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DrugBank target: P10721

DrugBank target: P10721 (KIT_HUMAN)     

Example drug-target structure: 3g0e

( There are 13 structures corresponding to this UniProt sequence in the PDB. Click the orange, plus icon above for a list. )

Mast/stem cell growth factor receptor Kit

Piebald trait protein, Proto-oncogene c-Kit, Tyrosine-protein kinase Kit, p145 c-kit, v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog, SCFR, PBT.

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..

Enzyme

2.7.10.1   [EC->PDB]   [IntEnz]   [ExPASy]   [KEGG]  

Catalytic activity

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

Disease(s)

Piebald trait (PBT) [MIM:172800]: Autosomal dominant genetic developmental abnormality of pigmentation characterized by congenital patches of white skin and hair that lack melanocytes. Note=The disease is caused by mutations affecting the gene represented in this entry.
Gastrointestinal stromal tumor (GIST) [MIM:606764]: 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. Note=The gene represented in this entry is involved in disease pathogenesis.
Testicular germ cell tumor (TGCT) [MIM:273300]: 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. Note=The gene represented in this entry may be involved in disease pathogenesis.
Leukemia, acute myelogenous (AML) [MIM:601626]: 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. Note=The gene represented in this entry is involved in disease pathogenesis. Somatic mutations that lead to constitutive activation of KIT are detected in AML patients. These mutations fall into two classes, the most common being in-frame internal tandem duplications of variable length in the juxtamembrane region that disrupt the normal regulation of the kinase activity. Likewise, point mutations in the kinase domain can result in a constitutively activated kinase.

Schematic diagram of Pfam domains in target sequence plus wiring diagrams of PDB structures containing drug molecules

3g0e
1t46

Key:    PfamA domain  Secondary structure  Bound drug molecule

Sequence length: 975 a.a.

Approved drugs targeting this protein

The DrugBank database identifies 8 drugs for this target protein:

 

Generic name: DB00398 sorafenib
BAX
Formula: C21H16Clf3N4O3
Structure: There are 6 PDB structures containing this molecule although none are bound to the above target protein.
Generic name: DB01268 sunitinib
B49
Formula: C22H27Fn4O2
Structure: There are 7 PDB structures containing this molecule of which 2 are bound to the above target protein.
 
Generic name: DB08896 regorafenib
Formula: C21H15Clf4N4O3
Structure: There are no structures of this molecule in the PDB.
Generic name: DB00619 imatinib
STI
Formula: C29H31N7O
Structure: There are 16 PDB structures containing this molecule of which 1 is bound to the above target protein.
Generic name: DB01254 dasatinib
1N1
Formula: C22H26Cln7O2S
Structure: There are 10 PDB structures containing this molecule although none are bound to the above target protein.
Generic name: DB04868 nilotinib
NIL
Formula: C28H22F3N7O
Structure: There are 2 PDB structures containing this molecule although none are bound to the above target protein.
Generic name: DB08901 ponatinib
0LI
Formula: C29H27F3N6O
Structure: There are 4 PDB structures containing this molecule although none are bound to the above target protein.
 
Generic name: DB06589 pazopanib
Formula: C21H23N7O2S
Structure: There are no structures of this molecule in the PDB.

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