KIT_HUMAN
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 03-AUG-2022, entry version 248.
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 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=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, 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="http://atlasgeneticsoncology.org/Genes/KITID127.html";
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://web.expasy.org/spotlight/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_000222.2. [P10721-1]
DR RefSeq; NP_001087241.1; NM_001093772.1. [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 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 AlphaFoldDB; P10721; -.
DR SMR; P10721; -.
DR BioGRID; 110015; 103.
DR CORUM; P10721; -.
DR DIP; DIP-1055N; -.
DR IntAct; P10721; 97.
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; DB01254; Dasatinib.
DR DrugBank; DB12147; Erdafitinib.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB00619; Imatinib.
DR DrugBank; DB09078; Lenvatinib.
DR DrugBank; DB06080; Linifanib.
DR DrugBank; DB06595; Midostaurin.
DR DrugBank; DB04868; Nilotinib.
DR DrugBank; DB05913; OSI-930.
DR DrugBank; DB06589; Pazopanib.
DR DrugBank; DB12978; Pexidartinib.
DR DrugBank; DB01962; Phosphonotyrosine.
DR DrugBank; DB08901; Ponatinib.
DR DrugBank; DB08896; Regorafenib.
DR DrugBank; DB14840; Ripretinib.
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 GlyGen; P10721; 10 sites, 4 N-linked glycans (2 sites).
DR iPTMnet; P10721; -.
DR PhosphoSitePlus; P10721; -.
DR BioMuta; KIT; -.
DR DMDM; 125472; -.
DR EPD; P10721; -.
DR jPOST; P10721; -.
DR MassIVE; P10721; -.
DR MaxQB; P10721; -.
DR PaxDb; P10721; -.
DR PeptideAtlas; P10721; -.
DR PRIDE; P10721; -.
DR ProteomicsDB; 52640; -. [P10721-1]
DR ProteomicsDB; 52641; -. [P10721-2]
DR ABCD; P10721; 2 sequenced antibodies.
DR Antibodypedia; 1392; 5458 antibodies from 57 providers.
DR DNASU; 3815; -.
DR Ensembl; ENST00000288135.6; ENSP00000288135.6; ENSG00000157404.17. [P10721-1]
DR Ensembl; ENST00000687295.1; ENSP00000509450.1; ENSG00000157404.17. [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 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 neXtProt; NX_P10721; -.
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; 544260; Selection of therapeutic option in melanoma.
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 PharmGKB; PA30128; -.
DR VEuPathDB; HostDB:ENSG00000157404; -.
DR eggNOG; KOG0200; Eukaryota.
DR GeneTree; ENSGT00940000155626; -.
DR HOGENOM; CLU_000288_49_0_1; -.
DR InParanoid; P10721; -.
DR OMA; KSSAYFN; -.
DR OrthoDB; 236292at2759; -.
DR PhylomeDB; P10721; -.
DR TreeFam; TF325768; -.
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 SignaLink; P10721; -.
DR SIGNOR; P10721; -.
DR BioGRID-ORCS; 3815; 9 hits in 1106 CRISPR screens.
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 191 other tissues.
DR Genevisible; P10721; HS.
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:0005887; C:integral component of plasma membrane; IBA:GO_Central.
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: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:0031532; P:actin cytoskeleton reorganization; 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:0097067; P:cellular response to thyroid hormone stimulus; IEA:Ensembl.
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: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:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0048170; P:positive regulation of long-term neuronal synaptic plasticity; IEA:Ensembl.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IBA:GO_Central.
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:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; TAS:UniProtKB.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; TAS:UniProtKB.
DR GO; GO:0010863; P:positive regulation of phospholipase C activity; 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:0048103; P:somatic stem cell division; IEA:Ensembl.
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:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR GO; GO:0008542; P:visual learning; IEA:Ensembl.
DR DisProt; DP02247; -.
DR Gene3D; 2.60.40.10; -; 5.
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.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
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 Pfam; PF00047; ig; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PIRSF; PIRSF500951; SCGF_recepter; 1.
DR SMART; SM00409; IG; 3.
DR SMART; SM00408; IGc2; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF48726; SSF48726; 3.
DR SUPFAM; SSF56112; SSF56112; 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; Proto-oncogene; Receptor;
KW Reference proteome; Repeat; Signal; Transferase; Transmembrane;
KW Transmembrane helix; Tyrosine-protein kinase; 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; unknown pathological
FT significance)"
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; unknown pathological 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 /evidence="ECO:0000269|PubMed:9438854"
FT /id="VAR_033123"
FT VARIANT 551..555
FT /note="Missing (in GIST; somatic mutation)"
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)"
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)"
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)"
FT /evidence="ECO:0000269|PubMed:7687267"
FT /id="VAR_004108"
FT VARIANT 816
FT /note="D -> F (in MASTC; sporadic case; somatic mutation;
FT requires 2 nucleotide substitutions; constitutively
FT activated and is much more rapidly autophosphorylated than
FT wild type)"
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:2E9W"
FT STRAND 93..99
FT /evidence="ECO:0007829|PDB:2EC8"
FT STRAND 104..110
FT /evidence="ECO:0007829|PDB:2EC8"
FT STRAND 125..130
FT /evidence="ECO:0007829|PDB:2E9W"
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 193..200
FT /evidence="ECO:0007829|PDB:2E9W"
FT STRAND 203..205
FT /evidence="ECO:0007829|PDB:2E9W"
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 TURN 573..575
FT /evidence="ECO:0007829|PDB:1T46"
FT HELIX 580..582
FT /evidence="ECO:0007829|PDB:1T46"
FT HELIX 586..588
FT /evidence="ECO:0007829|PDB:1T46"
FT STRAND 589..597
FT /evidence="ECO:0007829|PDB:1T46"
FT STRAND 599..613
FT /evidence="ECO:0007829|PDB:1T46"
FT STRAND 617..625
FT /evidence="ECO:0007829|PDB:1T46"
FT HELIX 627..629
FT /evidence="ECO:0007829|PDB:6HH1"
FT HELIX 631..647
FT /evidence="ECO:0007829|PDB:1T46"
FT STRAND 656..660
FT /evidence="ECO:0007829|PDB:1T46"
FT STRAND 662..665
FT /evidence="ECO:0007829|PDB:1T46"
FT STRAND 667..671
FT /evidence="ECO:0007829|PDB:1T46"
FT STRAND 674..677
FT /evidence="ECO:0007829|PDB:7KHK"
FT HELIX 678..684
FT /evidence="ECO:0007829|PDB:1T46"
FT TURN 685..688
FT /evidence="ECO:0007829|PDB:1T46"
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:1T46"
FT STRAND 788..790
FT /evidence="ECO:0007829|PDB:3G0F"
FT HELIX 795..797
FT /evidence="ECO:0007829|PDB:1T46"
FT STRAND 798..801
FT /evidence="ECO:0007829|PDB:1T46"
FT TURN 802..804
FT /evidence="ECO:0007829|PDB:1T46"
FT STRAND 805..808
FT /evidence="ECO:0007829|PDB:1T46"
FT HELIX 812..814
FT /evidence="ECO:0007829|PDB:1T46"
FT HELIX 817..819
FT /evidence="ECO:0007829|PDB:3G0E"
FT STRAND 823..825
FT /evidence="ECO:0007829|PDB:1T46"
FT STRAND 827..831
FT /evidence="ECO:0007829|PDB:1T46"
FT HELIX 833..835
FT /evidence="ECO:0007829|PDB:1T46"
FT HELIX 838..843
FT /evidence="ECO:0007829|PDB:1T46"
FT HELIX 848..863
FT /evidence="ECO:0007829|PDB:1T46"
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:1T46"
FT HELIX 897..906
FT /evidence="ECO:0007829|PDB:1T46"
FT HELIX 911..913
FT /evidence="ECO:0007829|PDB:1T46"
FT HELIX 917..930
FT /evidence="ECO:0007829|PDB:1T46"
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
