C4A

Complement component 4A (Rodgers blood group)
PDB rendering based on 1hzf.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1HZF​, 4FXG​, 4FXK​, 4XAM​
Identifiers
Symbols	C4A ; C4; C4A2; C4A3; C4A4; C4A6; C4AD; C4S; CO4; CPAMD2; RG
External IDs	OMIM: 120810 MGI: 88228 HomoloGene: 36030 GeneCards: C4A Gene
Gene ontology Molecular function • complement component C1q binding • endopeptidase inhibitor activity Cellular component • extracellular region • extracellular space • plasma membrane • extracellular exosome • blood microparticle Biological process • inflammatory response • complement activation • complement activation, classical pathway • negative regulation of endopeptidase activity • regulation of complement activation • innate immune response • positive regulation of apoptotic cell clearance Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	720	12268
Ensembl	ENSG00000206340	ENSMUSG00000073418
UniProt	P0C0L4	P01029
RefSeq (mRNA)	NM_001252204	NM_009780
RefSeq (protein)	NP_001239133	NP_033910
Location (UCSC)	Chr 6: 31.98 – 32 Mb	Chr 17: 34.73 – 34.74 Mb
PubMed search

Complement C4-A is a 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]} This gene localizes to 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.^[1]

See also

• Complement component 4

References

1. "Entrez Gene: C4A complement component 4A (Rodgers blood group)".
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.

Further reading

• Hugli TE (1987). "Biochemistry and biology of anaphylatoxins". Complement 3 (3): 111–27. PMID 3542363.
• Yu CY (1999). "Molecular genetics of the human MHC complement gene cluster". Experimental and Clinical Immunogenetics 15 (4): 213–30. doi:10.1159/000019075. PMID 10072631.
• Anderson MJ, Milner CM, Cotton RG, Campbell RD (May 1992). "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. PMID 1573268.
• Hessing M, van 't Veer C, Hackeng TM, Bouma BN, Iwanaga S (Oct 1990). "Importance of the alpha 3-fragment of complement C4 for the binding with C4b-binding protein". FEBS Letters 271 (1-2): 131–6. doi:10.1016/0014-5793(90)80389-Z. PMID 1699796.
• Yu CY (Feb 1991). "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. PMID 1988494.
• Ghiso J, Saball E, Leoni J, Rostagno A, Frangione B (Feb 1990). "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. doi:10.1073/pnas.87.4.1288. PMC 53459. PMID 2304899.
• Yu CY, Belt KT, Giles CM, Campbell RD, Porter RR (Nov 1986). "Structural basis of the polymorphism of human complement components C4A and C4B: gene size, reactivity and antigenicity". The EMBO Journal 5 (11): 2873–81. PMC 1167237. PMID 2431902.
• Speiser PW, White PC (Dec 1989). "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. doi:10.1089/dna.1989.8.745. PMID 2612324.
• Palsdottir A, Fossdal R, Arnason A, Edwards JH, Jensson O (1987). "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. doi:10.1007/BF00404422. PMID 2883116.
• Kishore N, Shah D, Skanes VM, Levine RP (Sep 1988). "The fluid-phase binding of human C4 and its genetic variants, C4A3 and C4B1, to immunoglobulins". Molecular Immunology 25 (9): 811–9. doi:10.1016/0161-5890(88)90117-4. PMID 3264881.
• Chakravarti DN, Campbell RD, Porter RR (Nov 1987). "The chemical structure of the C4d fragment of the human complement component C4". Molecular Immunology 24 (11): 1187–97. doi:10.1016/0161-5890(87)90165-9. PMID 3696167.
• Belt KT, Yu CY, Carroll MC, Porter RR (1985). "Polymorphism of human complement component C4". Immunogenetics 21 (2): 173–80. doi:10.1007/BF00364869. PMID 3838531.
• Hortin G, Sims H, Strauss AW (Feb 1986). "Identification of the site of sulfation of the fourth component of human complement". The Journal of Biological Chemistry 261 (4): 1786–93. PMID 3944109.
• Moon KE, Gorski JP, Hugli TE (Aug 1981). "Complete primary structure of human C4a anaphylatoxin". The Journal of Biological Chemistry 256 (16): 8685–92. PMID 6167582.
• Palsdottir A, Cross SJ, Edwards JH, Carroll MC (1984). "Correlation between a DNA restriction fragment length polymorphism and C4A6 protein". Nature 306 (5943): 615–6. doi:10.1038/306615a0. PMID 6316164.
• Belt KT, Carroll MC, Porter RR (Apr 1984). "The structural basis of the multiple forms of human complement component C4". Cell 36 (4): 907–14. doi:10.1016/0092-8674(84)90040-0. PMID 6546707.
• Carroll MC, Campbell RD, Bentley DR, Porter RR (1984). "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. doi:10.1038/307237a0. PMID 6559257.
• Carroll MC, Porter RR (Jan 1983). "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. doi:10.1073/pnas.80.1.264. PMC 393353. PMID 6572000.
• Whitehead AS, Goldberger G, Woods DE, Markham AF, Colten HR (Sep 1983). "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. doi:10.1073/pnas.80.17.5387. PMC 384261. PMID 6577433.