NKG2 Subfamily C (KLRC)

Abstract

NKG2 receptors are type II C-type, lectin-like, integral membrane glycoproteins, which are expressed on the cell surface as heterodimers with CD94, which is an invariant type II C-type, lectin-like polypeptide. CD94 lacks a cytoplasmic tail and therefore, cannot transduce signals. It is however essential for the expression of NKG2 receptors. Four distinct genes, A/B, C, E/H, and F, encode the NKG2 receptors. Of these receptors, CD94/NKG2A is an inhibitory one, as it contains a long cytoplasmic tail with two ITIMs. Others have short cytoplasmic tails, and each associates noncovalently with a homodimer of DAP-12, as in the case of activating KIRs. The NKG2 family of genes (HGMW-approved symbol KLRC) contains at least six members (NKG2-A, -B, -C, -E, -F and -H) which are localized to human chromosome 12p12.3-p13.2, in the same region where CD69 genes have been mapped. In addition, the human CD94 and NKR-P1A genes map to the short arm of chromosome 12. The physical distance spanned by NK gene complex (NKC) in humans ranges between 0.7 and 2.4 megabases (Renedo et al. 1997). The NKG2 and CD94 genes are localized in a small region (< 350 kb) and mapped in the following order: (NKG2-C/NKG2-A)/NKG2-E/NKG2-F/NKG2-D/CD94. Sequence analysis of 62 kb spanning the NKG2-A, -E, -F, and -D loci allowed the identification of two LINE elements that could have been involved in the duplication of the NKG2 genes. Presence of one MIR and one L1ME2 element at homologous positions in the NKG2-A and NKG2-F genes is consistent with the existence of rodent NKG2 gene(s). The 5{\textasciiacutex}-ends of the NKG2-A transcripts were mapped into two separate regions showing the existence of two separate transcriptional control regions upstream of the NKG2-A locus and defining putative promoter elements for these genes (Plougastel and Trowsdale 1998). Restriction mapping and sequencing revealed the NKG2-C, -D, -E, and -F genes to be closely linked to one another, and of the same transcriptional orientation. The NKG2-C, -E, and -F genes, despite being highly similar, are variable at their 3{\textasciiacutex} ends. It was found that NKG2-C consists of six exons, whereas NKG2-E has seven, and the splice acceptor site for the seventh exon occurs in an Alu repeat. NKG2-F consists of only four exons and part of exon IV is in some cases spliced to the 5{\textasciiacutex} end of the NKG2-D transcript. NKG2-D has only a low similarity to the other NKG2 genes Glienke et al. (1998). The murine NKG2-D-like sequence also maps to the murine NK complex near CD94 and Ly49 family members.