ID:CO4A_HUMAN DESCRIPTION: RecName: Full=Complement C4-A; AltName: Full=Acidic complement C4; AltName: Full=C3 and PZP-like alpha-2-macroglobulin domain-containing protein 2; Contains: RecName: Full=Complement C4 beta chain; Contains: RecName: Full=Complement C4-A alpha chain; Contains: RecName: Full=C4a anaphylatoxin; Contains: RecName: Full=C4b-A; Contains: RecName: Full=C4d-A; Contains: RecName: Full=Complement C4 gamma chain; Flags: Precursor; FUNCTION: C4 plays a central role in the activation of the classical pathway of the complement system. It is processed by activated C1 which removes from the alpha chain the C4a anaphylatoxin. The remaining alpha chain fragment C4b is the major activation product and is an essential subunit of the C3 convertase (C4b2a) and the C5 convertase (C3bC4b2a) enzymes of the classical complement pathway. FUNCTION: Derived from proteolytic degradation of complement C4, C4a anaphylatoxin is a mediator of local inflammatory process. It induces the contraction of smooth muscle, increases vascular permeability and causes histamine release from mast cells and basophilic leukocytes. SUBUNIT: Circulates in blood as a disulfide-linked trimer of an alpha, beta and gamma chain. SUBCELLULAR LOCATION: Secreted. PTM: Prior to secretion, the single-chain precursor is enzymatically cleaved to yield the non-identical chains (alpha, beta and gamma). During activation, the alpha chain is cleaved by C1 into C4a and C4b, and C4b stays linked to the beta and gamma chains. Further degradation of C4b by C1 into the inactive fragments C4c and C4d blocks the generation of C3 convertase. PTM: N- and O-glycosylated. O-glycosylated with a core 1 or possibly core 8 glycan. POLYMORPHISM: Human complement component C4 is polymorphic at two loci, C4A and C4B, that are responsible for Chido/Rodgers blood group system [MIM:614374]. 13 alleles of C4A and 22 alleles of C4B have been detected. The allele shown here is C4A4. The C4A alleles carry the Rodgers (Rg) while the C4B alleles carry the Chido (Ch) blood group antigens. The C4A6 allotype is totally deficient in hemolytic activity. DISEASE: Defects in C4A are the cause of complement component 4A deficiency (C4AD) [MIM:614380]. A rare defect of the complement classical pathway associated with the development of autoimmune disorders, mainly systemic lupus with or without associated glomerulonephritis. DISEASE: Defects in C4A are a cause of susceptibility to systemic lupus erythematosus (SLE) [MIM:152700]. A chronic, inflammatory and often febrile multisystemic disorder of connective tissue. It affects principally the skin, joints, kidneys and serosal membranes. It is thought to represent a failure of the regulatory mechanisms of the autoimmune system. Note=Interindividual copy- number variation (CNV) of complement component C4 and associated polymorphisms result in different susceptibilities to SLE. The risk of SLE susceptibility has been shown to be significantly increased among subjects with only two copies of total C4. A high copy number is a protective factor against SLE. MISCELLANEOUS: C4A allotypes react more rapidly with the amino group of peptide antigens while C4B allotypes react more rapidly with the hydroxyl group of carbohydrate antigens. SIMILARITY: Contains 1 anaphylatoxin-like domain. SIMILARITY: Contains 1 NTR domain. WEB RESOURCE: Name=dbRBC/BGMUT; Note=Blood group antigen gene mutation database; URL="http://www.ncbi.nlm.nih.gov/gv/mhc/xslcgi.cgi?cmd=bgmut/systems_info&system=chrg";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P0C0L4
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
