KIT

This gene encodes the human homolog of the proto-oncogene c-kit. C-kit was first identified as the cellular homolog of the feline sarcoma viral oncogene v-kit. This protein is a type 3 transmembrane receptor for MGF (mast cell growth factor, also known as stem cell factor). Mutations in this gene are associated with gastrointestinal stromal tumors, mast cell disease, acute myelogenous lukemia, and piebaldism. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

KIT Proto-Oncogene Receptor Tyrosine Kinase

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.

Actin cytoskeleton reorganizationManual Assertion Based On ExperimentIDA:UniProtKB
B cell differentiationManual Assertion Based On ExperimentIBA:GO_Central
Cell chemotaxisManual Assertion Based On ExperimentIDA:UniProtKB
Cellular response to thyroid hormone stimulusIEA:Ensembl
Cytokine-mediated signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Detection of mechanical stimulus involved in sensory perception of soundISS:UniProtKB
Digestive tract developmentISS:UniProtKB
Ectopic germ cell programmed cell deathIEA:Ensembl
Embryonic hemopoiesisISS:UniProtKB
Epithelial cell proliferationIEA:Ensembl
Erythrocyte differentiationISS:UniProtKB
Erythropoietin-mediated signaling pathwayISS:UniProtKB
Fc receptor signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Germ cell migrationIEA:Ensembl
Glycosphingolipid metabolic processIEA:Ensembl
Hematopoietic progenitor cell differentiationManual Assertion Based On ExperimentIBA:GO_Central
Hematopoietic stem cell migrationIEA:Ensembl
HemopoiesisManual Assertion Based On ExperimentTAS:UniProtKB
Immature B cell differentiationISS:UniProtKB
Inflammatory responseISS:UniProtKB
Intracellular signal transductionIEA:Ensembl
Kit signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Lamellipodium assemblyISS:UniProtKB
Lymphoid progenitor cell differentiationIEA:Ensembl
Male gonad developmentManual Assertion Based On ExperimentIEP:UniProtKB
Mast cell chemotaxisManual Assertion Based On ExperimentIDA:UniProtKB
Mast cell degranulationManual Assertion Based On ExperimentIMP:UniProtKB
Mast cell differentiationISS:UniProtKB
Mast cell proliferationManual Assertion Based On ExperimentTAS:UniProtKB
Megakaryocyte developmentISS:UniProtKB
Melanocyte adhesionISS:UniProtKB
Melanocyte differentiationISS:UniProtKB
Melanocyte migrationISS:UniProtKB
Myeloid progenitor cell differentiationIEA:Ensembl
Negative regulation of programmed cell deathIEA:Ensembl
Ovarian follicle developmentISS:UniProtKB
PigmentationISS:UniProtKB
Positive regulation of cell migrationManual Assertion Based On ExperimentIBA:GO_Central
Positive regulation of cell population proliferationIEA:Ensembl
Positive regulation of colon smooth muscle contractionIEA:Ensembl
Positive regulation of dendritic cell cytokine productionISS:UniProtKB
Positive regulation of DNA-binding transcription factor activityManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of kinase activityManual Assertion Based On ExperimentIBA:GO_Central
Positive regulation of long-term neuronal synaptic plasticityIEA:Ensembl
Positive regulation of MAP kinase activityManual Assertion Based On ExperimentIBA:GO_Central
Positive regulation of MAPK cascadeManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of mast cell cytokine productionManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of Notch signaling pathwayIEA:Ensembl
Positive regulation of phosphatidylinositol 3-kinase activityManual Assertion Based On ExperimentTAS:UniProtKB
Positive regulation of phosphatidylinositol 3-kinase signalingManual Assertion Based On ExperimentTAS:UniProtKB
Positive regulation of phospholipase C activityManual Assertion Based On ExperimentTAS:UniProtKB
Positive regulation of pseudopodium assemblyIEA:Ensembl
Positive regulation of pyloric antrum smooth muscle contractionIEA:Ensembl
Positive regulation of receptor signaling pathway via JAK-STATManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of small intestine smooth muscle contractionIEA:Ensembl
Positive regulation of tyrosine phosphorylation of STAT proteinManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of vascular associated smooth muscle cell differentiationManual Assertion Based On ExperimentIDA:BHF-UCL
Protein autophosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of bile acid metabolic processIEA:Ensembl
Regulation of cell population proliferationManual Assertion Based On ExperimentTAS:UniProtKB
Regulation of cell shapeISS:UniProtKB
Response to cadmium ionIEA:Ensembl
Signal transductionManual Assertion Based On ExperimentTAS:ProtInc
Somatic stem cell divisionIEA:Ensembl
Somatic stem cell population maintenanceIEA:Ensembl
Spermatid developmentIEA:Ensembl
SpermatogenesisISS:UniProtKB
Stem cell differentiationISS:UniProtKB
Stem cell population maintenanceManual Assertion Based On ExperimentTAS:UniProtKB
T cell differentiationISS:UniProtKB
Tongue developmentIEA:Ensembl
Transmembrane receptor protein tyrosine kinase signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central
Visual learningIEA:Ensembl

Isoform 1&2: Cell membrane
Isoform 3: Cytoplasm. Detected in the cytoplasm of spermatozoa, especially in the equatorial and subacrosomal region of the sperm head.

Piebald trait (PBT):
Autosomal dominant genetic developmental abnormality of pigmentation characterized by congenital patches of white skin and hair that lack melanocytes.
Gastrointestinal stromal tumor (GIST):
Common mesenchymal neoplasms arising in the gastrointestinal tract, most often in the stomach. They are histologically, immunohistochemically, and genetically different from typical leiomyomas, leiomyosarcomas, and schwannomas. Most GISTs are composed of a fairly uniform population of spindle-shaped cells. Some tumors are dominated by epithelioid cells or contain a mixture of spindle and epithelioid morphologies. Primary GISTs in the gastrointestinal tract commonly metastasize in the omentum and mesenteries, often as multiple nodules. However, primary tumors may also occur outside of the gastrointestinal tract, in other intra-abdominal locations, especially in the omentum and mesentery.
Testicular germ cell tumor (TGCT):
A common malignancy in males representing 95% of all testicular neoplasms. TGCTs have various pathologic subtypes including: unclassified intratubular germ cell neoplasia, seminoma (including cases with syncytiotrophoblastic cells), spermatocytic seminoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, and teratoma.
Leukemia, acute myelogenous (AML):
A subtype of acute leukemia, a cancer of the white blood cells. AML is a malignant disease of bone marrow characterized by maturational arrest of hematopoietic precursors at an early stage of development. Clonal expansion of myeloid blasts occurs in bone marrow, blood, and other tissue. Myelogenous leukemias develop from changes in cells that normally produce neutrophils, basophils, eosinophils and monocytes.
Mastocytosis, cutaneous (MASTC):
A form of mastocytosis, a heterogeneous group of disorders associated with abnormal proliferation and accumulation of mast cells in various tissues, especially in the skin and hematopoietic organs. MASTC is an autosomal dominant form characterized by macules, papules, nodules, or diffuse infiltration of the skin, often associated with localized hyperpigmentation. Gentle rubbing of the lesions induces histamine release from mechanically activated mast cells, causing local wheals, erythema, and often pruritus, a phenomenon termed Darier sign.
Mastocytosis, systemic (MASTSYS):
A severe form of mastocytosis characterized by abnormal proliferation and accumulation of mast cells in several organs, resulting in a systemic disease that may affect bone, gastrointestinal tract, lymphatics, spleen, and liver. In some cases, it is associated with a clonal hematologic non-mast-cell lineage disease, such as a myelodysplastic or myeloproliferative disorder. It can also lead to mast cell leukemia, which carries a high risk of mortality.

Extracellular: 26-524
Helical: 525-545
Cytoplasmic: 546-976

Ubiquitinated by SOCS6. KIT is rapidly ubiquitinated after autophosphorylation induced by KITLG/SCF binding, leading to internalization and degradation.
Autophosphorylated on tyrosine residues. KITLG/SCF binding enhances autophosphorylation. Isoform 1 shows low levels of tyrosine phosphorylation in the absence of added KITLG/SCF (in vitro). Kinase activity is down-regulated by phosphorylation on serine residues by protein kinase C family members. Phosphorylation at Tyr-568 is required for interaction with PTPN11/SHP-2, CRK (isoform Crk-II) and members of the SRC tyrosine-protein kinase family. Phosphorylation at Tyr-570 is required for interaction with PTPN6/SHP-1. Phosphorylation at Tyr-703, Tyr-823 and Tyr-936 is important for interaction with GRB2. Phosphorylation at Tyr-721 is important for interaction with PIK3R1. Phosphorylation at Tyr-823 and Tyr-936 is important for interaction with GRB7.