Alternative titles; symbols
HGNC Approved Gene Symbol: KIR2DS4
Cytogenetic location: 19q13.42 Genomic coordinates (GRCh38): 19:54,832,707-54,848,575 (from NCBI)
For background information on the KIR family of natural killer (NK) cell Ig-like receptors, see KIR2DL1 (604936).
Using a KIR2DL3 (604938) cDNA probe to screen an NK cell cDNA library, Wagtmann et al. (1995) isolated a KIR2DS4 cDNA, which they called clone 39 (CL39), encoding a type I transmembrane protein. Using primers known to amplify HLA-C-specific NK receptors to screen clones with NK-triggering activity, Bottino et al. (1996) also isolated a KIR2DS4 cDNA, which they termed KKA3. Sequence analysis revealed that KIR2DS4 encodes a deduced 304-amino acid protein with an extracellular domain similar to that of KIR2D p58 receptors; however, in the transmembrane region, there is a charged lysine residue, and the cytoplasmic tail has only 39 amino acids with no ITIM (immunoreceptor tyrosine-based inhibitory motif). KIRs with short cytoplasmic tails are associated with NK cell triggering rather than inhibition. Immunoprecipitation analysis showed that KIR2DS4 was expressed in 2 forms, one of 35 to 45 kD and the other of 55 to 58 kD. Flow cytometry analysis showed that KIR2DS4, unlike KIR2DS1 (604952) and KIR2DS2 (604953), was expressed in only a minority of individuals tested.
By analysis of somatic cell hybrids, Wagtmann et al. (1995) mapped the KIR gene family to chromosome 19. Wende et al. (1999) mapped the KIR2DS4 gene to chromosome 19q13.4 by long-range restriction analysis of YAC and PAC contigs.
By studying the distribution of KIR genes in individuals exposed to hyperendemic malaria (see 611162) in the Solomon Islands, Taniguchi and Kawabata (2009) identified a higher frequency of KIR3DL1 (604946) and KIR2DS4 in Plasmodium-positive individuals. Further analysis revealed increased KIR3DL1/KIR3DS1 (620778) heterozygosity in affected individuals. Taniguchi and Kawabata (2009) proposed that the balance of inhibitory and activating KIR3D genes may influence the status of NK cells and innate immunity in response to malaria infection.
Bottino, C., Sivori, S., Vitale, M., Cantoni, C., Falco, M., Pende, D., Morelli, L., Augugliaro, R., Semenzato, G., Biassoni, R., Moretta, L., Moretta, A. A novel surface molecule homologous to the p58/p50 family of receptors is selectively expressed on a subset of human natural killer cells and induces both triggering of cell functions and proliferation. Europ. J. Immun. 26: 1816-1824, 1996. [PubMed: 8765026] [Full Text: https://doi.org/10.1002/eji.1830260823]
Taniguchi, M., Kawabata, M. KIR3DL1/S1 genotypes and KIR2DS4 allelic variants in the AB KIR genotypes are associated with Plasmodium-positive individuals in malaria infection. Immunogenetics 61: 717-730, 2009. [PubMed: 19859704] [Full Text: https://doi.org/10.1007/s00251-009-0401-z]
Wagtmann, N., Biassoni, R., Cantoni, C., Verdiani, S., Malnati, M. S., Vitale, M., Bottino, C., Moretta, L., Moretta, A., Long, E. O. Molecular clones of the p58 NK cell receptor reveal immunoglobulin-related molecules with diversity in both the extra- and intracellular domains. Immunity 2: 439-449, 1995. [PubMed: 7749980] [Full Text: https://doi.org/10.1016/1074-7613(95)90025-x]
Wende, H., Colonna, M., Ziegler, A., Volz, A. Organization of the leukocyte receptor cluster (LRC) on human chromosome 19q13.4. Mammalian Genome 10: 154-160, 1999. [PubMed: 9922396] [Full Text: https://doi.org/10.1007/s003359900961]