Structural highlights
Function[SHPS1_HUMAN] Immunoglobulin-like cell surface receptor for CD47. Acts as docking protein and induces translocation of PTPN6, PTPN11 and other binding partners from the cytosol to the plasma membrane. Supports adhesion of cerebellar neurons, neurite outgrowth and glial cell attachment. May play a key role in intracellular signaling during synaptogenesis and in synaptic function (By similarity). Involved in the negative regulation of receptor tyrosine kinase-coupled cellular responses induced by cell adhesion, growth factors or insulin. Mediates negative regulation of phagocytosis, mast cell activation and dendritic cell activation. CD47 binding prevents maturation of immature dendritic cells and inhibits cytokine production by mature dendritic cells.[1] [2] 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 PubMedSignal regulatory protein (SIRP) alpha is a membrane receptor that sends inhibitory signals to myeloid cells by engagement of CD47. The high resolution x-ray structure of the N-terminal ligand binding domain shows it to have a distinctive immunoglobulin superfamily V-like fold. Site-directed mutagenesis suggests that CD47 is bound at a surface involving the BC, FG, and DE loops, which distinguishes it from other immunoglobulin superfamily surface proteins that use the faces of the fold, but resembles antigen receptors. The SIRP interaction is confined to a single domain, and its use of an extended DE loop strengthens the similarity with T cell receptor binding and the suggestion that they are closely related in evolution. The employment of loops to form the CD47-binding surface provides a mechanism for small sequence changes to modulate binding specificity, explaining the different binding properties of SIRP family members. The structure of the macrophage signal regulatory protein alpha (SIRPalpha) inhibitory receptor reveals a binding face reminiscent of that used by T cell receptors.,Hatherley D, Harlos K, Dunlop DC, Stuart DI, Barclay AN J Biol Chem. 2007 May 11;282(19):14567-75. Epub 2007 Mar 16. PMID:17369261[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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This page was last modified 09:47, 25 December 2014.