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 // ID NPM_HUMAN Reviewed; 294 AA. AC P06748; A8K3N7; B5BU00; D3DQL6; P08693; Q12826; Q13440; Q13441; Q14115; AC Q5EU94; Q5EU95; Q5EU96; Q5EU97; Q5EU98; Q5EU99; Q6V962; Q8WTW5; Q96AT6; AC Q96DC4; Q96EA5; Q9BYG9; Q9UDJ7; DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1990, sequence version 2. DT 28-JAN-2026, entry version 271. DE RecName: Full=Nucleophosmin; DE Short=NPM; DE AltName: Full=Nucleolar phosphoprotein B23; DE AltName: Full=Nucleolar protein NO38; DE AltName: Full=Numatrin; GN Name=NPM1 {ECO:0000312|HGNC:HGNC:7910}; Synonyms=NPM; 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). RC TISSUE=Placenta; RX PubMed=2713355; DOI=10.1021/bi00429a017; RA Chan W.-Y., Liu Q.R., Borjigin J., Busch H., Rennert O.M., Tease L.A., RA Chan P.-K.; RT "Characterization of the cDNA encoding human nucleophosmin and studies of RT its role in normal and abnormal growth."; RL Biochemistry 28:1033-1039(1989). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=B-cell lymphoma; RX PubMed=2775293; DOI=10.1016/0006-291x(89)92100-1; RA Li X., McNeilage L.J., Whittingham S.; RT "The nucleotide sequence of a human cDNA encoding the highly conserved RT nucleolar phosphoprotein B23."; RL Biochem. Biophys. Res. Commun. 163:72-78(1989). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Amnion; RX PubMed=2478125; DOI=10.1016/0006-291x(89)91699-9; RA Zhang X.T., Thomis D.C., Samuel C.E.; RT "Isolation and characterization of a molecular cDNA clone of a human mRNA RT from interferon-treated cells encoding nucleolar protein B23, numatrin."; RL Biochem. Biophys. Res. Commun. 164:176-184(1989). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1). RX PubMed=9092633; DOI=10.1093/nar/25.6.1225; RA Chan P.-K., Chan F.Y., Morris S.W., Xie Z.; RT "Isolation and characterization of the human nucleophosmin/B23 (NPM) gene: RT identification of the YY1 binding site at the 5' enhancer region."; RL Nucleic Acids Res. 25:1225-1232(1997). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). RA Okuwaki M., Nagata K.; RT "Human homologue of Rat B23.2."; RL Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, AND RP INVOLVEMENT IN ACUTE MYELOGENOUS LEUKEMIA. RC TISSUE=Bone marrow; RX PubMed=15659725; DOI=10.1056/nejmoa041974; RA Falini B., Mecucci C., Tiacci E., Alcalay M., Rosati R., Pasqualucci L., RA La Starza R., Diverio D., Colombo E., Santucci A., Bigerna B., Pacini R., RA Pucciarini A., Liso A., Vignetti M., Fazi P., Meani N., Pettirossi V., RA Saglio G., Mandelli F., Lo-Coco F., Pelicci P.-G., Martelli M.F.; RT "Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal RT karyotype."; RL N. Engl. J. Med. 352:254-266(2005). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=16574551; DOI=10.1016/s1470-2045(06)70661-1; RA Bolli N., Galimberti S., Martelli M.P., Tabarrini A., Roti G., Mecucci C., RA Martelli M.F., Petrini M., Falini B.; RT "Cytoplasmic nucleophosmin in myeloid sarcoma occurring 20 years after RT diagnosis of acute myeloid leukaemia."; RL Lancet Oncol. 7:350-352(2006). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Testis; RA Lu L., Huang X.Y., Yin L.L., Xu M., Li J.M., Zhou Z.M., Sha J.H.; RT "Cloning of a new transcript of nucleophosmin in testis."; RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Embryo; 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 [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=19054851; DOI=10.1038/nmeth.1273; RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R., RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y., RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B., RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y., RA Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A., RA Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y., RA Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T., RA Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y., RA Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S., RA Nomura N.; RT "Human protein factory for converting the transcriptome into an in vitro- RT expressed proteome."; RL Nat. Methods 5:1011-1017(2008). RN [12] 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [13] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3). RC TISSUE=Bone marrow, Brain, Kidney, Lung, Prostate, Testis, and RC Urinary bladder; 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 [14] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-133, AND CHROMOSOMAL TRANSLOCATION WITH RP RARA. RC TISSUE=Bone marrow; RX PubMed=8562957; RA Redner R.L., Rush E.A., Faas S., Rudert W.A., Corey S.J.; RT "The t(5;17) variant of acute promyelocytic leukemia expresses a RT nucleophosmin-retinoic acid receptor fusion."; RL Blood 87:882-886(1996). RN [15] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-117, AND CHROMOSOMAL TRANSLOCATION WITH RP ALK. RC TISSUE=T-cell lymphoma; RX PubMed=8122112; DOI=10.1126/science.8122112; RA Morris S.W., Kirstein M.N., Valentine M.B., Dittmer K.G., Shapiro D.N., RA Saltman D.L., Look A.T.; RT "Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non- RT Hodgkin's lymphoma."; RL Science 263:1281-1284(1994). RN [16] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-117, AND CHROMOSOMAL TRANSLOCATION WITH RP ALK. RC TISSUE=Lymphoma; RX PubMed=8633037; DOI=10.1073/pnas.93.9.4181; RA Fujimoto J., Shiota M., Iwahara T., Seki N., Satoh H., Mori S., RA Yamamoto T.; RT "Characterization of the transforming activity of p80, a RT hyperphosphorylated protein in a Ki-1 lymphoma cell line with chromosomal RT translocation t(2;5)."; RL Proc. Natl. Acad. Sci. U.S.A. 93:4181-4186(1996). RN [17] RP PROTEIN SEQUENCE OF 1-24; 33-101; 104-141; 240-248 AND 278-291, ACETYLATION RP AT MET-1, PHOSPHORYLATION AT SER-125, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RC TISSUE=Cervix carcinoma; RA Bienvenut W.V., Waridel P., Quadroni M.; RL Submitted (MAR-2009) to UniProtKB. RN [18] RP NUCLEOTIDE SEQUENCE [MRNA] OF 15-294 (ISOFORM 1). RC TISSUE=Placenta; RX PubMed=2602120; RA Hale T.K., Mansfield B.C.; RT "Nucleotide sequence of a cDNA clone representing a third allele of human RT protein B23."; RL Nucleic Acids Res. 17:10112-10112(1989). RN [19] RP PROTEIN SEQUENCE OF 33-54. RC TISSUE=Colon carcinoma; RX PubMed=9150948; DOI=10.1002/elps.1150180344; RA Ji H., Reid G.E., Moritz R.L., Eddes J.S., Burgess A.W., Simpson R.J.; RT "A two-dimensional gel database of human colon carcinoma proteins."; RL Electrophoresis 18:605-613(1997). RN [20] RP PROTEIN SEQUENCE OF 34-42; 50-67; 137-151; 218-227; 252-266 AND 277-286 RP (ISOFORM 1), AND INTERACTION WITH HTLV1 REX PROTEIN (MICROBIAL INFECTION). RX PubMed=8314759; DOI=10.1016/s0021-9258(19)85191-8; RA Adachi Y., Copeland T.D., Hatanaka M., Oroszlan S.; RT "Nucleolar targeting signal of Rex protein of human T-cell leukemia virus RT type I specifically binds to nucleolar shuttle protein B-23."; RL J. Biol. Chem. 268:13930-13934(1993). RN [21] RP PROTEIN SEQUENCE OF 33-42; 213-221; 251-257 AND 268-274, FUNCTION, RP INTERACTION WITH EIF2AK2, AND PHOSPHORYLATION. RX PubMed=12882984; DOI=10.1074/jbc.m301392200; RA Pang Q., Christianson T.A., Koretsky T., Carlson H., David L., Keeble W., RA Faulkner G.R., Speckhart A., Bagby G.C.; RT "Nucleophosmin interacts with and inhibits the catalytic function of RT eukaryotic initiation factor 2 kinase PKR."; RL J. Biol. Chem. 278:41709-41717(2003). RN [22] RP PROTEIN SEQUENCE OF 115-134. RX PubMed=3944116; DOI=10.1016/s0021-9258(17)36022-2; RA Chan P.-K., Aldrich M.B., Cook R.G., Busch H.; RT "Amino acid sequence of protein B23 phosphorylation site."; RL J. Biol. Chem. 261:1868-1872(1986). RN [23] RP NUCLEOTIDE SEQUENCE [MRNA] OF 213-294 (ISOFORM 1), AND PROTEIN SEQUENCE OF RP 227-294. RX PubMed=2429957; DOI=10.1016/s0021-9258(18)67023-1; RA Chan P.-K., Chan W.-Y., Yung B.Y.M., Cook R.G., Aldrich M.B., Ku D., RA Goldknopf I.L., Busch H.; RT "Amino acid sequence of a specific antigenic peptide of protein B23."; RL J. Biol. Chem. 261:14335-14341(1986). RN [24] RP INTERACTION WITH NOP2. RX PubMed=8089149; DOI=10.1016/s0021-9258(17)31583-1; RA Valdez B.C., Perlaky L., Henning D., Saijo Y., Chan P.K., Busch H.; RT "Identification of the nuclear and nucleolar localization signals of the RT protein p120. Interaction with translocation protein B23."; RL J. Biol. Chem. 269:23776-23783(1994). RN [25] RP ADP-RIBOSYLATION. RX PubMed=7631008; DOI=10.2307/3579152; RA Ramsamooj P., Notario V., Dritschilo A.; RT "Modification of nucleolar protein B23 after exposure to ionizing RT radiation."; RL Radiat. Res. 143:158-164(1995). RN [26] RP CHROMOSOMAL TRANSLOCATION WITH MLF1. RX PubMed=8570204; RA Yoneda-Kato N., Look A.T., Kirstein M.N., Valentine M.B., Raimondi S.C., RA Cohen K.J., Carroll A.J., Morris S.W.; RT "The t(3;5)(q25.1;q34) of myelodysplastic syndrome and acute myeloid RT leukemia produces a novel fusion gene, NPM-MLF1."; RL Oncogene 12:265-275(1996). RN [27] RP PHOSPHORYLATION BY CDK2. RX PubMed=11051553; DOI=10.1016/s0092-8674(00)00093-3; RA Okuda M., Horn H.F., Tarapore P., Tokuyama Y., Smulian A.G., Chan P.K., RA Knudsen E.S., Hofmann I.A., Snyder J.D., Bove K.E., Fukasawa K.; RT "Nucleophosmin/B23 is a target of CDK2/cyclin E in centrosome RT duplication."; RL Cell 103:127-140(2000). RN [28] RP INTERACTION WITH HEPATITIS DELTA VIRUS S-HDAG (MICROBIAL INFECTION). RX PubMed=11309377; DOI=10.1074/jbc.m010087200; RA Huang W.H., Yung B.Y., Syu W.J., Lee Y.H.; RT "The nucleolar phosphoprotein B23 interacts with hepatitis delta antigens RT and modulates the hepatitis delta virus RNA replication."; RL J. Biol. Chem. 276:25166-25175(2001). RN [29] RP PHOSPHORYLATION AT THR-199; THR-219 AND THR-237, AND MUTAGENESIS OF RP THR-199; THR-219; THR-234 AND THR-237. RX PubMed=12058066; DOI=10.1091/mbc.02-03-0036; RA Okuwaki M., Tsujimoto M., Nagata K.; RT "The RNA binding activity of a ribosome biogenesis factor, RT nucleophosmin/B23, is modulated by phosphorylation with a cell cycle- RT dependent kinase and by association with its subtype."; RL Mol. Biol. Cell 13:2016-2030(2002). RN [30] RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=12429849; DOI=10.1091/mbc.e02-05-0271; RA Scherl A., Coute Y., Deon C., Calle A., Kindbeiter K., Sanchez J.-C., RA Greco A., Hochstrasser D.F., Diaz J.-J.; RT "Functional proteomic analysis of human nucleolus."; RL Mol. Biol. Cell 13:4100-4109(2002). RN [31] RP REVIEW. RX PubMed=12214246; DOI=10.1038/sj.onc.1205708; RA Okuda M.; RT "The role of nucleophosmin in centrosome duplication."; RL Oncogene 21:6170-6174(2002). RN [32] RP IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION [LARGE SCALE RP ANALYSIS]. RC TISSUE=Lymphoblast; RX PubMed=14654843; DOI=10.1038/nature02166; RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., Mann M.; RT "Proteomic characterization of the human centrosome by protein correlation RT profiling."; RL Nature 426:570-574(2003). RN [33] RP SUBCELLULAR LOCATION, PHOSPHORYLATION, AND INTERACTION WITH NEK2. RX PubMed=15388344; DOI=10.1016/j.febslet.2004.08.047; RA Yao J., Fu C., Ding X., Guo Z., Zenreski A., Chen Y., Ahmed K., Liao J., RA Dou Z., Yao X.; RT "Nek2A kinase regulates the localization of numatrin to centrosome in RT mitosis."; RL FEBS Lett. 575:112-118(2004). RN [34] RP PHOSPHORYLATION AT SER-4 BY PLK1. RX PubMed=15190079; DOI=10.1074/jbc.m403264200; RA Zhang H., Shi X., Paddon H., Hampong M., Dai W., Pelech S.; RT "B23/nucleophosmin serine 4 phosphorylation mediates mitotic functions of RT polo-like kinase 1."; RL J. Biol. Chem. 279:35726-35734(2004). RN [35] RP INTERACTION WITH RPGR. RX PubMed=15772089; DOI=10.1093/hmg/ddi129; RA Shu X., Fry A.M., Tulloch B., Manson F.D., Crabb J.W., Khanna H., RA Faragher A.J., Lennon A., He S., Trojan P., Giessl A., Wolfrum U., RA Vervoort R., Swaroop A., Wright A.F.; RT "RPGR ORF15 isoform co-localizes with RPGRIP1 at centrioles and basal RT bodies and interacts with nucleophosmin."; RL Hum. Mol. Genet. 14:1183-1197(2005). RN [36] RP ACETYLATION AT LYS-212; LYS-229; LYS-230; LYS-250; LYS-257 AND LYS-292, AND RP FUNCTION AS A CHAPERONE. RX PubMed=16107701; DOI=10.1128/mcb.25.17.7534-7545.2005; RA Swaminathan V., Kishore A.H., Febitha K.K., Kundu T.K.; RT "Human histone chaperone nucleophosmin enhances acetylation-dependent RT chromatin transcription."; RL Mol. Cell. Biol. 25:7534-7545(2005). RN [37] RP SUMOYLATION AT LYS-230 AND LYS-263. RX PubMed=15897463; DOI=10.1073/pnas.0502978102; RA Tago K., Chiocca S., Sherr C.J.; RT "Sumoylation induced by the Arf tumor suppressor: a p53-independent RT function."; RL Proc. Natl. Acad. Sci. U.S.A. 102:7689-7694(2005). RN [38] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-70 AND THR-95, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [39] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-150; LYS-154 AND LYS-212, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=16916647; DOI=10.1016/j.molcel.2006.06.026; RA Kim S.C., Sprung R., Chen Y., Xu Y., Ball H., Pei J., Cheng T., Kho Y., RA Xiao H., Xiao L., Grishin N.V., White M., Yang X.-J., Zhao Y.; RT "Substrate and functional diversity of lysine acetylation revealed by a RT proteomics survey."; RL Mol. Cell 23:607-618(2006). RN [40] RP FUNCTION, AND INTERACTION WITH ROCK2. RX PubMed=17015463; DOI=10.1128/mcb.01383-06; RA Ma Z., Kanai M., Kawamura K., Kaibuchi K., Ye K., Fukasawa K.; RT "Interaction between ROCK II and nucleophosmin/B23 in the regulation of RT centrosome duplication."; RL Mol. Cell. Biol. 26:9016-9034(2006). RN [41] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-70; THR-199 AND SER-254, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17924679; DOI=10.1021/pr070152u; RA Yu L.R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.; RT "Improved titanium dioxide enrichment of phosphopeptides from HeLa cells RT and high confident phosphopeptide identification by cross-validation of RT MS/MS and MS/MS/MS spectra."; RL J. Proteome Res. 6:4150-4162(2007). RN [42] RP INTERACTION WITH NSUN2. RX PubMed=17215513; DOI=10.1091/mbc.e06-11-1021; RA Sakita-Suto S., Kanda A., Suzuki F., Sato S., Takata T., Tatsuka M.; RT "Aurora-B regulates RNA methyltransferase NSUN2."; RL Mol. Biol. Cell 18:1107-1117(2007). RN [43] RP INTERACTION WITH SENP3, AND MUTAGENESIS OF LYS-263. RX PubMed=18259216; DOI=10.1038/embor.2008.3; RA Haindl M., Harasim T., Eick D., Muller S.; RT "The nucleolar SUMO-specific protease SENP3 reverses SUMO modification of RT nucleophosmin and is required for rRNA processing."; RL EMBO Rep. 9:273-279(2008). RN [44] RP INTERACTION WITH SENP3, AND SUBCELLULAR LOCATION. RX PubMed=19015314; DOI=10.1083/jcb.200807185; RA Yun C., Wang Y., Mukhopadhyay D., Backlund P., Kolli N., Yergey A., RA Wilkinson K.D., Dasso M.; RT "Nucleolar protein B23/nucleophosmin regulates the vertebrate SUMO pathway RT through SENP3 and SENP5 proteases."; RL J. Cell Biol. 183:589-595(2008). RN [45] RP REVIEW. RX PubMed=18024471; DOI=10.1093/jb/mvm222; RA Okuwaki M.; RT "The structure and functions of NPM1/Nucleophosmin/B23, a multifunctional RT nucleolar acidic protein."; RL J. Biochem. 143:441-448(2008). RN [46] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-70; SER-125 AND THR-279, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18220336; DOI=10.1021/pr0705441; RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III; RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient RT phosphoproteomic analysis."; RL J. Proteome Res. 7:1346-1351(2008). RN [47] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-70 AND SER-125, AND RP IDENTIFICATION BY 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 [48] RP FUNCTION. RX PubMed=18809582; DOI=10.1128/mcb.01548-07; RA Maggi L.B. Jr., Kuchenruether M., Dadey D.Y., Schwope R.M., Grisendi S., RA Townsend R.R., Pandolfi P.P., Weber J.D.; RT "Nucleophosmin serves as a rate-limiting nuclear export chaperone for the RT Mammalian ribosome."; RL Mol. Cell. Biol. 28:7050-7065(2008). RN [49] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-70; THR-75; THR-95; SER-125; RP SER-139; THR-234; THR-237 AND SER-243, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [50] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-125, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=18318008; DOI=10.1002/pmic.200700884; RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D., RA Zou H., Gu J.; RT "Large-scale phosphoproteome analysis of human liver tissue by enrichment RT and fractionation of phosphopeptides with strong anion exchange RT chromatography."; RL Proteomics 8:1346-1361(2008). RN [51] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [52] RP INTERACTION WITH RRP1B. RX PubMed=19710015; DOI=10.1074/jbc.m109.023457; RA Crawford N.P., Yang H., Mattaini K.R., Hunter K.W.; RT "The metastasis efficiency modifier ribosomal RNA processing 1 homolog B RT (RRP1B) is a chromatin-associated factor."; RL J. Biol. Chem. 284:28660-28673(2009). RN [53] RP SUBCELLULAR LOCATION, UBIQUITINATION, AND DEUBIQUITINATION BY USP36. RX PubMed=19208757; DOI=10.1242/jcs.044461; RA Endo A., Matsumoto M., Inada T., Yamamoto A., Nakayama K.I., Kitamura N., RA Komada M.; RT "Nucleolar structure and function are regulated by the deubiquitylating RT enzyme USP36."; RL J. Cell Sci. 122:678-686(2009). RN [54] RP FUNCTION, INTERACTION WITH APEX1, IDENTIFICATION BY MASS SPECTROMETRY, AND RP SUBCELLULAR LOCATION. RX PubMed=19188445; DOI=10.1128/mcb.01337-08; RA Vascotto C., Fantini D., Romanello M., Cesaratto L., Deganuto M., RA Leonardi A., Radicella J.P., Kelley M.R., D'Ambrosio C., Scaloni A., RA Quadrifoglio F., Tell G.; RT "APE1/Ref-1 interacts with NPM1 within nucleoli and plays a role in the RT rRNA quality control process."; RL Mol. Cell. Biol. 29:1834-1854(2009). RN [55] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-125, 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 [56] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-70 AND SER-125, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [57] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-32; LYS-150; LYS-257; LYS-267 AND RP LYS-273, ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-257 (ISOFORM 3), AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [58] RP INTERACTION WITH CEBPA. RX PubMed=20075868; DOI=10.1038/emboj.2009.404; RA Muller C., Bremer A., Schreiber S., Eichwald S., Calkhoven C.F.; RT "Nucleolar retention of a translational C/EBPalpha isoform stimulates rDNA RT transcription and cell size."; RL EMBO J. 29:897-909(2010). RN [59] RP SUBCELLULAR LOCATION, AND INTERACTION WITH RPS10. RX PubMed=20159986; DOI=10.1074/jbc.m110.103911; RA Ren J., Wang Y., Liang Y., Zhang Y., Bao S., Xu Z.; RT "Methylation of ribosomal protein S10 by protein-arginine methyltransferase RT 5 regulates ribosome biogenesis."; RL J. Biol. Chem. 285:12695-12705(2010). RN [60] RP INTERACTION WITH RRP1B. RX PubMed=20926688; DOI=10.1091/mbc.e10-04-0287; RA Chamousset D., De Wever V., Moorhead G.B., Chen Y., Boisvert F.M., RA Lamond A.I., Trinkle-Mulcahy L.; RT "RRP1B targets PP1 to mammalian cell nucleoli and is associated with pre- RT 60S ribosomal subunits."; RL Mol. Biol. Cell 21:4212-4226(2010). RN [61] RP FUNCTION, PHOSPHORYLATION AT SER-4 BY PLK2, AND MUTAGENESIS OF SER-4; RP THR-95; SER-125 AND THR-199. RX PubMed=20352051; DOI=10.1371/journal.pone.0009849; RA Krause A., Hoffmann I.; RT "Polo-like kinase 2-dependent phosphorylation of NPM/B23 on serine 4 RT triggers centriole duplication."; RL PLoS ONE 5:E9849-E9849(2010). RN [62] RP PHOSPHORYLATION AT THR-199 BY CDK6. RX PubMed=20333249; DOI=10.1371/journal.ppat.1000818; RA Sarek G., Jaerviluoma A., Moore H.M., Tojkander S., Vartia S., RA Biberfeld P., Laiho M., Ojala P.M.; RT "Nucleophosmin phosphorylation by v-cyclin-CDK6 controls KSHV latency."; RL PLoS Pathog. 6:E1000818-E1000818(2010). RN [63] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE SCALE RP ANALYSIS] AT SER-4; SER-10; SER-70; THR-95; SER-125; SER-137; SER-139; RP THR-199; SER-242; SER-243; SER-260 AND THR-279, PHOSPHORYLATION [LARGE RP SCALE ANALYSIS] AT SER-254 (ISOFORM 3), AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [64] 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 [65] RP FUNCTION, AND INTERACTION WITH BRCA2. RX PubMed=21084279; DOI=10.1158/0008-5472.can-10-0030; RA Wang H.F., Takenaka K., Nakanishi A., Miki Y.; RT "BRCA2 and nucleophosmin coregulate centrosome amplification and form a RT complex with the Rho effector kinase ROCK2."; RL Cancer Res. 71:68-77(2011). RN [66] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CENPW. RX PubMed=22002061; DOI=10.1074/jbc.m111.228411; RA Chun Y., Park B., Koh W., Lee S., Cheon Y., Kim R., Che L., Lee S.; RT "New centromeric component CENP-W is an RNA-associated nuclear matrix RT protein that interacts with nucleophosmin/B23 protein."; RL J. Biol. Chem. 286:42758-42769(2011). RN [67] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE SCALE RP ANALYSIS] AT SER-4; SER-70; SER-125; SER-227; SER-243 AND SER-254, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [68] RP FUNCTION, INTERACTION WITH ATF5, AND SUBCELLULAR LOCATION. RX PubMed=22528486; DOI=10.1074/jbc.m112.363622; RA Liu X., Liu D., Qian D., Dai J., An Y., Jiang S., Stanley B., Yang J., RA Wang B., Liu X., Liu D.X.; RT "Nucleophosmin (NPM1/B23) interacts with activating transcription factor 5 RT (ATF5) protein and promotes proteasome- and caspase-dependent ATF5 RT degradation in hepatocellular carcinoma cells."; RL J. Biol. Chem. 287:19599-19609(2012). RN [69] RP INTERACTION WITH DDX31. RX PubMed=23019224; DOI=10.1158/0008-5472.can-12-1645; RA Fukawa T., Ono M., Matsuo T., Uehara H., Miki T., Nakamura Y., RA Kanayama H.O., Katagiri T.; RT "DDX31 regulates the p53-HDM2 pathway and rRNA gene transcription through RT its interaction with NPM1 in renal cell carcinomas."; RL Cancer Res. 72:5867-5877(2012). RN [70] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [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 [71] RP INTERACTION WITH NPM3. RX PubMed=22362753; DOI=10.1093/nar/gks162; RA Okuwaki M., Sumi A., Hisaoka M., Saotome-Nakamura A., Akashi S., RA Nishimura Y., Nagata K.; RT "Function of homo- and hetero-oligomers of human RT nucleoplasmin/nucleophosmin family proteins NPM1, NPM2 and NPM3 during RT sperm chromatin remodeling."; RL Nucleic Acids Res. 40:4861-4878(2012). RN [72] RP INTERACTION WITH ALKBH2. RX PubMed=23972994; DOI=10.1016/j.celrep.2013.07.027; RA Li P., Gao S., Wang L., Yu F., Li J., Wang C., Li J., Wong J.; RT "ABH2 couples regulation of ribosomal DNA transcription with DNA alkylation RT repair."; RL Cell Rep. 4:817-829(2013). RN [73] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-4; SER-10; SER-43; SER-70; RP THR-95; SER-125; SER-139; THR-234; THR-237; SER-242; SER-243; SER-254 AND RP SER-260, AND 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 [74] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-70 AND SER-243, AND 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 [75] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-27; LYS-32; LYS-248 AND LYS-250, RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25218447; DOI=10.1038/nsmb.2890; RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M., RA Vertegaal A.C.; RT "Uncovering global SUMOylation signaling networks in a site-specific RT manner."; RL Nat. Struct. Mol. Biol. 21:927-936(2014). RN [76] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-32; LYS-248; LYS-257 AND LYS-267, RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25114211; DOI=10.1073/pnas.1413825111; RA Impens F., Radoshevich L., Cossart P., Ribet D.; RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by RT external stimuli."; RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014). RN [77] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH MYC AND NOP53. RX PubMed=25956029; DOI=10.1016/j.ajpath.2015.03.016; RA Kim J.Y., Cho Y.E., Park J.H.; RT "The nucleolar protein GLTSCR2 is an upstream negative regulator of the RT oncogenic Nucleophosmin-MYC axis."; RL Am. J. Pathol. 185:2061-2068(2015). RN [78] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-32 AND LYS-215, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25772364; DOI=10.1016/j.celrep.2015.02.033; RA Hendriks I.A., Treffers L.W., Verlaan-de Vries M., Olsen J.V., RA Vertegaal A.C.; RT "SUMO-2 orchestrates chromatin modifiers in response to DNA damage."; RL Cell Rep. 10:1778-1791(2015). RN [79] RP SUBUNIT, SUBCELLULAR LOCATION, AND UBIQUITINATION. RX PubMed=25818168; DOI=10.1111/jcmm.12474; RA Kim J.Y., Cho Y.E., An Y.M., Kim S.H., Lee Y.G., Park J.H., Lee S.; RT "GLTSCR2 is an upstream negative regulator of nucleophosmin in cervical RT cancer."; RL J. Cell. Mol. Med. 19:1245-1252(2015). RN [80] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-32, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25755297; DOI=10.1074/mcp.o114.044792; RA Xiao Z., Chang J.G., Hendriks I.A., Sigurdsson J.O., Olsen J.V., RA Vertegaal A.C.; RT "System-wide analysis of SUMOylation dynamics in response to replication RT stress reveals novel small ubiquitin-like modified target proteins and RT acceptor lysines relevant for genome stability."; RL Mol. Cell. Proteomics 14:1419-1434(2015). RN [81] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [82] RP ADP-RIBOSYLATION AT SER-207. RX PubMed=28190768; DOI=10.1016/j.molcel.2017.01.003; RA Bonfiglio J.J., Fontana P., Zhang Q., Colby T., Gibbs-Seymour I., RA Atanassov I., Bartlett E., Zaja R., Ahel I., Matic I.; RT "Serine ADP-ribosylation depends on HPF1."; RL Mol. Cell 0:0-0(2017). RN [83] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-32; LYS-141; LYS-150; LYS-215; RP LYS-248; LYS-250; LYS-257; LYS-263; LYS-267 AND LYS-273, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [84] RP INTERACTION WITH ARID3C, AND SUBCELLULAR LOCATION. RX PubMed=38231884; DOI=10.1021/acs.jproteome.3c00509; RA Kim H.S., Kim Y.I., Cho J.Y.; RT "ARID3C Acts as a Regulator of Monocyte-to-Macrophage Differentiation RT Interacting with NPM1."; RL J. Proteome Res. 0:0-0(2024). RN [85] RP X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 9-124. RX PubMed=17879352; DOI=10.1002/prot.21504; RA Lee H.H., Kim H.S., Kang J.Y., Lee B.I., Ha J.Y., Yoon H.J., Lim S.O., RA Jung G., Suh S.W.; RT "Crystal structure of human nucleophosmin-core reveals plasticity of the RT pentamer-pentamer interface."; RL Proteins 69:672-678(2007). RN [86] RP STRUCTURE BY NMR OF 243-294, AND MUTAGENESIS OF LYS-248; LYS-250; LYS-267; RP PHE-268; PHE-276; TRP-288 AND TRP-290. RX PubMed=18511415; DOI=10.1074/jbc.m801706200; RA Grummitt C.G., Townsley F.M., Johnson C.M., Warren A.J., Bycroft M.; RT "Structural consequences of nucleophosmin mutations in acute myeloid RT leukemia."; RL J. Biol. Chem. 283:23326-23332(2008). CC -!- FUNCTION: Involved in diverse cellular processes such as ribosome CC biogenesis, centrosome duplication, protein chaperoning, histone CC assembly, cell proliferation, and regulation of tumor suppressors CC p53/TP53 and ARF. Binds ribosome presumably to drive ribosome nuclear CC export. Associated with nucleolar ribonucleoprotein structures and bind CC single-stranded nucleic acids. Acts as a chaperonin for the core CC histones H3, H2B and H4. Stimulates APEX1 endonuclease activity on CC apurinic/apyrimidinic (AP) double-stranded DNA but inhibits APEX1 CC endonuclease activity on AP single-stranded RNA. May exert a control of CC APEX1 endonuclease activity within nucleoli devoted to repair AP on CC rDNA and the removal of oxidized rRNA molecules. In concert with BRCA2, CC regulates centrosome duplication. Regulates centriole duplication: CC phosphorylation by PLK2 is able to trigger centriole replication. CC Negatively regulates the activation of EIF2AK2/PKR and suppresses CC apoptosis through inhibition of EIF2AK2/PKR autophosphorylation. CC Antagonizes the inhibitory effect of ATF5 on cell proliferation and CC relieves ATF5-induced G2/M blockade (PubMed:22528486). In complex with CC MYC enhances the transcription of MYC target genes (PubMed:25956029). CC May act as chaperonin or cotransporter in the nucleolar localization of CC transcription termination factor TTF1 (By similarity). CC {ECO:0000250|UniProtKB:Q61937, ECO:0000269|PubMed:12882984, CC ECO:0000269|PubMed:16107701, ECO:0000269|PubMed:17015463, CC ECO:0000269|PubMed:18809582, ECO:0000269|PubMed:19188445, CC ECO:0000269|PubMed:20352051, ECO:0000269|PubMed:21084279, CC ECO:0000269|PubMed:22002061, ECO:0000269|PubMed:22528486, CC ECO:0000269|PubMed:25956029}. CC -!- SUBUNIT: Decamer formed by two pentameric rings associated in a head- CC to-head fashion (By similarity). Disulfide-linked dimers under certain CC conditions (PubMed:25818168). The SWAP complex consists of NPM1, NCL, CC PARP1 and SWAP70 (By similarity). Interacts with NSUN2 and SENP3. CC Interacts with the methylated form of RPS10. Interacts (via N-terminal CC domain) with APEX1; the interaction is RNA-dependent and decreases in CC hydrogen peroxide-damaged cells. Interacts with isoform 1 of NEK2. CC Interacts with ROCK2 and BRCA2. Interacts with RPGR. Interacts with CC CENPW. Interacts with EIF2AK2/PKR. Interacts with CEBPA (isoform 4) CC (PubMed:20075868). Interacts with DDX31; this interaction prevents CC interaction between NPM1 and HDM2 (PubMed:23019224). Interacts with CC MYC; competitive with NOP53 (PubMed:25956029). Interacts with NOP53; CC the interaction is direct and competitive with MYC (PubMed:25956029). CC Interacts with LRRC34 (By similarity). Interacts with RRP1B CC (PubMed:19710015, PubMed:20926688). Interacts with NPM3 CC (PubMed:22362753). Interacts with ALKBH2 (PubMed:23972994). Interacts CC with TTF1 (via C-terminal region) (By similarity). Interacts with NOP2 CC (PubMed:8089149). Interacts with ARID3C (via REKLES DOMAIN); the CC interaction mediates ARID3C nuclear shuttling (PubMed:38231884). CC {ECO:0000250|UniProtKB:Q61937, ECO:0000269|PubMed:12882984, CC ECO:0000269|PubMed:15388344, ECO:0000269|PubMed:15772089, CC ECO:0000269|PubMed:17015463, ECO:0000269|PubMed:17215513, CC ECO:0000269|PubMed:18259216, ECO:0000269|PubMed:19015314, CC ECO:0000269|PubMed:19188445, ECO:0000269|PubMed:19710015, CC ECO:0000269|PubMed:20075868, ECO:0000269|PubMed:20159986, CC ECO:0000269|PubMed:20926688, ECO:0000269|PubMed:21084279, CC ECO:0000269|PubMed:22002061, ECO:0000269|PubMed:22362753, CC ECO:0000269|PubMed:22528486, ECO:0000269|PubMed:23019224, CC ECO:0000269|PubMed:23972994, ECO:0000269|PubMed:25818168, CC ECO:0000269|PubMed:25956029, ECO:0000269|PubMed:38231884, CC ECO:0000269|PubMed:8089149}. CC -!- SUBUNIT: (Microbial infection) Interacts with hepatitis delta virus S- CC HDAg. {ECO:0000269|PubMed:11309377}. CC -!- SUBUNIT: (Microbial infection) Interacts with HTLV1 Rex protein (via N- CC terminal nuclear localization signal). {ECO:0000269|PubMed:8314759}. CC -!- INTERACTION: CC P06748; O14965: AURKA; NbExp=3; IntAct=EBI-78579, EBI-448680; CC P06748; Q96GD4: AURKB; NbExp=6; IntAct=EBI-78579, EBI-624291; CC P06748; Q96CT7: CCDC124; NbExp=8; IntAct=EBI-78579, EBI-5461329; CC P06748; Q8N726: CDKN2A; NbExp=2; IntAct=EBI-78579, EBI-625922; CC P06748; Q96MT8: CEP63; NbExp=2; IntAct=EBI-78579, EBI-741977; CC P06748; P10176: COX8A; NbExp=3; IntAct=EBI-78579, EBI-3904738; CC P06748; Q10570: CPSF1; NbExp=2; IntAct=EBI-78579, EBI-347859; CC P06748; P19525: EIF2AK2; NbExp=4; IntAct=EBI-78579, EBI-640775; CC P06748; P60228: EIF3E; NbExp=3; IntAct=EBI-78579, EBI-347740; CC P06748; Q13547: HDAC1; NbExp=2; IntAct=EBI-78579, EBI-301834; CC P06748; Q92769: HDAC2; NbExp=2; IntAct=EBI-78579, EBI-301821; CC P06748; Q9BXL5: HEMGN; NbExp=7; IntAct=EBI-78579, EBI-3916399; CC P06748; Q92876: KLK6; NbExp=3; IntAct=EBI-78579, EBI-2432309; CC P06748; O00505: KPNA3; NbExp=2; IntAct=EBI-78579, EBI-358297; CC P06748; O00629: KPNA4; NbExp=2; IntAct=EBI-78579, EBI-396343; CC P06748; Q71RC2: LARP4; NbExp=3; IntAct=EBI-78579, EBI-2878091; CC P06748; Q9NX58: LYAR; NbExp=2; IntAct=EBI-78579, EBI-713507; CC P06748; Q00987: MDM2; NbExp=5; IntAct=EBI-78579, EBI-389668; CC P06748; Q9BZQ8: NIBAN1; NbExp=7; IntAct=EBI-78579, EBI-6916466; CC P06748; Q86SE8: NPM2; NbExp=8; IntAct=EBI-78579, EBI-6658150; CC P06748; Q86SE8-2: NPM2; NbExp=5; IntAct=EBI-78579, EBI-12193061; CC P06748; Q8IZL8: PELP1; NbExp=4; IntAct=EBI-78579, EBI-716449; CC P06748; Q96BK5: PINX1; NbExp=13; IntAct=EBI-78579, EBI-721782; CC P06748; P49207: RPL34; NbExp=2; IntAct=EBI-78579, EBI-1051893; CC P06748; P62753: RPS6; NbExp=3; IntAct=EBI-78579, EBI-356625; CC P06748; Q9H4L4: SENP3; NbExp=7; IntAct=EBI-78579, EBI-2880236; CC P06748; O14746: TERT; NbExp=5; IntAct=EBI-78579, EBI-1772203; CC P06748; P05549: TFAP2A; NbExp=6; IntAct=EBI-78579, EBI-347351; CC P06748; P04637: TP53; NbExp=6; IntAct=EBI-78579, EBI-366083; CC P06748; P63104: YWHAZ; NbExp=2; IntAct=EBI-78579, EBI-347088; CC P06748; Q64364: Cdkn2a; Xeno; NbExp=2; IntAct=EBI-78579, EBI-1202287; CC P06748; P24938: L2; Xeno; NbExp=4; IntAct=EBI-78579, EBI-7481199; CC P06748; P68951: L2; Xeno; NbExp=5; IntAct=EBI-78579, EBI-7481182; CC P06748; P0DOE7: M; Xeno; NbExp=3; IntAct=EBI-78579, EBI-10042882; CC P06748; Q6UPD4: NP; Xeno; NbExp=4; IntAct=EBI-78579, EBI-25616456; CC P06748; P03427: PB2; Xeno; NbExp=3; IntAct=EBI-78579, EBI-8430745; CC P06748; B1Q2W9: pre-C/C; Xeno; NbExp=8; IntAct=EBI-78579, EBI-9081051; CC P06748; Q98147; Xeno; NbExp=2; IntAct=EBI-78579, EBI-626601; CC P06748-1; P49450-1: CENPA; NbExp=3; IntAct=EBI-354150, EBI-15826012; CC P06748-1; P63165: SUMO1; NbExp=3; IntAct=EBI-354150, EBI-80140; CC P06748-1; P04637: TP53; NbExp=3; IntAct=EBI-354150, EBI-366083; CC P06748-1; Q14669: TRIP12; NbExp=2; IntAct=EBI-354150, EBI-308443; CC P06748-2; Q86SE8-2: NPM2; NbExp=4; IntAct=EBI-354154, EBI-12193061; CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus {ECO:0000269|PubMed:19208757, CC ECO:0000269|PubMed:22528486, ECO:0000269|PubMed:25818168, CC ECO:0000269|PubMed:25956029}. Nucleus, nucleoplasm CC {ECO:0000269|PubMed:25818168}. Cytoplasm, cytoskeleton, microtubule CC organizing center, centrosome {ECO:0000269|PubMed:14654843}. CC Note=Generally nucleolar, but is translocated to the nucleoplasm in CC case of serum starvation or treatment with anticancer drugs. Has been CC found in the cytoplasm in patients with primary acute myelogenous CC leukemia (AML), but not with secondary AML. Co-localizes with the CC methylated form of RPS10 in the granular component (GC) region of the CC nucleolus. Colocalized with nucleolin and APEX1 in nucleoli. Isoform 1 CC of NEK2 is required for its localization to the centrosome during CC mitosis. Can shuttle between cytoplasm and nucleus (PubMed:38231884). CC {ECO:0000269|PubMed:38231884}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P06748-1; Sequence=Displayed; CC Name=2; CC IsoId=P06748-2; Sequence=VSP_003616; CC Name=3; CC IsoId=P06748-3; Sequence=VSP_043599; CC -!- PTM: Acetylated at C-terminal lysine residues, thereby increasing CC affinity to histones. {ECO:0000269|PubMed:16107701, CC ECO:0000269|Ref.17}. CC -!- PTM: ADP-ribosylated. CC -!- PTM: Phosphorylated at Ser-4 by PLK1 and PLK2. Phosphorylation at Ser-4 CC by PLK2 in S phase is required for centriole duplication and is CC sufficient to trigger centriole replication. Phosphorylation at Ser-4 CC by PLK1 takes place during mitosis. Phosphorylated by CDK2 at Ser-125 CC and Thr-199. Phosphorylation at Thr-199 may trigger initiation of CC centrosome duplication. Phosphorylated by CDK1 at Thr-199, Thr-219, CC Thr-234 and Thr-237 during cell mitosis. When these four sites are CC phosphorylated, RNA-binding activity seem to be abolished. May be CC phosphorylated at Ser-70 by NEK2. The Thr-199 phosphorylated form has CC higher affinity for ROCK2. CDK6 triggers Thr-199 phosphorylation when CC complexed to Kaposi's sarcoma herpesvirus (KSHV) V-cyclin, leading to CC viral reactivation by reducing viral LANA levels. CC {ECO:0000269|PubMed:11051553, ECO:0000269|PubMed:12058066, CC ECO:0000269|PubMed:12882984, ECO:0000269|PubMed:15190079, CC ECO:0000269|PubMed:15388344, ECO:0000269|PubMed:20333249, CC ECO:0000269|PubMed:20352051, ECO:0000269|Ref.17}. CC -!- PTM: Sumoylated by ARF. {ECO:0000269|PubMed:15897463}. CC -!- PTM: Ubiquitinated. Ubiquitination leads to proteasomal degradation. CC Deubiquitinated by USP36 (PubMed:19208757). CC {ECO:0000269|PubMed:19208757, ECO:0000269|PubMed:25818168}. CC -!- DISEASE: Note=A chromosomal aberration involving NPM1 is found in a CC form of non-Hodgkin lymphoma. Translocation t(2;5)(p23;q35) with ALK. CC The resulting chimeric NPM1-ALK protein homodimerize and the kinase CC becomes constitutively activated. {ECO:0000269|PubMed:8122112, CC ECO:0000269|PubMed:8633037}. CC -!- DISEASE: Note=A chromosomal aberration involving NPM1 is found in a CC form of acute promyelocytic leukemia. Translocation t(5;17)(q32;q11) CC with RARA. {ECO:0000269|PubMed:8562957}. CC -!- DISEASE: Note=A chromosomal aberration involving NPM1 is a cause of CC myelodysplastic syndrome (MDS). Translocation t(3;5)(q25.1;q34) with CC MLF1. {ECO:0000269|PubMed:8570204}. CC -!- DISEASE: Note=Defects in NPM1 are associated with acute myelogenous CC leukemia (AML). Mutations in exon 12 affecting the C-terminus of the CC protein are associated with an aberrant cytoplasmic location. CC {ECO:0000269|PubMed:15659725}. CC -!- SIMILARITY: Belongs to the nucleoplasmin family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/22/NPM1"; 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; M23613; AAA36380.1; -; mRNA. DR EMBL; M28699; AAA58386.1; -; mRNA. DR EMBL; M26697; AAA36385.1; -; mRNA. DR EMBL; U89321; AAB94739.1; -; Genomic_DNA. DR EMBL; U89309; AAB94739.1; JOINED; Genomic_DNA. DR EMBL; U89310; AAB94739.1; JOINED; Genomic_DNA. DR EMBL; U89311; AAB94739.1; JOINED; Genomic_DNA. DR EMBL; U89313; AAB94739.1; JOINED; Genomic_DNA. DR EMBL; U89314; AAB94739.1; JOINED; Genomic_DNA. DR EMBL; U89317; AAB94739.1; JOINED; Genomic_DNA. DR EMBL; U89319; AAB94739.1; JOINED; Genomic_DNA. DR EMBL; AB042278; BAB40600.1; -; mRNA. DR EMBL; AY740634; AAW67752.1; -; mRNA. DR EMBL; AY740635; AAW67753.1; -; mRNA. DR EMBL; AY740636; AAW67754.1; -; mRNA. DR EMBL; AY740637; AAW67755.1; -; mRNA. DR EMBL; AY740638; AAW67756.1; -; mRNA. DR EMBL; AY740639; AAW67757.1; -; mRNA. DR EMBL; AY740640; AAW67758.1; -; mRNA. DR EMBL; DQ303464; ABC40399.1; -; mRNA. DR EMBL; AY347529; AAQ24860.1; -; mRNA. DR EMBL; BT007011; AAP35657.1; -; mRNA. DR EMBL; AK290652; BAF83341.1; -; mRNA. DR EMBL; AB451236; BAG70050.1; -; mRNA. DR EMBL; AB451361; BAG70175.1; -; mRNA. DR EMBL; CH471062; EAW61443.1; -; Genomic_DNA. DR EMBL; CH471062; EAW61446.1; -; Genomic_DNA. DR EMBL; BC002398; AAH02398.1; -; mRNA. DR EMBL; BC008495; AAH08495.1; -; mRNA. DR EMBL; BC009623; AAH09623.1; -; mRNA. DR EMBL; BC012566; AAH12566.1; -; mRNA. DR EMBL; BC014349; AAH14349.1; -; mRNA. DR EMBL; BC016716; AAH16716.1; -; mRNA. DR EMBL; BC016768; AAH16768.1; -; mRNA. DR EMBL; BC016824; AAH16824.1; -; mRNA. DR EMBL; BC021668; AAH21668.1; -; mRNA. DR EMBL; BC021983; AAH21983.1; -; mRNA. DR EMBL; BC050628; AAH50628.1; -; mRNA. DR EMBL; BC107754; AAI07755.1; -; mRNA. DR EMBL; U41742; AAB00112.1; ALT_TERM; mRNA. DR EMBL; U41743; AAB00113.1; ALT_TERM; mRNA. DR EMBL; U04946; AAA58698.1; ALT_TERM; mRNA. DR EMBL; D45915; BAA08343.1; ALT_TERM; mRNA. DR EMBL; X16934; CAA34809.1; -; mRNA. DR EMBL; J02590; AAA36473.1; -; mRNA. DR EMBL; M31004; AAA36474.1; -; mRNA. DR CCDS; CCDS43399.1; -. [P06748-3] DR CCDS; CCDS4376.1; -. [P06748-1] DR CCDS; CCDS4377.1; -. [P06748-2] DR PIR; A33423; A32915. DR PIR; I38491; I38491. DR RefSeq; NP_001032827.1; NM_001037738.3. [P06748-3] DR RefSeq; NP_001341935.1; NM_001355006.2. [P06748-1] DR RefSeq; NP_002511.1; NM_002520.7. [P06748-1] DR RefSeq; NP_954654.1; NM_199185.4. [P06748-2] DR PDB; 2LLH; NMR; -; A=225-294. DR PDB; 2P1B; X-ray; 2.75 A; A/B/C/D/E/F/G/H/I/J=9-122. DR PDB; 2VXD; NMR; -; A=243-294. DR PDB; 5EHD; X-ray; 2.55 A; A/B/C/D/E/F/G/H/I/J/a/b/c/d/e/f/g/h/i/j=9-124. DR PDB; 7OBG; X-ray; 1.80 A; B=284-294. DR PDB; 7OBH; X-ray; 2.00 A; B=284-294. DR PDB; 8AH2; X-ray; 2.90 A; A/C=44-55. DR PDB; 8AS5; EM; 2.50 A; A/B/C/D/E=1-294. DR PDBsum; 2LLH; -. DR PDBsum; 2P1B; -. DR PDBsum; 2VXD; -. DR PDBsum; 5EHD; -. DR PDBsum; 7OBG; -. DR PDBsum; 7OBH; -. DR PDBsum; 8AH2; -. DR PDBsum; 8AS5; -. DR AlphaFoldDB; P06748; -. DR BMRB; P06748; -. DR EMDB; EMD-15606; -. DR SMR; P06748; -. DR BioGRID; 110929; 1283. DR CORUM; P06748; -. DR DIP; DIP-30932N; -. DR FunCoup; P06748; 1923. DR IntAct; P06748; 1134. DR MINT; P06748; -. DR STRING; 9606.ENSP00000296930; -. DR BindingDB; P06748; -. DR ChEMBL; CHEMBL5178; -. DR DrugBank; DB11638; Artenimol. DR DrugCentral; P06748; -. DR GlyCosmos; P06748; 4 sites, 1 glycan. DR GlyGen; P06748; 8 sites, 1 O-linked glycan (8 sites). DR iPTMnet; P06748; -. DR MetOSite; P06748; -. DR PhosphoSitePlus; P06748; -. DR SwissPalm; P06748; -. DR BioMuta; NPM1; -. DR DMDM; 114762; -. DR REPRODUCTION-2DPAGE; IPI00549248; -. DR jPOST; P06748; -. DR MassIVE; P06748; -. DR PaxDb; 9606-ENSP00000296930; -. DR PeptideAtlas; P06748; -. DR PRIDE; P06748; -. DR ProteomicsDB; 51927; -. [P06748-1] DR ProteomicsDB; 51928; -. [P06748-2] DR ProteomicsDB; 51929; -. [P06748-3] DR Pumba; P06748; -. DR TopDownProteomics; P06748-1; -. [P06748-1] DR TopDownProteomics; P06748-2; -. [P06748-2] DR TopDownProteomics; P06748-3; -. [P06748-3] DR Antibodypedia; 1828; 1350 antibodies from 48 providers. DR DNASU; 4869; -. DR Ensembl; ENST00000296930.10; ENSP00000296930.5; ENSG00000181163.15. [P06748-1] DR Ensembl; ENST00000351986.10; ENSP00000341168.6; ENSG00000181163.15. [P06748-2] DR Ensembl; ENST00000393820.2; ENSP00000377408.2; ENSG00000181163.15. [P06748-3] DR Ensembl; ENST00000517671.5; ENSP00000428755.1; ENSG00000181163.15. [P06748-1] DR Ensembl; ENST00000678280.1; ENSP00000503235.1; ENSG00000181163.15. [P06748-3] DR GeneID; 4869; -. DR KEGG; hsa:4869; -. DR MANE-Select; ENST00000296930.10; ENSP00000296930.5; NM_002520.7; NP_002511.1. DR UCSC; uc003mbh.4; human. [P06748-1] DR AGR; HGNC:7910; -. DR CIViC; 4869; 1 clinical assertion and 37 evidence items across 4 molecular profiles. DR ClinPGx; PA31712; -. DR CTD; 4869; -. DR DisGeNET; 4869; -. DR GeneCards; NPM1; -. DR HGNC; HGNC:7910; NPM1. DR HPA; ENSG00000181163; Low tissue specificity. DR MalaCards; NPM1; -. DR MIM; 164040; gene. DR OpenTargets; ENSG00000181163; -. DR Orphanet; 98834; Acute myeloblastic leukemia with maturation. DR Orphanet; 98833; Acute myeloblastic leukemia without maturation. DR Orphanet; 402026; Acute myeloid leukemia with NPM1 somatic mutations. DR Orphanet; 520; Acute promyelocytic leukemia. DR Orphanet; 1775; Dyskeratosis congenita. DR Orphanet; 98842; Lymphomatoid papulosis. DR Orphanet; 300865; Primary cutaneous anaplastic large cell lymphoma. DR VEuPathDB; HostDB:ENSG00000181163; -. DR eggNOG; KOG0488; Eukaryota. DR GeneTree; ENSGT00940000153052; -. DR HOGENOM; CLU_058838_0_0_1; -. DR InParanoid; P06748; -. DR OMA; MEKGMNL; -. DR OrthoDB; 9946910at2759; -. DR PAN-GO; P06748; 16 GO annotations based on evolutionary models. DR PhylomeDB; P06748; -. DR PathwayCommons; P06748; -. DR Reactome; R-HSA-180746; Nuclear import of Rev protein. DR Reactome; R-HSA-3899300; SUMOylation of transcription cofactors. DR Reactome; R-HSA-606279; Deposition of new CENPA-containing nucleosomes at the centromere. DR Reactome; R-HSA-6804115; TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain. DR Reactome; R-HSA-8869496; TFAP2A acts as a transcriptional repressor during retinoic acid induced cell differentiation. DR Reactome; R-HSA-9692914; SARS-CoV-1-host interactions. DR Reactome; R-HSA-9700645; ALK mutants bind TKIs. DR Reactome; R-HSA-9725370; Signaling by ALK fusions and activated point mutants. DR Reactome; R-HSA-9725371; Nuclear events stimulated by ALK signaling in cancer. DR Reactome; R-HSA-9833482; PKR-mediated signaling. DR SignaLink; P06748; -. DR SIGNOR; P06748; -. DR Agora; ENSG00000181163; -. DR BioGRID-ORCS; 4869; 540 hits in 1103 CRISPR screens. DR CD-CODE; 6AB35885; Synthetic Condensate 000052. DR CD-CODE; 71F78BB1; Synthetic Condensate 000049. DR CD-CODE; 80B4651A; Granular component. DR CD-CODE; 8C2F96ED; Centrosome. DR CD-CODE; 91857CE7; Nucleolus. DR CD-CODE; 9E412E21; Synthetic Condensate 000044. DR CD-CODE; A3AA02E8; Synthetic Condensate 000061. DR CD-CODE; CBF57B02; Synthetic Condensate 000043. DR CD-CODE; D551D4B1; Synthetic Condensate 000051. DR CD-CODE; DEE660B4; Stress granule. DR ChiTaRS; NPM1; human. DR EvolutionaryTrace; P06748; -. DR GeneWiki; NPM1; -. DR GenomeRNAi; 4869; -. DR Pharos; P06748; Tbio. DR PRO; PR:P06748; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; P06748; protein. DR Bgee; ENSG00000181163; Expressed in calcaneal tendon and 191 other cell types or tissues. DR ExpressionAtlas; P06748; baseline and differential. DR GO; GO:0005813; C:centrosome; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB. DR GO; GO:0001652; C:granular component; TAS:Reactome. DR GO; GO:0015934; C:large ribosomal subunit; IEA:Ensembl. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0016607; C:nuclear speck; IEA:Ensembl. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; IDA:CAFA. DR GO; GO:0032993; C:protein-DNA complex; IDA:CAFA. DR GO; GO:1990904; C:ribonucleoprotein complex; IDA:MGI. DR GO; GO:0015935; C:small ribosomal subunit; IEA:Ensembl. DR GO; GO:0031616; C:spindle pole centrosome; IDA:UniProtKB. DR GO; GO:0003682; F:chromatin binding; IBA:GO_Central. DR GO; GO:0001046; F:core promoter sequence-specific DNA binding; IDA:CAFA. DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:CAFA. DR GO; GO:0042393; F:histone binding; IDA:UniProtKB. DR GO; GO:0060090; F:molecular adaptor activity; IDA:UniProt. DR GO; GO:0051059; F:NF-kappaB binding; IDA:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB. DR GO; GO:0004860; F:protein kinase inhibitor activity; IDA:UniProtKB. DR GO; GO:0043023; F:ribosomal large subunit binding; IDA:MGI. DR GO; GO:0043024; F:ribosomal small subunit binding; IDA:MGI. DR GO; GO:0003723; F:RNA binding; IDA:UniProtKB. DR GO; GO:0019843; F:rRNA binding; IPI:DisProt. DR GO; GO:0030957; F:Tat protein binding; IDA:UniProtKB. DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB. DR GO; GO:0051082; F:unfolded protein binding; IDA:UniProtKB. DR GO; GO:0006884; P:cell volume homeostasis; IEA:Ensembl. DR GO; GO:0034644; P:cellular response to UV; IDA:CAFA. DR GO; GO:0090398; P:cellular senescence; IMP:GO_Central. DR GO; GO:0007098; P:centrosome cycle; IMP:UniProtKB. DR GO; GO:0006338; P:chromatin remodeling; IBA:GO_Central. DR GO; GO:0006281; P:DNA repair; IDA:UniProtKB. DR GO; GO:0008104; P:intracellular protein localization; IDA:UniProtKB. DR GO; GO:0006886; P:intracellular protein transport; TAS:UniProtKB. DR GO; GO:0030225; P:macrophage differentiation; IDA:UniProt. DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:UniProtKB. DR GO; GO:0010826; P:negative regulation of centrosome duplication; IMP:UniProtKB. DR GO; GO:0048025; P:negative regulation of mRNA splicing, via spliceosome; IEA:Ensembl. DR GO; GO:0044387; P:negative regulation of protein kinase activity by regulation of protein phosphorylation; IDA:UniProtKB. DR GO; GO:0006913; P:nucleocytoplasmic transport; IDA:UniProtKB. DR GO; GO:0006334; P:nucleosome assembly; IDA:UniProtKB. DR GO; GO:1902751; P:positive regulation of cell cycle G2/M phase transition; IDA:UniProtKB. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:UniProtKB. DR GO; GO:0010825; P:positive regulation of centrosome duplication; IEA:Ensembl. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IMP:UniProtKB. DR GO; GO:1904751; P:positive regulation of protein localization to nucleolus; IEA:Ensembl. DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IEA:Ensembl. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:CAFA. DR GO; GO:0045727; P:positive regulation of translation; IDA:UniProtKB. DR GO; GO:0006606; P:protein import into nucleus; IDA:UniProt. DR GO; GO:0050821; P:protein stabilization; IEA:Ensembl. DR GO; GO:0001558; P:regulation of cell growth; IEA:Ensembl. DR GO; GO:0046599; P:regulation of centriole replication; IMP:UniProtKB. DR GO; GO:0010824; P:regulation of centrosome duplication; IBA:GO_Central. DR GO; GO:0043516; P:regulation of DNA damage response, signal transduction by p53 class mediator; IEA:Ensembl. DR GO; GO:0060735; P:regulation of eIF2 alpha phosphorylation by dsRNA; IDA:UniProtKB. DR GO; GO:1902629; P:regulation of mRNA stability involved in cellular response to UV; IMP:UniProtKB. DR GO; GO:0042273; P:ribosomal large subunit biogenesis; IBA:GO_Central. DR GO; GO:0000055; P:ribosomal large subunit export from nucleus; IBA:GO_Central. DR GO; GO:0042274; P:ribosomal small subunit biogenesis; IBA:GO_Central. DR GO; GO:0000056; P:ribosomal small subunit export from nucleus; IBA:GO_Central. DR GO; GO:0042255; P:ribosome assembly; TAS:UniProtKB. DR GO; GO:0007165; P:signal transduction; NAS:UniProtKB. DR DisProt; DP01474; -. DR FunFam; 1.10.10.2100:FF:000001; Nucleophosmin 1; 1. DR FunFam; 2.60.120.340:FF:000001; Nucleophosmin 1; 1. DR Gene3D; 1.10.10.2100; -; 1. DR Gene3D; 2.60.120.340; Nucleoplasmin core domain; 1. DR IDEAL; IID00295; -. DR InterPro; IPR032569; NPM1_C. DR InterPro; IPR004301; Nucleoplasmin. DR InterPro; IPR024057; Nucleoplasmin_core_dom. DR InterPro; IPR036824; Nucleoplasmin_core_dom_sf. DR PANTHER; PTHR22747:SF28; NUCLEOPHOSMIN; 1. DR PANTHER; PTHR22747; NUCLEOPLASMIN; 1. DR Pfam; PF16276; NPM1-C; 1. DR Pfam; PF03066; Nucleoplasmin; 1. DR SUPFAM; SSF69203; Nucleoplasmin-like core domain; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; ADP-ribosylation; Alternative splicing; KW Chaperone; Chromosomal rearrangement; Cytoplasm; Cytoskeleton; KW Direct protein sequencing; Disulfide bond; Host-virus interaction; KW Isopeptide bond; Nucleus; Phosphoprotein; Proteomics identification; KW Proto-oncogene; Reference proteome; RNA-binding; Ubl conjugation. FT CHAIN 1..294 FT /note="Nucleophosmin" FT /id="PRO_0000219481" FT REGION 1..186 FT /note="Required for interaction with SENP3" FT REGION 1..117 FT /note="Necessary for interaction with APEX1" FT /evidence="ECO:0000269|PubMed:19188445" FT REGION 120..247 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 187..215 FT /note="Interaction with NOP2" FT /evidence="ECO:0000269|PubMed:8089149" FT REGION 243..294 FT /note="Required for nucleolar localization" FT MOTIF 152..157 FT /note="Nuclear localization signal" FT /evidence="ECO:0000255" FT MOTIF 191..197 FT /note="Nuclear localization signal" FT /evidence="ECO:0000255" FT COMPBIAS 120..132 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 161..187 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 188..200 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 202..222 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 223..235 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 55 FT /note="Interaction between pentamers" FT /evidence="ECO:0000250" FT SITE 80 FT /note="Interaction between pentamers" FT /evidence="ECO:0000250" FT SITE 175..176 FT /note="Breakpoint for translocation to form NPM1-MLF1" FT /evidence="ECO:0000269|PubMed:8570204" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0000269|Ref.17, ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:22223895" FT MOD_RES 4 FT /note="Phosphoserine; by PLK1 and PLK2" FT /evidence="ECO:0000269|PubMed:15190079, FT ECO:0000269|PubMed:20352051, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 10 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 32 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 43 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 67 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q61937" FT MOD_RES 70 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:17924679, ECO:0007744|PubMed:18220336, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 75 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 95 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 125 FT /note="Phosphoserine; by CDK2" FT /evidence="ECO:0000269|Ref.17, ECO:0007744|PubMed:18220336, FT ECO:0007744|PubMed:18318008, ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 137 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 139 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" FT MOD_RES 150 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0007744|PubMed:16916647, FT ECO:0007744|PubMed:19608861" FT MOD_RES 154 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:16916647" FT MOD_RES 199 FT /note="Phosphothreonine; by CDK1, CDK2 and CDK6" FT /evidence="ECO:0000269|PubMed:12058066, FT ECO:0000269|PubMed:20333249, ECO:0007744|PubMed:17924679, FT ECO:0007744|PubMed:20068231" FT MOD_RES 207 FT /note="ADP-ribosylserine" FT /evidence="ECO:0000269|PubMed:28190768" FT MOD_RES 212 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:16107701, FT ECO:0007744|PubMed:16916647" FT MOD_RES 219 FT /note="Phosphothreonine; by CDK1" FT /evidence="ECO:0000305|PubMed:12058066" FT MOD_RES 227 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 229 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:16107701" FT MOD_RES 230 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000269|PubMed:16107701" FT MOD_RES 234 FT /note="Phosphothreonine; by CDK1" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 237 FT /note="Phosphothreonine; by CDK1" FT /evidence="ECO:0000269|PubMed:12058066, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163" FT MOD_RES 242 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 243 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 250 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000269|PubMed:16107701" FT MOD_RES 254 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17924679, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 257 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000269|PubMed:16107701, FT ECO:0007744|PubMed:19608861" FT MOD_RES 260 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 267 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 267 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q61937" FT MOD_RES 273 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 279 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18220336, FT ECO:0007744|PubMed:20068231" FT MOD_RES 292 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:16107701" FT CROSSLNK 27 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:25218447" FT CROSSLNK 32 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1); alternate" FT /evidence="ECO:0007744|PubMed:25114211" FT CROSSLNK 32 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:25114211, FT ECO:0007744|PubMed:25218447, ECO:0007744|PubMed:25755297, FT ECO:0007744|PubMed:25772364, ECO:0007744|PubMed:28112733" FT CROSSLNK 141 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 150 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 215 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:25772364, FT ECO:0007744|PubMed:28112733" FT CROSSLNK 230 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO); alternate" FT CROSSLNK 248 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1); alternate" FT /evidence="ECO:0007744|PubMed:25114211" FT CROSSLNK 248 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:25114211, FT ECO:0007744|PubMed:25218447, ECO:0007744|PubMed:28112733" FT CROSSLNK 250 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:25218447, FT ECO:0007744|PubMed:28112733" FT CROSSLNK 257 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1); alternate" FT /evidence="ECO:0007744|PubMed:25114211" FT CROSSLNK 257 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:25114211, FT ECO:0007744|PubMed:28112733" FT CROSSLNK 263 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO); alternate" FT /evidence="ECO:0000269|PubMed:15897463" FT CROSSLNK 263 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 267 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1); alternate" FT /evidence="ECO:0007744|PubMed:25114211" FT CROSSLNK 267 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 273 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:28112733" FT VAR_SEQ 195..223 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_003616" FT VAR_SEQ 258..294 FT /note="GGSLPKVEAKFINYVKNCFRMTDQEAIQDLWQWRKSL -> AH (in FT isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.5" FT /id="VSP_043599" FT MUTAGEN 4 FT /note="S->A: Abolishes phosphorylation by PLK2 and impairs FT centriole duplication." FT /evidence="ECO:0000269|PubMed:20352051" FT MUTAGEN 4 FT /note="S->D,E: Mimicks phosphorylation state, inducing FT accumulation of centrioles." FT /evidence="ECO:0000269|PubMed:20352051" FT MUTAGEN 95 FT /note="T->A: Does not affect phosphorylation by PLK2." FT /evidence="ECO:0000269|PubMed:20352051" FT MUTAGEN 125 FT /note="S->A: Does not affect phosphorylation by PLK2." FT /evidence="ECO:0000269|PubMed:20352051" FT MUTAGEN 199 FT /note="T->A: Partial loss of phosphorylation. Does not FT affect phosphorylation by PLK2." FT /evidence="ECO:0000269|PubMed:12058066, FT ECO:0000269|PubMed:20352051" FT MUTAGEN 219 FT /note="T->A: Partial loss of phosphorylation." FT /evidence="ECO:0000269|PubMed:12058066" FT MUTAGEN 234 FT /note="T->A: Partial loss of phosphorylation; when FT associated with A-237." FT /evidence="ECO:0000269|PubMed:12058066" FT MUTAGEN 237 FT /note="T->A: Partial loss of phosphorylation." FT /evidence="ECO:0000269|PubMed:12058066" FT MUTAGEN 248 FT /note="K->A: Partial destabilization of the structure." FT /evidence="ECO:0000269|PubMed:18511415" FT MUTAGEN 250 FT /note="K->A: Increase in the stabilization of the FT structure." FT /evidence="ECO:0000269|PubMed:18511415" FT MUTAGEN 263 FT /note="K->A: Increase in the stabilization of the structure FT and partial delocalization to the nucleoplasm. Complete FT delocalization to the nucleoplasm; when associated with A- FT 267." FT /evidence="ECO:0000269|PubMed:18259216" FT MUTAGEN 263 FT /note="K->R: No change in the sumoylation level." FT /evidence="ECO:0000269|PubMed:18259216" FT MUTAGEN 267 FT /note="K->A: Increase in the stabilization of the structure FT and complete delocalization to the nucleoplasm. Complete FT delocalization to the nucleoplasm; when associated with A- FT 263." FT /evidence="ECO:0000269|PubMed:18511415" FT MUTAGEN 268 FT /note="F->A: Complete destabilization of the structure and FT loss of nucleolus localization; when associated with A- FT 276." FT /evidence="ECO:0000269|PubMed:18511415" FT MUTAGEN 276 FT /note="F->A: Complete destabilization of the structure and FT loss of nucleolus localization; when associated with A- FT 268." FT /evidence="ECO:0000269|PubMed:18511415" FT MUTAGEN 288 FT /note="W->A: Complete destabilization of the structure; FT when associated with A-290." FT /evidence="ECO:0000269|PubMed:18511415" FT MUTAGEN 290 FT /note="W->A: Partial destabilization of the structure. FT Complete destabilization of the structure; when associated FT with A-288." FT /evidence="ECO:0000269|PubMed:18511415" FT CONFLICT 80 FT /note="K -> E (in Ref. 13; AAH21983)" FT /evidence="ECO:0000305" FT CONFLICT 129 FT /note="E -> D (in Ref. 22; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 168 FT /note="Missing (in Ref. 6; AAW67758)" FT /evidence="ECO:0000305" FT CONFLICT 178 FT /note="D -> G (in Ref. 13; AAH16768)" FT /evidence="ECO:0000305" FT CONFLICT 183 FT /note="D -> N (in Ref. 11; BAG70175/BAG70050)" FT /evidence="ECO:0000305" FT CONFLICT 213 FT /note="D -> P (in Ref. 23; AAA36473/AAA36474)" FT /evidence="ECO:0000305" FT CONFLICT 214 FT /note="S -> L (in Ref. 21; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 216 FT /note="P -> S (in Ref. 23; AAA36473)" FT /evidence="ECO:0000305" FT CONFLICT 219..221 FT /note="TPR -> SSS (in Ref. 23; AAA36473)" FT /evidence="ECO:0000305" FT CONFLICT 231 FT /note="Q -> R (in Ref. 8; AAQ24860)" FT /evidence="ECO:0000305" FT CONFLICT 271 FT /note="Y -> C (in Ref. 13; AAH16768)" FT /evidence="ECO:0000305" FT CONFLICT 287 FT /note="L -> F (in Ref. 13; AAH12566)" FT /evidence="ECO:0000305" FT CONFLICT 288..294 FT /note="WQWRKSL -> CLAVEEVSLRK (in Ref. 6; AAW67752/ FT AAW67755)" FT /evidence="ECO:0000305" FT CONFLICT 288..294 FT /note="WQWRKSL -> CMAVEEVSLRK (in Ref. 6; AAW67753 and 7; FT ABC40399)" FT /evidence="ECO:0000305" FT CONFLICT 288..294 FT /note="WQWRKSL -> CVAVEEVSLRK (in Ref. 6; AAW67754)" FT /evidence="ECO:0000305" FT CONFLICT 290..294 FT /note="WRKSL -> SLAQVSLRK (in Ref. 6; AAW67756)" FT /evidence="ECO:0000305" FT CONFLICT 290..294 FT /note="WRKSL -> SLEKVSLRK (in Ref. 6; AAW67757)" FT /evidence="ECO:0000305" FT STRAND 15..24 FT /evidence="ECO:0007829|PDB:5EHD" FT STRAND 29..31 FT /evidence="ECO:0007829|PDB:5EHD" FT STRAND 40..49 FT /evidence="ECO:0007829|PDB:5EHD" FT STRAND 58..65 FT /evidence="ECO:0007829|PDB:5EHD" FT STRAND 71..80 FT /evidence="ECO:0007829|PDB:5EHD" FT TURN 81..83 FT /evidence="ECO:0007829|PDB:5EHD" FT STRAND 84..94 FT /evidence="ECO:0007829|PDB:5EHD" FT STRAND 96..104 FT /evidence="ECO:0007829|PDB:5EHD" FT STRAND 109..117 FT /evidence="ECO:0007829|PDB:5EHD" FT HELIX 244..257 FT /evidence="ECO:0007829|PDB:2LLH" FT HELIX 265..275 FT /evidence="ECO:0007829|PDB:2LLH" FT HELIX 281..292 FT /evidence="ECO:0007829|PDB:2LLH" FT MOD_RES P06748-3:254 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES P06748-3:257 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" SQ SEQUENCE 294 AA; 32575 MW; 620BC7BA2E4A0054 CRC64; MEDSMDMDMS PLRPQNYLFG CELKADKDYH FKVDNDENEH QLSLRTVSLG AGAKDELHIV EAEAMNYEGS PIKVTLATLK MSVQPTVSLG GFEITPPVVL RLKCGSGPVH ISGQHLVAVE EDAESEDEEE EDVKLLSISG KRSAPGGGSK VPQKKVKLAA DEDDDDDDEE DDDEDDDDDD FDDEEAEEKA PVKKSIRDTP AKNAQKSNQN GKDSKPSSTP RSKGQESFKK QEKTPKTPKG PSSVEDIKAK MQASIEKGGS LPKVEAKFIN YVKNCFRMTD QEAIQDLWQW RKSL // ID S20A1_HUMAN Reviewed; 679 AA. AC Q8WUM9; Q08344; Q6DHX8; Q9UQ82; DT 20-DEC-2005, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2002, sequence version 1. DT 28-JAN-2026, entry version 170. DE RecName: Full=Sodium-dependent phosphate transporter 1; DE AltName: Full=Gibbon ape leukemia virus receptor 1; DE Short=GLVR-1; DE AltName: Full=Leukemia virus receptor 1 homolog; DE AltName: Full=Phosphate transporter 1; DE Short=PiT-1; DE AltName: Full=Solute carrier family 20 member 1; GN Name=SLC20A1; Synonyms=GLVR1, PIT1; 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], FUNCTION (MICROBIAL INFECTION), AND TISSUE RP SPECIFICITY. RX PubMed=2078500; RA O'Hara B., Johann S.V., Klinger H.P., Blair D.G., Rubinson H., Dunn K.J., RA Sass P., Vitek S.M., Robins T.; RT "Characterization of a human gene conferring sensitivity to infection by RT gibbon ape leukemia virus."; RL Cell Growth Differ. 1:119-127(1990). RN [2] 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Kidney, and Skin; 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 [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-646. RX PubMed=9889306; DOI=10.1016/s0378-1119(98)00572-1; RA Palmer G., Manen D., Bonjour J.-P., Caverzasio J.; RT "Characterization of the human Glvr-1 phosphate transporter/retrovirus RT receptor gene and promoter region."; RL Gene 226:25-33(1999). RN [5] RP FUNCTION (MICROBIAL INFECTION). RX PubMed=1309898; DOI=10.1128/jvi.66.2.1219-1222.1992; RA Takeuchi Y., Vile R.G., Simpson G., O'Hara B., Collins M.K., Weiss R.A.; RT "Feline leukemia virus subgroup B uses the same cell surface receptor as RT gibbon ape leukemia virus."; RL J. Virol. 66:1219-1222(1992). RN [6] RP IDENTIFICATION. RX PubMed=1531369; DOI=10.1128/jvi.66.3.1635-1640.1992; RA Johann S.V., Gibbons J.J., O'Hara B.; RT "GLVR1, a receptor for gibbon ape leukemia virus, is homologous to a RT phosphate permease of Neurospora crassa and is expressed at high levels in RT the brain and thymus."; RL J. Virol. 66:1635-1640(1992). RN [7] RP MUTAGENESIS OF 550-ASP--VAL-558 AND ASP-550, AND REGION. RX PubMed=8411375; DOI=10.1128/jvi.67.11.6733-6736.1993; RA Johann S.V., van Zeijl M., Cekleniak J., O'Hara B.; RT "Definition of a domain of GLVR1 which is necessary for infection by gibbon RT ape leukemia virus and which is highly polymorphic between species."; RL J. Virol. 67:6733-6736(1993). RN [8] RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND TRANSPORTER ACTIVITY. RX PubMed=7929240; DOI=10.1016/s0021-9258(18)47267-5; RA Olah Z., Lehel C., Anderson W.B., Eiden M.V., Wilson C.A.; RT "The cellular receptor for gibbon ape leukemia virus is a novel high RT affinity sodium-dependent phosphate transporter."; RL J. Biol. Chem. 269:25426-25431(1994). RN [9] RP FUNCTION (MICROBIAL FUNCTION). RX PubMed=7966619; DOI=10.1128/jvi.68.12.8270-8276.1994; RA Miller D.G., Miller A.D.; RT "A family of retroviruses that utilize related phosphate transporters for RT cell entry."; RL J. Virol. 68:8270-8276(1994). RN [10] RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, INDUCTION, AND TRANSPORTER RP ACTIVITY. RX PubMed=8041748; DOI=10.1073/pnas.91.15.7071; RA Kavanaugh M.P., Miller D.G., Zhang W., Law W., Kozak S.L., Kabat D., RA Miller A.D.; RT "Cell-surface receptors for gibbon ape leukemia virus and amphotropic RT murine retrovirus are inducible sodium-dependent phosphate symporters."; RL Proc. Natl. Acad. Sci. U.S.A. 91:7071-7075(1994). RN [11] RP FUNCTION, AND TRANSPORTER ACTIVITY. RX PubMed=11009570; DOI=10.1161/01.res.87.7.e10; RA Jono S., McKee M.D., Murry C.E., Shioi A., Nishizawa Y., Mori K., Morii H., RA Giachelli C.M.; RT "Phosphate regulation of vascular smooth muscle cell calcification."; RL Circ. Res. 87:E10-E17(2000). RN [12] RP FUNCTION (MICROBIAL INFECTION), MUTAGENESIS OF ASP-550, AND REGION. RX PubMed=12097582; DOI=10.1128/jvi.76.15.7683-7693.2002; RA Farrell K.B., Russ J.L., Murthy R.K., Eiden M.V.; RT "Reassessing the role of region A in Pit1-mediated viral entry."; RL J. Virol. 76:7683-7693(2002). RN [13] RP INDUCTION. RX PubMed=15641067; DOI=10.1002/art.20748; RA Cecil D.L., Rose D.M., Terkeltaub R., Liu-Bryan R.; RT "Role of interleukin-8 in PiT-1 expression and CXCR1-mediated inorganic RT phosphate uptake in chondrocytes."; RL Arthritis Rheum. 52:144-154(2005). RN [14] RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND TRANSPORTER ACTIVITY. RX PubMed=16790504; DOI=10.1152/ajpcell.00015.2006; RA Boettger P., Hede S.E., Grunnet M., Hoyer B., Klaerke D.A., Pedersen L.; RT "Characterization of transport mechanisms and determinants critical for RT Na+-dependent Pi symport of the PiT family paralogs human PiT1 and PiT2."; RL Am. J. Physiol. 291:C1377-C1387(2006). RN [15] RP FUNCTION, TRANSPORTER ACTIVITY, AND STOICHIOMETRY. RX PubMed=17494632; DOI=10.1152/ajpcell.00064.2007; RA Ravera S., Virkki L.V., Murer H., Forster I.C.; RT "Deciphering PiT transport kinetics and substrate specificity using RT electrophysiology and flux measurements."; RL Am. J. Physiol. 293:C606-C620(2007). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-269, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [18] RP FUNCTION, TRANSPORTER ACTIVITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF RP SER-128. RX PubMed=19726692; DOI=10.1074/jbc.m109.053132; RA Beck L., Leroy C., Salauen C., Margall-Ducos G., Desdouets C., RA Friedlander G.; RT "Identification of a novel function of PiT1 critical for cell proliferation RT and independent of its phosphate transport activity."; RL J. Biol. Chem. 284:31363-31374(2009). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-265 AND SER-269, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=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). CC -!- FUNCTION: Sodium-phosphate symporter which preferentially transports CC the monovalent form of phosphate with a stoichiometry of two sodium CC ions per phosphate ion (PubMed:11009570, PubMed:16790504, CC PubMed:17494632, PubMed:19726692, PubMed:7929240, PubMed:8041748). May CC play a role in extracellular matrix and cartilage calcification as well CC as in vascular calcification (PubMed:11009570). Essential for cell CC proliferation but this function is independent of its phosphate CC transporter activity (PubMed:19726692). {ECO:0000269|PubMed:11009570, CC ECO:0000269|PubMed:16790504, ECO:0000269|PubMed:17494632, CC ECO:0000269|PubMed:19726692, ECO:0000269|PubMed:7929240, CC ECO:0000269|PubMed:8041748}. CC -!- FUNCTION: (Microbial infection) May function as a retroviral receptor CC as it confers human cells susceptibility to infection to Gibbon Ape CC Leukemia Virus (GaLV), Simian sarcoma-associated virus (SSAV) and CC Feline leukemia virus subgroup B (FeLV-B) as well as 10A1 murine CC leukemia virus (10A1 MLV). {ECO:0000269|PubMed:12097582, CC ECO:0000269|PubMed:1309898, ECO:0000269|PubMed:2078500, CC ECO:0000269|PubMed:7966619}. CC -!- CATALYTIC ACTIVITY: CC Reaction=2 Na(+)(out) + phosphate(out) = 2 Na(+)(in) + phosphate(in); CC Xref=Rhea:RHEA:71259, ChEBI:CHEBI:29101, ChEBI:CHEBI:43474; CC Evidence={ECO:0000269|PubMed:11009570, ECO:0000269|PubMed:16790504, CC ECO:0000269|PubMed:17494632, ECO:0000269|PubMed:19726692, CC ECO:0000269|PubMed:7929240, ECO:0000269|PubMed:8041748}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=24.1 uM for phosphate {ECO:0000269|PubMed:7929240, CC ECO:0000269|PubMed:8041748}; CC KM=322.5 uM for phosphate {ECO:0000269|PubMed:16790504}; CC Vmax=1.9 nmol/min/mg enzyme (in the presence of 0.05-2 mM phosphate) CC {ECO:0000269|PubMed:7929240, ECO:0000269|PubMed:8041748}; CC Note=With an increase in pH, a decrease in phosphate uptake is CC observed.; CC pH dependence: CC Optimum pH is 6.5 and 7.5. {ECO:0000269|PubMed:7929240, CC ECO:0000269|PubMed:8041748}; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:19726692}; CC Multi-pass membrane protein {ECO:0000255}. CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. CC {ECO:0000269|PubMed:2078500}. CC -!- INDUCTION: By phosphate deprivation as well as by IL8/interleukin-8 in CC hypertrophic chondrocytes. {ECO:0000269|PubMed:15641067, CC ECO:0000269|PubMed:8041748}. CC -!- DOMAIN: Region A confers human cells susceptibility to infection by CC Gibbon Ape Leukemia Virus (GaLV) and Feline leukemia virus subgroup B CC (FeLV-B). Substitution of Human SLC20A1 region A by region A of murine CC SLC20A1 prevents viral infection. CC -!- SIMILARITY: Belongs to the inorganic phosphate transporter (PiT) (TC CC 2.A.20) family. {ECO:0000305}. 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; L20859; AAA52572.1; -; mRNA. DR EMBL; AC079922; AAY14922.1; -; Genomic_DNA. DR EMBL; BC019944; AAH19944.1; -; mRNA. DR EMBL; BC075818; AAH75818.1; -; mRNA. DR EMBL; AH007490; AAD20286.1; -; Genomic_DNA. DR CCDS; CCDS2099.1; -. DR PIR; I52822; I52822. DR RefSeq; NP_005406.3; NM_005415.4. DR AlphaFoldDB; Q8WUM9; -. DR SMR; Q8WUM9; -. DR BioGRID; 112462; 147. DR FunCoup; Q8WUM9; 855. DR IntAct; Q8WUM9; 79. DR MINT; Q8WUM9; -. DR STRING; 9606.ENSP00000272542; -. DR BindingDB; Q8WUM9; -. DR ChEMBL; CHEMBL4295909; -. DR DrugBank; DB11348; Calcium Phosphate. DR DrugBank; DB14481; Calcium phosphate dihydrate. DR DrugBank; DB01250; Olsalazine. DR DrugBank; DB14502; Sodium phosphate, dibasic. DR DrugBank; DB09449; Sodium phosphate, monobasic. DR DrugBank; DB14503; Sodium phosphate, monobasic, unspecified form. DR DrugBank; DB09436; Technetium Tc-99m succimer. DR TCDB; 2.A.20.2.7; the inorganic phosphate transporter (pit) family. DR GlyConnect; 2080; 1 N-Linked glycan (1 site). DR GlyCosmos; Q8WUM9; 1 site, 2 glycans. DR GlyGen; Q8WUM9; 3 sites, 2 N-linked glycans (1 site), 1 O-linked glycan (1 site). DR iPTMnet; Q8WUM9; -. DR PhosphoSitePlus; Q8WUM9; -. DR SwissPalm; Q8WUM9; -. DR BioMuta; SLC20A1; -. DR DMDM; 74730735; -. DR jPOST; Q8WUM9; -. DR MassIVE; Q8WUM9; -. DR PaxDb; 9606-ENSP00000272542; -. DR PeptideAtlas; Q8WUM9; -. DR ProteomicsDB; 74696; -. DR Pumba; Q8WUM9; -. DR Antibodypedia; 33281; 174 antibodies from 29 providers. DR DNASU; 6574; -. DR Ensembl; ENST00000272542.8; ENSP00000272542.3; ENSG00000144136.12. DR GeneID; 6574; -. DR KEGG; hsa:6574; -. DR MANE-Select; ENST00000272542.8; ENSP00000272542.3; NM_005415.5; NP_005406.3. DR UCSC; uc002tib.4; human. DR AGR; HGNC:10946; -. DR ClinPGx; PA35833; -. DR CTD; 6574; -. DR DisGeNET; 6574; -. DR GeneCards; SLC20A1; -. DR HGNC; HGNC:10946; SLC20A1. DR HPA; ENSG00000144136; Low tissue specificity. DR MIM; 137570; gene. DR OpenTargets; ENSG00000144136; -. DR VEuPathDB; HostDB:ENSG00000144136; -. DR eggNOG; KOG2493; Eukaryota. DR GeneTree; ENSGT00390000014879; -. DR HOGENOM; CLU_015355_3_1_1; -. DR InParanoid; Q8WUM9; -. DR OMA; AGFWFFG; -. DR OrthoDB; 260807at2759; -. DR PAN-GO; Q8WUM9; 2 GO annotations based on evolutionary models. DR PhylomeDB; Q8WUM9; -. DR BioCyc; MetaCyc:ENSG00000144136-MONOMER; -. DR BRENDA; 7.3.2.1; 2681. DR PathwayCommons; Q8WUM9; -. DR Reactome; R-HSA-427652; Sodium-coupled phosphate cotransporters. DR SignaLink; Q8WUM9; -. DR SIGNOR; Q8WUM9; -. DR Agora; ENSG00000144136; -. DR BioGRID-ORCS; 6574; 108 hits in 1162 CRISPR screens. DR ChiTaRS; SLC20A1; human. DR GeneWiki; SLC20A1; -. DR GenomeRNAi; 6574; -. DR Pharos; Q8WUM9; Tbio. DR PRO; PR:Q8WUM9; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q8WUM9; protein. DR Bgee; ENSG00000144136; Expressed in mucosa of transverse colon and 202 other cell types or tissues. DR ExpressionAtlas; Q8WUM9; baseline and differential. DR GO; GO:0016020; C:membrane; TAS:ProtInc. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0005316; F:high-affinity phosphate:sodium symporter activity; IEA:Ensembl. DR GO; GO:0005315; F:phosphate transmembrane transporter activity; IBA:GO_Central. DR GO; GO:0038023; F:signaling receptor activity; TAS:ProtInc. DR GO; GO:0005436; F:sodium:phosphate symporter activity; IDA:UniProtKB. DR GO; GO:0031214; P:biomineral tissue development; IEA:Ensembl. DR GO; GO:0008283; P:cell population proliferation; IDA:UniProtKB. DR GO; GO:0006811; P:monoatomic ion transport; TAS:Reactome. DR GO; GO:0035435; P:phosphate ion transmembrane transport; IBA:GO_Central. DR GO; GO:0006796; P:phosphate-containing compound metabolic process; TAS:ProtInc. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; HMP:UniProtKB. DR InterPro; IPR001204; Phos_transporter. DR PANTHER; PTHR11101; PHOSPHATE TRANSPORTER; 1. DR PANTHER; PTHR11101:SF46; SODIUM-DEPENDENT PHOSPHATE TRANSPORTER 1; 1. DR Pfam; PF01384; PHO4; 1. PE 1: Evidence at protein level; KW Cell membrane; Host-virus interaction; Membrane; Phosphate transport; KW Phosphoprotein; Proteomics identification; Receptor; Reference proteome; KW Symport; Transmembrane; Transmembrane helix; Transport. FT CHAIN 1..679 FT /note="Sodium-dependent phosphate transporter 1" FT /id="PRO_0000080771" FT TRANSMEM 21..41 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 62..82 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 100..120 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 158..178 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 203..223 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 230..250 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 511..531 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 558..578 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 600..620 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 650..670 FT /note="Helical" FT /evidence="ECO:0000255" FT REGION 550..558 FT /note="A" FT MOD_RES 265 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 269 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MUTAGEN 128 FT /note="S->A: Loss of sodium-dependent phosphate transporter FT activity. Able to restore cell proliferation in SLC20A1- FT deficient HeLa cells to a level identical to that observed FT in their wild-type counterpart. No effect on its FT localization to the cell membrane." FT /evidence="ECO:0000269|PubMed:19726692" FT MUTAGEN 550..558 FT /note="DTGDVSSKV->KQEASTKA: Loss of virus infectibility." FT /evidence="ECO:0000269|PubMed:8411375" FT MUTAGEN 550 FT /note="D->K: Drastic reduction of virus infectibility, but FT conserved virus binding ability." FT /evidence="ECO:0000269|PubMed:12097582, FT ECO:0000269|PubMed:8411375" FT MUTAGEN 550 FT /note="Missing: Loss of virus infectibility." FT /evidence="ECO:0000269|PubMed:12097582, FT ECO:0000269|PubMed:8411375" FT CONFLICT 376 FT /note="Y -> S (in Ref. 1; AAA52572)" FT /evidence="ECO:0000305" FT CONFLICT 443 FT /note="E -> R (in Ref. 4; AAD20286)" FT /evidence="ECO:0000305" FT CONFLICT 487 FT /note="E -> A (in Ref. 1; AAA52572)" FT /evidence="ECO:0000305" SQ SEQUENCE 679 AA; 73700 MW; 5545F6E6DC8F5EA8 CRC64; MATLITSTTA ATAASGPLVD YLWMLILGFI IAFVLAFSVG ANDVANSFGT AVGSGVVTLK QACILASIFE TVGSVLLGAK VSETIRKGLI DVEMYNSTQG LLMAGSVSAM FGSAVWQLVA SFLKLPISGT HCIVGATIGF SLVAKGQEGV KWSELIKIVM SWFVSPLLSG IMSGILFFLV RAFILHKADP VPNGLRALPV FYACTVGINL FSIMYTGAPL LGFDKLPLWG TILISVGCAV FCALIVWFFV CPRMKRKIER EIKCSPSESP LMEKKNSLKE DHEETKLSVG DIENKHPVSE VGPATVPLQA VVEERTVSFK LGDLEEAPER ERLPSVDLKE ETSIDSTVNG AVQLPNGNLV QFSQAVSNQI NSSGHYQYHT VHKDSGLYKE LLHKLHLAKV GDCMGDSGDK PLRRNNSYTS YTMAICGMPL DSFRAKEGEQ KGEEMEKLTW PNADSKKRIR MDSYTSYCNA VSDLHSASEI DMSVKAEMGL GDRKGSNGSL EEWYDQDKPE VSLLFQFLQI LTACFGSFAH GGNDVSNAIG PLVALYLVYD TGDVSSKVAT PIWLLLYGGV GICVGLWVWG RRVIQTMGKD LTPITPSSGF SIELASALTV VIASNIGLPI STTHCKVGSV VSVGWLRSKK AVDWRLFRNI FMAWFVTVPI SGVISAAIMA IFRYVILRM //