InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: SHC1

Summary

InnateDB Protein

IDBP-103011.7

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

SHC1

Protein Name

SHC (Src homology 2 domain containing) transforming protein 1

Synonyms

SHC; SHCA;

Species

Homo sapiens

Ensembl Protein

ENSP00000357435

InnateDB Gene

IDBG-103007 (SHC1)

Protein Structure

UniProt Annotation

Function

Signaling adapter that couples activated growth factor receptors to signaling pathways. Participates in a signaling cascade initiated by activated KIT and KITLG/SCF. 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 (By similarity). Participates in signaling downstream of the angiopoietin receptor TEK/TIE2, and plays a role in the regulation of endothelial cell migration and sprouting angiogenesis. {ECO:0000250, ECO:0000269PubMed:14665640}.

Subcellular Localization

Cytoplasm.Isoform p46Shc: Mitochondrion matrix {ECO:0000269PubMed:14573619}. Note=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 {ECO:0000250}. Note=In case of oxidative conditions, phosphorylation at 'Ser-36' of isoform p66Shc, leads to mitochondrial accumulation. {ECO:0000250}.

Disease Associations

Tissue Specificity

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

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 311 experimentally validated interaction(s) in this database.
They are also associated with 39 interaction(s) predicted by orthology.

Experimentally validated
Total	311 [view]
Protein-Protein	309 [view]
Protein-DNA	2 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	39 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004713	protein tyrosine kinase activity
GO:0005068	transmembrane receptor protein tyrosine kinase adaptor activity
GO:0005154	epidermal growth factor receptor binding
GO:0005158	insulin receptor binding
GO:0005159	insulin-like growth factor receptor binding
GO:0005168	neurotrophin TRKA receptor binding
GO:0005515	protein binding
GO:0005543	phospholipid binding
GO:0046875	ephrin receptor binding

Biological Process

GO:0000165	MAPK cascade
GO:0000187	activation of MAPK activity
GO:0006987	activation of signaling protein activity involved in unfolded protein response
GO:0007173	epidermal growth factor receptor signaling pathway
GO:0007176	regulation of epidermal growth factor-activated receptor activity
GO:0007265	Ras protein signal transduction
GO:0007596	blood coagulation
GO:0008284	positive regulation of cell proliferation
GO:0008286	insulin receptor signaling pathway
GO:0008543	fibroblast growth factor receptor signaling pathway
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0030168	platelet activation
GO:0030968	endoplasmic reticulum unfolded protein response
GO:0035556	intracellular signal transduction
GO:0038095	Fc-epsilon receptor signaling pathway
GO:0040008	regulation of growth
GO:0044267	cellular protein metabolic process
GO:0045087	innate immune response
GO:0045740	positive regulation of DNA replication
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0050900	leukocyte migration