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Description

Mast/stem cell growth factor receptor Kit (UniProt: P10721, also known as EC: 2.7.10.1, SCFR, Piebald trait protein, PBT, Proto-oncogene c-Kit, Tyrosine-protein kinase Kit, p145 c-kit, v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) is encoded by the KIT (also known as SCFR) gene (Gene ID: 3815) in human. C-Kit is a single-pass type I membrane protein with tyrosine protein kinase activity and serves as a cell-surface receptor for the cytokine KITLG/SCF and is shown to play a significant role in the regulation of cell survival, cell proliferation, stem cell maintenance, gametogenesis and other functions. c-Kit exists as a monomer in the absence of bound KITLG/SCF, however, it homodimerizes in the presence of bound KITLG/SCF and forms a heterotetramer with two KITLG/SCF molecules. c-Kit can be autophosphorylated on tyrosine residues and KITLG/SCF binding enhances its autophosphorylation. Its kinase activity is down-regulated by phosphorylation on serine residues by PKC family members. Phosphorylation at Tyrosine 568 is essential for its interaction with PTPN11/SHP-2, CRK (isoform Crk-II) and members of the SRC tyrosine-protein kinase family. c-Kit can be ubiquitinated by SOCS6 and it is rapidly ubiquitinated after autophosphorylation induced by KITLG/SCF binding, leading to its internalization and degradation. c-Kit is synthesized with a signal peptide (aa 1-25), which is subsequently cleaved off to produce the mature form with an extracellular domain (aa 26-524), a short transmembrane domain (aa 525-545), and a cytoplasmic domain (aa 546-976. Its two ATP-binding sites are localized to amino acids 596-603 and 671-677. Lack of c-Kit expression has been reported in multiple cancer types and c-Kit expressing cells display a regression of typical morphological features of malignancy.