InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Kit

Summary

InnateDB Protein

IDBP-172085.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Kit

Protein Name

kit oncogene

Synonyms

Bs; c-KIT; CD117; Fdc; Gsfsco1; Gsfsco5; Gsfsow3; SCO1; SCO5; SOW3; Ssm; Tr-kit; W;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000005815

InnateDB Gene

IDBG-172083 (Kit)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:1698611, ECO:0000269PubMed:1714377, ECO:0000269PubMed:18725415, ECO:0000269PubMed:21037083, ECO:0000269PubMed:7509796, ECO:0000269PubMed:9528781, ECO:0000269PubMed:9722617}.

Subcellular Localization

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. {ECO:0000250}.

Disease Associations

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.

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. {ECO:0000269PubMed:1378413, ECO:0000269PubMed:18447649, ECO:0000269PubMed:7527401}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 35 experimentally validated interaction(s) in this database.
They are also associated with 43 interaction(s) predicted by orthology.

Experimentally validated
Total	35 [view]
Protein-Protein	35 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	43 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0002020	protease binding
GO:0004672	protein kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0004714	transmembrane receptor protein tyrosine kinase activity
GO:0004716	receptor signaling protein tyrosine kinase activity
GO:0005020	stem cell factor receptor activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0019955	cytokine binding
GO:0042803	protein homodimerization activity
GO:0046872	metal ion binding

Biological Process

GO:0000187	activation of MAPK activity
GO:0001541	ovarian follicle development
GO:0002318	myeloid progenitor cell differentiation
GO:0002320	lymphoid progenitor cell differentiation
GO:0002327	immature B cell differentiation
GO:0002371	dendritic cell cytokine production
GO:0002551	mast cell chemotaxis
GO:0002573	myeloid leukocyte differentiation
GO:0006468	protein phosphorylation
GO:0006687	glycosphingolipid metabolic process
GO:0006935	chemotaxis
GO:0006954	inflammatory response
GO:0007169	transmembrane receptor protein tyrosine kinase signaling pathway
GO:0007281	germ cell development
GO:0007283	spermatogenesis
GO:0007286	spermatid development
GO:0008284	positive regulation of cell proliferation
GO:0008354	germ cell migration
GO:0008360	regulation of cell shape
GO:0008542	visual learning
GO:0008584	male gonad development
GO:0009314	response to radiation
GO:0010628	positive regulation of gene expression
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0019221	cytokine-mediated signaling pathway
GO:0023014	signal transduction by phosphorylation
GO:0030032	lamellipodium assembly
GO:0030097	hemopoiesis
GO:0030154	cell differentiation
GO:0030217	T cell differentiation
GO:0030218	erythrocyte differentiation
GO:0030318	melanocyte differentiation
GO:0030335	positive regulation of cell migration
GO:0031274	positive regulation of pseudopodium assembly
GO:0031532	actin cytoskeleton reorganization
GO:0032762	mast cell cytokine production
GO:0035019	somatic stem cell maintenance
GO:0035162	embryonic hemopoiesis
GO:0035234	ectopic germ cell programmed cell death
GO:0035556	intracellular signal transduction
GO:0035855	megakaryocyte development
GO:0038093	Fc receptor signaling pathway
GO:0038109	Kit signaling pathway
GO:0038162	erythropoietin-mediated signaling pathway
GO:0042511	positive regulation of tyrosine phosphorylation of Stat1 protein
GO:0042517	positive regulation of tyrosine phosphorylation of Stat3 protein
GO:0042523	positive regulation of tyrosine phosphorylation of Stat5 protein
GO:0043069	negative regulation of programmed cell death
GO:0043303	mast cell degranulation
GO:0043406	positive regulation of MAP kinase activity
GO:0043410	positive regulation of MAPK cascade
GO:0043473	pigmentation
GO:0045747	positive regulation of Notch signaling pathway
GO:0046427	positive regulation of JAK-STAT cascade
GO:0046777	protein autophosphorylation
GO:0048066	developmental pigmentation
GO:0048070	regulation of developmental pigmentation
GO:0048103	somatic stem cell division
GO:0048170	positive regulation of long-term neuronal synaptic plasticity
GO:0048565	digestive tract development
GO:0048863	stem cell differentiation
GO:0050673	epithelial cell proliferation
GO:0050910	detection of mechanical stimulus involved in sensory perception of sound
GO:0051091	positive regulation of sequence-specific DNA binding transcription factor activity
GO:0060326	cell chemotaxis
GO:0060374	mast cell differentiation
GO:0097067	cellular response to thyroid hormone stimulus
GO:0097324	melanocyte migration
GO:0097326	melanocyte adhesion

Cellular Component

GO:0001669	acrosomal vesicle
GO:0005615	extracellular space
GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005886	plasma membrane
GO:0005911	cell-cell junction
GO:0009897	external side of plasma membrane
GO:0009898	cytoplasmic side of plasma membrane
GO:0009986	cell surface
GO:0016021	integral component of membrane
GO:0042629	mast cell granule

Protein Structure and Domains

PDB ID

MGI:96677

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine- /dual specificity protein kinase, catalytic domain
IPR003598 Immunoglobulin subtype 2
IPR003599 Immunoglobulin subtype
IPR007110 Immunoglobulin-like domain
IPR011009 Protein kinase-like domain
IPR013098 Immunoglobulin I-set
IPR013151 Immunoglobulin
IPR016243 Tyrosine-protein kinase, CSF-1/PDGF receptor
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714
PF07679
PF00047

PRINTS

PR00109

PIRSF

PIRSF000615
PIRSF500947

SMART

SM00220
SM00408
SM00409
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References