CCR2 is a member of the superfamily of seven transmembrane domain G protein-coupled receptors, the largest receptor superfamily in the human genome. CCR2 acts as a receptor for MCP-1 (Monocytes Chemoattractive Protein type 1) and several other close structural homologues of MCP-1 (MCP-2, -3, -4, and -5). MCP-1 is a CC chemokine of the family of chemokines which specifically mediates monocyte chemotaxis. CCR2 also acts as co-receptor for human immunodeficiency virus-1 (HIV-1) infection.
CCR2 gene has been mapped to 3p21, and contains three exons distributed over 7 kb of the genomic sequence. The protein product of this gene comprises 374 amino acids long with a molecular mass of 41915 Da. Two receptors derived from alternative splicing in the carboxyl terminal- coding region of the protein have been identified (CCR2-alpha and CCR2-beta), both of which signal a highly specific response for MCP1.
Several polymorphic sites of the CCR2 gene have been studied. The most comprehensively studied polymorphism is caused by the nucleotide substitution of G by A at position 190 of the encoding part of the gene. This substitution results in the replacement of valine-64 (V) by isoleucine (I) in the first transmembrane domain of the protein. The frequency of the 64I allelic variant in different ethnic groups ranges from 10 to 30%. It was shown that the presence of this allele in the genotype significantly delays AIDS onset and increases the relative risks of diabetes mellitus I and bronchial asthma.
