MALIRDRKSHHSEMSKCHNYDLKPAKWDTSQEQQKQRLALTTSQPGENGIIRGRYPIEKLKISPMFVVRVLAIALAIRFTLNTLMWLAIFKETFQPVLCNKEVPVSSREGYCGPCPNNWICHRNNCYQFFNEEKTWNQSQASCLSQNSSLLKIYSKEEQDFLKLVKSYHWMGLVQIPANGSWQWEDGSSLSYNQLTLVEIPKGSCAVYGSSFKAYTEDCANLNTYICMKRAV
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Protein Length
full length protein
Tag Info
N-terminal 10xHis-tagged
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Functions 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 RAET1A, RAET1B, RAET1C, RAET1D, RAET1E, H60 and MULT1.
Gene References into Functions
Study demonstrated a novel outcome for Nkg2d in its capacity to promote rather than delay tumor progression in the context of liver carcinogenesis.PMID:28128200
Interaction between NKG2D and endogenous RAE-1delta desensitizes NK cells and impairs antitumor NK responses and tumor rejection.PMID:29231815
Results suggest that NKG2D+CD4+ T cells are involved in the pathogenesis of systemic lupus erythematosus by killing Treg cells in a NKG2D-NKG2DL-dependent manner.PMID:28455530
Loss of NKG2D expression accelerates rejection of cardiac allografts.PMID:28805342
IL-15 mediated up-regulation of the activation receptor NKG2D and its adaptor DAP10 in B-1a cells indicating their essential coupling with IL-15 receptor signaling pathway.PMID:28235675
NKG2DL low expressing cancer cells formed palpable allogeneic tumors in mice within a week after the inoculation, while NKG2DL high expressing cancer cells failed to proliferate and were prevented from forming tumors.PMID:27448968
NKG2D is upregulated, and ROS and caspase-3 are inhibited by Strongylocentrotus nudus egg polysaccharide-enhanced antitumor 5-FU in micePMID:27385218
High NKG2D expression is associated with the Development of Bronchiolitis Obliterans.PMID:28251796
tumoral NKG2D stimulates cell propagation and immune escape in acute myeloid leukemia cellsPMID:26740330
The authors observed that the mouse cytomegalovirus encoded protein m18 is necessary and sufficient to drive expression of the RAE-1 family of NKG2D ligands. RAE-1 is transcriptionally repressed by histone deacetylase inhibitor 3 (HDAC3) in healthy cells, and m18 relieves this repression by directly interacting with Casein Kinase II and preventing it from activating HDAC3.PMID:27874833
proposed that TLR9 regulates the NF-kappaB-NLRP3-IL-1beta pathway negatively in Salmonella-induced NKG2D-mediated intestinal inflammation and plays a critical role in defense against S. typhimurium infection and in the protection of intestinal integrity.PMID:28576980
NKG2D-deficient mice and mice constitutively expressing NKG2D ligands had increased incidence of B cell tumors, confirming that the inability to clear NKG2D ligand-expressing cells was important in tumor suppression and that NKG2D ligand expression is a marker of nascent tumorsPMID:27183590
data show that NKG2D has a nonredundant role in priming of CD8(+) T cells to produce antiviral cytokinesPMID:28378389
NKG2D augments Ly49H-dependent proliferation of NK cells; however, NKG2D signaling alone is inadequate for expansion of NK cells, likely due to only transient expression of the NKG2D-DAP12 complexPMID:28760883
study demonstrates that the effect of NKG2D on B1a cell development occurs at a developmental stage that precedes the common lymphoid progenitor; findings reveal an unexpected new role for NKG2D in the regulation of B1a cell developmentPMID:28087665
Sirt6 binds to promoters of NKG2D ligand genes and regulates the H3K9 and H3K56 acetylation levelsPMID:27045575
These results support the conclusion that svH1C mimics Neu5Ac-containing sequences and interacts with cell-surface receptor NKG2D, which contains a lectin-like domainPMID:26110603
These results indicate that, unlike in the pancreas, NKG2D-NKG2D ligand interaction does not play a critical role in obesity-induced inflammation in the adipose tissue.PMID:25333972
The results show that NK cells and the NKG2D receptor play a role in control of lymphomas, and that selection of NKG2D-ligand (MULT1) loss mutants provides a mechanism for tumor escape.PMID:26151313
these data support a novel role for NKG2D expression by CD8(+) T cells during allogeneic HSCT, which could be potentially therapeutically exploited to separate GVHD from GVT effects.PMID:25788701
NKG2D and NKG2DL are involved in allergen-induced activation of dendritic epidermal T cells and the NKG2D/NKG2DL pathway might be a potential target for treatment of contact hypersensitivity.PMID:25634359
Viral infection of cultured cells increased RAE-1 expression, resulting in enhanced NK cell-mediated killing through NKG2D recognition.PMID:24898518
Activation through the NKG2D receptor leads to the differential activation of the NF-kappaB signaling pathway and potentially enhances the anti-tumor and anti-viral functions of effector CD8(+) T cells.PMID:25089028
Desiccating stress-induced chemokine expression in the epithelium is dependent on upregulation of NKG2D/RAE-1 and release of IFN-gamma in experimental dry eye.PMID:25288568
Highly target-specific liver NKT cells selectively remove activated hepatic stellate cells through an NKG2D-Rae1 interaction to ameliorate liver fibrosis after IL-30 treatment.PMID:25351459
a protective role of NKG2D-activated natural killer cells in coxsackievirus B3 myocarditis leading to an effective virus clearancePMID:24797160
bystander memory CD8 T cells can participate in an unrelated immune response and induce immunopathology through an NKG2D dependent mechanism without providing increased protection.PMID:24586170
Doxorubicin plus IL-12 induces NKG2D in CD8+T cells in vivo and boosts NKG2D+CD8+T-dependent antitumor immune surveillancePMID:24565056
NKG2D ligation relieves 2B4-mediated NK-cell self-tolerance in mice.PMID:24610736
the induction of retinoic acid early transcript 1 (RAE1) ligands for NKG2D by the DDR relies on a STING-dependent DNA sensor pathway involving the effector molecules TBK1 and IRF3.PMID:24590060
Cigarette smoke - induced airway injury stimulates toll-like receptor signaling by endogenous nucleic acids leading to elevated NKG2D ligand expression.PMID:24130907
CD4(+) NKG2D(+) T cells induce NKG2D down-regulation in natural killer cells in CD86-RAE-1epsilon transgenic mice.PMID:24708417
The absence of NKG2D signaling in natural killer cells significantly improves neural progenitor cell-derived neuron survival and differentiation.PMID:23733329
studies established a pivotal role for NK-cell NKG2D and granzyme B in the pathogenesis of house dust mite-allergic lung disease, and identified novel therapeutic targets for the prevention and treatment of asthma.PMID:24290277
NKG2D can function as a coactivating stress receptor that directly triggers cytotoxicity in dendritic epidermal T cells.PMID:23962808
The severity of experimental autoimmune encephalitis was decreased in NKG2D-deficient mice.PMID:24211717
NKG2D enhances IL-15-mediated Phosphatidylinositol 3-Kinase signaling of activated CD8 T cells, in a specific phase of memory cell commitment, after activation but before terminal differentiation.PMID:23804716
NKp46 deficiency alone, or in combination with NKG2D deficiency, had no effect on frequency or function of NK cellsPMID:23649470
cytotoxic potential of NK cells against a wide spectrum of tumor subtypes could be markedly enhanced by expression of NKG2D-DAP10-CD3zeta receptorsPMID:23302231
The engagement of NKG2D by its ligand (Rae-1) elicits not only target cell lysis, but also natural killer cell fratricide.PMID:23690625
The constitutive levels of NKG2D ligand expression on IECs are regulated by microbial signaling in the gut.PMID:23136011
NKG2D is expressed by all natural killer (NK) cells but is not limited to NK cells, as it is also expressed by many T cells, including all activated CD8+ T cells in mice, subsets of gammadelta T cells, and subsets of NKT cells.PMID:23298206
Mouse tumor vasculature expresses NKG2D ligands and can be targeted by chimeric NKG2D-modified T cells.PMID:23355740
Simultaneous knockdown of multiple ligands of NKG2D prevents natural killer cell-mediated fulminant hepatitis.PMID:22806577
wound healing was delayed in mice lacking NKG2DPMID:23166357
NKG2D-mediated, but not Fc receptor-mediated, recognition increases natural killer (NK) cell degranulation; only NKG2D engagement substantially enhances degranulation.PMID:23183896
The expression of any of the murine ligands for the NK-cell activating receptor NKG2D results in a concomitant reduction in MHC class I expression.PMID:22740149
IL-4-induced innate CD8 T cells do not express NKG2D (or CCL5).PMID:22942430
NKG2D has no major role in the generation and expansion of memory CD8 T cells, but rather substantially enhances the cytolytic effector responses of reactivated memory T cells and thereby contributes to an efficacious tumor rejection.PMID:21607945
Upregulation of NKG2D ligands by H-RasV12 increased sensitivity of cells to NK cell-mediated cytotoxicityPMID:22798674
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Subcellular Location
Cell membrane; Single-pass type II membrane protein. Note=Colocalized with HCST and TYROBP on the cell surface.
Tissue Specificity
Expressed in natural killer (NK) cells, activated CD8(+) alpha-beta and gamma-delta T-cells and natural killer T (NKT) cells (at protein level). May be expressed on dendritic cell (DC). Isoform 1 is strongly expressed in natural killer (NK) cells. Isoform