Leukocyte surface antigen CD47 (CD47)
The protein contains 323 amino acids for an estimated molecular weight of 35214 Da.
Has a role in both cell adhesion by acting as an adhesion receptor for THBS1 on platelets, and in the modulation of integrins. Plays an important role in memory formation and synaptic plasticity in the hippocampus (By similarity). Receptor for SIRPA, binding to which prevents maturation of immature dendritic cells and inhibits cytokine production by mature dendritic cells. Interaction with SIRPG mediates cell-cell adhesion, enhances superantigen-dependent T-cell-mediated proliferation and costimulates T-cell activation. May play a role in membrane transport and/or integrin dependent signal transduction. May prevent premature elimination of red blood cells. May be involved in membrane permeability changes induced following virus infection. (updated: Feb. 4, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt, is predicted to be membranous by TOPCONS.
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Biological Process
ATP export
Blood coagulation
Cell adhesion
Cell migration
Cellular response to interferon-gamma
Cellular response to interleukin-1
Cellular response to interleukin-12
Extracellular matrix organization
Inflammatory response
Integrin-mediated signaling pathway
Leukocyte migration
Monocyte aggregation
Monocyte extravasation
Negative regulation of Fc-gamma receptor signaling pathway involved in phagocytosis
Neutrophil degranulation
Opsonization
Positive regulation of cell population proliferation
Positive regulation of cell-cell adhesion
Positive regulation of inflammatory response
Positive regulation of phagocytosis
Positive regulation of stress fiber assembly
Positive regulation of T cell activation
Regulation of interferon-gamma production
Regulation of interleukin-10 production
Regulation of interleukin-12 production
Regulation of interleukin-6 production
Regulation of nitric oxide biosynthetic process
Regulation of tumor necrosis factor production
Response to bacterium
The reference OMIM entry for this protein is 601028
Cd47 antigen; cd47
Surface antigen identified by monoclonal antibody 1d8; mer6
Integrin-associated protein; iap
Cd47 glycoprotein
CLONING
By testing hybrids containing various deletions of chromosome 3, Miller et al. (1987) described an IgM monoclonal antibody, 1D8, that recognized an antigen coded by a gene located in the region 3cen-q22. The monoclonal antibody was designated MER6. The antigen was absent in the Rh deficiency syndrome, Rh-null hemolytic anemia (268150). However, this antigen probably had no pathogenetic role in the Rh deficiency, which was shown by Cherif-Zahar et al. (1996) to be due to mutation in the Rh50 gene (180297) on chromosome 6. Cherif-Zahar et al. (1996) noted that many cell membrane components are missing from the multisubunit Rh complex when the RH50A gene is mutant. Lindberg et al. (1994) stated that IAP is a 50-kD membrane protein with an N-terminal immunoglobulin domain and a C-terminal multiple membrane-spanning region. IAP is identical to the ovarian tumor marker OA3 (Mawby et al., 1994). It is involved in the increase in intracellular calcium concentration that occurs upon cell adhesion to extracellular matrix. IAP is also expressed on erythrocytes, which have no known integrins. Lindberg et al. (1994) found that IAP expression was reduced on Rh(null) erythrocytes. Using FISH, Lindberg et al. (1994) mapped IAP within a region of chromosome 3 known to contain the gene encoding the Rh-associated 1D8 antigen. By expression studies on human erythrocytes and IAP transfectants, IAP was found to be identical to the 1D8 antigen and to CD47, a cell surface protein with broad tissue distribution and reduced expression on Rh(null) erythrocytes. Lindberg et al. (1994) stated that these studies demonstrated an unexpected link between integrin signal transduction and erythrocyte membrane structure.GENE FUNCTION
The immune system recognizes invaders as foreign because they express determinants that are absent on host cells or because they lack 'markers of self' that are normally present. Oldenborg et al. (2000) found that Cd47 functioned as a marker of self on murine red blood cells. Red blood cells lacking Cd47 were rapidly cleared from the bloodstream by splenic red pulp macrophages. Cd47 on normal red blood cells prevented this elimination by binding to the inhibitory receptor signal regulatory protein (SIRP)-alpha (PTPNS1; 602461). Oldenborg et al. (2000) concluded that macrophages may use a number of nonspecific activating receptors and rely on the presence or absence of CD47 to distinguish self from foreign. They suggested that CD47-SIRP-alpha may represent a potential pathway for the control of hemolytic anemia. Osteoclasts and giant cells are multinucleated and resorb the substrate onto which they adhere. They are thought to originate from the fusion of mononuclear phagocytes. Han et al. (2000) used immunofluorescence microscopy to show that at the onset of fusion macrophages express not only the macrophage fusion receptor (MFR, or SIRP-alpha) but also, at a lower level than MFR, the hemopoietic form of CD47. Immunoprecipitation and immunoblot experiments confirmed the association of the CD47 variable domain and the MFR immunoglobulin V1 domain. Macrophage fusion could be blocked by either anti-CD47 monoclonal antibodies or a CD47 fusion protein. Type III, or necrosis-like, programmed cell death (PCD) is defined exclusively by cytoplasmic features and seems to operate in a caspase-independent manner. Bras et al. (2007) showed that ligation of CD47 triggered type III PCD in B cells from healthy volunteers and pat ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 601028 was added.
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed