CD59 glycoprotein (CD59)
The protein contains 128 amino acids for an estimated molecular weight of 14177 Da.
Potent inhibitor of the complement membrane attack complex (MAC) action. Acts by binding to the C8 and/or C9 complements of the assembling MAC, thereby preventing incorporation of the multiple copies of C9 required for complete formation of the osmolytic pore. This inhibitor appears to be species-specific. Involved in signal transduction for T-cell activation complexed to a protein tyrosine kinase.', 'The soluble form from urine retains its specific complement binding activity, but exhibits greatly reduced ability to inhibit MAC assembly on cell membranes. (updated: March 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.
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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| Variant | Description |
|---|---|
| HACD59 |
Biological Process
Blood coagulation
Cell activation
Cell surface receptor signaling pathway
COPII vesicle coating
Endoplasmic reticulum to Golgi vesicle-mediated transport
Innate immune response
Negative regulation of activation of membrane attack complex
Negative regulation of apoptotic process
Neutrophil degranulation
Positive regulation of T cell proliferation
Regulation of complement activation
Regulation of complement-dependent cytotoxicity
Cellular Component
Anchored component of external side of plasma membrane
Cell surface
Compact myelin
Endoplasmic reticulum membrane
Endoplasmic reticulum-Golgi intermediate compartment membrane
ER to Golgi transport vesicle membrane
Extracellular exosome
Extracellular region
Extracellular space
Focal adhesion
Golgi membrane
Membrane
Plasma membrane
Sarcolemma
Specific granule membrane
Tertiary granule membrane
Transport vesicle
Vesicle
The reference OMIM entry for this protein is 107271
Cd59 antigen; cd59
Protectin
Human leukocyte antigen mic11; mic11
Surface antigen recognized by monoclonal antibody 16.3a5
CLONING
Okada et al. (1989) described a novel membrane inhibitor of the membrane attack complexes (MACs). A 20-kD protein, its function is the same as that of HRF (homologous restriction factor), which has a molecular mass of 65 kD. Therefore, they termed the new protein HRF20. HRF20 was also found to be identical to membrane attack complex inhibitory factor (MACIF) and CD59 (Davies et al., 1989); the sequences of cDNA encoding the 3 were essentially identical. By means of flow cytometric analysis, HRF20 was found to be expressed on most leukocytes and erythrocytes, indicating that it may have a role in preventing complement attack in the circulation. By searching for genes in a region of chromosome 11 associated with WAGR syndrome (194072), Gawin et al. (1999) identified and cloned CD59, which they designated clone 44686. Northern blot analysis detected variable expression of a 6-kb transcript in all human tissues examined.GENE FUNCTION
The CD59 antigen recognized by monoclonal antibody MEM-43 is an 18- to 25-kD glycoprotein expressed on all human peripheral blood leukocytes, erythrocytes, and several human cell lines. A close relationship to Ly6 of the mouse has been demonstrated. Antigens encoded by both Ly6 and CD59 genes are important to T-cell and NK-cell function. CD59 is also known as protectin. Its function is to restrict lysis of human erythrocytes and leukocytes by homologous complement. By directly incorporating protectin into membranes of heterologous cells, Meri et al. (1990) found that protectin does not prevent perforin-mediated killing (see 170280), whereas complement killing is effectively restricted. Thus, cell-mediated killing is unaffected by protectin. Meri et al. (1990) described the functional characteristics of protectin. Much attention has been focused on the Ly6 proteins because they may be involved in lymphocyte activation, and expression of some of them occurs at critical times in the differentiation of lymphocytes. Walsh et al. (1992) reviewed information on CD59, which they characterized as a multifunctional molecule with a role particularly in inhibition of formation of membrane attack complex. They raised the possibility that Ly6 is not a homolog and that the true MAC-inhibiting murine homolog of CD59 had yet to be found. Rother et al. (1994) demonstrated that retroviral transduction with a recombinant transmembrane form of CD59 of mouse L cells deficient in GPI anchoring resulted in surface expression of the CD59 protein and resistance of these cells to human complement-mediated membrane damage. Furthermore, a GPI anchoring-deficient complement-sensitive B-cell line derived from a PNH patient was successfully transduced with the particular form of recombinant CD59, resulting in surface expression of the protein. These cells were protected against classic complement-mediated membrane damage by human serum. The findings suggested that retroviral gene therapy with this molecule could provide a treatment for patients with paroxysmal nocturnal hemoglobinuria (PNH; 300818). Mao et al. (1996) suggested that the RIGE gene (601384) is the closest human homolog of the murine Ly6 gene family. Activated terminal complement proteins C5b (120900) to C9 (120940) form the MAC pore. Insertion of the MAC into endothelial cell membranes causes the release of growth factors that stimulate tissue growth and proliferation. The complement regulatory membrane protein CD59 restricts MAC formation. Because ... 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 107271 was added.
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed