| Structural highlights
1tce is a 2 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | NonStd Res: | |
| Gene: | SH2 DOMAIN OF SHC (Homo sapiens) |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Disease
[CD3Z_HUMAN] Defects in CD247 are the cause of immunodeficiency due to defect in CD3-zeta (CD3ZID) [MIM:610163]. An immunological deficiency characterized by T-cells impaired immune response to alloantigens, tetanus toxoid and mitogens.[1]
Function
[SHC1_HUMAN] 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.[2] [CD3Z_HUMAN] Probable role in assembly and expression of the TCR complex as well as signal transduction upon antigen triggering.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
She is a widely expressed adapter protein that plays an important role in signaling via a variety of cell surface receptors and has been implicated in coupling the stimulation of growth factor, cytokine, and antigen receptors to the Ras signaling pathway. She interacts with several tyrosine-phosphorylated receptors through its C-terminal SH2 domain, and one of the mechanisms of T-cell receptor-mediated Ras activation involves the interaction of the Shc SH2 domain with the tyrosine-phosphorylated zeta chain of the T-cell receptor. Here we describe a high-resolution NMR structure of the Shc SH2 domain complexed to a phosphopeptide (GHDGLpYQGLSTATK) corresponding to a portion of the zeta chain of the T-cell receptor. Although the overall architecture of the protein is similar to other SH2 domains, distinct structural differences were observed in the smaller beta-sheet, BG loop, (pY + 3) phosphopeptide-binding site, and relative position of the bound phosphopeptide.
Solution structure of the Shc SH2 domain complexed with a tyrosine-phosphorylated peptide from the T-cell receptor.,Zhou MM, Meadows RP, Logan TM, Yoon HS, Wade WS, Ravichandran KS, Burakoff SJ, Fesik SW Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7784-8. PMID:7544002[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Rieux-Laucat F, Hivroz C, Lim A, Mateo V, Pellier I, Selz F, Fischer A, Le Deist F. Inherited and somatic CD3zeta mutations in a patient with T-cell deficiency. N Engl J Med. 2006 May 4;354(18):1913-21. PMID:16672702 doi:354/18/1913
- ↑ Audero E, Cascone I, Maniero F, Napione L, Arese M, Lanfrancone L, Bussolino F. Adaptor ShcA protein binds tyrosine kinase Tie2 receptor and regulates migration and sprouting but not survival of endothelial cells. J Biol Chem. 2004 Mar 26;279(13):13224-33. Epub 2003 Dec 9. PMID:14665640 doi:10.1074/jbc.M307456200
- ↑ Zhou MM, Meadows RP, Logan TM, Yoon HS, Wade WS, Ravichandran KS, Burakoff SJ, Fesik SW. Solution structure of the Shc SH2 domain complexed with a tyrosine-phosphorylated peptide from the T-cell receptor. Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7784-8. PMID:7544002
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