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c-kit protein; mast/stem cell growth factor receptor; SCFR; proto-oncogene tyrosine-protein kinase Kit; c-kit; CD117 (KIT)

Function: - receptor for stem cell factor (mast cell growth factor) & fibroblast cell-surface protein - has a tyrosine-protein kinase activity - binding of the ligands leads to the autophosphorylation of KIT & its association with substrates such as PI-3-kinase (Pi3K) - interacts with APS - interacts with the tenth PDZ domain Structure: - belongs to the protein kinase superfamily, Tyr protein kinase family, CSF-1/PDGF receptor subfamily - contains 5 Ig-like C2-type domains (immunoglobulin-like) - contains 1 protein kinase domain Compartment: - membrane Expression: - interstitial cells of Cajal in the GI tract (autonomic nerve related) which regulate intestinal motility - mast cells (constituively expressed) - hematopoietic stem cells - melanocytes - germ cells - embryonic/fetal brain - certain cutaneous basal & skin adnexal epithelia - mammary ductal epithelia - endothelium [3,5] - gastrointestinal stromal tumor: ~100% cases - gastrointestinal autonomic tumors - mast cell neoplasms - angiosarcomas (> 50%) - angiomyolipoma - clear cell sarcoma - epithelioid sarcoma - melanoma - seminoma/dysgerminoma - synovial sarcoma: ~100% cases [4], ~10% [5] - osteosarcoma: ~83% cases [4] - Ewings sarcoma/PNET: ~71% cases [4] - Wilms tumor: ~52% cases [4] - neuroblastoma: ~55% cases [4] - embryonal rhabdomyosarcoma: ~77% cases [4] - AML - CML - granulocytic sarcoma - childhood acute myelogenous leukemia - Hodgkin's lymphoma (some Reed-Sternberg cells) - small cell lung cancer - adenoid cystic carcinoma of salivary gland negative staining with antibody seen in - alveolar rhabdomyosarcoma [4] - alveolar soft part sarcoma [4] - desmoplastic round small cell tumor [4] - glomus tumors - leiomyomas (retroperitoneal, colorectal) - leiomyosarcomas - myxomas (cardiac) - schwannomas (colorectal) - smooth muscle tumors of uncertain malignant potential - solitary fibrous tumors Pathology: - defects in KIT associated with 1) piebaldism 2) gastrointestinal stromal tumor (gain of function) 3) some mast cell disorders 4) testicular germ cell tumor - mutation(s) associated with acute myeloid leukemia Pharmacology: - tyrosine kinase activity of c-kit protein in gastrointestinal stromal tumors (GISTs) is inhibited by imatinib mesylate (Gleevec, STI571) Comparative biology: - mice with loss of function show - white coat color (disrupted melanogenesis) - macrocytic anemia - mast cell deficiency - sterility (disrupted gonadogenesis)

Interactions

molecular events

Related

CD117 (c-kit protein) Ag in blood CD117 (c-kit protein) Ag in bone marrow CD117 (c-kit protein) Ag in tissue CD117 (c-kit protein) cells in specimen kit proto-oncogene or white spotting locus [W] gene

General

cluster-of-differentiation antigen; cluster designation antigen; CD antigen glycoprotein proto oncogene protein tyrosine kinase receptor (RTK)

Properties

SIZE: entity length = 976 aa MW = 110 kD COMPARTMENT: cellular membrane STATE: active state MOTIF: signal sequence {1-25} immunoglobulin superfamily domain {27-112} MOTIF: cysteine residue {C58} MODIFICATION: cysteine residue {C97} cysteine residue {C97} MODIFICATION: cysteine residue {C58} immunoglobulin superfamily domain {121-205} MOTIF: N-glycosylation site {N130} N-glycosylation site {N145} cysteine residue {C151} MODIFICATION: cysteine residue {C183} cysteine residue {C183} MODIFICATION: cysteine residue {C151} immunoglobulin superfamily domain {212-308} MOTIF: cysteine residue {C233} MODIFICATION: cysteine residue {C290} N-glycosylation site {N283} cysteine residue {C290} MODIFICATION: cysteine residue {C233} N-glycosylation site {N293} N-glycosylation site {N300} immunoglobulin superfamily domain {317-410} MOTIF: N-glycosylation site {N320} N-glycosylation site {N352} N-glycosylation site {N367} immunoglobulin superfamily domain {413-507} MOTIF: cysteine residue {C428} MODIFICATION: cysteine residue {C491} N-glycosylation site {N463} N-glycosylation site {N486} cysteine residue {C491} MODIFICATION: cysteine residue {C428} transmembrane domain {525-545} tyrosine residue {568} Tyr phosphorylation site {Y568} Tyr phosphorylation site {Y570} kinase domain SITE: 589-937 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 595-603 ATP-binding site NAME: ATP-binding site SITE: 623-623 Tyr phosphorylation site {Y703} aspartate residue {D792} Tyr phosphorylation site {Y823} tyrosine residue {936} Tyr phosphorylation site {Y936}

Database Correlations

OMIM correlations MORBIDMAP 164920 UniProt P10721 PFAM correlations Entrez Gene 3815 KEGG correlations ENZYME 2.7.10.1

References

  1. UniProt :accession P10721
  2. Steele RE. Factor hunting made easier. Trends Biochem Sci. 1991 Apr;16(4):125-6. Review. PMID: 1652170
  3. Miettinen M, Lasota J. Gastrointestinal stromal tumors-definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis. Virchows Arch. 2001 Jan;438(1):1-12. Review. PMID: 11213830
  4. Smithey BE, Pappo AS, Hill DA. C-kit expression in pediatric solid tumors: a comparative immunohistochemical study. Am J Surg Pathol. 2002 Apr;26(4):486-92. PMID: 11914627
  5. http://www.pathologyoutlines.com/cd100247.html 21 June 2005
  6. Atlas of genetics & cytogenetics in oncology & haematology http://atlasgeneticsoncology.org/genes/KITID127.html
  7. GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=KIT
  8. Wikipedia; Note: CD117 entry http://en.wikipedia.org/wiki/CD117

Component-of

c kit protein/guanfacine chondroitin sulfate/c kit protein/hyaluronate bisacodyl/c kit protein