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/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 //