Complement receptor 1

1GKG, 1GKN, 1PPQ, 2Q7Z, 2MCY, 2MCZ, 5FO91378n/aENSG00000203710n/aP17927n/aNM_000573NM_000651n/aNP_000564NP_000642n/aComplement receptor type 1 (CR1) also known as C3b/C4b receptor or CD35 (cluster of differentiation 35) is a protein that in humans is encoded by the CR1 gene.1gkg: STRUCTURE DETERMINATION AND RATIONAL MUTAGENESIS REVEAL BINDING SURFACE OF IMMUNE ADHERENCE RECEPTOR, CR1 (CD35)1gkn: STRUCTURE DETERMINATION AND RATIONAL MUTAGENESIS REVEAL BINDING SURFACE OF IMMUNE ADHERENCE RECEPTOR, CR1 (CD35)1ppq: NMR structure of 16th module of Immune Adherence Receptor, Cr1 (Cd35) Complement receptor type 1 (CR1) also known as C3b/C4b receptor or CD35 (cluster of differentiation 35) is a protein that in humans is encoded by the CR1 gene. This gene is a member of the regulators 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, hyalocytes, 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. 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 mice, CR1 is an alternatively spliced variant of the complement receptor 2 (CR2) gene. Certain alleles of this gene have been statistically associated with an increased risk of developing late-onset Alzheimer's disease. In humans, the CR1 gene is located 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 canonical Cr2/CD21 gene of subprimate mammals produces two types of complement receptor (CR1, ca. 200 kDa; CR2, ca. 145 kDa) via alternative mRNA splicing. The murine Cr2 gene contains 25 exons; a common first exon is spliced to exon 2 and to exon 9 in transcripts encoding CR1 and CR2, respectively. A transcript with an open reading frame of 4,224 nucleotides encodes the long isoform, CR1; this is predicted to be a protein of 1,408 amino acids that includes 21 short consensus repeats (SCR) of ca. 60 amino acids each, plus transmembrane and cytoplasmic regions. Isoform CR2 (1,032 amino acids) is encoded by a shorter transcript (3,096 coding nucleotides) that lacks exons 2–8 encoding SCR1-6. CR1 and CR2 on murine B cells form complexes with a co-accessory activation complex containing CD19, CD81, and the fragilis/Ifitm (murine equivalents of LEU13) proteins. The complement receptor 2 (CR2) gene of primates produces only the smaller isoform, CR2; primate CR1, which recapitulates many of the structural domains and presumed functions of Cr2-derived CR1 in subprimates, is encoded by a distinct CR1 gene (apparently derived from the gene Crry of subprimates). Isoforms CR1 and CR2 derived from the Cr2 gene possess the same C-terminal sequence, such that association with and activation through CD19 should be equivalent. CR1 can bind to C4b and C3b complexes, whereas CR2 (murine and human) binds to C3dg-bound complexes. CR1, a surface protein produced primarily by follicular dendritic cells, appears to be critical for generation of appropriately activated B cells of the germinal centre and for mature antibody responses to bacterial infection.