Mast/stem cell growth factor receptor Kit
Also known as: KIT, SCFR
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.
Classification
- Family (Pfam)
- PF00047 ig, PF07714 PK_Tyr_Ser-Thr
- InterPro
- Ig-like_dom, Ig-like_dom_sf, Ig-like_fold, Ig_sub, Ig_sub2, Immunoglobulin_dom, Kinase-like_dom_sf, Prot_kinase_dom, Protein_kinase_ATP_BS, RTK, SCGF_receptor, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_AS, Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS
- Functional cluster
- Immunoglobulin-Domain Cell Adhesion Proteins
Experimental structures · PDB · 51
- 1PKG X-ray 2.90A
- 1T45 X-ray 1.90A
- 1T46 X-ray 1.60A
- 2E9W X-ray 3.50A
- 2EC8 X-ray 3.00A
- 2IUH X-ray 2.00A
- 2VIF X-ray 1.45A
- 3G0E X-ray 1.60A
- 3G0F X-ray 2.60A
- 4HVS X-ray 1.90A
- 4K94 X-ray 2.40A
- 4K9E X-ray 2.70A
- … and 39 more
A predicted model is available from AlphaFold.
Gene Ontology · 74
- GO:0001669 acrosomal vesicle
- GO:0005911 cell-cell junction
- GO:0009898 cytoplasmic side of plasma membrane
- GO:0009897 external side of plasma membrane
- GO:0005615 extracellular space
- GO:0005886 plasma membrane
- GO:0043235 receptor complex
- GO:0005524 ATP binding
- GO:0019955 cytokine binding
- GO:0019838 growth factor binding
- GO:0046872 metal ion binding
- GO:0002020 protease binding
- GO:0042803 protein homodimerization activity
- GO:0004713 protein tyrosine kinase activity
- GO:0042169 SH2 domain binding
- GO:0005020 stem cell factor receptor activity
- GO:0004714 transmembrane receptor protein tyrosine kinase activity
- GO:0030036 actin cytoskeleton organization
- GO:0030183 B cell differentiation
- GO:0060326 cell chemotaxis
- GO:0016477 cell migration
- GO:0019221 cytokine-mediated signaling pathway
- GO:0050910 detection of mechanical stimulus involved in sensory perception of sound
- GO:0048565 digestive tract development
- GO:0035162 embryonic hemopoiesis
- GO:0050673 epithelial cell proliferation
- GO:0030218 erythrocyte differentiation
- GO:0038162 erythropoietin-mediated signaling pathway
- GO:0038093 Fc receptor signaling pathway
- GO:0008354 germ cell migration
- GO:0002244 hematopoietic progenitor cell differentiation
- GO:0030097 hemopoiesis
- GO:0002327 immature B cell differentiation
- GO:0006954 inflammatory response
- GO:0038109 Kit signaling pathway
- GO:0030032 lamellipodium assembly
- GO:0008584 male gonad development
- GO:0002551 mast cell chemotaxis
- GO:0043303 mast cell degranulation
- GO:0060374 mast cell differentiation
- GO:0070662 mast cell proliferation
- GO:0035855 megakaryocyte development
- GO:0097326 melanocyte adhesion
- GO:0030318 melanocyte differentiation
- GO:0097324 melanocyte migration
- GO:0001541 ovarian follicle development
- GO:0043473 pigmentation
- GO:0030335 positive regulation of cell migration
- GO:0008284 positive regulation of cell population proliferation
- GO:1904343 positive regulation of colon smooth muscle contraction
- GO:0002732 positive regulation of dendritic cell cytokine production
- GO:0048170 positive regulation of long-term neuronal synaptic plasticity
- GO:0043410 positive regulation of MAPK cascade
- GO:0032765 positive regulation of mast cell cytokine production
- GO:0045747 positive regulation of Notch signaling pathway
- GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
- GO:0031274 positive regulation of pseudopodium assembly
- GO:0120072 positive regulation of pyloric antrum smooth muscle contraction
- GO:0046427 positive regulation of receptor signaling pathway via JAK-STAT
- GO:1904349 positive regulation of small intestine smooth muscle contraction
- GO:0042531 positive regulation of tyrosine phosphorylation of STAT protein
- GO:1905065 positive regulation of vascular associated smooth muscle cell differentiation
- GO:0046777 protein autophosphorylation
- GO:0042127 regulation of cell population proliferation
- GO:0008360 regulation of cell shape
- GO:0046686 response to cadmium ion
- GO:0007165 signal transduction
- GO:0035019 somatic stem cell population maintenance
- GO:0007283 spermatogenesis
- GO:0048863 stem cell differentiation
- GO:0019827 stem cell population maintenance
- GO:0030217 T cell differentiation
- GO:0043586 tongue development
- GO:0008542 visual learning
Disease associations
- cutaneous mastocytosis MONDO:0019023
- piebaldism MONDO:0008244
- testicular germ cell tumor MONDO:0010108
- acute myeloid leukemia MONDO:0018874
- gastrointestinal stromal tumor MONDO:0011719
Drugs targeting this protein · 31
- VATALANIB inhibitor
- SORAFENIB TOSYLATE inhibitor
- PAZOPANIB HYDROCHLORIDE inhibitor
- FORETINIB inhibitor
- TANDUTINIB inhibitor
- FAMITINIB inhibitor
- DASATINIB ANHYDROUS inhibitor
- SUNITINIB MALATE inhibitor
- OSI-930 inhibitor
- IMATINIB MESYLATE inhibitor
- SU-014813 inhibitor
- MASITINIB inhibitor
- REGORAFENIB inhibitor
- TELATINIB inhibitor
- AMUVATINIB inhibitor
- TIVOZANIB HYDROCHLORIDE inhibitor
- SEMAXANIB inhibitor
- PEXIDARTINIB inhibitor
- PEXIDARTINIB HYDROCHLORIDE inhibitor
- AVAPRITINIB inhibitor
- RIPRETINIB inhibitor
- CATEQUENTINIB inhibitor
- SERALUTINIB inhibitor
- ENMD-2076 inhibitor
- CEDIRANIB inhibitor
- DOVITINIB inhibitor
- XL-999 inhibitor
- SUNITINIB inhibitor
- MOTESANIB inhibitor
- QUIZARTINIB inhibitor
- MIDOSTAURIN inhibitor
Neighborhood · nearest proteins
Related proteins · sequence + function similarity
- Mast/stem cell growth factor receptor Kit 0.99
- Mast/stem cell growth factor receptor Kit 0.99
- Mast/stem cell growth factor receptor Kit 0.99
- Mast/stem cell growth factor receptor Kit 0.99
- Mast/stem cell growth factor receptor Kit 0.98
- Mast/stem cell growth factor receptor Kit 0.98
- Mast/stem cell growth factor receptor Kit 0.98
- Mast/stem cell growth factor receptor Kit 0.97
- Mast/stem cell growth factor receptor-related protein Kit 0.96
- Macrophage colony-stimulating factor 1 receptor 0.94
- Platelet-derived growth factor receptor alpha 0.94
- Platelet-derived growth factor receptor alpha 0.94
Co-cited proteins · studied together in the literature
- Kit ligand 3 shared papers
- Suppressor of cytokine signaling 6 2 shared papers
- Receptor-type tyrosine-protein phosphatase U 1 shared papers
- Serine/threonine-protein kinase 10 1 shared papers
- SH2B adapter protein 2 1 shared papers
- HMG domain-containing protein 3 1 shared papers
- Tyrosine-protein kinase Lyn 3 shared papers
- Multiple PDZ domain protein 1 shared papers
- Mast/stem cell growth factor receptor Kit 2 shared papers
- Growth factor receptor-bound protein 7 1 shared papers
- Erythropoietin receptor 1 shared papers
- Megakaryocyte-associated tyrosine-protein kinase 2 shared papers
Literature · 65 cited papers
- A new germline mutation in KIT associated with diffuse cutaneous mastocytosis in a Chinese family. Clin. Exp. Dermatol. · 2014
- Novel, activating KIT-N822I mutation in familial cutaneous mastocytosis. Exp. Hematol. · 2011
- Mechanism of activation of human c-KIT kinase by internal tandem duplications of the juxtamembrane domain and point mutations at aspartic acid 816. Biochem. Biophys. Res. Commun. · 2011
- Mechanisms of STAT protein activation by oncogenic KIT mutants in neoplastic mast cells. J. Biol. Chem. · 2011
- Tumor-intrinsic and -extrinsic roles of c-Kit: mast cells as the primary off-target of tyrosine kinase inhibitors. Oncogene · 2011
- Structural basis for c-KIT inhibition by the suppressor of cytokine signaling 6 (SOCS6) ubiquitin ligase. J. Biol. Chem. · 2011
- Retinoic acid enhances sensitivity of neuroblastoma cells for imatinib mesylate. Pediatr. Blood Cancer · 2010
- Expression of a truncated form of KIT tyrosine kinase in human spermatozoa correlates with sperm DNA integrity. Hum. Reprod. · 2010
- Function of activation loop tyrosine phosphorylation in the mechanism of c-Kit auto-activation and its implication in sunitinib resistance. J. Biochem. · 2010
- Pediatric mastocytosis is a clonal disease associated with D816V and other activating c-KIT mutations. J. Invest. Dermatol. · 2010
- Large-scale proteomics analysis of the human kinome. Mol. Cell. Proteomics · 2009
- The D816V mutation of c-Kit circumvents a requirement for Src family kinases in c-Kit signal transduction. J. Biol. Chem. · 2009
- … and 53 more in the literature graph