|CD47||IAP (integrin-associated protein), Rh-associated protein, gp42, neurophilin, OA3(ovarian carcinoma antigen), MEM-133, CDw149|
|Molecule Type||Antigen Expression||Molecular Weight|
Min / Max
|Non-lineage Restricted Molecule|
Type 3 glycoprotein, 5 span
|45 / 45|
60 / 60
|CD47 has a broad tissue distribution with expression on virtually all hematopoietic cells, including thymocytes, T and B cells, monocytes, platelets and erythrocytes, as well as on epithelial cells, endothelial cells, fibroblasts, sperm, tumor cell lines, mesenchymal cells and other tissue cells with a strong expression in the brain. Antibodies previously assigned to CD149 are now called CD47R. Their reactivity is similar to CD47 which is part of the Rh complex on erythrocytes but is not expressed on any Rh null erythrocytes. |
|MOLECULAR FAMILY NAME: Belongs to the immunoglobulin supergene family.|
CD47 is a multi-pass type-3, 5 span glycoprotein. It contains an 120 aa extracellular domain which contains 1 Ig-like V-type domain (the SIRPα binding site) and 6 potential N-glycosylation sites, 5 152 aa transmembrane domains and a short 30 aa hydrophobic C-terminal cytoplasmic tail domain. There are 4 alternatively spliced forms of the C-terminus which have been identified. These are generated by the variable usage of 3 short exons. There have been 2 predominant splice variants demonstrated in vivo and these have distinct tissue expression patterns. The form with the shorter cytoplasmic tail is expressed on bone marrow-derived cells, endothelial cells and fibroblasts, whereas the longer form is expressed mainly on neural tissue. Immunofluorescence microscopy has proven the C-terminal tail to be cytoplasmic.
Alternative splicing yields 4 different isoforms of mRNA which are derived by alternative splicing at the intercytoplasmic carboxyl termini.
There are 6 potential N-glycosylation sites are in the extracellular domain and 3 sites are glycosylated on erythrocytes.
|The CD47 molecule associates non-covalently with the CD61 b3 integrins, CD51/CD61 av/β3, CD41/CD61 (aII/β-b3) and CD49b/CD29 (α2/β1). The IgSF domain of CD47 is thought to mediate these interactions. A ligand for CD47 is the C-terminal cell binding domain of thrombospondin, an extracellular adhesion molecule which regulates motility and proliferation in many cell types.|
LIGANDS AND MOLECULES ASSOCIATED WITH CD47
|CD47 binds and activates the leukocyte inhibitory receptor protein α (SIRPα) on phagocytic cells thereby preventing phagocytosis of self blood cells. CD47 is involved in the increase in intracellular calcium concentration that occurs upon cell adhesion to the extracellular matrix. CD47 is a receptor for the C-terminal cell binding domain of thrombospondin and may play a role in membrane transporft and signal transduction. CD47 plays a role in the chemotactic and adhesive interactions of leukocytes with endothelial cells. The mechanism of action is not entirely understood, but is thought to involve the modulation of the function of integrins, with which CD47 is physically and functionally linked, and its binding to thrombospondin. The binding of thrombospondin to CD47 on endothelial cells in vitro induces a chemotactic response that is inhibited by a CD47 mAb. CD47 mAbs also inhibit neutrophil migration across the endothelium and epithelium, without affecting CD11b/CD18 integrin-mediated neutrophil adhesion to the epithelium. The thrombospondin (TS1) and CD47 interaction can mediate caspase-independent cell death un a number of cell types, including activated T cells, macrophages, dendritic cells and various tumor cells. Human cells that lack CD47 are deficient in some CD51 integrin ligand binding functions. CD47 knockout mice show increased susceptibility to bacterial infections due to granulocyte defects in CD61 integrin function, activation of oxidative burst and phagocytosis.|
BIOCHEMICAL ACTIVITY: No information.
DISEASE RELEVANCE AND FUNCTION OF CD47 IN INTACT ANIMAL
CD47 knockout mice showed a defect in host defense. Granulocytes from CD47 knockout mice were deficient in β3 integrin-dependent ligand binding cell migration and activation. Null mice have a defect in host defense and are sensitive to autoimmune hemolytic anemia.
|CD47 species homologues have been identified in the poxviruses vaccinia and variola major. The vaccinia virus A38L gene product is a 33 kDa membrane glycoprotein with 28% sequence identity to mammalian CD47. Proteolysis studies of A38L translated in vitro in microsomal membranes are consistent with the proposed membrane topology of human CD47. The A38L protein is expressed at a low level in infected cells in vivo but its function is not clear, since deletion of the A38L gene does not affect virus particle production or virulence.|
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD47: No information.
SUBSTRATES: No information.
ENZYMES WHICH MODIFY CD47: No information.
Database accession numbers
Revised June 25, 2008