Alternative titles; symbols
HGNC Approved Gene Symbol: KLRC4
Cytogenetic location: 12p13.2 Genomic coordinates (GRCh38): 12:10,407,384-10,409,757 (from NCBI)
Plougastel and Trowsdale (1997) identified a gene located 25 kb from the 3-prime end of NKG2A (161555) that they designated NKG2F. By genomic sequencing and RT-PCR, they determined that the complete NKG2D (611817) transcript is a splice variant of NKG2F that shares the same first 4 exons. There is a consensus splice donor site within the fourth exon. In the long 13-exon NKG2D mRNA this donor site is spliced to exon 5. In the shorter NKG2F cDNA, the donor site is not used, and the fourth exon contains an additional 245 bp. Sequence analysis showed that both transcripts could encode the same predicted 158-amino acid protein, and that the second open reading frame spanning the last 6 exons of NKG2D is probably not translated. The NKG2F/NKG2D protein does not contain an extracellular lectin domain, but does have a 24-amino acid motif in the extracellular region that is 100% identical to that of other NKG2 family members.
Glienke et al. (1998) confirmed that, in some cases, part of the fourth exon of NKG2F is spliced to the 5-prime end of NKG2D, which has only a low similarity to the other NKG2 genes. They noted, however, that additional NKG2D cDNAs have been isolated that do not encompass any NKG2F sequences, suggesting that a functional NKG2D-specific promoter exists.
Using RT-PCR and Western blot analysis, Kim et al. (2004) showed that NKG2F was expressed intracellularly in natural killer (NK) cells. Immunoprecipitation analysis revealed failure of NKG2F to associate with CD94 (KLRD1; 602894), possibly explaining the lack of surface expression. Flow cytometric analysis demonstrated association of NKG2F with DAP12 (TYROBP; 604142), indicating activation potential. However, phosphorylation did not occur on tyrosine in the immunoreceptor tyrosine-based inhibitory motif (ITIM) of NKG2F, suggesting that the motif is a mock ITIM. Kim et al. (2004) concluded that NKG2F may have as-yet-unidentified partners and functions or that it may be a vestigial gene product.
Glienke et al. (1998) determined that the NKG2C (602891), NKG2E (602892), and NKG2F 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 NKG2F and NKG2D genes and other members of the NKG2 gene family are clustered within 350 kb on chromosome 12p13.2-p12.3. This cluster is located within the NK complex, a region that contains C-type lectin genes preferentially expressed on NK cells.
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]
Kim, D.-K., Kabat, J., Borrego, F., Sanni, T. B., You, C., Coligan, J. E. Human NKG2F is expressed and can associate with DAP12. Molec. Immun. 41: 53-62, 2004. [PubMed: 15140575] [Full Text: https://doi.org/10.1016/j.molimm.2004.01.004]
Plougastel, B., Trowsdale, J. Cloning of NKG2-F, a new member of the NKG2 family of human natural killer cell receptor genes. Europ. J. Immun. 27: 2835-2839, 1997. [PubMed: 9394807] [Full Text: https://doi.org/10.1002/eji.1830271114]
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]