KIT - Mast/stem cell growth factor receptor Kit - human protein (Function)
 
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KIT »  Mast/stem cell growth factor receptor Kit   [ EC 2.7.10.1 ]  (SCFR)
 
Protein also known as:  v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog; CD antigen CD117.
Gene name:  KIT
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

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Overview 
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.  
11
  • UniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
1
  • UniProtKB KW
Cytokine bindingdefinition[GO:0019955]  
1
  • UniProtKB
Metal ion bindingdefinition[GO:0046872]  
1
  • UniProtKB KW
Protease bindingdefinition[GO:0002020] silver  
1
  • Ortholog Compara
Protein bindingdefinition[GO:0005515]  
7
  • IntAct
Protein homodimerization activitydefinition[GO:0042803]  
1
  • UniProtKB
Protein tyrosine kinase activitydefinition[GO:0004713]  
1
  • PINC
Receptor signaling protein tyrosine kinase activitydefinition[GO:0004716] silver  
1
  • InterPro 2 GO
Stem cell factor receptor activitydefinition[GO:0005020] silver  
1
  • Ortholog Compara
Transmembrane receptor protein tyrosine kinase activitydefinition[GO:0004714]  
1
  • UniProtKB
GO biological process 
Actin cytoskeleton reorganizationdefinition[GO:0031532]  
1
  • UniProtKB
Activation of MAPK activitydefinition[GO:0000187]  
1
  • UniProtKB
Cell chemotaxisdefinition[GO:0060326]  
1
  • UniProtKB
Cellular response to thyroid hormone stimulusdefinition[GO:0097067] silver  
1
  • Ortholog Compara
Cytokine-mediated signaling pathwaydefinition[GO:0019221]  
1
  • UniProtKB
Dendritic cell cytokine productiondefinition[GO:0002371]  
1
  • Ortholog Curator
Detection of mechanical stimulus involved in sensory perception of sounddefinition[GO:0050910]  
1
  • Ortholog Curator
Digestive tract developmentdefinition[GO:0048565]  
1
  • Ortholog Curator
Ectopic germ cell programmed cell deathdefinition[GO:0035234] silver  
1
  • Ortholog Compara
Embryonic hemopoiesisdefinition[GO:0035162]  
1
  • Ortholog Curator
Epithelial cell proliferationdefinition[GO:0050673] silver  
1
  • Ortholog Compara
Erythrocyte differentiationdefinition[GO:0030218]  
1
  • Ortholog Curator
Erythropoietin-mediated signaling pathwaydefinition[GO:0038162]  
1
  • Ortholog Curator
Fc receptor signaling pathwaydefinition[GO:0038093]  
1
  • UniProtKB
Germ cell migrationdefinition[GO:0008354] silver  
1
  • Ortholog Compara
Glycosphingolipid metabolic processdefinition[GO:0006687] silver  
1
  • Ortholog Compara
Hemopoiesisdefinition[GO:0030097]  
1
  • UniProtKB
Immature B cell differentiationdefinition[GO:0002327]  
1
  • Ortholog Curator
Inflammatory responsedefinition[GO:0006954]  
1
  • Ortholog Curator
Kit signaling pathwaydefinition[GO:0038109]  
1
  • UniProtKB
Lamellipodium assemblydefinition[GO:0030032]  
1
  • Ortholog Curator
Lymphoid progenitor cell differentiationdefinition[GO:0002320] silver  
1
  • Ortholog Compara
Male gonad developmentdefinition[GO:0008584]  
1
  • UniProtKB
Mast cell chemotaxisdefinition[GO:0002551]  
1
  • UniProtKB
Mast cell cytokine productiondefinition[GO:0032762]  
1
  • UniProtKB
Mast cell degranulationdefinition[GO:0043303]  
1
  • UniProtKB
Mast cell differentiationdefinition[GO:0060374]  
2
  • UniProtKB
  • Ortholog Curator
Mast cell proliferationdefinition[GO:0070662]  
1
  • UniProtKB
Megakaryocyte developmentdefinition[GO:0035855]  
1
  • Ortholog Curator
Melanocyte adhesiondefinition[GO:0097326]  
1
  • Ortholog Curator
Melanocyte differentiationdefinition[GO:0030318]  
2
  • UniProtKB
  • Ortholog Curator
Melanocyte migrationdefinition[GO:0097324]  
1
  • Ortholog Curator
Myeloid progenitor cell differentiationdefinition[GO:0002318] silver  
1
  • Ortholog Compara
Negative regulation of programmed cell deathdefinition[GO:0043069] silver  
1
  • Ortholog Compara
Ovarian follicle developmentdefinition[GO:0001541]  
1
  • Ortholog Curator
Peptidyl-tyrosine phosphorylationdefinition[GO:0018108]  
1
  • UniProtKB
Pigmentationdefinition[GO:0043473]  
1
  • Ortholog Curator
Positive regulation of cell migrationdefinition[GO:0030335] silver  
1
  • Ortholog Compara
Positive regulation of cell proliferationdefinition[GO:0008284] silver  
1
  • Ortholog Compara
Positive regulation of gene expressiondefinition[GO:0010628] silver  
1
  • Ortholog Compara
Positive regulation of JAK-STAT cascadedefinition[GO:0046427]  
1
  • UniProtKB
Positive regulation of long-term neuronal synaptic plasticitydefinition[GO:0048170] silver  
1
  • Ortholog Compara
Positive regulation of MAPK cascadedefinition[GO:0043410]  
1
  • UniProtKB
Positive regulation of Notch signaling pathwaydefinition[GO:0045747] silver  
1
  • Ortholog Compara
Positive regulation of phosphatidylinositol 3-kinase activitydefinition[GO:0043552]  
1
  • UniProtKB
Positive regulation of phosphatidylinositol 3-kinase signalingdefinition[GO:0014068]  
1
  • UniProtKB
Positive regulation of phospholipase C activitydefinition[GO:0010863]  
1
  • UniProtKB
Positive regulation of pseudopodium assemblydefinition[GO:0031274] silver  
1
  • Ortholog Compara
Positive regulation of sequence-specific DNA binding transcription factor activitydefinition[GO:0051091]  
1
  • UniProtKB
Positive regulation of tyrosine phosphorylation of Stat1 proteindefinition[GO:0042511]  
1
  • UniProtKB
Positive regulation of tyrosine phosphorylation of Stat3 proteindefinition[GO:0042517]  
1
  • UniProtKB
Positive regulation of tyrosine phosphorylation of Stat5 proteindefinition[GO:0042523]  
1
  • UniProtKB
Protein autophosphorylationdefinition[GO:0046777]  
1
  • UniProtKB
Regulation of cell proliferationdefinition[GO:0042127]  
2
  • UniProtKB
Regulation of cell shapedefinition[GO:0008360]  
1
  • Ortholog Curator
Regulation of developmental pigmentationdefinition[GO:0048070] silver  
1
  • Ortholog Compara
Signal transductiondefinition[GO:0007165]  
1
  • PINC
Signal transduction by phosphorylationdefinition[GO:0023014]  
2
  • GOC
  • InterPro 2 GO
Somatic stem cell divisiondefinition[GO:0048103] silver  
1
  • Ortholog Compara
Somatic stem cell maintenancedefinition[GO:0035019] silver  
1
  • Ortholog Compara
Spermatid developmentdefinition[GO:0007286] silver  
1
  • Ortholog Compara
Spermatogenesisdefinition[GO:0007283]  
2
  • UniProtKB
  • Ortholog Curator
Stem cell differentiationdefinition[GO:0048863]  
1
  • Ortholog Curator
Stem cell maintenancedefinition[GO:0019827]  
1
  • UniProtKB
T cell differentiationdefinition[GO:0030217]  
1
  • Ortholog Curator
Visual learningdefinition[GO:0008542] silver  
1
  • Ortholog Compara
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reactions
EC 2.7.10.1: ATP + a [protein]-L-tyrosine ADP + a [protein]-L-tyrosine phosphate.  
6
  • UniProtKB
  • PROSITE-ProRule
EC 2.7.10.1: ATP + a [protein]-L-tyrosine ADP + a [protein]-L-tyrosine phosphate.  
6
  • UniProtKB
  • PROSITE-ProRule
It is regulated in the following manner
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.  
6
  • UniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Acute myeloid leukemia  hsa05221+3815  
Cytokine-cytokine receptor interaction  hsa04060+3815  
Endocytosis  hsa04144+3815  
Hematopoietic cell lineage  hsa04640+3815  
Melanogenesis  hsa04916+3815  
Pathways in cancer  hsa05200+3815  
According to Reactome, this protein belongs to the following pathways:
Constitutive PI3K/AKT Signaling in Cancer  REACT_147727  
PIP3 activates AKT signaling  REACT_75829  
Regulation of KIT signaling  REACT_111225  
Signaling by SCF-KIT  REACT_111040  
Note 
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.  
1
  • UniProtKB
 

Keywords

Molecular function 
Kinase  definition   [KW-0418]
Receptor  definition   [KW-0675]
Transferase  definition   [KW-0808]
Tyrosine-protein kinase  definition   [KW-0829]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: CD117
GenomeRNAi: 3815
PRO: PR:P10721
Chemistry
GuidetoPHARMACOLOGY: 1805