C4A

C4A
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1HZF, 4FXG, 4FXK, 4XAM
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
Gene location (Human)
Chr.	Chromosome 6 (human)
End	32,002,681 bp
Gene location (Mouse)
Chr.	Chromosome 17 (mouse)
End	34,962,856 bp
RNA expression pattern
	Top expressed in
	right lobe of liver; ; right lobe of thyroid gland; ; left lobe of thyroid gland; ; tibial nerve; ; anterior pituitary; ; spleen; ; kidney; ; left uterine tube; ; gallbladder; ; substantia nigra;
	Top expressed in
	zone of skin; ; adrenal gland; ; white adipose tissue; ; synovial joint; ; ankle joint; ; spleen; ; liver; ; uterus; ; esophagus; ; urinary bladder;
	More reference expression data
	; ;
	More reference expression data
Gene ontology
Molecular function	endopeptidase inhibitor activity; complement component C1q complex binding; serine-type endopeptidase activity;
Cellular component	extracellular region; plasma membrane; extracellular exosome; blood microparticle; cell projection; dendrite; cell junction; synapse; axon; neuronal cell body; extracellular space; endoplasmic reticulum lumen;
Biological process	complement activation; inflammatory response; positive regulation of apoptotic cell clearance; regulation of complement activation; negative regulation of endopeptidase activity; complement activation, classical pathway; immune system process; innate immune response; proteolysis; post-translational protein modification;
	Sources:Amigo / QuickGO
Orthologs
	720
	12268
	ENSG00000244207; ENSG00000206340; ENSG00000244731; ENSG00000227746
	ENSMUSG00000073418
	P0C0L4
	P01029
	NM_001252204; NM_007293
	NM_009780
	NP_001239133; NP_009224
	NP_033910
	Wikidata
View/Edit Human	View/Edit Mouse

Complement C4-A is a 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 is associated with schizophrenia and bipolar disorder with psychosis.^[12] 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.^[5]

References

^ ^a ^b ^c ENSG00000206340, ENSG00000244731, ENSG00000227746 GRCh38: Ensembl release 89: ENSG00000244207, ENSG00000206340, ENSG00000244731, ENSG00000227746 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000073418 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b "Entrez Gene: C4A complement component 4A (Rodgers blood group)".
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ Sharma, RP (2018). "C4A mRNA expression in PBMCs predicts the presence and severity of delusions in schizophrenia and bipolar disorder with psychosis". Schizophr. Res. 197: 321–327. doi:10.1016/j.schres.2018.01.018. PMC 6087677. PMID 29449061.

External links

Media related to C4A at Wikimedia Commons
Human C4A genome location and C4A gene details page in the UCSC Genome Browser.

Hugli TE (1987). "Biochemistry and biology of anaphylatoxins". Complement. 3 (3): 111–27. doi:10.1159/000467889. 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. Bibcode:1990PNAS...87.1288G. 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. doi:10.1002/j.1460-2075.1986.tb04582.x. 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. Bibcode:1984Natur.307..237C. 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. Bibcode:1983PNAS...80..264C. 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. Bibcode:1983PNAS...80.5387W. doi:10.1073/pnas.80.17.5387. PMC 384261. PMID 6577433.

This article on a gene on human chromosome 6 is a stub. You can help Wikipedia by expanding it.

[refGRCh38Ensembl-1] ENSG00000206340, ENSG00000244731, ENSG00000227746 GRCh38: Ensembl release 89: ENSG00000244207, ENSG00000206340, ENSG00000244731, ENSG00000227746 – Ensembl, May 2017

[refGRCm38Ensembl-2] 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.

[entrez-5] "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.

[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.

[12] Sharma, RP (2018). "C4A mRNA expression in PBMCs predicts the presence and severity of delusions in schizophrenia and bipolar disorder with psychosis". Schizophr. Res. 197: 321–327. doi:10.1016/j.schres.2018.01.018. PMC 6087677. PMID 29449061.

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C4A

Function

See also

References

External links

Further reading