Gene Symbol: KLRC4-KLRK1
Description: KLRC4-KLRK1 readthrough
Alias: NKG2-D type II integral membrane protein, NK cell receptor D, NKG2-D-activating NK receptor, killer cell lectin-like receptor subfamily K member 1
Species: human
Products:     KLRC4-KLRK1

Top Publications

  1. Plougastel B, Trowsdale J. Sequence analysis of a 62-kb region overlapping the human KLRC cluster of genes. Genomics. 1998;49:193-9 pubmed
  2. Bauer S, Groh V, Wu J, Steinle A, Phillips J, Lanier L, et al. Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA. Science. 1999;285:727-9 pubmed
    ..These results define an activating immunoreceptor-MHC ligand interaction that may promote antitumor NK and T cell responses. ..
  3. Hosomi S, Chen Z, Baker K, Chen L, Huang Y, Olszak T, et al. CEACAM1 on activated NK cells inhibits NKG2D-mediated cytolytic function and signaling. Eur J Immunol. 2013;43:2473-83 pubmed publisher
    ..Thus, CEACAM1 on activated NK cells functions as an inhibitory receptor for NKG2D-mediated cytolysis, which has important implications for understanding the means by which CEACAM1 expression adversely affects tumor immunity. ..
  4. McFarland B, Kortemme T, Yu S, Baker D, Strong R. Symmetry recognizing asymmetry: analysis of the interactions between the C-type lectin-like immunoreceptor NKG2D and MHC class I-like ligands. Structure. 2003;11:411-22 pubmed
    ..Rather, the divergent ligands appear to utilize different strategies to interact with structurally conserved elements of the consensus NKG2D binding site. ..
  5. Chan C, Crafton E, Fan H, Flook J, Yoshimura K, Skarica M, et al. Interferon-producing killer dendritic cells provide a link between innate and adaptive immunity. Nat Med. 2006;12:207-13 pubmed
    ..By virtue of their capacity to kill target cells, followed by antigen presentation, IKDCs provide a link between innate and adaptive immunity. ..
  6. Houchins J, Yabe T, McSherry C, Bach F. 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. 1991;173:1017-20 pubmed
    ..This family is characterized by the presence of a C-type animal lectin domain, and several of its members have demonstrated transmembrane signaling capability. ..
  7. Serrano Pertierra E, Cernuda Morollón E, Lopez Larrea C. Wiskott-Aldrich syndrome protein (WASp) and N-WASp are involved in the regulation of NK-cell migration upon NKG2D activation. Eur J Immunol. 2012;42:2142-51 pubmed publisher
    ..Therefore, our results provide a new mechanism that may contribute to the immune response or evasion in tumors. ..
  8. Eagle R, Traherne J, Hair J, Jafferji I, Trowsdale J. ULBP6/RAET1L is an additional human NKG2D ligand. Eur J Immunol. 2009;39:3207-16 pubmed publisher
    ..Expression of ULBP6 on target cells induced a significant increase in NK-cell killing. Comparison of ULBP6 with ULBP4 and ULBP5 indicated that differences in recombinant NKG2D binding correlated with differences in NK-cell activation. ..
  9. Renedo M, Arce I, Montgomery K, Roda Navarro P, Lee E, Kucherlapati R, et al. A sequence-ready physical map of the region containing the human natural killer gene complex on chromosome 12p12.3-p13.2. Genomics. 2000;65:129-36 pubmed
    ..This map would facilitate the cloning of new KLR genes and the complete sequencing of this region. ..

More Information


  1. Kong Y, Cao W, Xi X, Ma C, Cui L, He W. The NKG2D ligand ULBP4 binds to TCRgamma9/delta2 and induces cytotoxicity to tumor cells through both TCRgammadelta and NKG2D. Blood. 2009;114:310-7 pubmed publisher
    ..Taken together, our data suggest that ULBP4 functions as a ligand for both TCRgammadelta and NKG2D and may play a key role in immune surveillance of tumor development and clearance of viral infection. ..
  2. Wittenbrink M, Spreu J, Steinle A. Differential NKG2D binding to highly related human NKG2D ligands ULBP2 and RAET1G is determined by a single amino acid in the alpha2 domain. Eur J Immunol. 2009;39:1642-51 pubmed publisher
    ..Altogether, RAET1G, like ULBP2, appears broadly expressed, but exhibits a lower apparent avidity for NKG2D due to a mutation in the center of the MHC-like fold. ..
  3. Hoffmann S, Schellack C, Textor S, Konold S, Schmitz D, Cerwenka A, et al. Identification of CLEC12B, an inhibitory receptor on myeloid cells. J Biol Chem. 2007;282:22370-5 pubmed
  4. Yabe T, McSherry C, Bach F, Fisch P, Schall R, Sondel P, et al. A multigene family on human chromosome 12 encodes natural killer-cell lectins. Immunogenetics. 1993;37:455-60 pubmed
    ..The limited distribution of these proteins and their sequence similarity with known receptor molecules suggest that they may function as receptors on human NK cells. ..
  5. Waldhauer I, Goehlsdorf D, Gieseke F, Weinschenk T, Wittenbrink M, Ludwig A, et al. Tumor-associated MICA is shed by ADAM proteases. Cancer Res. 2008;68:6368-76 pubmed publisher
    ..Hence, therapeutic blockade of ADAM10 and ADAM17 seems promising for cancer treatment by targeting both growth and immune escape of tumors. ..
  6. Rosen D, Araki M, Hamerman J, Chen T, Yamamura T, Lanier L. A Structural basis for the association of DAP12 with mouse, but not human, NKG2D. J Immunol. 2004;173:2470-8 pubmed
  7. Bacon L, Eagle R, Meyer M, Easom N, Young N, Trowsdale J. Two human ULBP/RAET1 molecules with transmembrane regions are ligands for NKG2D. J Immunol. 2004;173:1078-84 pubmed
    ..The expression of diverse NKG2D-binding molecules in different tissues and with different properties is consistent with multiple modes of infection- or stress-induced activation. ..
  8. Vivier E, Tomasello E, Paul P. Lymphocyte activation via NKG2D: towards a new paradigm in immune recognition?. Curr Opin Immunol. 2002;14:306-11 pubmed
  9. Radaev S, Rostro B, Brooks A, Colonna M, Sun P. Conformational plasticity revealed by the cocrystal structure of NKG2D and its class I MHC-like ligand ULBP3. Immunity. 2001;15:1039-49 pubmed
    ..Unlike the KIR receptors that recognize a conserved HLA region by a lock-and-key mechanism, NKG2D recognizes diverse ligands by an induced-fit mechanism. ..
  10. Shum B, Flodin L, Muir D, Rajalingam R, Khakoo S, Cleland S, et al. Conservation and variation in human and common chimpanzee CD94 and NKG2 genes. J Immunol. 2002;168:240-52 pubmed
    ..Each species gave distinctive typing patterns, with NKG2A and CD94 being most conserved. Seven different NK complex genotypes within the panel of 48 common chimpanzees were due to differences in Pt-NKG2C and Pt-NKG2D genes...
  11. Sobanov Y, Glienke J, Brostjan C, Lehrach H, Francis F, Hofer E. Linkage of the NKG2 and CD94 receptor genes to D12S77 in the human natural killer gene complex. Immunogenetics. 1999;49:99-105 pubmed
    ..The tight genomic linkage of these genes and the identical orientation of the NKG2 genes suggest coordinate regulation of expression during the differentiation of natural killer cells. ..
  12. Glienke J, Sobanov Y, Brostjan C, Steffens C, Nguyen C, Lehrach H, et al. The genomic organization of NKG2C, E, F, and D receptor genes in the human natural killer gene complex. Immunogenetics. 1998;48:163-73 pubmed
    ..NKG2F consists of only four exons and part of exon IV is in some cases spliced to the 5' end of the NKG2D transcript. NKG2D has only a low similarity to the other NKG2 genes. ..
  13. Li P, Morris D, Willcox B, Steinle A, Spies T, Strong R. Complex structure of the activating immunoreceptor NKG2D and its MHC class I-like ligand MICA. Nat Immunol. 2001;2:443-51 pubmed
    ..The extensive flexibility of the interdomain linker of MICA is shown by its altered conformation when crystallized alone or in complex with NKG2D. ..
  14. Wu J, Song Y, Bakker A, Bauer S, Spies T, Lanier L, et al. An activating immunoreceptor complex formed by NKG2D and DAP10. Science. 1999;285:730-2 pubmed
    ..Thus, NKG2D-DAP10 receptor complexes may activate NK and T cell responses against MICA-bearing tumors. ..
  15. Tsuboi S, Sutoh M, Hatakeyama S, Hiraoka N, Habuchi T, Horikawa Y, et al. A novel strategy for evasion of NK cell immunity by tumours expressing core2 O-glycans. EMBO J. 2011;30:3173-85 pubmed publisher
    ..This new mode of NK cell silencing promotes immune evasion of C2GnT-expressing bladder tumour cells, resulting in tumour metastasis. ..
  16. Kirino Y, Bertsias G, Ishigatsubo Y, Mizuki N, Tugal Tutkun I, Seyahi E, et al. Genome-wide association analysis identifies new susceptibility loci for Behçet's disease and epistasis between HLA-B*51 and ERAP1. Nat Genet. 2013;45:202-7 pubmed publisher
  17. Zuo J, Willcox C, Mohammed F, Davey M, Hunter S, Khan K, et al. A disease-linked ULBP6 polymorphism inhibits NKG2D-mediated target cell killing by enhancing the stability of NKG2D ligand binding. Sci Signal. 2017;10: pubmed publisher
    ..Our results reveal that ULBP polymorphisms affect the strength of human lymphocyte responses to cellular stress signals and may offer opportunities for therapeutic intervention. ..