   DrugBank; DB12978; Pexidartinib.
DR   DrugBank; DB01962; Phosphonotyrosine.
DR   DrugBank; DB08901; Ponatinib.
DR   DrugBank; DB08896; Regorafenib.
DR   DrugBank; DB14840; Ripretinib.
DR   DrugBank; DB06436; Semaxanib.
DR   DrugBank; DB00398; Sorafenib.
DR   DrugBank; DB01268; Sunitinib.
DR   DrugBank; DB11800; Tivozanib.
DR   DrugBank; DB05146; XL820.
DR   DrugCentral; P10721; -.
DR   GuidetoPHARMACOLOGY; 1805; -.
DR   CarbonylDB; P10721; -.
DR   GlyConnect; 1492; 3 N-Linked glycans (2 sites).
DR   GlyCosmos; P10721; 10 sites, 4 glycans.
DR   GlyGen; P10721; 12 sites, 26 N-linked glycans (6 sites).
DR   iPTMnet; P10721; -.
DR   PhosphoSitePlus; P10721; -.
DR   BioMuta; KIT; -.
DR   DMDM; 125472; -.
DR   CPTAC; CPTAC-3066; -.
DR   CPTAC; CPTAC-3067; -.
DR   jPOST; P10721; -.
DR   MassIVE; P10721; -.
DR   PaxDb; 9606-ENSP00000288135; -.
DR   PeptideAtlas; P10721; -.
DR   ProteomicsDB; 52640; -. [P10721-1]
DR   ProteomicsDB; 52641; -. [P10721-2]
DR   Pumba; P10721; -.
DR   ABCD; P10721; 2 sequenced antibodies.
DR   Antibodypedia; 1392; 5560 antibodies from 59 providers.
DR   DNASU; 3815; -.
DR   Ensembl; ENST00000288135.6; ENSP00000288135.6; ENSG00000157404.18. [P10721-1]
DR   Ensembl; ENST00000687295.1; ENSP00000509450.1; ENSG00000157404.18. [P10721-2]
DR   GeneID; 3815; -.
DR   KEGG; hsa:3815; -.
DR   MANE-Select; ENST00000288135.6; ENSP00000288135.6; NM_000222.3; NP_000213.1.
DR   UCSC; uc010igr.4; human. [P10721-1]
DR   AGR; HGNC:6342; -.
DR   CIViC; 3815; 1 clinical assertion and 310 evidence items across 136 molecular profiles.
DR   ClinPGx; PA30128; -.
DR   CTD; 3815; -.
DR   DisGeNET; 3815; -.
DR   GeneCards; KIT; -.
DR   HGNC; HGNC:6342; KIT.
DR   HPA; ENSG00000157404; Tissue enhanced (breast).
DR   MalaCards; KIT; -.
DR   MIM; 154800; phenotype.
DR   MIM; 164920; gene.
DR   MIM; 172800; phenotype.
DR   MIM; 273300; phenotype.
DR   MIM; 601626; phenotype.
DR   MIM; 606764; phenotype.
DR   OpenTargets; ENSG00000157404; -.
DR   Orphanet; 566393; Acute mast cell leukemia.
DR   Orphanet; 98834; Acute myeloblastic leukemia with maturation.
DR   Orphanet; 98829; Acute myeloid leukemia with abnormal bone marrow eosinophils inv(16)(p13q22) or t(16;16)(p13;q22).
DR   Orphanet; 102724; Acute myeloid leukemia with t(8;21)(q22;q22) translocation.
DR   Orphanet; 280785; Bullous diffuse cutaneous mastocytosis.
DR   Orphanet; 566396; Chronic mast cell leukemia.
DR   Orphanet; 79455; Cutaneous mastocytoma.
DR   Orphanet; 44890; Gastrointestinal stromal tumor.
DR   Orphanet; 158778; Isolated bone marrow mastocytosis.
DR   Orphanet; 158772; Nodular urticaria pigmentosa.
DR   Orphanet; 2884; Piebaldism.
DR   Orphanet; 158769; Plaque-form urticaria pigmentosa.
DR   Orphanet; 280794; Pseudoxanthomatous diffuse cutaneous mastocytosis.
DR   Orphanet; 158775; Smoldering systemic mastocytosis.
DR   Orphanet; 98849; Systemic mastocytosis with associated hematologic neoplasm.
DR   Orphanet; 90389; Telangiectasia macularis eruptiva perstans.
DR   Orphanet; 842; Testicular seminomatous germ cell tumor.
DR   Orphanet; 158766; Typical urticaria pigmentosa.
DR   VEuPathDB; HostDB:ENSG00000157404; -.
DR   eggNOG; KOG0200; Eukaryota.
DR   GeneTree; ENSGT00940000155626; -.
DR   HOGENOM; CLU_000288_49_0_1; -.
DR   InParanoid; P10721; -.
DR   OMA; ANEECEW; -.
DR   OrthoDB; 6077854at2759; -.
DR   PAN-GO; P10721; 10 GO annotations based on evolutionary models.
DR   PhylomeDB; P10721; -.
DR   BRENDA; 2.7.10.1; 2681.
DR   PathwayCommons; P10721; -.
DR   Reactome; R-HSA-1257604; PIP3 activates AKT signaling.
DR   Reactome; R-HSA-1433557; Signaling by SCF-KIT.
DR   Reactome; R-HSA-1433559; Regulation of KIT signaling.
DR   Reactome; R-HSA-2219530; Constitutive Signaling by Aberrant PI3K in Cancer.
DR   Reactome; R-HSA-5673001; RAF/MAP kinase cascade.
DR   Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR   Reactome; R-HSA-8866910; TFAP2 (AP-2) family regulates transcription of growth factors and their receptors.
DR   Reactome; R-HSA-9669914; Dasatinib-resistant KIT mutants.
DR   Reactome; R-HSA-9669917; Imatinib-resistant KIT mutants.
DR   Reactome; R-HSA-9669921; KIT mutants bind TKIs.
DR   Reactome; R-HSA-9669924; Masitinib-resistant KIT mutants.
DR   Reactome; R-HSA-9669926; Nilotinib-resistant KIT mutants.
DR   Reactome; R-HSA-9669929; Regorafenib-resistant KIT mutants.
DR   Reactome; R-HSA-9669933; Signaling by kinase domain mutants of KIT.
DR   Reactome; R-HSA-9669934; Sunitinib-resistant KIT mutants.
DR   Reactome; R-HSA-9669935; Signaling by juxtamembrane domain KIT mutants.
DR   Reactome; R-HSA-9669936; Sorafenib-resistant KIT mutants.
DR   Reactome; R-HSA-9670439; Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants.
DR   Reactome; R-HSA-9680187; Signaling by extracellular domain mutants of KIT.
DR   Reactome; R-HSA-9856649; Transcriptional and post-translational regulation of MITF-M expression and activity.
DR   SignaLink; P10721; -.
DR   SIGNOR; P10721; -.
DR   Agora; ENSG00000157404; -.
DR   BioGRID-ORCS; 3815; 9 hits in 1192 CRISPR screens.
DR   CD-CODE; 91857CE7; Nucleolus.
DR   ChiTaRS; KIT; human.
DR   EvolutionaryTrace; P10721; -.
DR   GeneWiki; CD117; -.
DR   GenomeRNAi; 3815; -.
DR   Pharos; P10721; Tclin.
DR   PRO; PR:P10721; -.
DR   Proteomes; UP000005640; Chromosome 4.
DR   RNAct; P10721; protein.
DR   Bgee; ENSG00000157404; Expressed in lateral nuclear group of thalamus and 193 other cell types or tissues.
DR   GO; GO:0001669; C:acrosomal vesicle; IEA:Ensembl.
DR   GO; GO:0005911; C:cell-cell junction; IEA:Ensembl.
DR   GO; GO:0009898; C:cytoplasmic side of plasma membrane; IEA:Ensembl.
DR   GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl.
DR   GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR   GO; GO:0001650; C:fibrillar center; IDA:HPA.
DR   GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR   GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0019955; F:cytokine binding; IDA:UniProtKB.
DR   GO; GO:0019838; F:growth factor binding; IBA:GO_Central.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0002020; F:protease binding; IEA:Ensembl.
DR   GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR   GO; GO:0004713; F:protein tyrosine kinase activity; TAS:Reactome.
DR   GO; GO:0042169; F:SH2 domain binding; IEA:Ensembl.
DR   GO; GO:0005020; F:stem cell factor receptor activity; IEA:Ensembl.
DR   GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IDA:UniProtKB.
DR   GO; GO:0030036; P:actin cytoskeleton organization; IDA:UniProtKB.
DR   GO; GO:0030183; P:B cell differentiation; IBA:GO_Central.
DR   GO; GO:0060326; P:cell chemotaxis; IDA:UniProtKB.
DR   GO; GO:0016477; P:cell migration; IBA:GO_Central.
DR   GO; GO:0019221; P:cytokine-mediated signaling pathway; IDA:UniProtKB.
DR   GO; GO:0050910; P:detection of mechanical stimulus involved in sensory perception of sound; ISS:UniProtKB.
DR   GO; GO:0048565; P:digestive tract development; ISS:UniProtKB.
DR   GO; GO:0035234; P:ectopic germ cell programmed cell death; IEA:Ensembl.
DR   GO; GO:0035162; P:embryonic hemopoiesis; ISS:UniProtKB.
DR   GO; GO:0050673; P:epithelial cell proliferation; IEA:Ensembl.
DR   GO; GO:0030218; P:erythrocyte differentiation; ISS:UniProtKB.
DR   GO; GO:0038162; P:erythropoietin-mediated signaling pathway; ISS:UniProtKB.
DR   GO; GO:0038093; P:Fc receptor signaling pathway; IDA:UniProtKB.
DR   GO; GO:0008354; P:germ cell migration; IEA:Ensembl.
DR   GO; GO:0006687; P:glycosphingolipid metabolic process; IEA:Ensembl.
DR   GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IBA:GO_Central.
DR   GO; GO:0035701; P:hematopoietic stem cell migration; IEA:Ensembl.
DR   GO; GO:0030097; P:hemopoiesis; TAS:UniProtKB.
DR   GO; GO:0002327; P:immature B cell differentiation; ISS:UniProtKB.
DR   GO; GO:0006954; P:inflammatory response; ISS:UniProtKB.
DR   GO; GO:0035556; P:intracellular signal transduction; IEA:Ensembl.
DR   GO; GO:0038109; P:Kit signaling pathway; IDA:UniProtKB.
DR   GO; GO:0030032; P:lamellipodium assembly; ISS:UniProtKB.
DR   GO; GO:0002320; P:lymphoid progenitor cell differentiation; IEA:Ensembl.
DR   GO; GO:0008584; P:male gonad development; IEP:UniProtKB.
DR   GO; GO:0002551; P:mast cell chemotaxis; IDA:UniProtKB.
DR   GO; GO:0043303; P:mast cell degranulation; IMP:UniProtKB.
DR   GO; GO:0060374; P:mast cell differentiation; ISS:UniProtKB.
DR   GO; GO:0070662; P:mast cell proliferation; TAS:UniProtKB.
DR   GO; GO:0035855; P:megakaryocyte development; ISS:UniProtKB.
DR   GO; GO:0097326; P:melanocyte adhesion; ISS:UniProtKB.
DR   GO; GO:0030318; P:melanocyte differentiation; ISS:UniProtKB.
DR   GO; GO:0097324; P:melanocyte migration; ISS:UniProtKB.
DR   GO; GO:0002318; P:myeloid progenitor cell differentiation; IEA:Ensembl.
DR   GO; GO:0051093; P:negative regulation of developmental process; IEA:Ensembl.
DR   GO; GO:0043069; P:negative regulation of programmed cell death; IEA:Ensembl.
DR   GO; GO:2000242; P:negative regulation of reproductive process; IEA:Ensembl.
DR   GO; GO:0001541; P:ovarian follicle development; ISS:UniProtKB.
DR   GO; GO:0043473; P:pigmentation; ISS:UniProtKB.
DR   GO; GO:0030335; P:positive regulation of cell migration; IBA:GO_Central.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; IBA:GO_Central.
DR   GO; GO:1904343; P:positive regulation of colon smooth muscle contraction; IEA:Ensembl.
DR   GO; GO:0002732; P:positive regulation of dendritic cell cytokine production; ISS:UniProtKB.
DR   GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IMP:UniProtKB.
DR   GO; GO:0048170; P:positive regulation of long-term neuronal synaptic plasticity; IEA:Ensembl.
DR   GO; GO:0043410; P:positive regulation of MAPK cascade; IMP:UniProtKB.
DR   GO; GO:0032765; P:positive regulation of mast cell cytokine production; IDA:UniProtKB.
DR   GO; GO:0070668; P:positive regulation of mast cell proliferation; IEA:Ensembl.
DR   GO; GO:0045747; P:positive regulation of Notch signaling pathway; IEA:Ensembl.
DR   GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; TAS:UniProtKB.
DR   GO; GO:0031274; P:positive regulation of pseudopodium assembly; IEA:Ensembl.
DR   GO; GO:0120072; P:positive regulation of pyloric antrum smooth muscle contraction; IEA:Ensembl.
DR   GO; GO:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; IMP:UniProtKB.
DR   GO; GO:1904349; P:positive regulation of small intestine smooth muscle contraction; IEA:Ensembl.
DR   GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IMP:UniProtKB.
DR   GO; GO:1905065; P:positive regulation of vascular associated smooth muscle cell differentiation; IDA:BHF-UCL.
DR   GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR   GO; GO:1904251; P:regulation of bile acid metabolic process; IEA:Ensembl.
DR   GO; GO:0042127; P:regulation of cell population proliferation; TAS:UniProtKB.
DR   GO; GO:0008360; P:regulation of cell shape; ISS:UniProtKB.
DR   GO; GO:0046686; P:response to cadmium ion; IEA:Ensembl.
DR   GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR   GO; GO:0035019; P:somatic stem cell population maintenance; IEA:Ensembl.
DR   GO; GO:0007286; P:spermatid development; IEA:Ensembl.
DR   GO; GO:0007283; P:spermatogenesis; ISS:UniProtKB.
DR   GO; GO:0048863; P:stem cell differentiation; ISS:UniProtKB.
DR   GO; GO:0019827; P:stem cell population maintenance; TAS:UniProtKB.
DR   GO; GO:0030217; P:T cell differentiation; ISS:UniProtKB.
DR   GO; GO:0043586; P:tongue development; IEA:Ensembl.
DR   GO; GO:0008542; P:visual learning; IEA:Ensembl.
DR   CDD; cd00096; Ig; 2.
DR   CDD; cd05860; IgI_4_SCFR; 1.
DR   CDD; cd05104; PTKc_Kit; 1.
DR   DisProt; DP02247; -.
DR   FunFam; 1.10.510.10:FF:000177; Mast/stem cell growth factor receptor; 1.
DR   FunFam; 2.60.40.10:FF:000422; Mast/stem cell growth factor receptor; 1.
DR   FunFam; 2.60.40.10:FF:000429; Mast/stem cell growth factor receptor; 1.
DR   FunFam; 2.60.40.10:FF:000469; Mast/stem cell growth factor receptor; 1.
DR   FunFam; 2.60.40.10:FF:000544; Mast/stem cell growth factor receptor; 1.
DR   FunFam; 2.60.40.10:FF:000815; Mast/stem cell growth factor receptor; 1.
DR   FunFam; 3.30.200.20:FF:000025; Platelet-derived growth factor receptor alpha; 1.
DR   Gene3D; 2.60.40.10; Immunoglobulins; 5.
DR   Gene3D; 3.30.200.20; Phosphorylase Kinase, domain 1; 1.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR   InterPro; IPR007110; Ig-like_dom.
DR   InterPro; IPR036179; Ig-like_dom_sf.
DR   InterPro; IPR013783; Ig-like_fold.
DR   InterPro; IPR003599; Ig_sub.
DR   InterPro; IPR003598; Ig_sub2.
DR   InterPro; IPR013151; Immunoglobulin_dom.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR000719; Prot_kinase_dom.
DR   InterPro; IPR017441; Protein_kinase_ATP_BS.
DR   InterPro; IPR050122; RTK.
DR   InterPro; IPR027263; SCGF_receptor.
DR   InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR   InterPro; IPR008266; Tyr_kinase_AS.
DR   InterPro; IPR020635; Tyr_kinase_cat_dom.
DR   InterPro; IPR001824; Tyr_kinase_rcpt_3_CS.
DR   PANTHER; PTHR24416:SF46; MAST_STEM CELL GROWTH FACTOR RECEPTOR KIT; 1.
DR   PANTHER; PTHR24416; TYROSINE-PROTEIN KINASE RECEPTOR; 1.
DR   Pfam; PF00047; ig; 1.
DR   Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR   PIRSF; PIRSF500951; SCGF_recepter; 1.
DR   PIRSF; PIRSF000615; TyrPK_CSF1-R; 1.
DR   SMART; SM00409; IG; 3.
DR   SMART; SM00408; IGc2; 1.
DR   SMART; SM00219; TyrKc; 1.
DR   SUPFAM; SSF48726; Immunoglobulin; 3.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR   PROSITE; PS50835; IG_LIKE; 1.
DR   PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR   PROSITE; PS00240; RECEPTOR_TYR_KIN_III; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; ATP-binding; Cell membrane; Cytoplasm;
KW   Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein;
KW   Immunoglobulin domain; Kinase; Magnesium; Membrane; Metal-binding;
KW   Nucleotide-binding; Phosphoprotein; Proteomics identification;
KW   Proto-oncogene; Receptor; Reference proteome; Repeat; Signal; Transferase;
KW   Transmembrane; Transmembrane helix; Tyrosine-protein kinase;
KW   Ubl conjugation.
FT   SIGNAL          1..25
FT                   /evidence="ECO:0000255"
FT   CHAIN           26..976
FT                   /note="Mast/stem cell growth factor receptor Kit"
FT                   /id="PRO_0000016754"
FT   TOPO_DOM        26..524
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        525..545
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        546..976
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          27..112
FT                   /note="Ig-like C2-type 1"
FT   DOMAIN          121..205
FT                   /note="Ig-like C2-type 2"
FT   DOMAIN          212..308
FT                   /note="Ig-like C2-type 3"
FT   DOMAIN          317..410
FT                   /note="Ig-like C2-type 4"
FT   DOMAIN          413..507
FT                   /note="Ig-like C2-type 5"
FT   DOMAIN          589..937
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   REGION          568..570
FT                   /note="Important for interaction with phosphotyrosine-
FT                   binding proteins"
FT   ACT_SITE        792
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT                   ECO:0000255|PROSITE-ProRule:PRU10028"
FT   BINDING         568
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT   BINDING         596..603
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT   BINDING         623
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT   BINDING         671..677
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT   BINDING         796
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT   BINDING         797
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT   BINDING         810
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT   SITE            936
FT                   /note="Important for interaction with phosphotyrosine-
FT                   binding proteins"
FT   MOD_RES         547
FT                   /note="Phosphotyrosine; by autocatalysis"
FT                   /evidence="ECO:0000305|PubMed:20147452"
FT   MOD_RES         553
FT                   /note="Phosphotyrosine; by autocatalysis"
FT                   /evidence="ECO:0000305|PubMed:20147452"
FT   MOD_RES         568
FT                   /note="Phosphotyrosine; by autocatalysis"
FT                   /evidence="ECO:0000269|PubMed:12824176,
FT                   ECO:0000269|PubMed:19265199, ECO:0000269|PubMed:21030588,
FT                   ECO:0000269|PubMed:9038210"
FT   MOD_RES         570
FT                   /note="Phosphotyrosine; by autocatalysis"
FT                   /evidence="ECO:0000269|PubMed:12824176,
FT                   ECO:0000269|PubMed:9038210"
FT   MOD_RES         703
FT                   /note="Phosphotyrosine; by autocatalysis"
FT                   /evidence="ECO:0000269|PubMed:10377264,
FT                   ECO:0000269|PubMed:19265199, ECO:0000269|PubMed:20147452"
FT   MOD_RES         721
FT                   /note="Phosphotyrosine; by autocatalysis"
FT                   /evidence="ECO:0000269|PubMed:19265199,
FT                   ECO:0000269|PubMed:20147452, ECO:0000269|PubMed:9038210"
FT   MOD_RES         730
FT                   /note="Phosphotyrosine; by autocatalysis"
FT                   /evidence="ECO:0000305|PubMed:20147452"
FT   MOD_RES         741
FT                   /note="Phosphoserine; by PKC/PRKCA"
FT                   /evidence="ECO:0000269|PubMed:7539802"
FT   MOD_RES         746
FT                   /note="Phosphoserine; by PKC/PRKCA"
FT                   /evidence="ECO:0000269|PubMed:7539802"
FT   MOD_RES         821
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:7539802"
FT   MOD_RES         823
FT                   /note="Phosphotyrosine; by autocatalysis"
FT                   /evidence="ECO:0000269|PubMed:20147452"
FT   MOD_RES         891
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:12878163"
FT   MOD_RES         900
FT                   /note="Phosphotyrosine; by autocatalysis"
FT                   /evidence="ECO:0000269|PubMed:12878163,
FT                   ECO:0000269|PubMed:20147452"
FT   MOD_RES         936
FT                   /note="Phosphotyrosine; by autocatalysis"
FT                   /evidence="ECO:0000269|PubMed:10377264,
FT                   ECO:0000269|PubMed:19265199"
FT   MOD_RES         959
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:7539802,
FT                   ECO:0007744|PubMed:19369195"
FT   CARBOHYD        130
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:16335952,
FT                   ECO:0000269|PubMed:17662946"
FT   CARBOHYD        145
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        283
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:17662946"
FT   CARBOHYD        293
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:17662946"
FT   CARBOHYD        300
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:17662946"
FT   CARBOHYD        320
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:17662946"
FT   CARBOHYD        352
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:17662946"
FT   CARBOHYD        367
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:17662946"
FT   CARBOHYD        463
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        486
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        58..97
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT                   ECO:0000269|PubMed:17662946"
FT   DISULFID        136..186
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT                   ECO:0000269|PubMed:17662946"
FT   DISULFID        151..183
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT                   ECO:0000269|PubMed:17662946"
FT   DISULFID        233..290
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT                   ECO:0000269|PubMed:17662946"
FT   DISULFID        428..491
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT                   ECO:0000269|PubMed:17662946"
FT   VAR_SEQ         1..744
FT                   /note="MRGARGAWDFLCVLLLLLRVQTGSSQPSVSPGEPSPPSIHPGKSDLIVRVGD
FT                   EIRLLCTDPGFVKWTFEILDETNENKQNEWITEKAEATNTGKYTCTNKHGLSNSIYVFV
FT                   RDPAKLFLVDRSLYGKEDNDTLVRCPLTDPEVTNYSLKGCQGKPLPKDLRFIPDPKAGI
FT                   MIKSVKRAYHRLCLHCSVDQEGKSVLSEKFILKVRPAFKAVPVVSVSKASYLLREGEEF
FT                   TVTCTIKDVSSSVYSTWKRENSQTKLQEKYNSWHHGDFNYERQATLTISSARVNDSGVF
FT                   MCYANNTFGSANVTTTLEVVDKGFINIFPMINTTVFVNDGENVDLIVEYEAFPKPEHQQ
FT                   WIYMNRTFTDKWEDYPKSENESNIRYVSELHLTRLKGTEGGTYTFLVSNSDVNAAIAFN
FT                   VYVNTKPEILTYDRLVNGMLQCVAAGFPEPTIDWYFCPGTEQRCSASVLPVDVQTLNSS
FT                   GPPFGKLVVQSSIDSSAFKHNGTVECKAYNDVGKTSAYFNFAFKGNNKEQIHPHTLFTP
FT                   LLIGFVIVAGMMCIIVMILTYKYLQKPMYEVQWKVVEEINGNNYVYIDPTQLPYDHKWE
FT                   FPRNRLSFGKTLGAGAFGKVVEATAYGLIKSDAAMTVAVKMLKPSAHLTEREALMSELK
FT                   VLSYLGNHMNIVNLLGACTIGGPTLVITEYCCYGDLLNFLRRKRDSFICSKQEDHAEAA
FT                   LYKNLLHSKESSCSDSTNEYMDMKPGVSYVVPTKADKRRSVRI -> MSLPLSFPFLTF
FT                   MVVIAKKNPLFLT (in isoform 3)"
FT                   /id="VSP_060976"
FT   VAR_SEQ         510..513
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039,
FT                   ECO:0000303|PubMed:20658618, ECO:0000303|Ref.7"
FT                   /id="VSP_038385"
FT   VARIANT         451
FT                   /note="S -> C (in MASTC; uncertain significance;
FT                   dbSNP:rs1060502556)"
FT                   /evidence="ECO:0000269|PubMed:24289326"
FT                   /id="VAR_081062"
FT   VARIANT         532
FT                   /note="V -> I (in dbSNP:rs55792975)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_042021"
FT   VARIANT         533
FT                   /note="A -> D (in MASTC; uncertain significance;
FT                   dbSNP:rs753212327)"
FT                   /evidence="ECO:0000269|PubMed:15173254"
FT                   /id="VAR_081063"
FT   VARIANT         541
FT                   /note="M -> L (in dbSNP:rs3822214)"
FT                   /evidence="ECO:0000269|PubMed:17344846,
FT                   ECO:0000269|PubMed:19865100"
FT                   /id="VAR_042022"
FT   VARIANT         541
FT                   /note="M -> V (in dbSNP:rs3822214)"
FT                   /id="VAR_061289"
FT   VARIANT         550..558
FT                   /note="Missing (in GIST; somatic mutation)"
FT                   /evidence="ECO:0000269|PubMed:15824741,
FT                   ECO:0000269|PubMed:9438854"
FT                   /id="VAR_033124"
FT   VARIANT         550
FT                   /note="K -> I (in GIST; somatic mutation;
FT                   dbSNP:rs2109775477)"
FT                   /evidence="ECO:0000269|PubMed:9438854"
FT                   /id="VAR_033123"
FT   VARIANT         551..555
FT                   /note="Missing (in GIST; somatic mutation;
FT                   dbSNP:rs2109775521)"
FT                   /evidence="ECO:0000269|PubMed:9438854"
FT                   /id="VAR_033125"
FT   VARIANT         559..560
FT                   /note="Missing (in GIST; somatic mutation;
FT                   dbSNP:rs121913685)"
FT                   /evidence="ECO:0000269|PubMed:9438854"
FT                   /id="VAR_033128"
FT   VARIANT         559
FT                   /note="V -> A (in GIST; dbSNP:rs121913517)"
FT                   /evidence="ECO:0000269|PubMed:11505412"
FT                   /id="VAR_033126"
FT   VARIANT         559
FT                   /note="V -> D (in GIST; somatic mutation;
FT                   dbSNP:rs121913517)"
FT                   /evidence="ECO:0000269|PubMed:9438854"
FT                   /id="VAR_033127"
FT   VARIANT         559
FT                   /note="Missing (in GIST; dbSNP:rs121913685)"
FT                   /evidence="ECO:0000269|PubMed:9697690"
FT                   /id="VAR_007965"
FT   VARIANT         583
FT                   /note="E -> K (in PBT; dbSNP:rs121913680)"
FT                   /evidence="ECO:0000269|PubMed:1376329"
FT                   /id="VAR_004104"
FT   VARIANT         584
FT                   /note="F -> C (in PBT; dbSNP:rs28933371)"
FT                   /evidence="ECO:0000269|PubMed:11074500"
FT                   /id="VAR_033129"
FT   VARIANT         584
FT                   /note="F -> L (in PBT; dbSNP:rs794726671)"
FT                   /evidence="ECO:0000269|PubMed:1370874"
FT                   /id="VAR_004105"
FT   VARIANT         601
FT                   /note="G -> R (in PBT; dbSNP:rs2109779521)"
FT                   /evidence="ECO:0000269|PubMed:11074500"
FT                   /id="VAR_033130"
FT   VARIANT         656
FT                   /note="L -> P (in PBT)"
FT                   /evidence="ECO:0000269|PubMed:11074500"
FT                   /id="VAR_033131"
FT   VARIANT         664
FT                   /note="G -> R (in PBT; dbSNP:rs121913679)"
FT                   /evidence="ECO:0000269|PubMed:1717985"
FT                   /id="VAR_004106"
FT   VARIANT         691
FT                   /note="C -> S (in dbSNP:rs35200131)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_042023"
FT   VARIANT         715
FT                   /note="S -> N (in dbSNP:rs56094246)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_042024"
FT   VARIANT         737
FT                   /note="D -> N (in a colorectal adenocarcinoma sample;
FT                   somatic mutation; dbSNP:rs751005114)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_042025"
FT   VARIANT         791
FT                   /note="R -> G (in PBT; dbSNP:rs1722708855)"
FT                   /evidence="ECO:0000269|PubMed:7687267"
FT                   /id="VAR_004107"
FT   VARIANT         796
FT                   /note="R -> G (in PBT; with sensorineural deafness;
FT                   dbSNP:rs121913684)"
FT                   /evidence="ECO:0000269|PubMed:9450866"
FT                   /id="VAR_033132"
FT   VARIANT         804
FT                   /note="R -> W (in a colorectal adenocarcinoma sample;
FT                   somatic mutation; dbSNP:rs145602440)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_042026"
FT   VARIANT         812
FT                   /note="G -> V (in PBT; dbSNP:rs2109801595)"
FT                   /evidence="ECO:0000269|PubMed:7687267"
FT                   /id="VAR_004108"
FT   VARIANT         816
FT                   /note="D -> F (in MASTC; sporadic case; somatic mutation;
FT                   constitutively activated and is much more rapidly
FT                   autophosphorylated than wild type; requires 2 nucleotide
FT                   substitutions; dbSNP:rs1057519709)"
FT                   /evidence="ECO:0000269|PubMed:9990072"
FT                   /id="VAR_033133"
FT   VARIANT         816
FT                   /note="D -> H (in a testicular tumor; seminoma; somatic
FT                   mutation; constitutively activated; dbSNP:rs121913506)"
FT                   /evidence="ECO:0000269|PubMed:10362788,
FT                   ECO:0000269|PubMed:19164557, ECO:0000269|PubMed:20147452"
FT                   /id="VAR_033134"
FT   VARIANT         816
FT                   /note="D -> I (in MASTC; somatic mutation; constitutively
FT                   activated; requires 2 nucleotide substitutions;
FT                   dbSNP:rs1057519709)"
FT                   /evidence="ECO:0000269|PubMed:19865100"
FT                   /id="VAR_081064"
FT   VARIANT         816
FT                   /note="D -> V (in MASTSYS, MASTC and mast cell leukemia;
FT                   somatic mutation; constitutively activated; loss of
FT                   interaction with MPDZ; dbSNP:rs121913507)"
FT                   /evidence="ECO:0000269|PubMed:11018522,
FT                   ECO:0000269|PubMed:17595334, ECO:0000269|PubMed:19164557,
FT                   ECO:0000269|PubMed:19265199, ECO:0000269|PubMed:19865100,
FT                   ECO:0000269|PubMed:21640708, ECO:0000269|PubMed:7691885,
FT                   ECO:0000269|PubMed:9990072"
FT                   /id="VAR_004109"
FT   VARIANT         816
FT                   /note="D -> Y (in MASTSYS and MASTC; also found in acute
FT                   myeloid leukemia and a germ cell tumor of the testis;
FT                   somatic mutation; constitutively activated;
FT                   dbSNP:rs121913506)"
FT                   /evidence="ECO:0000269|PubMed:16175573,
FT                   ECO:0000269|PubMed:17344846, ECO:0000269|PubMed:19865100,
FT                   ECO:0000269|PubMed:9657776, ECO:0000269|PubMed:9990072"
FT                   /id="VAR_023828"
FT   VARIANT         820
FT                   /note="D -> G (in mast cell disease; systemic;
FT                   dbSNP:rs121913682)"
FT                   /evidence="ECO:0000269|PubMed:9029028"
FT                   /id="VAR_033135"
FT   VARIANT         822
FT                   /note="N -> I (in MASTC; constitutively activated;
FT                   dbSNP:rs993022333)"
FT                   /evidence="ECO:0000269|PubMed:21689725"
FT                   /id="VAR_081065"
FT   VARIANT         822
FT                   /note="N -> K (in a germ cell tumor of the testis; somatic
FT                   mutation; dbSNP:rs121913514)"
FT                   /evidence="ECO:0000269|PubMed:16175573,
FT                   ECO:0000269|PubMed:17344846"
FT                   /id="VAR_023829"
FT   VARIANT         829
FT                   /note="A -> P (in a germ cell tumor of the testis; somatic
FT                   mutation; dbSNP:rs1057519713)"
FT                   /evidence="ECO:0000269|PubMed:16175573,
FT                   ECO:0000269|PubMed:17344846"
FT                   /id="VAR_023830"
FT   VARIANT         839
FT                   /note="E -> K (in MASTC; sporadic case; somatic mutation;
FT                   dominant negative mutation; loss of autophosphorylation;
FT                   dbSNP:rs121913509)"
FT                   /evidence="ECO:0000269|PubMed:9990072"
FT                   /id="VAR_033136"
FT   VARIANT         847
FT                   /note="T -> P (in PBT; dbSNP:rs121913687)"
FT                   /evidence="ECO:0000269|PubMed:9699740"
FT                   /id="VAR_033137"
FT   VARIANT         893..896
FT                   /note="Missing (in PBT; severe)"
FT                   /evidence="ECO:0000269|PubMed:8680409"
FT                   /id="VAR_004110"
FT   MUTAGEN         381
FT                   /note="R->A: Reduces autophosphorylation in response to
FT                   KITLG/SCF."
FT                   /evidence="ECO:0000269|PubMed:17662946"
FT   MUTAGEN         386
FT                   /note="E->A: Reduces autophosphorylation in response to
FT                   KITLG/SCF."
FT                   /evidence="ECO:0000269|PubMed:17662946"
FT   MUTAGEN         571
FT                   /note="I->A: Reduction in SH2B2/APS binding. Abolishes
FT                   SH2B2/APS binding; when associated with A-939."
FT                   /evidence="ECO:0000269|PubMed:12444928"
FT   MUTAGEN         623
FT                   /note="K->M: Stronger interaction with MPDZ."
FT                   /evidence="ECO:0000269|PubMed:11018522"
FT   MUTAGEN         741
FT                   /note="S->A: Abolishes down-regulation of kinase activity
FT                   by PKC/PRKCA-mediated phosphorylation; when associated with
FT                   A-746."
FT                   /evidence="ECO:0000269|PubMed:7539802"
FT   MUTAGEN         746
FT                   /note="S->A: Abolishes down-regulation of kinase activity
FT                   by PKC/PRKCA-mediated phosphorylation; when associated with
FT                   A-741."
FT                   /evidence="ECO:0000269|PubMed:7539802"
FT   MUTAGEN         823
FT                   /note="Y->F: No decrease in activity. Leads to
FT                   autophosphorylation at Tyr-900."
FT                   /evidence="ECO:0000269|PubMed:20147452"
FT   MUTAGEN         939
FT                   /note="L->A: Reduction in SH2B2/APS binding. Abolishes
FT                   SH2B2/APS binding; when associated with A-571."
FT                   /evidence="ECO:0000269|PubMed:12444928"
FT   CONFLICT        764
FT                   /note="L -> I (in Ref. 10; AAH71593)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        838
FT                   /note="P -> H (in Ref. 10; AAH71593)"
FT                   /evidence="ECO:0000305"
FT   STRAND          38..41
FT                   /evidence="ECO:0007829|PDB:2EC8"
FT   STRAND          44..47
FT                   /evidence="ECO:0007829|PDB:2EC8"
FT   STRAND          54..59
FT                   /evidence="ECO:0007829|PDB:2EC8"
FT   STRAND          63..72
FT                   /evidence="ECO:0007829|PDB:2EC8"
FT   STRAND          75..77
FT                   /evidence="ECO:0007829|PDB:2EC8"
FT   STRAND          79..86
FT                   /evidence="ECO:0007829|PDB:2EC8"
FT   HELIX           89..91
FT                   /evidence="ECO:0007829|PDB:8DFP"
FT   STRAND          93..99
FT                   /evidence="ECO:0007829|PDB:2EC8"
FT   STRAND          104..110
FT                   /evidence="ECO:0007829|PDB:2EC8"
FT   STRAND          125..127
FT                   /evidence="ECO:0007829|PDB:8DFP"
FT   STRAND          132..134
FT                   /evidence="ECO:0007829|PDB:2EC8"
FT   STRAND          146..149
FT                   /evidence="ECO:0007829|PDB:2EC8"
FT   STRAND          151..153
FT                   /evidence="ECO:0007829|PDB:2EC8"
FT   STRAND          161..165
FT                   /evidence="ECO:0007829|PDB:2EC8"
FT   TURN            166..168
FT                   /evidence="ECO:0007829|PDB:2EC8"
FT   STRAND          169..174
FT                   /evidence="ECO:0007829|PDB:2EC8"
FT   HELIX           177..179
FT                   /evidence="ECO:0007829|PDB:2EC8"
FT   STRAND          183..188
FT                   /evidence="ECO:0007829|PDB:2EC8"
FT   STRAND          194..196
FT                   /evidence="ECO:0007829|PDB:8DFP"
FT   STRAND          200..205
FT                   /evidence="ECO:0007829|PDB:8DFP"
FT   STRAND          213..215
FT                   /evidence="ECO:0007829|PDB:2EC8"
FT   STRAND          219..224
FT                   /evidence="ECO:0007829|PDB:2EC8"
FT   STRAND          229..239
FT                   /evidence="ECO:0007829|PDB:2EC8"
FT   STRAND          243..248
FT                   /evidence="ECO:0007829|PDB:2EC8"
FT   STRAND          258..263
FT                   /evidence="ECO:0007829|PDB:2EC8"
FT   STRAND          265..267
FT                   /evidence="ECO:0007829|PDB:2EC8"
FT   STRAND          269..279
FT                   /evidence="ECO:0007829|PDB:2EC8"
FT   TURN            282..284
FT                   /evidence="ECO:0007829|PDB:2EC8"
FT   STRAND          286..293
FT                   /evidence="ECO:0007829|PDB:2EC8"
FT   STRAND          298..310
FT                   /evidence="ECO:0007829|PDB:2EC8"
FT   STRAND          312..319
FT                   /evidence="ECO:0007829|PDB:4K94"
FT   STRAND          321..325
FT                   /evidence="ECO:0007829|PDB:4K94"
FT   STRAND          331..341
FT                   /evidence="ECO:0007829|PDB:4K94"
FT   STRAND          344..350
FT                   /evidence="ECO:0007829|PDB:4K94"
FT   STRAND          356..364
FT                   /evidence="ECO:0007829|PDB:4K94"
FT   STRAND          367..369
FT                   /evidence="ECO:0007829|PDB:2EC8"
FT   STRAND          372..379
FT                   /evidence="ECO:0007829|PDB:4K94"
FT   HELIX           384..386
FT                   /evidence="ECO:0007829|PDB:4K94"
FT   STRAND          388..395
FT                   /evidence="ECO:0007829|PDB:4K94"
FT   STRAND          400..409
FT                   /evidence="ECO:0007829|PDB:4K94"
FT   STRAND          411..420
FT                   /evidence="ECO:0007829|PDB:4K94"
FT   HELIX           422..424
FT                   /evidence="ECO:0007829|PDB:4K94"
FT   STRAND          425..434
FT                   /evidence="ECO:0007829|PDB:4K94"
FT   STRAND          437..444
FT                   /evidence="ECO:0007829|PDB:4K94"
FT   STRAND          445..449
FT                   /evidence="ECO:0007829|PDB:4PGZ"
FT   STRAND          452..454
FT                   /evidence="ECO:0007829|PDB:4PGZ"
FT   STRAND          458..462
FT                   /evidence="ECO:0007829|PDB:4K94"
FT   STRAND          465..468
FT                   /evidence="ECO:0007829|PDB:4PGZ"
FT   STRAND          472..479
FT                   /evidence="ECO:0007829|PDB:4K94"
FT   HELIX           481..483
FT                   /evidence="ECO:0007829|PDB:4PGZ"
FT   STRAND          485..494
FT                   /evidence="ECO:0007829|PDB:4K94"
FT   STRAND          499..506
FT                   /evidence="ECO:0007829|PDB:4K94"
FT   HELIX           550..552
FT                   /evidence="ECO:0007829|PDB:7KHG"
FT   STRAND          558..564
FT                   /evidence="ECO:0007829|PDB:3G0E"
FT   STRAND          567..570
FT                   /evidence="ECO:0007829|PDB:3G0E"
FT   HELIX           573..575
FT                   /evidence="ECO:0007829|PDB:8PQD"
FT   HELIX           580..582
FT                   /evidence="ECO:0007829|PDB:8PQD"
FT   HELIX           586..588
FT                   /evidence="ECO:0007829|PDB:8PQD"
FT   STRAND          589..597
FT                   /evidence="ECO:0007829|PDB:8PQD"
FT   STRAND          599..609
FT                   /evidence="ECO:0007829|PDB:8PQD"
FT   STRAND          611..613
FT                   /evidence="ECO:0007829|PDB:8PQD"
FT   STRAND          617..625
FT                   /evidence="ECO:0007829|PDB:8PQD"
FT   HELIX           627..629
FT                   /evidence="ECO:0007829|PDB:6HH1"
FT   HELIX           631..647
FT                   /evidence="ECO:0007829|PDB:8PQD"
FT   STRAND          656..660
FT                   /evidence="ECO:0007829|PDB:8PQD"
FT   STRAND          662..664
FT                   /evidence="ECO:0007829|PDB:8PQD"
FT   STRAND          667..671
FT                   /evidence="ECO:0007829|PDB:8PQD"
FT   STRAND          674..677
FT                   /evidence="ECO:0007829|PDB:7KHK"
FT   HELIX           678..685
FT                   /evidence="ECO:0007829|PDB:8PQD"
FT   HELIX           686..689
FT                   /evidence="ECO:0007829|PDB:3G0E"
FT   STRAND          719..721
FT                   /evidence="ECO:0007829|PDB:2IUH"
FT   HELIX           754..756
FT                   /evidence="ECO:0007829|PDB:4HVS"
FT   STRAND          757..759
FT                   /evidence="ECO:0007829|PDB:4HVS"
FT   HELIX           760..762
FT                   /evidence="ECO:0007829|PDB:4HVS"
FT   HELIX           766..785
FT                   /evidence="ECO:0007829|PDB:8PQD"
FT   STRAND          788..790
FT                   /evidence="ECO:0007829|PDB:3G0F"
FT   HELIX           795..797
FT                   /evidence="ECO:0007829|PDB:8PQD"
FT   STRAND          798..801
FT                   /evidence="ECO:0007829|PDB:8PQD"
FT   HELIX           802..804
FT                   /evidence="ECO:0007829|PDB:8PQD"
FT   STRAND          805..808
FT                   /evidence="ECO:0007829|PDB:8PQD"
FT   HELIX           812..814
FT                   /evidence="ECO:0007829|PDB:1T46"
FT   TURN            818..820
FT                   /evidence="ECO:0007829|PDB:8PQD"
FT   STRAND          821..824
FT                   /evidence="ECO:0007829|PDB:8PQD"
FT   STRAND          827..831
FT                   /evidence="ECO:0007829|PDB:1T46"
FT   HELIX           833..835
FT                   /evidence="ECO:0007829|PDB:8PQD"
FT   HELIX           838..843
FT                   /evidence="ECO:0007829|PDB:8PQD"
FT   HELIX           848..863
FT                   /evidence="ECO:0007829|PDB:8PQD"
FT   TURN            864..866
FT                   /evidence="ECO:0007829|PDB:1T46"
FT   STRAND          869..872
FT                   /evidence="ECO:0007829|PDB:6ITT"
FT   HELIX           877..885
FT                   /evidence="ECO:0007829|PDB:8PQD"
FT   HELIX           897..906
FT                   /evidence="ECO:0007829|PDB:8PQD"
FT   HELIX           911..913
FT                   /evidence="ECO:0007829|PDB:8PQD"
FT   HELIX           917..930
FT                   /evidence="ECO:0007829|PDB:8PQD"
FT   TURN            931..933
FT                   /evidence="ECO:0007829|PDB:1T45"
SQ   SEQUENCE   976 AA;  109865 MW;  81B0CD76817F3454 CRC64;
     MRGARGAWDF LCVLLLLLRV QTGSSQPSVS PGEPSPPSIH PGKSDLIVRV GDEIRLLCTD
     PGFVKWTFEI LDETNENKQN EWITEKAEAT NTGKYTCTNK HGLSNSIYVF VRDPAKLFLV
     DRSLYGKEDN DTLVRCPLTD PEVTNYSLKG CQGKPLPKDL RFIPDPKAGI MIKSVKRAYH
     RLCLHCSVDQ EGKSVLSEKF ILKVRPAFKA VPVVSVSKAS YLLREGEEFT VTCTIKDVSS
     SVYSTWKREN SQTKLQEKYN SWHHGDFNYE RQATLTISSA RVNDSGVFMC YANNTFGSAN
     VTTTLEVVDK GFINIFPMIN TTVFVNDGEN VDLIVEYEAF PKPEHQQWIY MNRTFTDKWE
     DYPKSENESN IRYVSELHLT RLKGTEGGTY TFLVSNSDVN AAIAFNVYVN TKPEILTYDR
     LVNGMLQCVA AGFPEPTIDW YFCPGTEQRC SASVLPVDVQ TLNSSGPPFG KLVVQSSIDS
     SAFKHNGTVE CKAYNDVGKT SAYFNFAFKG NNKEQIHPHT LFTPLLIGFV IVAGMMCIIV
     MILTYKYLQK PMYEVQWKVV EEINGNNYVY IDPTQLPYDH KWEFPRNRLS FGKTLGAGAF
     GKVVEATAYG LIKSDAAMTV AVKMLKPSAH LTEREALMSE LKVLSYLGNH MNIVNLLGAC
     TIGGPTLVIT EYCCYGDLLN FLRRKRDSFI CSKQEDHAEA ALYKNLLHSK ESSCSDSTNE
     YMDMKPGVSY VVPTKADKRR SVRIGSYIER DVTPAIMEDD ELALDLEDLL SFSYQVAKGM
     AFLASKNCIH RDLAARNILL THGRITKICD FGLARDIKND SNYVVKGNAR LPVKWMAPES
     IFNCVYTFES DVWSYGIFLW ELFSLGSSPY PGMPVDSKFY KMIKEGFRML SPEHAPAEMY
     DIMKTCWDAD PLKRPTFKQI VQLIEKQISE STNHIYSNLA NCSPNRQKPV VDHSVRINSV
     GSTASSSQPL LVHDDV
//