{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P10721","secondaryAccessions":["B5A956","D5LXN2","D5M931","F5H8F8","Q6IQ28","Q99662","Q9UM99"],"uniProtkbId":"KIT_HUMAN","entryAudit":{"firstPublicDate":"1989-07-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"1989-07-01","entryVersion":267,"sequenceVersion":1},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"Mast/stem cell growth factor receptor Kit"},"shortNames":[{"value":"SCFR"}],"ecNumbers":[{"value":"2.7.10.1"}]},"alternativeNames":[{"fullName":{"value":"Piebald trait protein"},"shortNames":[{"value":"PBT"}]},{"fullName":{"value":"Proto-oncogene c-Kit"}},{"fullName":{"value":"Tyrosine-protein kinase Kit"}},{"fullName":{"value":"p145 c-kit"}},{"fullName":{"value":"v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog"}}],"cdAntigenNames":[{"value":"CD117"}],"flag":"Precursor"},"genes":[{"geneName":{"value":"KIT"},"synonyms":[{"value":"SCFR"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10397721"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12444928"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12511554"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12878163"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17904548"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19265199"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21135090"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21640708"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7520444"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9528781"}],"value":"Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. In response to KITLG/SCF binding, KIT can activate several signaling pathways. Phosphorylates PIK3R1, PLCG1, SH2B2/APS and CBL. Activates the AKT1 signaling pathway by phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Activated KIT also transmits signals via GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3, STAT5A and STAT5B. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. KIT signaling is modulated by protein phosphatases, and by rapid internalization and degradation of the receptor. Activated KIT promotes phosphorylation of the protein phosphatases PTPN6/SHP-1 and PTPRU, and of the transcription factors STAT1, STAT3, STAT5A and STAT5B. Promotes phosphorylation of PIK3R1, CBL, CRK (isoform Crk-II), LYN, MAPK1/ERK2 and/or MAPK3/ERK1, PLCG1, SRC and SHC1"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:10596"},{"database":"Rhea","id":"RHEA-COMP:10136"},{"database":"Rhea","id":"RHEA-COMP:20101"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:30616"},{"database":"ChEBI","id":"CHEBI:46858"},{"database":"ChEBI","id":"CHEBI:61978"},{"database":"ChEBI","id":"CHEBI:456216"}],"ecNumber":"2.7.10.1","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU10028"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17662946"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19164557"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21640708"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"2448137"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15123710"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19164557"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21640708"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7520444"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7539802"}],"value":"Present in an inactive conformation in the absence of bound ligand. KITLG/SCF binding leads to dimerization and activation by autophosphorylation on tyrosine residues. Activity is down-regulated by PRKCA-mediated phosphorylation on serine residues. Inhibited by imatinib/STI-571 (Gleevec) and sunitinib; these compounds maintain the kinase in an inactive conformation"}],"commentType":"ACTIVITY REGULATION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P05532"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10377264"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10397721"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11018522"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11825908"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12444928"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12824176"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12878163"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17595334"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17662946"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17904548"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19164557"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21030588"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21640708"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7520444"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9038210"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9341198"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9528781"}],"value":"Monomer in the absence of bound KITLG/SCF. Homodimer in the presence of bound KITLG/SCF, forming a heterotetramer with two KITLG/SCF molecules. Interacts (via phosphorylated tyrosine residues) with the adapter proteins GRB2 and GRB7 (via SH2 domain), and SH2B2/APS. Interacts (via C-terminus) with MPDZ (via the tenth PDZ domain). Interacts (via phosphorylated tyrosine residues) with PIK3R1 and PIK3 catalytic subunit. Interacts (via phosphorylated tyrosine) with CRK (isoform Crk-II), FYN, SHC1 and MATK/CHK (via SH2 domain). Interacts with LYN and FES/FPS. Interacts (via phosphorylated tyrosine residues) with the protein phosphatases PTPN6/SHP-1 (via SH2 domain), PTPN11/SHP-2 (via SH2 domain) and PTPRU. Interacts with PLCG1. Interacts with DOK1 and TEC. Interacts (KITLG/SCF-bound) with IL1RL1. Interacts with IL1RAP (independent of stimulation with KITLG/SCF). A mast cell-specific KITLG/SCF-induced interleukin-33 signaling complex contains IL1RL1, IL1RAP, KIT and MYD88"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"P10721","intActId":"EBI-1379503"},"interactantTwo":{"uniProtKBAccession":"P00519","geneName":"ABL1","intActId":"EBI-375543"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P10721","intActId":"EBI-1379503"},"interactantTwo":{"uniProtKBAccession":"P42684","geneName":"ABL2","intActId":"EBI-1102694"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P10721","intActId":"EBI-1379503"},"interactantTwo":{"uniProtKBAccession":"Q99767","geneName":"APBA2","intActId":"EBI-81711"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P10721","intActId":"EBI-1379503"},"interactantTwo":{"uniProtKBAccession":"O75815","geneName":"BCAR3","intActId":"EBI-702336"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P10721","intActId":"EBI-1379503"},"interactantTwo":{"uniProtKBAccession":"P51451","geneName":"BLK","intActId":"EBI-2105445"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P10721","intActId":"EBI-1379503"},"interactantTwo":{"uniProtKBAccession":"Q8WV28","geneName":"BLNK","intActId":"EBI-2623522"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P10721","intActId":"EBI-1379503"},"interactantTwo":{"uniProtKBAccession":"P46108","geneName":"CRK","intActId":"EBI-886"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P10721","intActId":"EBI-1379503"},"interactantTwo":{"uniProtKBAccession":"Q12959","geneName":"DLG1","intActId":"EBI-357481"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P10721","intActId":"EBI-1379503"},"interactantTwo":{"uniProtKBAccession":"Q15700","geneName":"DLG2","intActId":"EBI-80426"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P10721","intActId":"EBI-1379503"},"interactantTwo":{"uniProtKBAccession":"Q92796","geneName":"DLG3","intActId":"EBI-80440"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P10721","intActId":"EBI-1379503"},"interactantTwo":{"uniProtKBAccession":"P78352","geneName":"DLG4","intActId":"EBI-80389"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P10721","intActId":"EBI-1379503"},"interactantTwo":{"uniProtKBAccession":"P07332","geneName":"FES","intActId":"EBI-1055635"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P10721","intActId":"EBI-1379503"},"interactantTwo":{"uniProtKBAccession":"P09769","geneName":"FGR","intActId":"EBI-1383732"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P10721","intActId":"EBI-1379503"},"interactantTwo":{"uniProtKBAccession":"Q68DX3","geneName":"FRMPD2","intActId":"EBI-53993476"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P10721","intActId":"EBI-1379503"},"interactantTwo":{"uniProtKBAccession":"O75791","geneName":"GRAP2","intActId":"EBI-740418"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P10721","intActId":"EBI-1379503"},"interactantTwo":{"uniProtKBAccession":"P62993","geneName":"GRB2","intActId":"EBI-401755"},"numberOfExperiments":6,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P10721","intActId":"EBI-1379503"},"interactantTwo":{"uniProtKBAccession":"Q14451","geneName":"GRB7","intActId":"EBI-970191"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P10721","intActId":"EBI-1379503"},"interactantTwo":{"uniProtKBAccession":"A4D2P6","geneName":"GRID2IP","intActId":"EBI-15893226"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P10721","intActId":"EBI-1379503"},"interactantTwo":{"uniProtKBAccession":"Q9Y3R0","geneName":"GRIP1","intActId":"EBI-5349621"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P10721","intActId":"EBI-1379503"},"interactantTwo":{"uniProtKBAccession":"Q9C0E4","geneName":"GRIP2","intActId":"EBI-949557"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P10721","intActId":"EBI-1379503"},"interactantTwo":{"uniProtKBAccession":"P08631","geneName":"HCK","intActId":"EBI-346340"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P10721","intActId":"EBI-1379503"},"interactantTwo":{"uniProtKBAccession":"Q96JZ2","geneName":"HSH2D","intActId":"EBI-3919324"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P10721","intActId":"EBI-1379503"},"interactantTwo":{"uniProtKBAccession":"Q14005","geneName":"IL16","intActId":"EBI-2831580"},"numberOfExperiments":3,"organismDif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Expression is maintained in ejaculated spermatozoa (at protein level) (PubMed:20601678)"}],"commentType":"TISSUE SPECIFICITY","molecule":"Isoform 3"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20658618"}],"value":"Up-regulated by cis-retinoic acid in neuroblastoma cell lines"}],"commentType":"INDUCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17904548"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19265199"}],"value":"Ubiquitinated by SOCS6. KIT is rapidly ubiquitinated after autophosphorylation induced by KITLG/SCF binding, leading to internalization and degradation"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10377264"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12824176"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19265199"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20147452"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21030588"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9038210"}],"value":"Autophosphorylated on tyrosine residues. KITLG/SCF binding enhances autophosphorylation. Isoform 1 shows low levels of tyrosine phosphorylation in the absence of added KITLG/SCF (in vitro). Kinase activity is down-regulated by phosphorylation on serine residues by protein kinase C family members. Phosphorylation at Tyr-568 is required for interaction with PTPN11/SHP-2, CRK (isoform Crk-II) and members of the SRC tyrosine-protein kinase family. Phosphorylation at Tyr-570 is required for interaction with PTPN6/SHP-1. Phosphorylation at Tyr-703, Tyr-823 and Tyr-936 is important for interaction with GRB2. Phosphorylation at Tyr-721 is important for interaction with PIK3R1. Phosphorylation at Tyr-823 and Tyr-936 is important for interaction with GRB7"}],"commentType":"PTM"},{"commentType":"DISEASE","disease":{"diseaseId":"Piebald trait","diseaseAccession":"DI-02164","acronym":"PBT","description":"Autosomal dominant genetic developmental abnormality of pigmentation characterized by congenital patches of white skin and hair that lack melanocytes.","diseaseCrossReference":{"database":"MIM","id":"172800"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11074500"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1370874"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1376329"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1717985"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7687267"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8680409"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9450866"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9699740"}]},"note":{"texts":[{"value":"The disease is caused by variants affecting the gene represented in this entry"}]}},{"commentType":"DISEASE","disease":{"diseaseId":"Gastrointestinal stromal tumor","diseaseAccession":"DI-01646","acronym":"GIST","description":"Common mesenchymal neoplasms arising in the gastrointestinal tract, most often in the stomach. They are histologically, immunohistochemically, and genetically different from typical leiomyomas, leiomyosarcomas, and schwannomas. Most GISTs are composed of a fairly uniform population of spindle-shaped cells. Some tumors are dominated by epithelioid cells or contain a mixture of spindle and epithelioid morphologies. Primary GISTs in the gastrointestinal tract commonly metastasize in the omentum and mesenteries, often as multiple nodules. However, primary tumors may also occur outside of the gastrointestinal tract, in other intra-abdominal locations, especially in the omentum and mesentery.","diseaseCrossReference":{"database":"MIM","id":"606764"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11505412"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15824741"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9438854"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9697690"}]},"note":{"texts":[{"value":"The gene represented in this entry is involved in disease pathogenesis"}]}},{"commentType":"DISEASE","disease":{"diseaseId":"Testicular germ cell tumor","diseaseAccession":"DI-02749","acronym":"TGCT","description":"A common malignancy in males representing 95% of all testicular neoplasms. TGCTs have various pathologic subtypes including: unclassified intratubular germ cell neoplasia, seminoma (including cases with syncytiotrophoblastic cells), spermatocytic seminoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, and teratoma.","diseaseCrossReference":{"database":"MIM","id":"273300"}},"note":{"texts":[{"value":"The gene represented in this entry may be involved in disease pathogenesis"}]}},{"commentType":"DISEASE","disease":{"diseaseId":"Leukemia, acute myelogenous","diseaseAccession":"DI-01171","acronym":"AML","description":"A subtype of acute leukemia, a cancer of the white blood cells. AML is a malignant disease of bone marrow characterized by maturational arrest of hematopoietic precursors at an early stage of development. Clonal expansion of myeloid blasts occurs in bone marrow, blood, and other tissue. Myelogenous leukemias develop from changes in cells that normally produce neutrophils, basophils, eosinophils and monocytes.","diseaseCrossReference":{"database":"MIM","id":"601626"}},"note":{"texts":[{"value":"The gene represented in this entry is involved in disease pathogenesis. Somatic mutations that lead to constitutive activation of KIT are detected in AML patients. These mutations fall into two classes, the most common being in-frame internal tandem duplications of variable length in the juxtamembrane region that disrupt the normal regulation of the kinase activity. 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Gentle rubbing of the lesions induces histamine release from mechanically activated mast cells, causing local wheals, erythema, and often pruritus, a phenomenon termed Darier sign.","diseaseCrossReference":{"database":"MIM","id":"154800"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15173254"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19865100"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21689725"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24289326"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9990072"}]},"note":{"texts":[{"value":"The disease is caused by variants affecting the gene represented in this entry"}]}},{"commentType":"DISEASE","disease":{"diseaseId":"Mastocytosis, systemic","diseaseAccession":"DI-05278","acronym":"MASTSYS","description":"A severe form of mastocytosis characterized by abnormal proliferation and accumulation of mast cells in several organs, resulting in a systemic disease that may affect bone, gastrointestinal tract, lymphatics, spleen, and liver. 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