Medicine:C4A
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.[1]
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.[2][3][4][5][6][7] 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.[8] This gene localizes to the RCCX locus within the major histocompatibility complex (MHC) class III region on chromosome 6.[9][10] Varying haplotypes of this gene cluster exist, such that individuals may have 1, 2, or 3 copies of this gene.[1] Each copy of the gene, due to five adjacent nucleotide substitutions cause four amino acid changes and immunological subfunctionalization,[11] can be of one of two types: C4A and C4B.[12] 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.[10]
See also
References
- ↑ 1.0 1.1 "Entrez Gene: C4A complement component 4A (Rodgers blood group)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=720.
- ↑ "Low C4 concentrations in insulin dependent diabetes mellitus". British Medical Journal 287 (6395): 839. Sep 1983. doi:10.1136/bmj.287.6395.839-b. PMID 6412852.
- ↑ "Low serum C4 concentrations: an inherited predisposition to insulin dependent diabetes?". British Medical Journal 286 (6369): 926–8. Mar 1983. doi:10.1136/bmj.286.6369.926. PMID 6403137.
- ↑ "Low C4 levels in type 1 (insulin-dependent) diabetes". Diabetologia 30 (10): 824. Oct 1987. doi:10.1007/bf00275752. PMID 3428499.
- ↑ "The susceptibility to insulin-dependent diabetes mellitus is associated with C4 allotypes independently of the association with HLA-DQ alleles in HLA-DR3,4 heterozygotes". Immunogenetics 28 (5): 320–7. 1988. doi:10.1007/BF00364230. PMID 3139557.
- ↑ "C4 polymorphism in multiplex families with insulin dependent diabetes in the Tunisian population: standard C4 typing methods and RFLP analysis". Journal of Autoimmunity 5 (2): 149–60. Apr 1992. doi:10.1016/0896-8411(92)90196-w. PMID 1352685.
- ↑ "Polymorphism of complement C4 and susceptibility to IDDM and microvascular complications". Diabetes Care 19 (1): 53–55. 1996. doi:10.2337/diacare.19.1.53. PMID 8720534.
- ↑ "C4A mRNA expression in PBMCs predicts the presence and severity of delusions in schizophrenia and bipolar disorder with psychosis". Schizophrenia Research 197: 321–327. July 2018. doi:10.1016/j.schres.2018.01.018. PMID 29449061.
- ↑ "Human Complement C4B Allotypes and Deficiencies in Selected Cases With Autoimmune Diseases". Front Immunol 12: 739430. 2021. doi:10.3389/fimmu.2021.739430. PMID 34764957.
- ↑ 10.0 10.1 "Genes and Pseudogenes: Complexity of the RCCX Locus and Disease". Front Endocrinol (Lausanne) 12: 709758. 2021. doi:10.3389/fendo.2021.709758. PMID 34394006.
- ↑ "Intraspecific evolution of human RCCX copy number variation traced by haplotypes of the CYP21A2 gene". Genome Biol Evol 5 (1): 98–112. 2013. doi:10.1093/gbe/evs121. PMID 23241443.
- ↑ "A unique haplotype of RCCX copy number variation: from the clinics of congenital adrenal hyperplasia to evolutionary genetics". Eur J Hum Genet 25 (6): 702–710. June 2017. doi:10.1038/ejhg.2017.38. PMID 28401898.
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.
Original source: https://en.wikipedia.org/wiki/C4A.
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