The reference OMIM entry for this protein is 217050

Complement component 6; c6

DESCRIPTION

The final consequence of complement activation is formation of the membrane attack complex (MAC), a multiprotein assembly that perforates cell membranes, forming transmembrane channels. C6 is 1 of 5 late-acting proteins of complement that participate in assembly and function of the MAC (DiScipio and Hugli, 1989).

CLONING

DiScipio and Hugli (1989) isolated a cDNA encoding C6 from a human liver cDNA library. The deduced C6 protein contains 934 amino acids, including a 21-amino acid N-terminal signal sequence and 2 N-glycosylation sites. The mature 913-amino acid C6 protein shares 29% amino acid identity with C7 (217070), and 55 of 56 cysteines in C7 match those in C6. The C6 polypeptide chain is cross-linked by 32 disulfide bonds, and most cysteines are located in short, discrete segments that exhibit homology with a variety of proteins, including thrombospondin (see 188060), low density lipoprotein receptor (LDLR; 606945), epidermal growth factor (EGF; 131530), and complement factors H (CFH; 134370) and I (CFI; 217030). Independently, Haefliger et al. (1989) cloned C6 from a human liver cDNA library. They determined that the mature C6 protein shares 33.5% amino acid identity with C7, including conservation of all 56 cysteines.

GENE FUNCTION

Binding studies by Haefliger et al. (1989) showed that the C5b (120900)-binding domain of C6 was located in a C-terminal region consisting of 2 short consensus repeats and 2 factor I modules.

GENE STRUCTURE

Hobart et al. (1993) reported that the C6 gene contains 18 exons.

MAPPING

Studying structural variants of C6, Hobart et al. (1977) found no evidence of linkage to HLA or any of the other marker loci tested. Hobart et al. (1978) identified 3 structural forms of C7 (217070), concluded they are the products of 3 codominant alleles at an autosomal locus, and found that the C6 and C7 loci are closely linked to each other but are not linked to the HLA complex. Olving et al. (1979) excluded linkage of C6 and some 19 marker loci including HLA, Bf, PGM-3, GLO-1 and C3. Bender et al. (1983) studied linkage with 28 marker loci with negative results that excluded the C6 locus from large parts of autosomes 1, 2, 4, 6, 8, 9, 13, 14, 16, 19, and 20. Lachmann et al. (1978) gave evidence that the coding regions of C6 and C7 lie physically close in the human genome. C6 and C7 have many physicochemical similarities, suggesting that they may have arisen through tandem duplication of an ancestral gene. C6 and C7 show close physicochemical similarities (Podack et al., 1976). Nakamura et al. (1984) found positive linkage disequilibrium suggesting close proximity of the 2 loci. Using polyacrylamide gel isoelectric focusing followed by immunoblotting, Tokunaga et al. (1986) studied polymorphisms of C6 and C7 in Japanese. Family studies confirmed close linkage between the C6 and C7 loci; the maximum lod score was 8.43 at theta = 0. No significant linkage disequilibrium was found between C6 and C7 in directly determined haplotypes of unrelated parents. By Southern blot analysis of hybrid cell DNAs using cDNA probes, Jeremiah et al. (1989, 1990) demonstrated that the human C6 and C7 genes are located on chromosome 5. See Coto et al. (1991) for evidence of linkage to C7 and C9, which are located in a tight cluster at 5p13. Rogne et al. (1991) used DNA polymorphism of C9 and protein variants of C6 to show that the 2 genes are closely linked (maximum lod = 9.28 a ... More on the omim web site

Subscribe to this protein entry history

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 217050 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).