Medicine:C4A

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

Complement C4-A is a kind of the Complement component 4 protein that in humans is encoded by the C4A gene.

Function

This gene encodes the acidic form of complement factor 4, part of the classical activation pathway. The protein is expressed as a single chain precursor which is proteolytically cleaved into a trimer of alpha, beta, and gamma chains prior to secretion. The trimer provides a surface for interaction between the antigen-antibody complex and other complement components. The alpha chain may be cleaved to release C4 anaphylatoxin, a mediator of local inflammation. Deficiency of this protein is associated with systemic lupus erythematosus and type I diabetes mellitus. Excess production due to a copy number that is higher than normal has shown a high probability of a causal relationship with schizophrenia and bipolar disorder with psychosis, which could explain the hereditary nature of these illnesses. This gene localizes to the RCCX locus within the major histocompatibility complex (MHC) class III region on chromosome 6. Varying haplotypes of this gene cluster exist, such that individuals may have 1, 2, or 3 copies of this gene. Each copy of the gene, due to five adjacent nucleotide substitutions cause four amino acid changes and immunological subfunctionalization, can be of one of two types: C4A and C4B. Each gene contains 41 exons and has a dichotomous size variation between approximately 22 kb and 16 kb, with the longer variant being the result of the integration of the endogenous retrovirus HERV-K(C4) into intron 9.

See also

• Complement component 4
  • Complement component 4B
• HLA A1-B8-DR3-DQ2 haplotype
• Complement system
• Complement deficiency

Further reading

• "Biochemistry and biology of anaphylatoxins". Complement 3 (3): 111–27. 1987. doi:10.1159/000467889. PMID 3542363. 
• "Molecular genetics of the human MHC complement gene cluster". Experimental and Clinical Immunogenetics 15 (4): 213–30. 1999. doi:10.1159/000019075. PMID 10072631. 
• "The coding sequence of the hemolytically inactive C4A6 allotype of human complement component C4 reveals that a single arginine to tryptophan substitution at beta-chain residue 458 is the likely cause of the defect". Journal of Immunology 148 (9): 2795–802. May 1992. doi:10.4049/jimmunol.148.9.2795. PMID 1573268. 
• "Importance of the alpha 3-fragment of complement C4 for the binding with C4b-binding protein". FEBS Letters 271 (1–2): 131–6. Oct 1990. doi:10.1016/0014-5793(90)80389-Z. PMID 1699796. 
• "The complete exon-intron structure of a human complement component C4A gene. DNA sequences, polymorphism, and linkage to the 21-hydroxylase gene". Journal of Immunology 146 (3): 1057–66. Feb 1991. doi:10.4049/jimmunol.146.3.1057. PMID 1988494. 
• "Binding of cystatin C to C4: the importance of sense-antisense peptides in their interaction". Proceedings of the National Academy of Sciences of the United States of America 87 (4): 1288–91. Feb 1990. doi:10.1073/pnas.87.4.1288. PMID 2304899. Bibcode: 1990PNAS...87.1288G. 
• "Structural basis of the polymorphism of human complement components C4A and C4B: gene size, reactivity and antigenicity". The EMBO Journal 5 (11): 2873–81. Nov 1986. doi:10.1002/j.1460-2075.1986.tb04582.x. PMID 2431902. 
• "Structure of the human RD gene: a highly conserved gene in the class III region of the major histocompatibility complex". DNA 8 (10): 745–51. Dec 1989. doi:10.1089/dna.1989.8.745. PMID 2612324. 
• "Heterogeneity of human C4 gene size. A large intron (6.5 kb) is present in all C4A genes and some C4B genes". Immunogenetics 25 (5): 299–304. 1987. doi:10.1007/BF00404422. PMID 2883116. 
• "The fluid-phase binding of human C4 and its genetic variants, C4A3 and C4B1, to immunoglobulins". Molecular Immunology 25 (9): 811–9. Sep 1988. doi:10.1016/0161-5890(88)90117-4. PMID 3264881. 
• "The chemical structure of the C4d fragment of the human complement component C4". Molecular Immunology 24 (11): 1187–97. Nov 1987. doi:10.1016/0161-5890(87)90165-9. PMID 3696167. 
• "Polymorphism of human complement component C4". Immunogenetics 21 (2): 173–80. 1985. doi:10.1007/BF00364869. PMID 3838531. 
• "Identification of the site of sulfation of the fourth component of human complement". The Journal of Biological Chemistry 261 (4): 1786–93. Feb 1986. doi:10.1016/S0021-9258(17)36009-X. PMID 3944109. 
• "Complete primary structure of human C4a anaphylatoxin". The Journal of Biological Chemistry 256 (16): 8685–92. Aug 1981. doi:10.1016/S0021-9258(19)68898-8. PMID 6167582. 
• "Correlation between a DNA restriction fragment length polymorphism and C4A6 protein". Nature 306 (5943): 615–6. 1984. doi:10.1038/306615a0. PMID 6316164. 
• "The structural basis of the multiple forms of human complement component C4". Cell 36 (4): 907–14. Apr 1984. doi:10.1016/0092-8674(84)90040-0. PMID 6546707. 
• "A molecular map of the human major histocompatibility complex class III region linking complement genes C4, C2 and factor B". Nature 307 (5948): 237–41. 1984. doi:10.1038/307237a0. PMID 6559257. Bibcode: 1984Natur.307..237C. 
• "Cloning of a human complement component C4 gene". Proceedings of the National Academy of Sciences of the United States of America 80 (1): 264–7. Jan 1983. doi:10.1073/pnas.80.1.264. PMID 6572000. Bibcode: 1983PNAS...80..264C. 
• "Use of a cDNA clone for the fourth component of human complement (C4) for analysis of a genetic deficiency of C4 in guinea pig". Proceedings of the National Academy of Sciences of the United States of America 80 (17): 5387–91. Sep 1983. doi:10.1073/pnas.80.17.5387. PMID 6577433. Bibcode: 1983PNAS...80.5387W. 

External links

• Human C4A genome location and C4A gene details page in the UCSC Genome Browser.