C8 is a constituent of the membrane attack complex. C8 binds to the C5B-7 complex, forming the C5B-8 complex. C5-B8 binds C9 and acts as a catalyst in the polymerization of C9. The gamma subunit seems to be able to bind retinol. (updated: Sept. 12, 2018)
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.
No sequence conservation computed yet.
Total structural coverage: 90%
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The reference OMIM entry for this protein is 120930
Complement component 8, gamma subunit; c8g
C8c
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;
120950)-gamma (CG) 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).
CLONING
Ng et al. (1987) identified a cDNA clone containing the entire coding region for the human gamma polypeptide, and its sequence supported the existence of a separate gamma mRNA. Whereas the alpha chain and beta chain of C8 show an overall sequence homology to C6, C7, and C9 (which like C8 are involved in the membrane-attack complex that leads to lysis of target cells), the gamma chain was found by Haefliger et al. (1987) to show structural homology to protein HC (alpha-1-microglobulin/bikunin precursor; AMBP;
176870). This suggested a similar 3-dimensional structure of the 2 proteins and a possible functional relationship. Hunt et al. (1987) also pointed out the close sequence homology of C8G to alpha-1-microglobulin. Kaufman et al. (1989) noted that the C8G gene and its protein product belong to the lipocalin superfamily, a group of distantly related and similarly folded proteins that are able to carry small lipophilic molecules such as retinol, odorants, and steroids. The lipocalin superfamily has a very ancient origin since lipocalins are found in arthropods as well as in vertebrates.
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.
MAPPING
Kaufman et al. (1989) assigned the C8G locus to chromosome 9q by probing a panel of hybrid DNAs with a C8-gamma probe clone. C5 (
120900) and 2 genes from the same family, alpha-1-microglobulin (inter-alpha-trypsin inhibitor, light chain; ITIL) and alpha-1-acid-glycoprotein (orosomucoid-1; ORM1;
138600), map to the same area. This indicated a common evolutionary origin of these genes. In the mouse, the lipocalin genes coding for orosomucoid, the alpha-1-microglobulin/bikunin precursor, and the major urinary protein (MUP) map to chromosome 4, while their human counterparts map to the homologous 9q34 area where 3 other lipocalin genes, those for C8G, progestagen-associated endometrial protein (PAEP;
173310) and prostaglandin D synthase (PTGDS;
176803), are also located (Chan et al., 1994). Dewald et al. (1996) described the first known polymorphisms in the C8G gene, namely a polymorphic site in exon 1 (207T/G) and 2 mor ...
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Subscribe to this protein entry history
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 120930 was added.
Feb. 23, 2019: Protein entry updated
Automatic update: comparative model was added.
Feb. 23, 2019: Protein entry updated
Automatic update: model status changed
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).