Human complement C3b/C4b receptor (CR1) mRNA polymorphism that correlates with the CR1 allelic molecular weight polymorphism.
The human C3b/C4b receptor (CR1) is a Mr approximately equal to 200,000 single-chain integral membrane glycoprotein of human erythrocytes and leukocytes. It functions both as a receptor for C3b- and C4b-coated ligands and as a regulator of complement activation. Prior structural studies have defined an unusual molecular weight allelic polymorphism in which the allelic products differ in molecular weight by as much as 90,000. On peripheral blood cells there is codominant expression of CR1 gene products of Mr 190,000 (A), 220,000 (B), 160,000 (C), and 250,000 (D). Results of prior biosynthetic and tryptic peptide mapping experiments have suggested that the most likely basis for the allelic molecular weight differences is at the polypeptide level. In order to define further the molecular basis for these molecular weight differences, human CR1 was purified to homogeneity, tryptic peptide fragments were isolated by HPLC and sequenced, oligonucleotide probes were prepared, and a CR1 cDNA was identified. A subclone of this CR1 cDNA was used as a probe of RNA blots of Epstein-Barr virus-transformed cell lines expressing the allelic variants. Each allelic variant encodes two distinct transcripts. A mRNA size polymorphism was identified that correlated with the gene product molecular weight polymorphism. This finding, in addition to a prior report of several homologous repeats in CR1, is consistent with the hypothesis that the molecular weight polymorphism is determined at the genomic level and may have been generated by unequal crossing-over.
D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D003176:Complement C3 / Q000378:metabolism; D004262:DNA Restriction Enzymes; D005796:Genes; D006801:Humans; D010446:Peptide Fragments / Q000032:analysis; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000235:genetics*; D011951:Receptors, Complement / Q000235:genetics* / Q000302:isolation & purification; D017463:Receptors, Complement 3b
D003176:Complement C3; D010446:Peptide Fragments; D012333:RNA, Messenger; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D004262:DNA Restriction Enzymes