RBCC Red Blood Cell Collection

CO4A_HUMAN

Source: PM23856902
BGMUT ; ID: chrg
Marked as 'Non-membrane protein'
Confidence: high (a blood group or CD marker) Search PubMed for
(RBC AND this entry)
Gene names: C4A , CO4, CPAMD2
Protein names and data: CO4A_HUMAN , Complement C4-A , Acidic complement C4; C3 and PZP-like alpha-2-macroglobulin domain-containing protein 2; Complement C4 beta chain; Complement C4-A alpha chain; C4a anaphylatoxin; C4b-A; C4d-A; Complement C4 gamma chain; Flags: Precursor Lenght: 1744 a.a.
Mass: 192785 Da
fasta formatted sequence
Function: Non-enzymatic component of C3 and C5 convertases and thus essential for the propagation of the classical complement pathway. Covalently binds to immunoglobulins and immune complexes and enhances the solubilization of immune aggregates and the clearance of IC through CR1 on erythrocytes. C4A isotype is responsible for effective binding to form amide bonds with immune aggregates or protein antigens, while C4B isotype catalyzes the transacylation of the thioester carbonyl group to form ester bonds with carbohydrate antigens. 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.
Disease: ( OMIM: 120790 120810 152700 614374 614380 ) 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. Note=The disease is caused by mutations affecting the gene represented in this entry. Systemic lupus erythematosus (SLE) [MIM:152700]: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. 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.
Cellular location: Secreted.
Tissue specificity: Complement component C4 is expressed at highest levels in the liver, at moderate levels in the adrenal cortex, adrenal medulla, thyroid gland,and the kidney, and at lowest levels in the heart, ovary, small intestine, thymus, pancreas and spleen. The extra-hepatic sites of expression may be important for the local protection and inflammatory response.

Genetic variants

The complement component C4 is the most polymorphic protein of the complement system. It is the product of 2 closely linked and highly homologous genes, C4A and C4B. Once polymorphic variation is discounted, the 2 isotypes differ by only 4 amino acids at positions 1120-1125: PCPVLD for C4A and LSPVIH for C4B. The 2 isotypes bear several antigenic determinants defining Chido/Rodgers blood group system [MIM:614374]. Rodgers determinants are generally associated with C4A allotypes, and Chido with C4B. Variations at these loci involve not only nucleotide polymorphisms, but also gene number and gene size. Some individuals may lack either C4A, or C4B gene. Partial deficiency of C4A or C4B is the most commonly inherited immune deficiency known in humans with a combined frequency over 31% in the normal Caucasian population (PubMed:11367523). C4A6 allotype is deficient in hemolytic activity. Allotype C4A13 is infrequent.

141 - 141 L -> V (in dbSNP:rs9296005). VAR_069154 9296005
347 - 347 S -> Y (in allotype C4A3a, allotype C4A6; dbSNP:rs150969927). VAR_019778 150969927
418 - 418 V -> A (in allotype C4A4). VAR_069155
477 - 477 R -> W (in allotype C4A6). VAR_001987
549 - 549 H -> P (in dbSNP:rs2229405). VAR_069156 2229405
564 - 564 A -> D (in dbSNP:rs35277227). VAR_069157 35277227
726 - 726 P -> L (in allotype C4A3a). VAR_001988
727 - 727 D -> N. VAR_019779
907 - 907 A -> T (in dbSNP:rs141302872). VAR_019780 141302872
1073 - 1073 D -> G (in allotype C4A1, allotype C4A2; dbSNP:rs147162052). VAR_069158 147162052
1176 - 1176 N -> S (in allotype C4A1; dbSNP:rs17874654). VAR_069159 17874654
1201 - 1201 T -> S (in allotype C4A4). VAR_001992
1207 - 1207 V -> A (in allotype C4A1, allotype C4A13; dbSNP:rs28357075). VAR_001993 28357075
1210 - 1210 L -> R (in allotype C4A1, allotype C4A13; dbSNP:rs28357076). VAR_001994 28357076
1286 - 1286 S -> A (in allotype C4A1, allotype C4A3a, allotype C4A6; dbSNP:rs201016130). VAR_001995 201016130

Database cross-references

UniProt: P0C0L4
Ensembl: ENST00000383325
Ensembl: ENST00000421274
Ensembl: ENST00000428956
Ensembl: ENST00000498271
MIM: 120790
MIM: 120810
MIM: 152700
MIM: 614374
MIM: 614380
neXtProt: NX_P0C0L4
Antibodypedia: P0C0L4 (may not find the protein thus also not any antibody)
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