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Shc1
an adaptor protein containing a SH2 domain and a PID domain within a PH domain-like fold. Three isoforms (p66, p52 and p46), produced by alternative initiation, variously regulate growth factor signaling, oncogenesis, intracellular oxidant levels, and apoptosis. Isoforms p46 and p52, once phosphorylated, couple activated receptor tyrosine kinases to Ras via the recruitment of the GRB2/SOS complex, thus initiating the cytoplasmic proliferative Ras signaling cascade in various non-neuronal systems. Isoform p66 does not mediate Ras activation, but associates with mitochondria where it controls intracellular redox status, mitochondrial permeability, life span, and stress-induced apoptosis. p66 acts as a downstream target of the tumor suppressor p53 and is required for the ability of stress-activated p53 to induce elevation of intracellular oxidants, cytochrome c release and apoptosis. P66 deletion in mice decreases the incidence of aging-associated diseases, such as atherosclerosis, and significantly prolongs life span. Participates in signaling downstream of TIE2, the tyrosine kinase receptor for angiopoietin, and plays a role in the regulation of endothelial cell migration and sprouting angiogenesis. p66Shc is known to be activated by the mutant SOD1 associated with familial forms of amyotrophic lateral sclerosis (ALS), causing a decrease in the activity of Rac1 through a redox-sensitive regulation. p66 plays a role in mediating mitophagy and determining neuronal cell fate following acute oxygen glucose deprivation. Note: This description may include information from UniProtKB.
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| Protein type: Adaptor/scaffold; Mitochondrial; Motility/polarity/chemotaxis; Apoptosis |
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Cellular Component: mitochondrial matrix; plasma membrane; endosome membrane; cytosol; nucleus
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Molecular Function: insulin-like growth factor receptor binding; protein binding; ephrin receptor binding; phosphotyrosine binding; protein-tyrosine kinase activity; neurotrophin TRKA receptor binding; phospholipid binding; transmembrane receptor protein tyrosine kinase adaptor protein activity; insulin receptor binding; epidermal growth factor receptor binding
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Biological Process: response to nicotine; nerve growth factor receptor signaling pathway; activation of MAPK activity; positive regulation of smooth muscle cell proliferation; heart development; response to toxin; response to glucocorticoid stimulus; cell-cell adhesion; regulation of growth; positive regulation of cell proliferation; angiogenesis; neurite development; aging; epidermal growth factor receptor signaling pathway; platelet activation; organ regeneration; fibroblast growth factor receptor signaling pathway; unfolded protein response; regulation of epidermal growth factor receptor activity; MAPKKK cascade; unfolded protein response, activation of signaling protein activity; response to hydrogen peroxide; actin cytoskeleton reorganization; Ras protein signal transduction; insulin receptor signaling pathway; response to hypoxia; positive regulation of vasoconstriction; blood coagulation; leukocyte migration; positive regulation of DNA replication
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Reference #:
P29353 (UniProtKB)
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| Alt. Names/Synonyms: FLJ26504; SH2 domain protein C1; SHC; SHC (Src homology 2 domain containing) transforming protein 1; SHC (Src homology 2 domain-containing) transforming protein 1; SHC-transforming protein 1; SHC-transforming protein 3; SHC-transforming protein A; SHC1; SHCA; Src homology 2 domain-containing-transforming protein C1 |
| Gene Symbols: SHC1 |
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Molecular weight: 62,822 Da
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Basal Isoelectric point: 6.01
Predict pI for various phosphorylation states
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CST Pathways:
B Cell Receptor Signaling
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ErbB/HER Signaling
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Insulin Receptor Signaling
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Jak/Stat/IL-6 Signaling
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MAPK/Erk in Growth and Differentiation
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SAPK/JNK Signaling Cascades
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TGF-ß Signaling
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Protein-Specific Antibodies or siRNAs from Cell Signaling Technology®
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