Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

KIT (P10721) - Overview - Molecular Target Synopsis

Protein


KIT, Mast/stem cell growth factor receptor Kit
Enzyme Classification 2.7.10.1
UniProt P10721

Also Known as KIT_HUMAN, KIT, SCFR

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. 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 PIK3R1 and PIK3 catalytic subunit. Interacts (via phosphorylated tyrosine) with CRK (isoform Crk-II), FYN, SHC1 and MATK/CHK (via SH2 domain). Interacts with LYN and FES/FPS. 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 PLCG1. Interacts with DOK1 and TEC. Interacts (KITLG/SCF-bound) with IL1RL1. Interacts with IL1RAP (independent of stimulation with KITLG/SCF). A mast cell-specific KITLG/SCF-induced interleukin-33 signaling complex contains IL1RL1, IL1RAP, KIT and MYD88.

6GQM
CRYSTAL STRUCTURE OF HUMAN C-KIT KINASE DOMAIN IN COMPLEX WITH A SMALL MOLECULE INHIBITOR, AZD3229
RCSB/PDB
Inspect Structure
See all 3D Structures for KIT

Isoforms / Transcripts (Protein Coding)


Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform
976ENSG00000157404ENST00000288135ENSP00000288135P10721-1
972ENSG00000157404ENST00000412167ENSP00000390987P10721-2
413P10721-3

Drugs


KIT is targeted by Approved Drugs Imatinib, Axitinib, Sunitinib, Sorafenib, Dasatinib, Pazopanib. (see details)
Imatinib
Axitinib
Sunitinib
Sorafenib
Dasatinib
Pazopanib

Sub-cellular localization


UniProt: KIT is active in the following subcellular-locations: cell membrane, cytoplasm.
GO terms: KIT is active in the following subcellular-locations: acrosomal vesicle, cell-cell junction, cytoplasmic side of plasma membrane, external side of plasma membrane, extracellular space, integral component of plasma membrane, mast cell granule, plasma membrane, receptor complex.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project KIT has gain in 6 cell-lines, loss in 4 cell-lines and no signal in 995 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: MALME_3M, SF_268, HL_60

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: OCI-M1, NCI-H1930, HCC1599

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: HUVEC, NHLF, CD34-positive mobilized cell

(see details)

RNA Interference


KIT was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: H1975, HEC1A. (see details)

3D Structures


For KIT there are:
18 structures (27 chains) solved
15 are solved in complex with at least one small molecule ligand
4 are solved with an approved drug

KIT is solved in complex with the approved drug(s):

B49/SUNITINIB (3G0E_A, 3G0F_A, 3G0F_B),
0LI/PONATINIB (4U0I_A),
STI/IMATINIB (1T46_A).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


KIT has been screened with 2197 compounds (6547 bioactivities), 823 compounds have bioactivities that show binding affinity of <= 500nM (1498 bioactivities). (see details)