Names & Taxonomy
- Uniprot ID:
- P10721
- Entry Name:
- KIT_HUMAN
- Status:
- reviewed
- Protein Names:
- Mast/stem cell growth factor receptor Kit (SCFR) (EC 2.7.10.1) (Piebald trait protein) (PBT) (Proto-oncogene c-Kit) (Tyrosine-protein kinase Kit) (p145 c-kit) (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) (CD antigen CD117)
- Gene Names:
- KIT SCFR
- Gene Names Primary:
- KIT
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 976
- Sequence:
- MRGARGAWDFLCVLLLLLRVQTGSSQPSVSPGEPSPPSIHPGKSDLIVRVGDEIRLLCTDPGFVKWTFEILDETNENKQNEWITEKAEATNTGKYTCTNKHGLSNSIYVFVRDPAKLFLVDRSLYGKEDNDTLVRCPLTDPEVTNYSLKGCQGKPLPKDLRFIPDPKAGIMIKSVKRAYHRLCLHCSVDQEGKSVLSEKFILKVRPAFKAVPVVSVSKASYLLREGEEFTVTCTIKDVSSSVYSTWKRENSQTKLQEKYNSWHHGDFNYERQATLTISSARVNDSGVFMCYANNTFGSANVTTTLEVVDKGFINIFPMINTTVFVNDGENVDLIVEYEAFPKPEHQQWIYMNRTFTDKWEDYPKSENESNIRYVSELHLTRLKGTEGGTYTFLVSNSDVNAAIAFNVYVNTKPEILTYDRLVNGMLQCVAAGFPEPTIDWYFCPGTEQRCSASVLPVDVQTLNSSGPPFGKLVVQSSIDSSAFKHNGTVECKAYNDVGKTSAYFNFAFKGNNKEQIHPHTLFTPLLIGFVIVAGMMCIIVMILTYKYLQKPMYEVQWKVVEEINGNNYVYIDPTQLPYDHKWEFPRNRLSFGKTLGAGAFGKVVEATAYGLIKSDAAMTVAVKMLKPSAHLTEREALMSELKVLSYLGNHMNIVNLLGACTIGGPTLVITEYCCYGDLLNFLRRKRDSFICSKQEDHAEAALYKNLLHSKESSCSDSTNEYMDMKPGVSYVVPTKADKRRSVRIGSYIERDVTPAIMEDDELALDLEDLLSFSYQVAKGMAFLASKNCIHRDLAARNILLTHGRITKICDFGLARDIKNDSNYVVKGNARLPVKWMAPESIFNCVYTFESDVWSYGIFLWELFSLGSSPYPGMPVDSKFYKMIKEGFRMLSPEHAPAEMYDIMKTCWDADPLKRPTFKQIVQLIEKQISESTNHIYSNLANCSPNRQKPVVDHSVRINSVGSTASSSQPLLVHDDV
- Proteomes:
- UP000005640
Subcellular location
- Subcellular Location:
- Isoform 1: Cell membrane; Single-pass type I membrane protein.; Isoform 2: Cell membrane; Single-pass type I membrane protein.; Isoform 3: Cytoplasm. Note=Detected in the cytoplasm of spermatozoa, especially in the equatorial and subacrosomal region of the sperm head.
Function
- 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.
- Catalytic Activity:
- ATP + a -L-tyrosine = ADP + a -L-tyrosine phosphate.
- Enzyme Regulation:
- ENZYME 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.
- Active Site:
- ACT_SITE 792 792 Proton acceptor.
- Cross Reference Drug Bank:
- DB01254 DB00619 DB09078 DB04868 DB06589 DB08901 DB08896 DB00398 DB01268
- Gene Ontology Go:
- 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
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
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
hematopoietic stem cell migration
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 - Gene Ontology Biological Process:
- 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-epsilon receptor signaling pathway
Fc receptor signaling pathway
fibroblast growth factor receptor signaling pathway
germ cell migration
glycosphingolipid metabolic process
hematopoietic stem cell migration
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 - Gene Ontology Molecular Function:
- 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 - Gene Ontology Cellular Component:
- 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 - Keywords:
- 3D-structure
ATP-binding
Alternative splicing
Cell membrane
Complete proteome
Cytoplasm
Direct protein sequencing
Disease mutation
Disulfide bond
Glycoprotein
Immunoglobulin domain
Kinase
Magnesium
Membrane
Metal-binding
Nucleotide-binding
Phosphoprotein
Polymorphism
Proto-oncogene
Receptor
Reference proteome
Repeat
Signal
Transferase
Transmembrane
Transmembrane helix
Tyrosine-protein kinase
Ubl conjugation - Interacts With:
- P00519; P42684; O75815; P51451; Q8WV28; P46108; P07332; P09769; O75791; P62993; Q14451; P08631; Q96JZ2; P21583; P06239; P07948; Q8VBX6; P16333; O43639; P27986; O00459; Q92569; P19174; P16885; Q13882; Q06124; P35235; Q92729; P20936; Q9UQQ2; O14796; Q9NP31; Q8N5H7; P78314; Q15464; P29353; P98077; Q92529; Q9H6Q3; O14508; O14543; O14544; P12931; Q9ULZ2; Q9HBL0; Q63HR2; Q68CZ2; P42681; P07947; P43403
Publication
- PubMed ID:
- 2448137 1279499 9027509 18593464 20658618 14702039 15815621 15489334 7506248 7520444 7539802 9038210 9341198 9528781 10377264 10397721 11018522 11825908 12444928 12878163 12511554 16335952 17595334 17904548 19265199 19369195 20601678 20147452 21640708 21135090 15526160 16129412 15625120 18381929 21057534 12824176 15123710 17662946 19164557 21030588 1376329 1370874 1717985 7691885 7687267 8680409 9029028 9450866 9657776 9699740 9697690 9438854 10362788 9990072 11074500 11505412 15824741 16175573 17344846