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This gene encodes a receptor tyrosine kinase. This gene was initially identified as a homolog of the feline sarcoma viral oncogene v-kit and is often referred to as proto-oncogene c-Kit. The canonical form of this glycosylated transmembrane protein has an N-terminal extracellular region with five immunoglobulin-like domains, a transmembrane region, and an intracellular tyrosine kinase domain at the C-terminus. Upon activation by its cytokine ligand, stem cell factor (SCF), this protein phosphorylates multiple intracellular proteins that play a role in in the proliferation, differentiation, migration and apoptosis of many cell types and thereby plays an important role in hematopoiesis, stem cell maintenance, gametogenesis, melanogenesis, and in mast cell development, migration and function. This protein can be a membrane-bound or soluble protein. Mutations in this gene are associated with gastrointestinal stromal tumors, mast cell disease, acute myelogenous leukemia, and piebaldism. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2020]
c-KIT activation has been shown to have oncogenic activity in gastrointestinal stromal tumors (GISTs), melanomas, lung cancer, and other tumor types. The targeted therapeutics nilotinib and sunitinib have shown efficacy in treating KIT overactive patients, and are in late-stage trials in melanoma and GIST. KIT overactivity can be the result of many genomic events from genomic amplification to overexpression to missense mutations. Missense mutations have been shown to be key players in mediating clinical response and acquired resistance in patients being treated with these targeted therapeutics.
KIT (KIT Proto-Oncogene, Receptor Tyrosine Kinase) is a Protein Coding gene. Diseases associated with KIT include Gastrointestinal Stromal Tumor and Piebald Trait. Among its related pathways are Downstream signaling events of B Cell Receptor (BCR) and ERK Signaling. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and protein kinase activity. An important paralog of this gene is CSF1R.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000166 | nucleotide binding | IEA | -- |
GO:0002020 | protease binding | IEA | -- |
GO:0004672 | protein kinase activity | IEA | -- |
GO:0004713 | protein tyrosine kinase activity | TAS | 1717985 |
GO:0004714 | transmembrane receptor protein tyrosine kinase activity | IBA,IDA | 21640708 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0001650 | fibrillar center | IDA | -- |
GO:0001669 | acrosomal vesicle | IEA | -- |
GO:0005615 | extracellular space | IDA | 14625290 |
GO:0005737 | cytoplasm | IEA | -- |
GO:0005886 | plasma membrane | TAS | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | RET signaling |
.92
|
.92
|
2 | Apoptotic Pathways in Synovial Fibroblasts |
Cellular Apoptosis Pathway
.85
Mitochondrial Apoptosis
.85
Apoptotic Pathways in Synovial Fibroblasts
.84
p53 Mediated Apoptosis
.84
DHA Signaling
.74
Telomerase Components in Cell Signaling
.72
|
PPAR Pathway
.66
Rac1 Pathway
.65
Actin-Based Motility by Rho Family GTPases
.62
ERK5 Signaling
.61
eIF2 Pathway
.60
Nuclear Receptor Activation by Vitamin-A
.57
|
3 | GPCR Pathway |
Paxillin Interactions
.73
Ras Pathway
.73
GPCR Pathway
.62
Pancreatic Adenocarcinoma
.59
|
Breast Cancer Regulation by Stathmin1
.58
NFAT in Immune Response
.58
Estrogen Pathway
.55
P2Y Receptor Signaling
.38
|
4 | GAB1 signalosome |
.89
|
|
5 | ERK Signaling |
ERK Signaling
.61
Rho Family GTPases
.61
MAPK Signaling
.58
|
Molecular Mechanisms of Cancer
.51
ILK Signaling
.49
|
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000165 | MAPK cascade | TAS | -- |
GO:0000187 | activation of MAPK activity | IDA | 21640708 |
GO:0001541 | ovarian follicle development | IEA,ISS | -- |
GO:0002244 | hematopoietic progenitor cell differentiation | IBA | 21873635 |
GO:0002318 | myeloid progenitor cell differentiation | IEA | -- |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Sunitinib | Approved, Investigational | Pharma | Target, inhibitor | VEGFR/PDGFRβ/ KIT/ FLT3/RET/CSF-1R inhibitor, RTK inhibitor, Potent VEGFR, PDGFRbeta and KIT inhibitor, Kinase Inhibitors, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors | 556 | |
Dasatinib | Approved, Investigational | Pharma | Target, antagonist, Inhibition, inhibitor | Kinase Inhibitors, SRC/BCR-ABL tyrosine kinase inhibitors | 332 | |
imatinib | Approved | Pharma | Target, antagonist, multitarget, inhibitor | Kinase Inhibitors, SRC/BCR-ABL tyrosine kinase inhibitors | 0 | |
Sorafenib | Approved, Investigational | Pharma | Target, antagonist, inhibitors, inhibitor | Raf kinases and tyrosine kinases inhibitor, RAF, VEGFR2, and PDGFR-beta inhibitors, Kinase Inhibitors, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors | 795 | |
midostaurin | Approved, Investigational | Pharma | Target, antagonist, inhibitor | Kinase Inhibitors | 50 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
ADP |
|
58-64-0 |
|
|||
N-desmethylimatinib |
|
Compound | Action | Cas Number |
---|---|---|
Amuvatinib (MP-470, HPK 56) | Tyrosine kinase inhibitor | 850879-09-3 |
Apatinib | VEGFR2 inhibitor, orally bioavailable, selective | 811803-05-1 |
Axitinib (AG 013736) | VEGFR1/ c-Kit inhibitor | 319460-85-0 |
AZD2932 | inhibitor of VEGFR-2, PDGFRβ, Flt-3, and c-Kit | 883986-34-3 |
Cabozantinib (XL184, BMS-907351) | VEGFR2/Met/Ret/Kit/FLT//AXL inhibitor | 849217-68-1 |
Dovitinib (TKI-258, CHIR-258) | Multitargeted RTK inhibitor | 405169-16-6 |
Dovitinib Dilactic acid | 852433-84-2 | |
Imatinib (STI571) | Protein-tyrosine kinase inhibitor | 152459-95-5 |
Imatinib hydrochloride | V-Abl/c-Kit/PDGFR inhibitor | 862366-25-4 |
Imatinib Mesylate (STI571) | Abl/c-kit/PDGFR inhibitor | 220127-57-1 |
Linifanib (ABT-869) | VEGFR/PDGFR inhibitor | 796967-16-3 |
Masitinib (AB1010) | Tyrosine kinase inhibitor, potent and selective | 790299-79-5 |
Motesanib | Inhibitor of Flk-1/Flt-4/PDGFR-/c-Kit | 453562-69-1 |
Motesanib Diphosphate (AMG-706) | VEGFR/ PDGFR/c-Kit/Ret inhibitor | 857876-30-3 |
OSI-930 | Inhibitor of Kit, KDR, Flt, CSF-1R, c-Raf and Lck | 728033-96-3 |
Pazopanib (GW-786034) | VEGFR/PDGFR/FGFR inhibitor | 635702-64-6 |
Pazopanib Hydrochloride | VEGFR/PDGFR/FGFR/c-Kit/ c-Fms inhibitor | 635702-64-6 |
Regorafenib | Inhibitor of VEGFR/PDGFR/FGFR/mutant kit/RET/Raf-1 | 755037-03-7 |
SU14813 | Tyrosine kinase inhibitor | 627908-92-3 |
SU14813 maleate | VEGFR/PDGFR/Kit/FLT-3 inhibitor | 849643-15-8 |
SU5416 | VEGF receptor inhibitor and AHR agonist | 204005-46-9 |
Sunitinib | RTK inhibitor | 557795-19-4 |
Sunitinib malate | VEGFR/PDGFRβ/ KIT/ FLT3/RET/CSF-1R inhibitor | 341031-54-7 |
Telatinib (BAY 57-9352) | VEGFR-2/-3,PDGFR-β and c-Kit inhibitor | 332012-40-5 |
TG 100801 | Multi-kinase inhibitor | 867331-82-6 |
Toceranib | c-Kit/VEGFR/PDGFR inhibtor | 356068-94-5 |
Vatalanib (PTK787) 2HCl | Tyrosine kinase receptor inhibitor | 212141-51-0 |
ExUns: | 1 | ^ | 2a | · | 2b | ^ | 3 | ^ | 4a | · | 4b | ^ | 5 | ^ | 6 | ^ | 7 | ^ | 8a | · | 8b | ^ | 9a | · | 9b | ^ | 10 | ^ | 11a | · | 11b | ^ | 12 | ^ | 13a | · | 13b | ^ | 14a | · | 14b | ^ | 15 | ^ | 16a | · | 16b | ^ | 17a | · | 17b | ^ |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SP1: | - | - | - | |||||||||||||||||||||||||||||||||||||||||||||||||
SP2: | - | |||||||||||||||||||||||||||||||||||||||||||||||||||
SP3: | ||||||||||||||||||||||||||||||||||||||||||||||||||||
SP4: | - | |||||||||||||||||||||||||||||||||||||||||||||||||||
SP5: | ||||||||||||||||||||||||||||||||||||||||||||||||||||
SP6: |
ExUns: | 18 | ^ | 19 | ^ | 20 | ^ | 21 |
---|---|---|---|---|---|---|---|
SP1: | |||||||
SP2: | |||||||
SP3: | |||||||
SP4: | |||||||
SP5: | |||||||
SP6: |
This gene was present in the common ancestor of animals.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | KIT 30 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | KIT 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | KIT 30 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Kit 30 |
|
||
Mouse (Mus musculus) |
Mammalia | Kit 30 17 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | KIT 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | KIT 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | KIT 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | KIT 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | kit 30 |
|
||
Str.17605 30 |
|
||||
African clawed frog (Xenopus laevis) |
Amphibia | kit-A 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | kita 30 31 |
|
OneToMany | |
kitb 31 |
|
OneToMany | |||
-- 30 |
|
||||
Fruit Fly (Drosophila melanogaster) |
Insecta | CG3277 32 |
|
|
|
Worm (Caenorhabditis elegans) |
Secernentea | old-1 32 |
|
|
|
old-2 32 |
|
|
|||
ver-2 32 |
|
|
|||
kin-16 32 |
|
|
|||
Y50D4B.6 32 |
|
|