Browse KLRK1

Summary
SymbolKLRK1
Namekiller cell lectin-like receptor subfamily K, member 1
Aliases NKG2D; KLR; NKG2-D; CD314; D12S2489E; DNA segment on chromosome 12 (unique) 2489 expressed sequence; CD anti ......
Chromosomal Location12p13.2-p12.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cell membrane Single-pass type II membrane protein Note=Colocalized with HCST on the cell surface.
Domain PF00059 Lectin C-type domain
Function

Function as an activating and costimulatory receptor involved in immunosurveillance upon binding to various cellular stress-inducible ligands displayed at the surface of autologous tumor cells and virus-infected cells. Provides both stimulatory and costimulatory innate immune responses on activated killer (NK) cells, leading to cytotoxic activity. Acts as a costimulatory receptor for T-cell receptor (TCR) in CD8(+) T-cell-mediated adaptive immune responses by amplifying T-cell activation. Stimulates perforin-mediated elimination of ligand-expressing tumor cells. Signaling involves calcium influx, culminating in the expression of TNF-alpha. Participates in NK cell-mediated bone marrow graft rejection. May play a regulatory role in differentiation and survival of NK cells. Binds to ligands belonging to various subfamilies of MHC class I-related glycoproteins including MICA, MICB, RAET1E, RAET1G, RAET1L/ULBP6, ULBP1, ULBP2, ULBP3 (ULBP2>ULBP1>ULBP3) and ULBP4.

> Gene Ontology
 
Biological Process GO:0001819 positive regulation of cytokine production
GO:0001906 cell killing
GO:0001909 leukocyte mediated cytotoxicity
GO:0001910 regulation of leukocyte mediated cytotoxicity
GO:0001912 positive regulation of leukocyte mediated cytotoxicity
GO:0002218 activation of innate immune response
GO:0002220 innate immune response activating cell surface receptor signaling pathway
GO:0002223 stimulatory C-type lectin receptor signaling pathway
GO:0002228 natural killer cell mediated immunity
GO:0002237 response to molecule of bacterial origin
GO:0002250 adaptive immune response
GO:0002429 immune response-activating cell surface receptor signaling pathway
GO:0002443 leukocyte mediated immunity
GO:0002449 lymphocyte mediated immunity
GO:0002683 negative regulation of immune system process
GO:0002685 regulation of leukocyte migration
GO:0002686 negative regulation of leukocyte migration
GO:0002688 regulation of leukocyte chemotaxis
GO:0002689 negative regulation of leukocyte chemotaxis
GO:0002694 regulation of leukocyte activation
GO:0002696 positive regulation of leukocyte activation
GO:0002697 regulation of immune effector process
GO:0002699 positive regulation of immune effector process
GO:0002703 regulation of leukocyte mediated immunity
GO:0002705 positive regulation of leukocyte mediated immunity
GO:0002706 regulation of lymphocyte mediated immunity
GO:0002708 positive regulation of lymphocyte mediated immunity
GO:0002715 regulation of natural killer cell mediated immunity
GO:0002717 positive regulation of natural killer cell mediated immunity
GO:0002757 immune response-activating signal transduction
GO:0002758 innate immune response-activating signal transduction
GO:0002764 immune response-regulating signaling pathway
GO:0002768 immune response-regulating cell surface receptor signaling pathway
GO:0006809 nitric oxide biosynthetic process
GO:0007159 leukocyte cell-cell adhesion
GO:0022407 regulation of cell-cell adhesion
GO:0022409 positive regulation of cell-cell adhesion
GO:0030101 natural killer cell activation
GO:0030336 negative regulation of cell migration
GO:0030595 leukocyte chemotaxis
GO:0031294 lymphocyte costimulation
GO:0031295 T cell costimulation
GO:0031341 regulation of cell killing
GO:0031343 positive regulation of cell killing
GO:0031349 positive regulation of defense response
GO:0032102 negative regulation of response to external stimulus
GO:0032496 response to lipopolysaccharide
GO:0032609 interferon-gamma production
GO:0032649 regulation of interferon-gamma production
GO:0032729 positive regulation of interferon-gamma production
GO:0034260 negative regulation of GTPase activity
GO:0035747 natural killer cell chemotaxis
GO:0040013 negative regulation of locomotion
GO:0042110 T cell activation
GO:0042267 natural killer cell mediated cytotoxicity
GO:0042269 regulation of natural killer cell mediated cytotoxicity
GO:0042742 defense response to bacterium
GO:0045088 regulation of innate immune response
GO:0045089 positive regulation of innate immune response
GO:0045428 regulation of nitric oxide biosynthetic process
GO:0045429 positive regulation of nitric oxide biosynthetic process
GO:0045785 positive regulation of cell adhesion
GO:0045954 positive regulation of natural killer cell mediated cytotoxicity
GO:0046209 nitric oxide metabolic process
GO:0048247 lymphocyte chemotaxis
GO:0050830 defense response to Gram-positive bacterium
GO:0050863 regulation of T cell activation
GO:0050865 regulation of cell activation
GO:0050867 positive regulation of cell activation
GO:0050870 positive regulation of T cell activation
GO:0050900 leukocyte migration
GO:0050920 regulation of chemotaxis
GO:0050922 negative regulation of chemotaxis
GO:0051249 regulation of lymphocyte activation
GO:0051251 positive regulation of lymphocyte activation
GO:0051271 negative regulation of cellular component movement
GO:0051346 negative regulation of hydrolase activity
GO:0060326 cell chemotaxis
GO:0070486 leukocyte aggregation
GO:0070489 T cell aggregation
GO:0071216 cellular response to biotic stimulus
GO:0071219 cellular response to molecule of bacterial origin
GO:0071222 cellular response to lipopolysaccharide
GO:0071396 cellular response to lipid
GO:0071593 lymphocyte aggregation
GO:0072593 reactive oxygen species metabolic process
GO:0072676 lymphocyte migration
GO:0098542 defense response to other organism
GO:1901623 regulation of lymphocyte chemotaxis
GO:1901624 negative regulation of lymphocyte chemotaxis
GO:1903037 regulation of leukocyte cell-cell adhesion
GO:1903039 positive regulation of leukocyte cell-cell adhesion
GO:1903409 reactive oxygen species biosynthetic process
GO:1903426 regulation of reactive oxygen species biosynthetic process
GO:1903428 positive regulation of reactive oxygen species biosynthetic process
GO:1904407 positive regulation of nitric oxide metabolic process
GO:2000146 negative regulation of cell motility
GO:2000377 regulation of reactive oxygen species metabolic process
GO:2000379 positive regulation of reactive oxygen species metabolic process
GO:2000401 regulation of lymphocyte migration
GO:2000402 negative regulation of lymphocyte migration
GO:2000501 regulation of natural killer cell chemotaxis
GO:2000502 negative regulation of natural killer cell chemotaxis
GO:2001057 reactive nitrogen species metabolic process
Molecular Function GO:0030246 carbohydrate binding
GO:0032394 MHC class Ib receptor activity
GO:0042287 MHC protein binding
GO:0042288 MHC class I protein binding
Cellular Component GO:0009897 external side of plasma membrane
GO:0098552 side of membrane
> KEGG and Reactome Pathway
 
KEGG hsa04650 Natural killer cell mediated cytotoxicity
Reactome R-HSA-1280218: Adaptive Immune System
R-HSA-2172127: DAP12 interactions
R-HSA-2424491: DAP12 signaling
R-HSA-168256: Immune System
R-HSA-198933: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-168249: Innate Immune System
Summary
SymbolKLRK1
Namekiller cell lectin-like receptor subfamily K, member 1
Aliases NKG2D; KLR; NKG2-D; CD314; D12S2489E; DNA segment on chromosome 12 (unique) 2489 expressed sequence; CD anti ......
Chromosomal Location12p13.2-p12.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between KLRK1 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between KLRK1 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
28128200Hepatocellular CarcinomaPromote immunityThus, the NKG2D/NKG2D-ligand pathway provides an additional mechanism linking chronic inflammation to tumour development in hepatocellular carcinoma.
26151313LymphomaPromote immunityCritical role of the NKG2D receptor for NK cell-mediated control and immune escape of B-cell lymphoma. This indicates that NK cells and the NKG2D receptor play a role for control of lymphomas and that selection for NKG2D-L loss mutants provides a mechanism of tumor escape.
27777574Colorectal carcinomaPromote immunity (NK cell function)CRC-NK cells displayed underexpression of CD16, NKG2D, DNAM-1, CD161, NKp46, and NKp30 activating receptors, while inhibitory receptors CD85j and NKG2A were overexpressed. This inhibited phenotype affected cytotoxic functionality against CRC cells and interferon-γ production.
24615495Gastric CarcinomaPromote immunity (NK cell function); increase the efficacy of immunotherapyIn conclusion, gastric cancer tumors express NKG2D ligands and are highly susceptible to killing by NK cells stimulated by K562-mb15-4.1BBL. These results provide a strong rationale for clinical testing of these NK cells in patients and suggest their use to augment the effects of antibody therapy.
23192659Mesothelioma and lung carcinoma; breast carcinoma; colon carcinoma; gastric carcinoma; bladder carcinoma; uterus carcinomaPromote immunityTumor cell lysis was primarily mediated by NKG2D and NKp30 and partially by NKp46 and DNAM-1, in agreement with the expression of the corresponding ligands on tumor cells.
19430493Ovarian carcinomaPromote immunityThe expression of the NKG2D ligands on cancer cells leads to their recognition and elimination by host immune responses mediated by natural killer and T cells. UL16-binding proteins (ULBPs) are NKG2D ligands, which are scarcely expressed in epithelial tumours, favouring their evasion from the immune system.
28443091Head and Neck Squamous Cell CarcinomaPromote immunity (NK and T cell function)The natural killer group 2D (NKG2D) receptors on natural killer (NK) cells and several T cell subsets play an important role for immunosurveillance of HNSCC and are thus targeted by tumor immune evasion strategies in particular by shedding of various NKG2D ligands (NKG2DLs).
23526433Breast Carcinoma; Pancreatic Carcinoma; Prostate CarcinomaPromote immunity (NK cell function)The interaction of the MHC class I-related chain molecules A and B (MICA and MICB) with the corresponding natural killer group 2, member D (NKG2D) receptor triggers cytotoxic effector activity of natural killer cells and certain T-cell subsets and provides a costimulatory signal for cytokine production. Flow cytometry and enzyme-linked immunosorbent assay (ELISA) revealed that all tested tumor cells constitutively expressed MICA and MICB on the cell surface and also released NKG2D ligands into the supernatant. Studies using RNA interference not only revealed a prominent role of ADAM10 and ADAM17 in NKG2D ligand shedding but also a tumor cell-specific role of ADAM10 and/or ADAM17 in shedding of MICA or MICB. These data indicate that the release of NKG2D ligands from individual tumor entities is by far more complex than suggested in previously reported MICA/B transfection systems.
23509364Breast Carcinoma; Hepatocellular Carcinoma; Colorectal CarcinomaPromote immunityNK group 2, member D (NKG2D) is an NK cell-activating receptor crucially involved in cancer immunosurveillance.
23459515Hodgkin LymphomaPromote immunityHodgkin lymphoma (HL) is characterized by CD30(+) tumor cells and a massive infiltration of immune effector cells in affected lymph nodes. Impaired NK cell function correlated with elevated serum levels of soluble ligands for NK cell receptors NKp30 (BAG6/BAT3) and NKG2D (MICA), factors known to constrict NK cell function. In vitro, NK cell cytotoxicity could be restored by an NKG2D/NKp30-independent bispecific antibody construct (CD30xCD16A).
21257710Colorectal CarcinomaPromote immunityExposure to NKG2D-neutralizing antibodies partially restored STAT3 activity, suggesting that it prevented NKG2D-mediated NK cell activation.
21224372MelanomaPromote immunity (NK cell function)A dynamic label free assay was used to determine the pathways involved in the lysis of melanoma cells by IL-2-activated NK cells. NKG2D, NCR (natural cytotoxicity receptor), and DNAM-1 are involved in the NK-mediated lysis of melanoma cells.
21159634Breast CarcinomaPromote immunity (NK cell function)NKG2D ligands link the innate and adapative immune response by activating the receptors expressed on effector cells of both the innate (NK) and adaptive immune systems (CD8(+) T cells). Our findings demonstrate that administration of an antibody-NKG2D ligand fusion protein can enhance innate and adaptive immune antitumor responses, also evoking additional nontargeted antigens to enhance the potential clinical utility of this approach.
19549909Breast Carcinoma; Head and Neck Squamous Cell CarcinomaPromote immunityExpression of exogenous WSX1 in epithelial tumor cells suppresses tumorigenicity in vitro and inhibits tumor growth in vivo. Different from the role of WSX1 in immune cells, the antitumor activity of WSX1 in epithelial tumor cells is independent of IL-27 signaling but is mainly dependent on natural killer (NK) cell surveillance. Deficiency of either the IL-27 subunit EBV-induced gene 3 or the IL-27 receptor WSX1 in the host animals had no effect on tumor growth inhibition induced by WSX1 expression in tumor cells. Expression of WSX1 in epithelial tumor cells enhances NK cell cytolytic activity against tumor cells, whereas the absence of functional NK cells impairs the WSX1-mediated inhibition of epithelial tumor growth. Our results reveal an IL-27-independent function of WSX1: sensitizing NK cell-mediated antitumor surveillance via a NKG2D-dependent mechanism.
16754847MelanomaPromote immunity (NK cell function)Therapy-induced antibodies to MHC class I chain-related protein A antagonize immune suppression and stimulate antitumor cytotoxicity. The activation of NKG2D on innate and adaptive cytotoxic lymphocytes contributes to immune-mediated tumor destruction. Nonetheless, tumor cell shedding of NKG2D ligands, such as MHC class I chain-related protein A (MICA), results in immune suppression through down-regulation of NKG2D surface expression. Together, these findings establish a key role for the NKG2D pathway in the clinical activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade and granulocyte-macrophage colony-stimulating factor secreting tumor cell vaccines.
16621962LymphomaPromote immunity (NK cell function)ULBPs, human ligands of the NKG2D receptor, stimulate tumor immunity with enhancement by IL-15. ULBPs are human ligands for NKG2D, an activating receptor expressed on natural killer (NK) cells, NK1.1(+) T cells, and T cells. We report that ectopic expression of ULBP1 or ULBP2 on murine EL4 or RMA tumor cells elicits potent antitumor responses in syngeneic C57BL/6 and SCID mice. Although binding of ULBP3 to murine NKG2D could not be demonstrated in vitro, ULBP3 can also stimulate antitumor responses, suggesting that ULBP3 binds to murine NKG2D or possibly another receptor in vivo. IL-15 was found to strongly enhance the immune response directed against ULBP-expressing tumors.
16585609LeukemiaPromote immunity (NK cell function)MHC class I chain-related molecules (MIC) participate in immune surveillance of cancer through engagement of the NKG2D-activating receptor on NK and T cells. Decreased NKG2D expression and function upon chronic exposure to NKG2D ligands and/or soluble forms of MIC (sMIC) may participate in immune escape. At diagnosis, chronic myeloid leukemia patients had abnormally high serum levels of sMICA and weak NKG2D expression on NK and CD8+ T cells, which were restored by imatinib mesylate (IM) therapy.
23820258Acute Myeloid Leukemia; AdenocarcinomaPromote immunity (NK cell function); essential for immunotherapyThese ligands are present on cancer cells and are recognised by NKG2D in a cell-structure-sensing manner, triggering natural killer (NK) cell cytotoxicity. 1,25(OH)2D3 facilitates the immuno-attack of NK cells against malignant cells partly through downregulation of miR-302c and miR-520c and hence upregulation of the NKG2D ligands MICA/B and ULBP2.
23628805Ovarian Carcinoma; LymphomaPromote immunity (NK cell function)Mice bearing the ID8 ovarian or RMA lymphoma tumors were treated with T cells transduced with a NKG2D-based CAR (chNKG2D). NKG2D CAR T-cell therapy protected mice from heterogeneous RMA tumors.
22419581MyelomaPromote immunity (NK cell function)Expanded natural killer cells killed both allogeneic and autologous primary myeloma cells avidly via a perforin-mediated mechanism in which the activating receptor NKG2D, natural cytotoxicity receptors, and DNAX-accessory molecule-1 played a central role. The transferred, expanded natural killer cells proliferated in vivo in an interleukin-2 dose-dependent fashion, persisted up to 4 weeks, were readily detectable in the human bone, inhibited myeloma growth and protected bone from myeloma-induced osteolysis.
22258454MelanomaPromote immunity (NK cell function)We found that melanoma cells inhibited the expression of major NK receptors that trigger their immune function, including NKp30, NKp44, and NKG2D, with consequent impairment of NK cell-mediated cytolytic activity against various melanoma cell lines. This inhibitory effect was primarily mediated by indoleamine 2,3-dioxygenase (IDO) and prostaglandin E2 (PGE2).
22251483MelanomaPromote immunityBlockade of NKG2D in mice also resulted in significantly diminished antitumor effects after immunotherapy. Human melanoma tissue biopsies obtained from patients after topically applied immunodulatory treatment resulted in increased numbers of these CD8(+) CD25(-) cells within the tumor site.
18094430MelanomaPromote immunity (T cell function)Moreover, the engagement of NKG2D occurred in antitumor activity by both freshly isolated and in vitro cultured TILs. These findings indicate that NKG2D+ T cells have a role in the immunologic response against tumor.
25046567leukemiaPromote immunity (NK cell function)WT already enhanced antileukemia reactivity by inducing antibody-dependent cellular cytotoxicity (ADCC) with NKG2D-Fc-ADCC mediating significantly stronger effects. Thus, NKG2D-Fc-ADCC potently enhances NK antileukemia reactivity despite the inevitable reduction of activating signals upon binding to NKG2DL and may constitute an attractive means for immunotherapy of leukemia.
29683892Esophageal squamous cell carcinomaPromote immunity (NK cell function); essential for immunotherapyBlocking of NKG2D with anti-NKG2D monoclonal antibody dampened expanded NK cell cytotoxicity, suggesting that the NKG2DLs-NKG2D interaction is crucial for NK cells to eliminate ESCC cells.
29581297hepatocellular carcinomaPromote immunity (NK cell function); essential for immunotherapyBecause the down-regulation of NKG2D ligands occurred at the transcriptional level, we tested 32 chemical inhibitors of epigenetic regulators for their ability to re-express NKG2D ligands and enhance HCC cell eradication by NK cells and found that Enhancer of zeste homolog 2 (EZH2) was a transcriptional repressor of NKG2D ligands.
24018560Prostate CarcinomaPromote immunity (NK cell function); essential for immunotherapyThe activating receptor NK cell group 2 member D (NKG2D) mediates antitumor immunity in experimental animal models. Bi-Tg TRAMP/MICB mice exhibited a markedly increased incidence of progressed carcinomas and metastasis, whereas TRAMP/MICB.A2 mice enjoyed long-term tumor-free survival conferred by sustained NKG2D-mediated antitumor immunity. Our findings suggest that the impact of soluble NKG2D ligands should be considered in NK cell-based cancer immunotherapy
20150362GlioblastomaPromote immunity (NK and T cell function)The activating receptor NKG2D, expressed by natural killer (NK) cells and CD8(+) T cells, has a role in the specific killing of transformed cells. Expression of NKG2D on lymphocytes significantly increased following tumor resection and correlated with an increased ability to kill NKG2D ligand-positive tumor targets.
20101024Leukemia; LymphomaPromote immunityConsistent with this, blockade of NKG2D, the receptor for ULBP1 expressed on all Vgamma9(+) T cells, significantly inhibits lymphoma cell killing.
29308322MelanomaPromote immunity (NK cell function)We demonstrate that BRAFV600E mutant melanoma cells cultured in the presence of vemurafenib, strongly decreased surface expression of ligands for NK activating receptors including the NKG2D-ligand, MICA, and the DNAM-1 ligand, CD155, and became significantly less susceptible to NK cell attack.
18559521Prostate CarcinomaPromote immunityThe MHC class I chain-related (MIC) molecules play important roles in tumor immune surveillance through their interaction with the NKG2D receptor on natural killer and cytotoxic T cells. Thus, shedding of the MIC molecules from the tumor cell membrane represents a potential mechanism of escape from NKG2D-mediated immune surveillance.
18490733Ovarian CarcinomaPromote immunity (NK cell function)Functionally, we find that MIF may contribute to the immune escape of ovarian carcinoma by transcriptionally down-regulating NKG2D in vitro and in vivo which impairs NK cell cytotoxicity toward tumor cells.
24336127LeukemiaPromote immunityUpregulation of NKG2D (NK group 2, member D) ligands in MLL/ENL leukemia cells caused elimination of leukemia cells by NK cells.
22975165Plasma Cell MyelomaPromote immunityNKG2D is a natural killer (NK) cell activating receptor that mediates non-MHC restricted and TCR-independent cell lysis. When compared to posttransplantation IL-2 therapy alone in this patient population, the addition of cells enriched for NKG2D(+)CD3(+)CD8(+) T cells increased tumor-specific immunity, as demonstrated by enhanced lysis of autologous myeloma cells (P = .02).
21607945LymphomaPromote immunityTo address these issues, we made use of a transgenic mouse model (H2-K(b)-MICA mice) where the human NKG2D ligand MICA is ubiquitously and constitutively expressed resulting in a severe dysfunction of NKG2D. Both, ovalbumin (OVA)-specific (H2-K(b)/OVA(257-264)) memory CD8 T cells arisen from the endogenous T cell pool and adoptively transferred OVA-specific OT-I memory cells were unable to control growth of an OVA-expressing lymphoma in H2-K(b)-MICA mice.
20473905Pancreatic Ductal AdenocarcinomaPromote immunityIndeed, blocking of the natural cytotoxicity receptors-NKp30, 44 and 46 in combination, and NKG2D and DNAM1 alone inhibit the killing of Panc-1 cells.
20378565RhabdomyosarcomaPromote immunityAntibody-mediated masking of either NKG2D molecule on cytokine-induced killer cells or its ligands on rhabdomyosarcoma cells (major histocompatibility antigen related chain A and B and UL16 binding protein 2) diminished this effect by 50%, suggesting a major role for the NKG2D molecule in rhabdomyosarcoma cell killing.
19629084Prostate AdenocarcinomaPromote immunity (NK and T cell function)Engagement of NKG2D on NK and T cells could lead to the killing of pathogen-infected target cells as well as tumor cells. For example, in different murine models, rejection of transplanted tumors and a reduced incidence of spontaneous tumors were associated with enhanced NKG2D-mediated cytotoxicity
25217158breast carcinomaPromote immunity(NK cell function)A prominent additional modulator of NK reactivity is the C-type lectin-like receptor NKG2D that potently induces antitumor immunity after recognition of its ligands (NKG2DL)
25164008breast carcinomaPromote immunityPrimary BCSCs were resistant to cytotoxicity mediated by autologous/allogeneic NK cells due to reduced expression of MICA and MICB, two ligands for the stimulatory NK cell receptor NKG2D. Furthermore, the downregulation of MICA/MICB in BCSCs was mediated by aberrantly expressed oncogenic miR20a, which promoted the resistance of BCSC to NK cell cytotoxicity and resultant lung metastasis.
25136121breast carcinoma; prostate carcinoma; hepatocellular carcinomaInhibit immunityTogether, these findings reveal a previously unidentified immune evasion strategy whereby tumors produce soluble factors that induce NKG2D ligands on myeloid cells, subverting antitumor immune responses
21937679Breast CarcinomaPromote immunityFunctional experiments in breast cancer subtypes expressing various levels of NK cell ligands showed that NK-mediated cytotoxicity is mainly HLA, NKG2D, and DNAM dependent
21844012MelanomaPromote immunityHowever, the persistent NK cells in the circulation expressed significantly lower levels of the key activating receptor NKG2D and could not lyse tumor cell targets in vitro unless reactivated with IL-2.
21841316Breast CarcinomaPromote immunityWith disease progression, we found that expression of activating NK cell receptors (such as NKp30, NKG2D, DNAM-1, and CD16) decreased while expression of inhibitory receptors (such as NKG2A) increased and that this correlated with decreased NK cell function, most notably cytotoxicity
16929491pancreatic carcinomaPromote immunityOur results demonstrate that sMIC impairs NKG2D-mediated immunity against pancreatic carcinoma by directly diminishing cytotoxicity of gammadelta T cells and NK cells. IFN-alpha, which is used in adjuvant treatment of pancreatic carcinoma, might partly act via up-regulation of MIC without induction of sMIC release.
16891318GlioblastomaPromote immunityNKG2D ligands (NKG2DL) are expressed by infected and transformed cells. They transmit danger signals to NKG2D-expressing immune cells, leading to lysis of NKG2DL-expressing cells.
16860661PAN-CancerPromote immunityIn particular, NKG2D is a type II transmembrane-anchored glycoprotein expressed as a disulfide-linked homodimer on the surface of all mouse and human natural killer cells (NK cells). Stimulation of NK cell through NKG2D triggers cell-mediated cytotoxicity and in some cases induces production of cytokines. NKG2D binds to family of ligands with structural homology to major histocompatibility complex (MHC) class I, however, NKG2D ligands often display upregulated surface expression on stressed cells and are frequently overexpressed by tumors unlike conventional MHC class I molecules. Evidence clearly implicate that NKG2D recognition plays an important role in tumor immune surveillance.
Summary
SymbolKLRK1
Namekiller cell lectin-like receptor subfamily K, member 1
Aliases NKG2D; KLR; NKG2-D; CD314; D12S2489E; DNA segment on chromosome 12 (unique) 2489 expressed sequence; CD anti ......
Chromosomal Location12p13.2-p12.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of KLRK1 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolKLRK1
Namekiller cell lectin-like receptor subfamily K, member 1
Aliases NKG2D; KLR; NKG2-D; CD314; D12S2489E; DNA segment on chromosome 12 (unique) 2489 expressed sequence; CD anti ......
Chromosomal Location12p13.2-p12.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of KLRK1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.3720.516
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.4320.731
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.3340.751
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.9210.0815
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.5690.661
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-1.3640.395
729033130MelanomaallAnti-PD-1 (nivolumab) 262301
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 151101
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 111201
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 482.2720.0616
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 282.1770.226
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.3770.143
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of KLRK1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277302.7-2.71
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275903.4-3.41
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)211705.9-5.90.447
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)131109.1-9.10.458
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolKLRK1
Namekiller cell lectin-like receptor subfamily K, member 1
Aliases NKG2D; KLR; NKG2-D; CD314; D12S2489E; DNA segment on chromosome 12 (unique) 2489 expressed sequence; CD anti ......
Chromosomal Location12p13.2-p12.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of KLRK1. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolKLRK1
Namekiller cell lectin-like receptor subfamily K, member 1
Aliases NKG2D; KLR; NKG2-D; CD314; D12S2489E; DNA segment on chromosome 12 (unique) 2489 expressed sequence; CD anti ......
Chromosomal Location12p13.2-p12.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of KLRK1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by KLRK1.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolKLRK1
Namekiller cell lectin-like receptor subfamily K, member 1
Aliases NKG2D; KLR; NKG2-D; CD314; D12S2489E; DNA segment on chromosome 12 (unique) 2489 expressed sequence; CD anti ......
Chromosomal Location12p13.2-p12.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of KLRK1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolKLRK1
Namekiller cell lectin-like receptor subfamily K, member 1
Aliases NKG2D; KLR; NKG2-D; CD314; D12S2489E; DNA segment on chromosome 12 (unique) 2489 expressed sequence; CD anti ......
Chromosomal Location12p13.2-p12.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of KLRK1 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolKLRK1
Namekiller cell lectin-like receptor subfamily K, member 1
Aliases NKG2D; KLR; NKG2-D; CD314; D12S2489E; DNA segment on chromosome 12 (unique) 2489 expressed sequence; CD anti ......
Chromosomal Location12p13.2-p12.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between KLRK1 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolKLRK1
Namekiller cell lectin-like receptor subfamily K, member 1
Aliases NKG2D; KLR; NKG2-D; CD314; D12S2489E; DNA segment on chromosome 12 (unique) 2489 expressed sequence; CD anti ......
Chromosomal Location12p13.2-p12.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting KLRK1 collected from DrugBank database.
> Drugs from DrugBank database
 

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