Mast/stem cell growth factor receptor Kit

Details

Name
Mast/stem cell growth factor receptor Kit
Synonyms
  • 2.7.10.1
  • p145 c-kit
  • PBT
  • Piebald trait protein
  • Proto-oncogene c-Kit
  • SCFR
  • Tyrosine-protein kinase Kit
  • v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog
Gene Name
KIT
Organism
Humans
Amino acid sequence
>lcl|BSEQ0000903|Mast/stem cell growth factor receptor Kit
MRGARGAWDFLCVLLLLLRVQTGSSQPSVSPGEPSPPSIHPGKSDLIVRVGDEIRLLCTD
PGFVKWTFEILDETNENKQNEWITEKAEATNTGKYTCTNKHGLSNSIYVFVRDPAKLFLV
DRSLYGKEDNDTLVRCPLTDPEVTNYSLKGCQGKPLPKDLRFIPDPKAGIMIKSVKRAYH
RLCLHCSVDQEGKSVLSEKFILKVRPAFKAVPVVSVSKASYLLREGEEFTVTCTIKDVSS
SVYSTWKRENSQTKLQEKYNSWHHGDFNYERQATLTISSARVNDSGVFMCYANNTFGSAN
VTTTLEVVDKGFINIFPMINTTVFVNDGENVDLIVEYEAFPKPEHQQWIYMNRTFTDKWE
DYPKSENESNIRYVSELHLTRLKGTEGGTYTFLVSNSDVNAAIAFNVYVNTKPEILTYDR
LVNGMLQCVAAGFPEPTIDWYFCPGTEQRCSASVLPVDVQTLNSSGPPFGKLVVQSSIDS
SAFKHNGTVECKAYNDVGKTSAYFNFAFKGNNKEQIHPHTLFTPLLIGFVIVAGMMCIIV
MILTYKYLQKPMYEVQWKVVEEINGNNYVYIDPTQLPYDHKWEFPRNRLSFGKTLGAGAF
GKVVEATAYGLIKSDAAMTVAVKMLKPSAHLTEREALMSELKVLSYLGNHMNIVNLLGAC
TIGGPTLVITEYCCYGDLLNFLRRKRDSFICSKQEDHAEAALYKNLLHSKESSCSDSTNE
YMDMKPGVSYVVPTKADKRRSVRIGSYIERDVTPAIMEDDELALDLEDLLSFSYQVAKGM
AFLASKNCIHRDLAARNILLTHGRITKICDFGLARDIKNDSNYVVKGNARLPVKWMAPES
IFNCVYTFESDVWSYGIFLWELFSLGSSPYPGMPVDSKFYKMIKEGFRMLSPEHAPAEMY
DIMKTCWDADPLKRPTFKQIVQLIEKQISESTNHIYSNLANCSPNRQKPVVDHSVRINSV
GSTASSSQPLLVHDDV
Number of residues
976
Molecular Weight
109863.655
Theoretical pI
6.96
GO Classification
Functions
ATP binding / cytokine binding / metal ion binding / protein homodimerization activity / protein tyrosine kinase activity / receptor signaling protein tyrosine kinase activity / stem cell factor receptor activity / transmembrane receptor protein tyrosine kinase activity
Processes
actin cytoskeleton reorganization / activation of MAPK activity / activation of MAPKK activity / axon guidance / cell chemotaxis / cellular response to thyroid hormone stimulus / cytokine-mediated signaling pathway / dendritic cell cytokine production / detection of mechanical stimulus involved in sensory perception of sound / digestive tract development / ectopic germ cell programmed cell death / embryonic hemopoiesis / epidermal growth factor receptor signaling pathway / epithelial cell proliferation / erythrocyte differentiation / erythropoietin-mediated signaling pathway / Fc receptor signaling pathway / Fc-epsilon receptor signaling pathway / fibroblast growth factor receptor signaling pathway / germ cell migration / glycosphingolipid metabolic process / hemopoiesis / immature B cell differentiation / inflammatory response / innate immune response / insulin receptor signaling pathway / Kit signaling pathway / lamellipodium assembly / lymphoid progenitor cell differentiation / male gonad development / MAPK cascade / mast cell chemotaxis / mast cell cytokine production / mast cell degranulation / mast cell differentiation / mast cell proliferation / megakaryocyte development / melanocyte adhesion / melanocyte differentiation / melanocyte migration / myeloid progenitor cell differentiation / negative regulation of programmed cell death / neurotrophin TRK receptor signaling pathway / ovarian follicle development / peptidyl-tyrosine phosphorylation / phosphatidylinositol-mediated signaling / pigmentation / positive regulation of cell migration / positive regulation of cell proliferation / positive regulation of JAK-STAT cascade / positive regulation of long-term neuronal synaptic plasticity / positive regulation of MAPK cascade / positive regulation of Notch signaling pathway / positive regulation of phosphatidylinositol 3-kinase activity / positive regulation of phosphatidylinositol 3-kinase signaling / positive regulation of phospholipase C activity / positive regulation of pseudopodium assembly / positive regulation of sequence-specific DNA binding transcription factor activity / positive regulation of tyrosine phosphorylation of Stat1 protein / positive regulation of tyrosine phosphorylation of Stat3 protein / positive regulation of tyrosine phosphorylation of Stat5 protein / protein autophosphorylation / Ras protein signal transduction / regulation of cell proliferation / regulation of cell shape / regulation of developmental pigmentation / signal transduction / small GTPase mediated signal transduction / somatic stem cell division / somatic stem cell population maintenance / spermatid development / spermatogenesis / stem cell differentiation / stem cell population maintenance / T cell differentiation / vascular endothelial growth factor receptor signaling pathway / visual learning
Components
acrosomal vesicle / cell-cell junction / cytoplasmic side of plasma membrane / external side of plasma membrane / extracellular space / integral component of membrane / mast cell granule / plasma membrane
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Tyrosine-protein kinase that acts as 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.
Pfam Domain Function
Transmembrane Regions
525-545
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0020461|Mast/stem cell growth factor receptor Kit (KIT)
ATGAGAGGCGCTCGCGGCGCCTGGGATTTTCTCTGCGTTCTGCTCCTACTGCTTCGCGTC
CAGACAGGCTCTTCTCAACCATCTGTGAGTCCAGGGGAACCGTCTCCACCATCCATCCAT
CCAGGAAAATCAGACTTAATAGTCCGCGTGGGCGACGAGATTAGGCTGTTATGCACTGAT
CCGGGCTTTGTCAAATGGACTTTTGAGATCCTGGATGAAACGAATGAGAATAAGCAGAAT
GAATGGATCACGGAAAAGGCAGAAGCCACCAACACCGGCAAATACACGTGCACCAACAAA
CACGGCTTAAGCAATTCCATTTATGTGTTTGTTAGAGATCCTGCCAAGCTTTTCCTTGTT
GACCGCTCCTTGTATGGGAAAGAAGACAACGACACGCTGGTCCGCTGTCCTCTCACAGAC
CCAGAAGTGACCAATTATTCCCTCAAGGGGTGCCAGGGGAAGCCTCTTCCCAAGGACTTG
AGGTTTATTCCTGACCCCAAGGCGGGCATCATGATCAAAAGTGTGAAACGCGCCTACCAT
CGGCTCTGTCTGCATTGTTCTGTGGACCAGGAGGGCAAGTCAGTGCTGTCGGAAAAATTC
ATCCTGAAAGTGAGGCCAGCCTTCAAAGCTGTGCCTGTTGTGTCTGTGTCCAAAGCAAGC
TATCTTCTTAGGGAAGGGGAAGAATTCACAGTGACGTGCACAATAAAAGATGTGTCTAGT
TCTGTGTACTCAACGTGGAAAAGAGAAAACAGTCAGACTAAACTACAGGAGAAATATAAT
AGCTGGCATCACGGTGACTTCAATTATGAACGTCAGGCAACGTTGACTATCAGTTCAGCG
AGAGTTAATGATTCTGGAGTGTTCATGTGTTATGCCAATAATACTTTTGGATCAGCAAAT
GTCACAACAACCTTGGAAGTAGTAGATAAAGGATTCATTAATATCTTCCCCATGATAAAC
ACTACAGTATTTGTAAACGATGGAGAAAATGTAGATTTGATTGTTGAATATGAAGCATTC
CCCAAACCTGAACACCAGCAGTGGATCTATATGAACAGAACCTTCACTGATAAATGGGAA
GATTATCCCAAGTCTGAGAATGAAAGTAATATCAGATACGTAAGTGAACTTCATCTAACG
AGATTAAAAGGCACCGAAGGAGGCACTTACACATTCCTAGTGTCCAATTCTGACGTCAAT
GCTGCCATAGCATTTAATGTTTATGTGAATACAAAACCAGAAATCCTGACTTACGACAGG
CTCGTGAATGGCATGCTCCAATGTGTGGCAGCAGGATTCCCAGAGCCCACAATAGATTGG
TATTTTTGTCCAGGAACTGAGCAGAGATGCTCTGCTTCTGTACTGCCAGTGGATGTGCAG
ACACTAAACTCATCTGGGCCACCGTTTGGAAAGCTAGTGGTTCAGAGTTCTATAGATTCT
AGTGCATTCAAGCACAATGGCACGGTTGAATGTAAGGCTTACAACGATGTGGGCAAGACT
TCTGCCTATTTTAACTTTGCATTTAAAGGTAACAACAAAGAGCAAATCCATCCCCACACC
CTGTTCACTCCTTTGCTGATTGGTTTCGTAATCGTAGCTGGCATGATGTGCATTATTGTG
ATGATTCTGACCTACAAATATTTACAGAAACCCATGTATGAAGTACAGTGGAAGGTTGTT
GAGGAGATAAATGGAAACAATTATGTTTACATAGACCCAACACAACTTCCTTATGATCAC
AAATGGGAGTTTCCCAGAAACAGGCTGAGTTTTGGGAAAACCCTGGGTGCTGGAGCTTTC
GGGAAGGTTGTTGAGGCAACTGCTTATGGCTTAATTAAGTCAGATGCGGCCATGACTGTC
GCTGTAAAGATGCTCAAGCCGAGTGCCCATTTGACAGAACGGGAAGCCCTCATGTCTGAA
CTCAAAGTCCTGAGTTACCTTGGTAATCACATGAATATTGTGAATCTACTTGGAGCCTGC
ACCATTGGAGGGCCCACCCTGGTCATTACAGAATATTGTTGCTATGGTGATCTTTTGAAT
TTTTTGAGAAGAAAACGTGATTCATTTATTTGTTCAAAGCAGGAAGATCATGCAGAAGCT
GCACTTTATAAGAATCTTCTGCATTCAAAGGAGTCTTCCTGCAGCGATAGTACTAATGAG
TACATGGACATGAAACCTGGAGTTTCTTATGTTGTCCCAACCAAGGCCGACAAAAGGAGA
TCTGTGAGAATAGGCTCATACATAGAAAGAGATGTGACTCCCGCCATCATGGAGGATGAC
GAGTTGGCCCTAGACTTAGAAGACTTGCTGAGCTTTTCTTACCAGGTGGCAAAGGGCATG
GCTTTCCTCGCCTCCAAGAATTGTATTCACAGAGACTTGGCAGCCAGAAATATCCTCCTT
ACTCATGGTCGGATCACAAAGATTTGTGATTTTGGTCTAGCCAGAGACATCAAGAATGAT
TCTAATTATGTGGTTAAAGGAAACGCTCGACTACCTGTGAAGTGGATGGCACCTGAAAGC
ATTTTCAACTGTGTATACACGTTTGAAAGTGACGTCTGGTCCTATGGGATTTTTCTTTGG
GAGCTGTTCTCTTTAGGAAGCAGCCCCTATCCTGGAATGCCGGTCGATTCTAAGTTCTAC
AAGATGATCAAGGAAGGCTTCCGGATGCTCAGCCCTGAACACGCACCTGCTGAAATGTAT
GACATAATGAAGACTTGCTGGGATGCAGATCCCCTAAAAAGACCAACATTCAAGCAAATT
GTTCAGCTAATTGAGAAGCAGATTTCAGAGAGCACCAATCATATTTACTCCAACTTAGCA
AACTGCAGCCCCAACCGACAGAAGCCCGTGGTAGACCATTCTGTGCGGATCAATTCTGTC
GGCAGCACCGCTTCCTCCTCCCAGCCTCTGCTTGTGCACGACGATGTCTGA
Chromosome Location
4
Locus
4q11-q12
External Identifiers
ResourceLink
UniProtKB IDP10721
UniProtKB Entry NameKIT_HUMAN
GenBank Protein ID34085
GenBank Gene IDX06182
GenAtlas IDKIT
HGNC IDHGNC:6342
General References
  1. Yarden Y, Kuang WJ, Yang-Feng T, Coussens L, Munemitsu S, Dull TJ, Chen E, Schlessinger J, Francke U, Ullrich A: Human proto-oncogene c-kit: a new cell surface receptor tyrosine kinase for an unidentified ligand. EMBO J. 1987 Nov;6(11):3341-51. [PubMed:2448137]
  2. Giebel LB, Strunk KM, Holmes SA, Spritz RA: Organization and nucleotide sequence of the human KIT (mast/stem cell growth factor receptor) proto-oncogene. Oncogene. 1992 Nov;7(11):2207-17. [PubMed:1279499]
  3. Andre C, Hampe A, Lachaume P, Martin E, Wang XP, Manus V, Hu WX, Galibert F: Sequence analysis of two genomic regions containing the KIT and the FMS receptor tyrosine kinase genes. Genomics. 1997 Jan 15;39(2):216-26. [PubMed:9027509]
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  13. Linnekin D, DeBerry CS, Mou S: Lyn associates with the juxtamembrane region of c-Kit and is activated by stem cell factor in hematopoietic cell lines and normal progenitor cells. J Biol Chem. 1997 Oct 24;272(43):27450-5. [PubMed:9341198]
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  36. Mol CD, Lim KB, Sridhar V, Zou H, Chien EY, Sang BC, Nowakowski J, Kassel DB, Cronin CN, McRee DE: Structure of a c-kit product complex reveals the basis for kinase transactivation. J Biol Chem. 2003 Aug 22;278(34):31461-4. Epub 2003 Jun 24. [PubMed:12824176]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00398Sorafenibapproved, investigationalyesantagonistDetails
DB00619ImatinibapprovedyesantagonistmultitargetDetails
DB01254Dasatinibapproved, investigationalunknownantagonistDetails
DB01268Sunitinibapproved, investigationalyesinhibitorDetails
DB01962PhosphonotyrosineexperimentalunknownDetails
DB04868Nilotinibapproved, investigationalunknownantagonistDetails
DB12742AmuvatinibinvestigationalunknownDetails
DB05146XL820investigationalunknownDetails
DB06080ABT-869investigationalunknownDetails
DB05913OSI-930investigationalunknownDetails
DB06589PazopanibapprovedyesinhibitorDetails
DB06595Midostaurinapproved, investigationalunknownantagonistinhibitorDetails
DB08896RegorafenibapprovedyesinhibitorDetails
DB08901Ponatinibapproved, investigationalunknowninhibitorDetails
DB09078Lenvatinibapproved, investigationalyesinhibitorDetails
DB09103Ancestimapproved, investigational, withdrawnyesagonistDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails
DB12147Erdafitinibapproved, investigationalunknownsubstrateDetails
DB12978Pexidartinibapproved, investigationalunknowninhibitorDetails