SHC1

SHC-transforming protein 1 ;
SHC-transforming protein 3 ;
SHC-transforming protein A ;
Src homology 2 domain-containing-transforming protein C1 ;
SH2 domain protein C1 ;

domain:In response to a variety of growth factors, isoform p46Shc and isoform p52Shc bind to phosphorylated Trk receptors through their phosphotyrosine binding (PID) and/or SH2 domains. The PID and SH2 domains bind to specific phosphorylated tyrosine residues in the Asn-Pro-Xaa-Tyr(P) motif of the Trk receptors. Isoform p46Shc and isoform p52Shc are in turn phosphorylated on three tyrosine residues within the extended proline-rich domain. These phosphotyrosines act as docking site for GRB2 and thereby are involved in Ras activation.,function:Signaling adapter that couples activated growth factor receptors to signaling pathway. Isoform p46Shc and isoform p52Shc, once phosphorylated, couple activated receptor tyrosine kinases to Ras via the recruitment of the GRB2/SOS complex and are implicated in the cytoplasmic propagation of mitogenic signals. Isoform p46Shc and isoform p52Shc may thus function as initiators of the Ras signaling cascade in various non-neuronal systems. Isoform p66Shc does not mediate Ras activation, but is involved in signal transduction pathways that regulate the cellular response to oxidative stress and life span. Isoform p66Shc acts as a downstream target of the tumor suppressor p53 and is indispensable for the ability of stress-activated p53 to induce elevation of intracellular oxidants, cytochrome c release and apoptosis. The expression of isoform p66Shc has been correlated with life span.,PTM:Phosphorylated by activated epidermal growth factor receptor. Isoform p46Shc and isoform p52Shc are phosphorylated on tyrosine residues of the Pro-rich domain. Isoform p66Shc is phosphorylated on Ser-36 upon treatment with insulin, hydrogen peroxide or irradiation with ultraviolet light.,similarity:Contains 1 PID domain.,similarity:Contains 1 SH2 domain.,subcellular location:Localized to the mitochondria matrix. Targeting of isoform p46Shc to mitochondria is mediated by its first 32 amino acids, which behave as a bona fide mitochondrial targeting sequence. Isoform p52Shc and isoform p66Shc, that contain the same sequence but more internally located, display a different subcellular localization.,subunit:Interacts with the Trk receptors in a phosphotyrosine-dependent manner. Interacts with the NPXY motif of tyrosine-phosphorylated IGF1R and INSR in vitro via the PID domain. Once activated, binds to GRB2. Interacts with tyrosine-phosphorylated CD3T. Interacts with the N-terminal region of APS. Interacts with phosphorylated LRP1 and IRS4. Interacts with INPP5D/SHIP1 and INPPL1/SHIP2.,tissue specificity:Widely expressed. Expressed in neural stem cells but absent in mature neurons.,

MAPKKK cascade, activation of MAPK activity, regulation of DNA replication, protein amino acid phosphorylation,phosphorus metabolic process, phosphate metabolic process, cell surface receptor linked signal transduction, enzyme linked receptor protein signaling pathway, transmembrane receptor protein tyrosine kinase signaling pathway,epidermal growth factor receptor signaling pathway, regulation of epidermal growth factor receptor activity,intracellular signaling cascade, protein kinase cascade, small GTPase mediated signal transduction, Ras protein signal transduction, positive regulation of cell proliferation, insulin receptor signaling pathway, response to endogenous stimulus, response to hormone stimulus, positive regulation of biosynthetic process, response to organic substance,regulation of receptor activity, positive regulation of macromolecule biosynthetic process, positive regulation of macromolecule metabolic process, phosphorylation, regulation of phosphate metabolic process, positive regulation of cellular biosynthetic process, response to insulin stimulus, cellular response to insulin stimulus, cellular response to hormone stimulus, positive regulation of kinase activity, regulation of growth, regulation of epidermal growth factor receptor signaling pathway, regulation of cell proliferation, regulation of phosphorylation, positive regulation of catalytic activity, regulation of MAP kinase activity, positive regulation of MAP kinase activity, response to peptide hormone stimulus, regulation of kinase activity, positive regulation of molecular function, positive regulation of DNA replication, regulation of protein kinase activity, positive regulation of protein kinase activity, positive regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolic process, regulation of DNA metabolic process, positive regulation of DNA metabolic process, positive regulation of nitrogen compound metabolic process, regulation of phosphorus metabolic process, regulation of transferase activity, positive regulation of transferase activity,

Cytoplasm.; [Isoform p46Shc]: Mitochondrion matrix . Localized to the mitochondria matrix. Targeting of isoform p46Shc to mitochondria is mediated by its first 32 amino acids, which behave as a bona fide mitochondrial targeting sequence. Isoform p52Shc and isoform p66Shc, that contain the same sequence but more internally located, display a different subcellular localization.; [Isoform p66Shc]: Mitochondrion . In case of oxidative conditions, phosphorylation at 'Ser-36' of isoform p66Shc, leads to mitochondrial accumulation. .

Widely expressed. Expressed in neural stem cells but absent in mature neurons.