| C4A | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| 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 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Complement C4-A is a kind of the Complement component 4 protein that in humans is encoded by the C4A gene. [5]
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]
Complement C2 is a protein that in humans is encoded by the C2 gene. The protein encoded by this gene is part of the classical pathway of the complement system, acting as a multi-domain serine protease. Deficiency of C2 has been associated with certain autoimmune diseases.
Complement factor B is a protein that in humans is encoded by the CFB gene.
The C3a receptor also known as complement component 3a receptor 1 (C3AR1) is a G protein-coupled receptor protein involved in the complement system.
Steroid 21-hydroxylase is an enzyme that hydroxylates steroids at the C21 position and is involved in biosynthesis of aldosterone and cortisol. The enzyme converts progesterone and 17α-hydroxyprogesterone into 11-deoxycorticosterone and 11-deoxycortisol, respectively, within metabolic pathways that ultimately lead to aldosterone and cortisol. Deficiency in the enzyme may cause congenital adrenal hyperplasia.
Complement component 4 (C4), in humans, is a protein involved in the intricate complement system, originating from the human leukocyte antigen (HLA) system. It serves a number of critical functions in immunity, tolerance, and autoimmunity with the other numerous components. Furthermore, it is a crucial factor in connecting the recognition pathways of the overall system instigated by antibody-antigen (Ab-Ag) complexes to the other effector proteins of the innate immune response. For example, the severity of a dysfunctional complement system can lead to fatal diseases and infections. Complex variations of it can also lead to schizophrenia. The C4 protein was thought to derive from a simple two-locus allelic model, which however has been replaced by a much more sophisticated multimodular RCCX gene complex model which contain long and short forms of the C4A or C4B genes usually in tandem RCCX cassettes with copy number variation, that somewhat parallels variation in the levels of their respective proteins within a population along with CYP21 in some cases depending on the number of cassettes and whether it contains the functional gene instead of pseudogenes or fragments. Originally defined in the context of the Chido/Rodgers blood group system, the C4A-C4B genetic model is under investigation for its possible role in schizophrenia risk and development.
The word allotype comes from two Greek roots, allo meaning 'other or differing from the norm' and typos meaning 'mark'. In immunology, allotype is an immunoglobulin variation that can be found among antibody classes and is manifested by heterogeneity of immunoglobulins present in a single vertebrate species. The structure of immunoglobulin polypeptide chain is dictated and controlled by number of genes encoded in the germ line. However, these genes, as it was discovered by serologic and chemical methods, could be highly polymorphic. This polymorphism is subsequently projected to the overall amino acid structure of antibody chains. Polymorphic epitopes can be present on immunoglobulin constant regions on both heavy and light chains, differing between individuals or ethnic groups and in some cases may pose as immunogenic determinants. Exposure of individuals to a non-self allotype might elicit an anti- allotype response and became cause of problems for example in a patient after transfusion of blood or in a pregnant woman. However, it is important to mention that not all variations in immunoglobulin amino acid sequence pose as a determinant responsible for immune response. Some of these allotypic determinants may be present at places that are not well exposed and therefore can be hardly serologically discriminated. In other cases, variation in one isotype can be compensated by the presence of this determinant on another antibody isotype in one individual. This means that divergent allotype of heavy chain of IgG antibody may be balanced by presence of this allotype on heavy chain of for example IgA antibody and therefore is called isoallotypic variant. Especially large number of polymorphisms were discovered in IgG antibody subclasses. Which were practically used in forensic medicine and in paternity testing, before replaced by modern day DNA fingerprinting.
Major histocompatibility complex, class II, DR beta 4, also known as HLA-DRB4, is a human gene.
HLA class II histocompatibility antigen, DRB5 beta chain is a protein that in humans is encoded by the HLA-DRB5 gene.
Transporter associated with antigen processing 1 (TAP1) is a protein that in humans is encoded by the TAP1 gene. A member of the ATP-binding cassette transporter family, it is also known as ABCB2.
Major histocompatibility complex, class II, DQ alpha 1, also known as HLA-DQA1, is a human gene present on short arm of chromosome 6 (6p21.3) and also denotes the genetic locus which contains this gene. The protein encoded by this gene is one of two proteins that are required to form the DQ heterodimer, a cell surface receptor essential to the function of the immune system.
HLA class II histocompatibility antigen, DP(W2) beta chain is a protein that in humans is encoded by the HLA-DPB1 gene.
HLA class II histocompatibility antigen, DRB3-1 beta chain is a protein that in humans is encoded by the HLA-DRB3 gene.
Killer cell immunoglobulin-like receptor 3DL1 is a protein that in humans is encoded by the KIR3DL1 gene.
Large proline-rich protein BAT2 is a protein that in humans is encoded by the BAT2 gene.
HLA class II histocompatibility antigen, DQ(6) alpha chain is a protein that in humans is encoded by the HLA-DQA2 gene. Also known as HLA-DXA or DAAP-381D23.2, it is part of the human leucocyte antigen system.
Serine/threonine-protein kinase 19 is an enzyme that in humans is encoded by the STK19 gene.
TAP2 is a gene in humans that encodes the protein Antigen peptide transporter 2.
Complement factor H-related protein 2 is a protein that in humans is encoded by the CFHR2 gene.
Complement component 4B (Chido blood group) is a kind of the Complement component 4 protein that in humans is encoded by the C4B gene.
RCCX is a multiallelic copy number variation human DNA locus on chromosome 6p21.3.
Media related to C4A at Wikimedia CommonsPDB gallery | |
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