Complement component C8 alpha chain (C8A)
The protein contains 584 amino acids for an estimated molecular weight of 65163 Da.
Constituent of the membrane attack complex (MAC) that plays a key role in the innate and adaptive immune response by forming pores in the plasma membrane of target cells. C8A inserts into the target membrane, but does not form pores by itself. (updated: Feb. 1, 1995)
Protein identification was indicated in the following studies:
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 UniProt.
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| Variant | Description |
|---|---|
| allele C8A*B | |
| dbSNP:rs706479 | |
| dbSNP:rs17114555 | |
| dbSNP:rs1620075 | |
| dbSNP:rs1342440 | |
| dbSNP:rs17300936 |
No binding partner found
Biological Process
Complement activation
Complement activation, alternative pathway
Complement activation, classical pathway
Cytolysis
Immune response
Regulation of complement activation
The reference OMIM entry for this protein is 120950
Complement component 8, alpha subunit; c8a
C8 alpha
DESCRIPTION
The eighth component of complement (C8) belongs to the late-acting complement proteins (C5-C9) forming the membrane attack complex. C8 is a serum protein that consists of 3 nonidentical subunits arranged asymmetrically as a disulfide-linked alpha (C8A)-gamma (C8G; 120930) dimer and a noncovalently associated beta chain (C8B; 120960). Each component is encoded by a different gene (Kolb and Muller-Eberhard, 1976; Ng et al., 1987).BIOCHEMICAL FEATURES
By separating the alpha-gamma dimer of C8 from the beta chain and then subjecting the alpha-beta dimer to further treatment, Brickner and Sodetz (1985) purified the alpha and gamma chains. When mixed, purified alpha and gamma exhibited high affinity for each other, and purified gamma also had affinity for C8-prime, which is composed of the alpha and beta chains only. Brickner and Sodetz (1985) concluded that alpha possesses a specific site for interaction with gamma and that the site remains accessible in the isolated alpha subunit and when alpha is associated with beta. They found that gamma associated specifically with membrane-bound C5b-8-prime and C5b-(8-prime)9 complexes. Brickner and Sodetz (1985) concluded that the gamma interaction site on alpha remains accessible in C5b-8-prime and is not shielded by C9 within C5b-(8-prime)9, and that the gamma subunit of C8 is located on the surface of membrane-bound C5b-8 and C5b-9. Hadders et al. (2007) determined the crystal structure of the MACPF (membrane attack complex perforin) domain of the complement component C8-alpha at 2.5-angstrom resolution and showed that it is structurally homologous to the bacterial, pore-forming, cholesterol-dependent cytolysins. The structure displayed 2 regions that in the bacterial cytolysins refold into transmembrane beta hairpins, forming the lining of a barrel pore. Local hydrophobicity explained why C8-alpha is the first complement protein to insert into the membrane. The size of the MACPF domain is consistent with known C9 pore sizes. Hadders et al. (2007) concluded that their data implied that these mammalian and bacterial cytolytic proteins share a common mechanism of membrane insertion. Rosado et al. (2007) determined the crystal structure of a bacterial MACPF protein, Plu-MACPF from Photorhabdus luminescens, to 2.0-angstrom resolution. The MACPF domain revealed structural similarity with pore-forming cholesterol-dependent cytolysins from gram-positive bacteria. Rosado et al. (2007) suggested that lytic MACPF proteins may use a cholesterol-dependent cytolysin-like mechanism to form pores and disrupt cell membranes.GENE STRUCTURE
Michelotti et al. (1995) isolated overlapping genomic clones and used them to decipher the organization of the human C8A gene. The gene contains at least 11 exons and spans approximately 70 kb of DNA. C8A genomic organization was found to be remarkably similar to that of C6, C8B, and C9.MAPPING
Rogde et al. (1984) found that the polymorphism detected by anti-C8 was determined by a locus linked to PGM1 on 1p (maximal lod score, sexes combined, of 8.0 at theta = 0.10). They interpreted their evidence as suggesting that this polymorphism is in the alpha-gamma subunit. By 2-dimensional electrophoresis, Rogde et al. (1985) showed that the C8 polymorphism resides in the structural gene for the alpha chain. Using separation by isoelectric focusing followed by immunoblotting, Rogde et al. (1985, 1986) concluded that C8A and C8B a ... More on the omim web site
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 120950 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).