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Erythrocyte complement receptor 1 (CR1, also known as CD35, C3b/C4b receptor and immune adherence receptor) is a human gene.[1][2]
This protein encoded by this gene is a member of the receptors of complement activation (RCA) family and is located in the ‘cluster RCA’ region of chromosome 1. The gene encodes a monomeric single-pass type I membrane glycoprotein found on erythrocytes, leukocytes, glomerular podocytes, and splenic follicular dendritic cells. The Knops blood group system is a system of antigens located on this protein. The protein mediates cellular binding to particles and immune complexes that have activated complement. Decreases in expression of this protein and/or mutations in its gene have been associated with gallbladder carcinomas, mesangiocapillary glomerulonephritis, systemic lupus erythematosus and sarcoidosis. Mutations in this gene have also been associated with a reduction in Plasmodium falciparum rosetting, conferring protection against severe malaria. Alternate allele-specific splice variants, encoding different isoforms, have been characterized. Additional allele specific isoforms, including a secreted form, have been described but have not been fully characterized.[1]
In primates, CR1 serves as the main system for processing and clearance of complement opsonized immune complexes. It has been shown that CR1 can act as a negative regulator of the complement cascade, mediate immune adherence and phagocytosis and inhibit both the classic and alternative pathways. The number of CR1 molecules decreases with aging of erythrocytes in normal individuals and is also decreased in pathological conditions such as systemic lupus erythematosus (SLE), HIV infection, some haemolytic anaemias and other conditions featuring immune complexes.
In humans, the CR1 gene is located at on the long arm of chromosome 1 at band 32 (1q32) and lies within a complex of immunoregulatory genes. In 5’-3’ order the genes in this region are: membrane cofactor protein – CR1- complement receptor type 2 – decay-accelerating factor – C4-binding protein.
Factor H, another immunoregulatory protein, also maps to this location.
The most common form of the CR1 gene (CR1*1) is composed of 38 exons spanning 133kb encoding a protein of 2039 amino acids and has a predicted molecular weight of 220 kDa. Large insertions and deletions have given rise to four structurally variant genes and some alleles may extend up to 160 kb and 9 additional exons. The transcription start site has been mapped to 111 bp upstream of the translation initiation codon ATG and there is another possible start site 29 bp further upstream. The promoter region lacks a distinct TATA box sequence. The gene is expressed principally on erythrocytes, monocytes, neutrophils and B cells but is also present on some T lymphocytes, mast cells and glomerular podocytes.
The mean number of complement receptor 1 (CR1) molecules on erythrocytes in normal individuals lies within the range of 100-1000 molecules per cell. Two codominant alleles exist – one controlling high and the other low expression. Homozygotes differ by a factor of 10-20: heterozygotes typically have 500-600 copies per erythrocyte. These two alleles appear to have originated before the divergence of the European and African populations.
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