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Details on Person UniProt:P10721 KIT
| Class:Id | ReferenceGeneProduct:58103 |
|---|---|
| _chainChangeLog | signal peptide:1-25 added on Fri February 6 2015;chain:26-976 added on Fri February 6 2015 |
| _displayName | UniProt:P10721 KIT |
| _timestamp | 2025-02-21 20:00:22 |
| chain | signal peptide:1-25 chain:26-976 |
| checksum | 81B0CD76817F3454 |
| comment | FUNCTION 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.CATALYTIC ACTIVITY L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+)ACTIVITY REGULATION 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.SUBUNIT 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.INTERACTION Detected in the cytoplasm of spermatozoa, especially in the equatorial and subacrosomal region of the sperm head.ALTERNATIVE PRODUCTS In testis, detected in spermatogonia in the basal layer and in interstitial Leydig cells but not in Sertoli cells or spermatocytes inside the seminiferous tubules (at protein level) (PubMed:20601678). Expression is maintained in ejaculated spermatozoa (at protein level) (PubMed:20601678).INDUCTION Up-regulated by cis-retinoic acid in neuroblastoma cell lines.PTM Ubiquitinated by SOCS6. KIT is rapidly ubiquitinated after autophosphorylation induced by KITLG/SCF binding, leading to internalization and degradation.PTM 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.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The gene represented in this entry is involved in disease pathogenesis.DISEASE The gene represented in this entry may be involved in disease pathogenesis.DISEASE 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. Likewise, point mutations in the kinase domain can result in a constitutively activated kinase.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.MISCELLANEOUS Numerous proteins are phosphorylated in response to KIT signaling, but it is not evident to determine which are directly phosphorylated by KIT under in vivo conditions.SIMILARITY Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.SEQUENCE CAUTION Probable cloning artifact.ONLINE INFORMATION CD117 entryONLINE INFORMATION two's company - Issue 163 of August 2014 |
| description | recommendedName: Mast/stem cell growth factor receptor Kit shortName: SCFR ecNumber: 2.7.10.1 alternativeName: Piebald trait protein shortName: PBT alternativeName: Proto-oncogene c-Kit alternativeName: Tyrosine-protein kinase Kit alternativeName: p145 c-kit alternativeName: v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog cdAntigenNameCD117/cdAntigenName |
| geneName | KIT SCFR |
| identifier | P10721 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Alternative splicing ATP-binding Cell membrane Cytoplasm Direct protein sequencing Disease variant Disulfide bond Glycoprotein Immunoglobulin domain Kinase Magnesium Membrane Metal-binding Nucleotide-binding Phosphoprotein Proteomics identification Proto-oncogene Receptor Reference proteome Repeat Signal Transferase Transmembrane Transmembrane helix Tyrosine-protein kinase Ubl conjugation |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9862192] Weiser, Joel, 2024-02-26 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 |
| name | KIT |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8864686] ENSEMBL:ENSG00000157404 KIT [Homo sapiens] |
| secondaryIdentifier | KIT_HUMAN B5A956 D5LXN2 D5M931 F5H8F8 Q6IQ28 Q99662 Q9UM99 |
| sequenceLength | 976 |
| species | [Species:48887] Homo sapiens |
| (isoformParent) | [ReferenceIsoform:8977062] UniProt:P10721-1 KIT [Homo sapiens] [ReferenceIsoform:8977063] UniProt:P10721-2 KIT [Homo sapiens] [ReferenceIsoform:9730086] UniProt:P10721-4 KIT [Homo sapiens] |
| (referenceEntity) | [EntityWithAccessionedSequence:197662] KIT [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:205207] p-7Y-KIT [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:1433492] p-S741,S746-KIT [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:1472116] p-8Y-KIT [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:9669426] KIT A829P [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:9669428] KIT D816A [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:9669433] KIT P551_V555del [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:9669435] KIT D816Y [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:9669436] KIT D816E [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:9669437] KIT N822H [plasma membrane] [Homo sapiens] |
| (referenceSequence) | [ModifiedResidue:205169] O4'-phospho-L-tyrosine at 570 [ModifiedResidue:205171] O4'-phospho-L-tyrosine at 721 [ModifiedResidue:205176] O4'-phospho-L-tyrosine at 568 [ModifiedResidue:205191] O4'-phospho-L-tyrosine at 900 [ModifiedResidue:205235] O4'-phospho-L-tyrosine at 823 [ModifiedResidue:205246] O4'-phospho-L-tyrosine at 936 [ModifiedResidue:205278] O4'-phospho-L-tyrosine at 703 [ModifiedResidue:205288] O4'-phospho-L-tyrosine at 730 [ModifiedResidue:1472113] O4'-phospho-L-tyrosine at 900 [ModifiedResidue:3214804] O-phospho-L-serine at 746 |
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No pathways have been reviewed or authored by UniProt:P10721 KIT (58103)
