Alternative titles; symbols
HGNC Approved Gene Symbol: KLRC2
Cytogenetic location: 12p13.2 Genomic coordinates (GRCh38): 12:10,430,599-10,436,010 (from NCBI)
Houchins et al. (1991) reported the cDNA sequences of a series of related transcripts that are expressed primarily in natural killer (NK) cells. This group of genes, designated NKG2, encodes a family of C-type lectins. See NKG2A, 161555. By Northern blot analysis, Yabe et al. (1993) found that one of the genes, NKG2C, was expressed as 3 transcripts of 1.1 to 1.6 kb in NK cell lines and in 1 of the T-cell lines tested.
The protein HLA-E (143010) is a nonclassical MHC molecule of limited sequence variability. Its expression on the cell surface is regulated by the binding of peptides derived from the signal sequence of some other MHC class I molecules. Braud et al. (1998) reported the identification of ligands for HLA-E. Braud et al. (1998) constructed tetramers in which recombinant HLA-E and beta-2 microglobulin were refolded with an MHC leader-sequence peptide, biotinylated, and conjugated to Extravidin. This HLA-E tetramer bound to natural killer cells and a small subset of T cells from peripheral blood. On transfectants, the tetramer bound to the CD94/NKG2A, CD94/NKG2B, and CD94/NKG2C NK cell receptors, but did not bind to the immunoglobulin family of NK cell receptors (KIRs; see 604936). Surface expression of HLA-E was enough to protect target cells from lysis by CD94/NKG2A+ NK cell clones. A subset of HLA class I alleles had been shown to inhibit killing by CD94/NKG2A+ NK cell clones. Only the HLA alleles that possess a leader peptide capable of upregulating HLA-E surface expression confer resistance to NK cell-mediated lysis, implying that their action is mediated by HLA-E, the predominant ligand for the NK cell inhibitory receptor CD94/NKG2A.
Glienke et al. (1998) determined that the NKG2C, NKG2E (602892), and NKG2F (602893) genes are highly similar except for variability at their 3-prime ends. The NKG2C gene contains 6 exons, whereas NKG2E has 7 exons and NKG2F has only 4 exons.
By analysis of a cosmid contig, Plougastel and Trowsdale (1998) found that the NKG2C gene and other members of the NKG2 gene family are clustered within 350 kb on 12p13.2-p12.3, a region known as the NK complex.
Braud, V. M., Allan, D. S. J., O'Callaghan, C. A., Soderstrom, K., D'Andrea, A., Ogg, G. S., Lazetic, S., Young, N. T., Bell, J. I., Phillips, J. H., Lanier, L. L., McMichael, A. J. HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C. Nature 391: 795-799, 1998. [PubMed: 9486650] [Full Text: https://doi.org/10.1038/35869]
Glienke, J., Sobanov, Y., Brostjan, C., Steffens, C., Nguyen, C., Lehrach, H., Hofer, E., Francis, F. The genomic organization of NKG2C, E, F, and D receptor genes in the human natural killer gene complex. Immunogenetics 48: 163-173, 1998. [PubMed: 9683661] [Full Text: https://doi.org/10.1007/s002510050420]
Houchins, J. P., Yabe, T., McSherry, C., Bach, F. H. DNA sequence analysis of NKG2, a family of related cDNA clones encoding type II integral membrane proteins on human natural killer cells. J. Exp. Med. 173: 1017-1020, 1991. [PubMed: 2007850] [Full Text: https://doi.org/10.1084/jem.173.4.1017]
Plougastel, B., Trowsdale, J. Sequence analysis of a 62-kb region overlapping the human KLRC cluster of genes. Genomics 49: 193-199, 1998. [PubMed: 9598306] [Full Text: https://doi.org/10.1006/geno.1997.5197]
Yabe, T., McSherry, C., Bach, F. H., Fisch, P., Schall, R. P., Sondel, P. M., Houchins, J. P. A multigene family on human chromosome 12 encodes natural killer-cell lectins. Immunogenetics 37: 455-460, 1993. [PubMed: 8436421] [Full Text: https://doi.org/10.1007/BF00222470]