C4A

Last updated
C4A
Protein C4A PDB 1hzf.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases C4A , C4, C4A2, C4A3, C4A4, C4A6, C4AD, C4S, CO4, CPAMD2, RG, complement component 4A (Rodgers blood group), complement C4A (Rodgers blood group)
External IDs OMIM: 120810; MGI: 88228; HomoloGene: 36030; GeneCards: C4A; OMA:C4A - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl

Contents

UniProt
RefSeq (mRNA)

NM_001252204
NM_007293

NM_009780

RefSeq (protein)

NP_001239133
NP_009224

NP_033910

Location (UCSC) Chr 6: 31.98 – 32 Mb Chr 17: 34.95 – 34.96 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Complement C4-A is a kind of the Complement component 4 protein that in humans is encoded by the C4A gene. [5]

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. [6] [7] [8] [9] [10] [11] 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. [12] This gene localizes to the RCCX locus within the major histocompatibility complex (MHC) class III region on chromosome 6. [13] [14] Varying haplotypes of this gene cluster exist, such that individuals may have 1, 2, or 3 copies of this gene. [5] Each copy of the gene, due to five adjacent nucleotide substitutions cause four amino acid changes and immunological subfunctionalization, [15] can be of one of two types: C4A and C4B . [16] 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. [14]

See also

References

  1. 1 2 3 ENSG00000206340, ENSG00000244731, ENSG00000227746 GRCh38: Ensembl release 89: ENSG00000244207, ENSG00000206340, ENSG00000244731, ENSG00000227746 Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000073418 Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 "Entrez Gene: C4A complement component 4A (Rodgers blood group)".
  6. Dawkins RL, Uko G, Christiansen FT, Kay PH (Sep 1983). "Low C4 concentrations in insulin dependent diabetes mellitus". British Medical Journal. 287 (6395): 839. doi:10.1136/bmj.287.6395.839-b. PMC   1549128 . PMID   6412852.
  7. Vergani D, Johnston C, B-Abdullah N, Barnett AH (Mar 1983). "Low serum C4 concentrations: an inherited predisposition to insulin dependent diabetes?". British Medical Journal. 286 (6369): 926–8. doi:10.1136/bmj.286.6369.926. PMC   1547358 . PMID   6403137.
  8. Mijovic CH, Fletcher JA, Bradwell AR, Barnett AH (Oct 1987). "Low C4 levels in type 1 (insulin-dependent) diabetes". Diabetologia. 30 (10): 824. doi: 10.1007/bf00275752 . PMID   3428499.
  9. Thomsen M, Mølvig J, Zerbib A, de Preval C, Abbal M, Dugoujon JM, Ohayon E, Svejgaard A, Cambon-Thomsen A, Nerup J (1988). "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. doi:10.1007/BF00364230. PMID   3139557. S2CID   6521141.
  10. Jenhani F, Bardi R, Gorgi Y, Ayed K, Jeddi M (Apr 1992). "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. doi:10.1016/0896-8411(92)90196-w. PMID   1352685.
  11. Lhotta K, Auinger M, Kronenberg F, Irsigler K, König P (1996). "Polymorphism of complement C4 and susceptibility to IDDM and microvascular complications". Diabetes Care. 19 (1): 53–55. doi:10.2337/diacare.19.1.53. PMID   8720534. S2CID   8999525.
  12. Melbourne JK, Rosen C, Feiner B, Sharma RP (July 2018). "C4A mRNA expression in PBMCs predicts the presence and severity of delusions in schizophrenia and bipolar disorder with psychosis". Schizophrenia Research. 197: 321–327. doi:10.1016/j.schres.2018.01.018. PMC   6087677 . PMID   29449061.
  13. Zhou D, Rudnicki M, Chua GT, Lawrance SK, Zhou B, Drew JL, Barbar-Smiley F, Armstrong TK, Hilt ME, Birmingham DJ, Passler W, Auletta JJ, Bowden SA, Hoffman RP, Wu YL, Jarjour WN, Mok CC, Ardoin SP, Lau YL, Yu CY (2021). "Human Complement C4B Allotypes and Deficiencies in Selected Cases With Autoimmune Diseases". Front Immunol. 12: 739430. doi: 10.3389/fimmu.2021.739430 . PMC   8577214 . PMID   34764957.
  14. 1 2 Carrozza C, Foca L, De Paolis E, Concolino P (2021). "Genes and Pseudogenes: Complexity of the RCCX Locus and Disease". Front Endocrinol (Lausanne). 12: 709758. doi: 10.3389/fendo.2021.709758 . PMC   8362596 . PMID   34394006.
  15. Bánlaki Z, Szabó JA, Szilágyi Á, Patócs A, Prohászka Z, Füst G, Doleschall M (2013). "Intraspecific evolution of human RCCX copy number variation traced by haplotypes of the CYP21A2 gene". Genome Biol Evol. 5 (1): 98–112. doi:10.1093/gbe/evs121. PMC   3595039 . PMID   23241443.
  16. Doleschall M, Luczay A, Koncz K, Hadzsiev K, Erhardt É, Szilágyi Á, Doleschall Z, Németh K, Török D, Prohászka Z, Gereben B, Fekete G, Gláz E, Igaz P, Korbonits M, Tóth M, Rácz K, Patócs A (June 2017). "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. doi:10.1038/ejhg.2017.38. PMC   5477366 . PMID   28401898.

Further reading