SHC1
Description
The SHC1 (SHC adaptor protein 1) is a protein-coding gene located on chromosome 1.
SHC-transforming protein 1 is a protein that in humans is encoded by the SHC1 gene. SHC has been found to be important in the regulation of apoptosis and drug resistance in mammalian cells. SCOP classifies the 3D structure as belonging to the SH2 domain family.
== Gene and expression == The gene SHC1 is located on chromosome 1 and encodes 3 main protein isoforms: p66SHC, p52SHC and p46SHC. These proteins differ in activity and subcellular locations, p66 is the longest and while the p52 and p46 link activated receptor tyrosine kinase to the RAS pathway. The protein SHC1 also acts as a scaffold protein which is used in cell surface receptors. The three proteins that SHC1 codes for have distinctly different molecular weights. All three SHC1 proteins share the same domain arrangement consisting of an N-terminal phosphotyrosine-binding(PTB) domain and a C-terminal Src-homology2(SH2) domain. Both of the domains for the three proteins can bind to tyrosine-phosphorylated proteins but they are different in their phosphopeptide-binding specificities. P66SHC is characterized by having an additional N-terminal CH2 domain.
== Function == Overexpression of SHC proteins are associated with cancer mitogenesis, carcinogenesis and metastasis.
SHC1 is a signaling adapter protein that connects activated growth factor receptors to downstream signaling pathways. It participates in a signaling cascade triggered by activated KIT and KITLG/SCF. The p46Shc and p52Shc isoforms, upon phosphorylation, connect activated receptor tyrosine kinases to Ras through the recruitment of the GRB2/SOS complex, contributing to the spread of mitogenic signals within the cell. These isoforms are considered initiators of the Ras signaling cascade in various non-neuronal systems. The p66Shc isoform, on the other hand, does not activate Ras but is involved in pathways regulating the cell's response to oxidative stress and lifespan. It acts as a target for the tumor suppressor p53, crucial for p53's ability to induce oxidative stress, cytochrome c release, and apoptosis. The expression of p66Shc is linked to lifespan. SHC1 also plays a role in signaling downstream of the angiopoietin receptor TEK/TIE2, regulating endothelial cell migration and angiogenesis.
SHC1 is also known as SHC, SHCA.
