Mouse Gene Kit (ENSMUST00000144270.7) from GENCODE VM23 Comprehensive Transcript Set (only Basic displayed by default)
Description: Mus musculus KIT proto-oncogene receptor tyrosine kinase (Kit), transcript variant 2, mRNA. (from RefSeq NM_021099) RefSeq Summary (NM_001122733): The c-Kit proto-oncogene is the cellular homolog of the transforming gene of a feline retrovirus (v-Kit). The c-kit protein includes characteristics of a protein kinase transmembrane receptor. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]. Gencode Transcript: ENSMUST00000144270.7 Gencode Gene: ENSMUSG00000005672.12 Transcript (Including UTRs) Position: mm10 chr5:75,574,916-75,656,722 Size: 81,807 Total Exon Count: 21 Strand: + Coding Region Position: mm10 chr5:75,575,052-75,654,545 Size: 79,494 Coding Exon Count: 21
ID:KIT_MOUSE DESCRIPTION: RecName: Full=Mast/stem cell growth factor receptor Kit; Short=SCFR; EC=2.7.10.1; AltName: Full=Proto-oncogene c-Kit; AltName: Full=Tyrosine-protein kinase Kit; AltName: CD_antigen=CD117; Flags: Precursor; 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 [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. ENZYME REGULATION: Present in an inactive conformation in the absence of bound ligand. KITLG/SCF binding leads to dimerization and activation by autophosphorylation. SUBUNIT: Monomer in the absence of bound KITLG/SCF. Homodimer in the presence of bound KITLG/SCF, forming a heterotetramer with two KITLG/SCF molecules. Interacts (via phosphorylated tyrosine residues) with the adapter proteins GRB2 and GRB7 (via SH2 domain), and SH2B2/APS. Interacts (via C-terminus) with MPDZ (via the tenth PDZ domain). Interacts (via phosphorylated tyrosine residues) with the protein phosphatases PTPN6/SHP-1 (via SH2 domain), PTPN11/SHP-2 (via SH2 domain) and PTPRU. Interacts with DOK1 and TEC (By similarity). Interacts with the protein kinase FES/FPS. Interacts with PLCG1. Interacts (via phosphorylated tyrosine residues) with PIK3R1 and PIK3 catalytic subunit. SUBCELLULAR LOCATION: Isoform 1: Cell membrane; Single-pass type I membrane protein. SUBCELLULAR LOCATION: Isoform 2: Cell membrane; Single-pass type I membrane protein. SUBCELLULAR LOCATION: Isoform 3: Cytoplasm. Note=Detected in the cytoplasm of spermatozoa, especially in the equatorial and subacrosomal region of the sperm head (By similarity). TISSUE SPECIFICITY: Isoform 1 and isoform 2 are detected in bone marrow cells, spermatogonia and spermatocytes, but not in round spermatids, elongating spermatids and spermatozoa. Isoform 3 is detected in round spermatids, elongating spermatids and spermatozoa, but not in spermatogonia and spermatocytes (at protein level). Isoform 1 is widely expressed and detected in fetal liver and bone marrow. Isoform 3 is detected in bone marrow cells enriched in hematopoietic stem cells. PTM: Ubiquitinated by SOCS6. KIT is rapidly ubiquitinated after autophosphorylation induced by KITLG/SCF binding, leading to internalization and degradation (By similarity). PTM: Autophosphorylated on tyrosine residues. KITLG/SCF binding promotes autophosphorylation of isoform 1 and isoform 2. Isoform 1 shows low levels of tyrosine phosphorylation in the absence of added KITLG/SCF, while isoform 2 requires stimulation by KITLG/SCF for phosphorylation (in vitro). Phosphorylation of Tyr-573 is required for interaction with PTPN6/SHP-1. Phosphorylation of Tyr- 571 is required for interaction with PTPN11/SHP-2. Phosphorylated tyrosine residues are important for interaction with specific binding partners. DISEASE: Note=Defects in Kit are the cause of the white-spotting phenotype (W). White-spotting variants induces severe effects on pigmentation, gametogenesis and hematopoiesis. Mice homozygous for W42 die perinatally of macrocytic anemia. MISCELLANEOUS: 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. SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily. SIMILARITY: Contains 5 Ig-like C2-type (immunoglobulin-like) domains. SIMILARITY: Contains 1 protein kinase domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P05532
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
KEGG - Kyoto Encyclopedia of Genes and Genomes mmu04060 - Cytokine-cytokine receptor interaction mmu04144 - Endocytosis mmu04640 - Hematopoietic cell lineage mmu04916 - Melanogenesis mmu05200 - Pathways in cancer mmu05221 - Acute myeloid leukemia
BioCarta from NCI Cancer Genome Anatomy Project m_badPathway - Regulation of BAD phosphorylation m_melanocytepathway - Melanocyte Development and Pigmentation Pathway
Reactome (by CSHL, EBI, and GO)
Protein P05532 (Reactome details) participates in the following event(s):