NCR2 (natural cytotoxicity triggering receptor 2)

2013-06-01   Nathan Horton , Kelly Bowen , Porunelloor Mathew 

Department of Molecular Biology, Immunology, Institute for Cancer Research, University of North Texas Health Science Center, Fort Worth Texas 76107, USA

Identity

HGNC
LOCATION
6p21.1
LOCUSID
ALIAS
CD336,LY95,NK-p44,NKP44,dJ149M18.1

DNA/RNA

Note

NKp44 is located on chromosome 6, centromeric to the Major Histocompatibility Complex. It is located in a cluster of single immunoglobulin variable domain receptors including Trem-1 and Trem-2 (Allcock et al., 2003).
Atlas Image
Three splice variants of NKp44. NKp44 is encoded on 5 exons (NM_004828.3). One splice variant contains an additional exon (NM_001199510.1), adding 35 amino acids resulting in a shift in the reading frame, truncating the cytoplasmic tail by 18 amino acids (Allcock et al., 2003). A second splice variant (NM_001199509.1) adds 12 amino acids, but maintains the reading frame with a 36 base pair extension on the 5 side of exon 4 (Allcock et al., 2003).

Description

NKp44 gene spans 15098 bases located on positive strand of chromosome 6 from 41303528 to 41318625 bp. NKp44 is centromeric to Trem-1, with its leader sequence nearest to Trem-1 on the telomeric side and its cytoplasmic domain encoded towards the centromere (Allcock et al., 2003). NKp44 is encoded in 5 exons with one splice variant containing an extra exon (NM_001199510.1), adding 35 amino acids (Allcock et al., 2003). This addition alters the reading frame which truncates the cytoplasmic tail by 18 amino acids (Allcock et al., 2003). A second splice variant (NM_001199509.1) with an extra exon contains a 36 base pair extension of exon 4 on the 5 side, adding 12 amino acids, but maintaining the reading frame (Allcock et al., 2003).

Transcription

There are three transcript variants of NKp44. Isoform 1 (NM_004828.3) encodes the longest isoform. Isoform 2 (NM_001199509.1) encodes a frame shift due to an extra in-frame segment and an additional exon compared to isoform 1. This results in an additional internal segment and a shorter C-terminus. Isoform 3 (NM001199510.1) has an additional exon with a shorter C-terminus similar to isoform 2.

Proteins

Note

NKp44 is a type I transmembrane protein belonging to the Ig Superfamily (Vitale et al., 1998; Cantoni et al., 1999; Cantoni et al., 2003). Surface expression of the receptor and signalling physically requires the transmembrane accessory protein DAP12 which bears Immunoreceptor Tyrosine Activation Motifs (Cantoni et al., 1999). NKp44 activates NK cells through DAP12 linked directly to Lysine 183 in the transmembrane domain (Campbell et al., 2004). NKp44 inhibits NK cells through a tyrosine-based inhibitory motif located in the cytoplasmic tail of the receptor (Rosental et al., 2011).

Description

NKp44 has a molecular weight of 44 kDa and consists of a 169 amino acid extracellular domain followed by 23 and 63 amino acid sequences in the transmembrane and cytoplasmic tail domains respectively (Cantoni et al., 1999; Cantoni et al., 2003). A 55 amino acid domain connects the extracellular Ig domain to the transmembrane segment and has 13 predicted O-glycosylation sites and a single N-glycosylation site (Cantoni et al., 1999; Cantoni et al., 2003). Crystallography of the receptor demonstrates a surface groove made by two facing β hairpin loops extending from the Ig fold core stabilized by a disulfide bridge between Cystine 37 and Cystine 45 (Cantoni et al., 2003). The Ig domain contains an arrangement of positively charged residues at the groove surface, suggesting NKp44 ligands are anionic (Cantoni et al., 2003). The groove appears wide enough to host a sialic acid or an elongated branched ligand. The cytoplasmic tail of NKp44 also contains a tyrosine sequence resembling a tyrosine-based inhibitory motif (Cantoni et al., 1999; Campbell et al., 2004). This motif is functional and inhibits the release of cytotoxic agents and IFN-γ (Rosental et al., 2011).

Expression

NKp44 is expressed on IL-2 and IL-15 activated NK Cells and NK cells in the decidua (Cantoni et al., 1999; de Rham et al., 2007; Manaster and Mandelboim, 2010). The receptor is also expressed on isolated polyclonal γδ T cells when cultured for 2 weeks in IL-15 and IL-2 (Cantoni et al., 1999; von Lilienfeld-Toal et al., 2006; Hudspeth et al., 2013). Natural Interferon-producing cells located in the T-cell zone in lymph nodes draining a site of viral infection are reported to express NKp44, believed to be induced by IL-3 from local memory CD8 T cells (Fuchs et al., 2005). NKp44 is also induced in TCR αβ intestinal intraepithelial lymphocytes by IL-15 (Meresse et al., 2004). Cytolytic T cells isolated from cord blood express NKp44 when induced with IL-2 or IL-15 (Tang et al., 2008). Finally NKp44 is expressed on a subset of cells located in human tonsils, similar to lymphoid tissue induce cells, which produce IL-22 and express Rorγt (Fuchs et al., 2005; Cella et al., 2009).

Localisation

NKp44 is a type I transmembrane protein expressed on the surface of IL-2 activated NK cells and induced in γδ T cells by IL-15 and IL-2 (Cantoni et al., 1999; von Lilienfeld-Toal et al., 2006; Hudspeth et al., 2013). Expression is also reported on the cell surface of natural interferon-producing cells exposed to IL-3 (Fuchs et al., 2005).

Function

NKp44 may functions as either an activating or inhibitory receptor on the surface of the NK cell. The identities of activating ligands are currently unknown, but bind NKp44 to induce activating signals through Dap12 (Vitale et al., 1998; Cantoni et al., 1999; Campbell et al., 2004). NKp44 inhibits NK cell function through recognition of cell surface exosomal PCNA which colocalizes with HLA I (Rosental et al., 2011; Horton et al., 2013).

Homology

- NCR 2 Natural Cytotoxicity Trigger Receptor 2 [Pan troglodytes] NC_006473.3
- NCR 2 Natural Cytotoxicity Trigger Receptor 2 [Macaca mulatta] NC_007861.1
- NCR 2 Natural Cytotoxicity Trigger Receptor 2 [Canis lupus familiaris] NC_006594.3

Mutations

Note

None identified.

Implicated in

Entity name
Various cancers
Note
NKp44 is implicated in recognition of numerous types of cancer (neuralblastoma, choriocarcinoma, pancreatic, breast, lung adenocarcinoma, colon, cervix, hepatocellular carcinoma, Burkitt lymphoma, diffuse B cell lymphoma, prostate) (Sivori et al., 2000a; Sivori et al., 2000b; Byrd et al., 2007; Rosental et al., 2011; Horton et al., 2013). Ligands for NKp44 appear to be cell cycle regulated, with down regulation of expression during mitosis (Byrd et al., 2007). Recognition of tumor cells is partially mediated through charged based binding of NKp44 with heparin sulfate proteoglycans (HSPG) on the surface of tumor cells (Hershkovitz et al., 2007). Specifically, the 2-O-sulfation of iduronic acid and N-acetylation of glucosamine on HSPGs are important for interaction with NKp44 (Hecht et al., 2009). Glycans containing α2,6-N¬-acetylneuraminic acid are also recognized on the surface of cancer cells by NKp44 (Ito et al., 2012). HSPGs are believed to be a coligand for NKp44 and the other NCRs, potentially facilitating binding with other cellular ligands. Recognition of HSPG only evokes IFN-γ release by NK cells, not cellular cytotoxicity (Hershkovitz et al., 2007).
Entity name
Tumor escape of immunosurveillance
Note
Tumors employ numerous mechanisms to avoid killing by NK cells. By engaging NKp44, as well as the other NCRs, tumors can induce NK cell death via up regulation of Fas Ligand in the NK cell, inducing Fas mediated apoptosis (Poggi et al., 2005). NKp44 surface expression can be down regulated by soluble MHC Class I chain-related molecules shed by colorectal tumors or by indoleamine 2,3-dioxygenase and prostaglandin E2 released by melanoma cells (Doubrovina et al., 2003; Pietra et al., 2012). Mesenchymal stem cells also release indoleamine 2,3-dioxygenase and prostaglandin E2 which inhibit NKp44 induction in the tumor microenvironment, but may also be harnessed as a therapeutic approach to inhibit Graft-versus-host or autoimmune disease (Spaggiari et al., 2008). Tumors may also down regulate NKp44 ligand expression to escape NK cell killing, as is the case with Acute Myeloid Leukemia (AML) (Nowbakht et al., 2005). In the case of normal myelonocytic differentiation of bone marrow cells, a ligand for NKp44 is expressed upon loss of the CD34 hematopoietic marker and acquisition of CD33 and CD14 myeloid markers (Nowbakht et al., 2005). Ligand expression if further increased by the presence of IFN-γ (Nowbakht et al., 2005). Yet in AML, ligand expression is absent, possibly contributing to disease manifestation. Finally, tumor cells may also induce expression of exosomal PCNA when physically contacted by NKp44 expressing NK cells to inhibit NK cell effector function (Rosental et al., 2011).
Entity name
Viral infection
Note
NKp44 recognizes α2,6-N¬-acetylneuraminic acid of hemagglutinin of Influenza and Sendai viruses and hemagglutinin-neuraminidase of the Newcastle disease virus, requiring sialyation of the receptor (Arnon et al., 2001; Jarahian et al., 2009; Ito et al., 2012). Binding of NKp44 to hemagglutinin enables lysis of viral infected cells. Specifically, NKp44 recognizes hemagglutinins from H5-type influenza virus strains (Ho et al., 2008). Two flaviviruses, Dengue and West Nile, are directly recognized by NKp44. Envelope proteins of these viruses, in particular domain III of West Nile, directly bind to NKp44, increasing lysis of infected cells and NK cell IFN-γ release (Hershkovitz et al., 2009). NKp44 is also implicated in recognizing a ligand expressed on cells infected with Vaccina virus (Chisholm and Reyburn, 2006). Viruses have also evolved immune escape mechanisms by down regulating expression of the ligand for NKp44. In the case of Kaposis sarcoma-associated herpes virus, the extracellular ligand expression is reduced during de novo infection. Interestingly, during lytic infection, only surface levels of the NKp44 ligand are reduced as overall cellular levels are unchanged, indicating a defect in cellular trafficking (Madrid and Ganem, 2012). Also, while the NKp44 ligand is typically located outside of the nucleus, during lytic infection the ligand is found localizing to the nucleus (Madrid and Ganem, 2012). This localization is concurrent with a burst of lytic gene expression, mainly consisting of immune related genes (Madrid and Ganem, 2012).
Entity name
HIV
Note
A hallmark of HIV infection is the progressive depletion of CD4+ T cells via destruction of both uninfected CD4+ T cells and HIV-infected CD4+ T cells. In regards to NK cells, HIV modulates both the expression of NK cell receptors and their ligands. NKp44 is no exception as it is expressed at a lower surface density on in vitro activated NK cells from HIV-1 patients compared to healthy controls, resulting in decreased killing of various tumor target cells (De Maria et al., 2003; Mavilio et al., 2003; Fogli et al., 2004). HIV also modulates NK cell receptor ligand expression. NKp44 cellular ligand (NKp44L) is expressed on uninfected CD4+ T cells during an HIV infection, correlating with the loss of CD4+ T cells and increase of viral load (Vieillard et al., 2005). NKp44L is only expressed in high amounts on uninfected CD4+ T cells and is not responsible for inducing NK lysis of HIV-infected cells (Ward et al., 2007). To avoid NK killing of HIV infected CD4+ T cells, the Nef protein of HIV-1 retains NKp44L intracellularly, preventing cell surface expression and interaction with NKp44 (Fausther-Bovendo et al., 2009). Studies by Vieillard et al. have shown a highly conserved 3S peptide motif of the HIV-1 gp41 protein is involved in the induction of NKp44L on the surface of uninfected CD4+ T cells. An envelope protein of the HIV virus, gp41 is vital for viral entry into target cells (Vieillard et al., 2005). The 3S peptide of gp41 binds to its receptor gC1qR, a receptor for the globular domain of complement component 1q, on CD4+ T cells (Fausther-Bovendo et al., 2010). Binding of the 3S motif to this receptor activates a signaling cascade involving PI3K, NADPH-oxidase, Rho-A, and TC10 (Fausther-Bovendo et al., 2010). NKp44L is translocated from the cytoplasm to the plasma membrane and is expressed on the cell surface, where it can bind to NKp44 of activated NK cells. NKp44L+ expressing CD4+ T cells are more susceptible to lysis by activated NK cells (Vieillard et al., 2005). Understanding the role of NKp44L during HIV infection could help identify new therapeutic strategies to prevent the progressive loss of uninfected CD4+ T cells. Possible therapeutic strategies are to inhibit the expression of NKp44L by using an anti-gp41 Ab or an anti-gC1qR Ab to block the 3S motif and gC1qR interaction (Vieillard et al., 2005; Fausther-Bovendo et al., 2010). Anti-3S immunization has also proven efficacious in preliminary studies in macaques (Vieillard et al., 2008).
Entity name
Microbial infection
Note
Nkp44 is reported to directly bind to the surface of Mycobacterium and other related genera. After in vitro stimulation with Mycobacterium bovis bacillus Calmette-Guérin (BCG) for 3 to 4 days, CD56bright NK cells significantly increase NKp44 expression (Esin et al., 2008). The Mycobacterium genus, including the causative agent of tuberculosis, Mycobacterium tuberculosis, express a conserved NKp44 ligand while the mycobacterium related, Gram-positive Nocardia and Corynbacterium genera, also express a ligand (Esin et al., 2008; Esin et al., 2013). Interestingly, both Nocardia, Corynbacterium, and Mycobacterium genera express mycolic acids in their cell walls, which is lacking in other mycobacterium related species which do not express a ligand for NKp44 (Esin et al., 2008). Furthermore, the BCG NKp44 ligand was found to be resistant to trypsin degradation and stable at 80°C, indicating the ligand is most likely not a protein but a heat stable structural component of the cell wall (Esin et al., 2008). In a subsequent study, Esin et al. further proved NKp44 specifically binds mycolyl-arabinogalactan-peptidoglycan, mycolic acid, and arabinogalactan found in the cell wall of Mycobacterium tuberculosis to maintain NK cell activation (Esin et al., 2013). Finally, Pseudomonas aeruginosa also express a ligand for NKp44 (Esin et al., 2008).
Entity name
Formation of placenta
Note
Decidual NK cells (dNK) make up 50-90% of lymphocytes in the uterine mucosa during pregnancy and constitutively express NKp44 (Kopcow et al., 2005; Hanna et al., 2006; Vacca et al., 2008). In close contact with fetal extravillous trophoblasts cells invading the maternal decidua, dNK cells exhibit reduced cytotoxicity but crucially produce Interleukin-8, Interferon-inducible protein 10, Vascular Endothelial Growth Factor (VEGF), and Placental Growth Factor (PGF) in response to NKp44 triggering (Hanna et al., 2006; Vacca et al., 2008). Trophoblast cells and maternal stromal cells of the decidua both express unidentified NKp44 ligands (Hanna et al., 2006; Vacca et al., 2008). This ligand may be PCNA as the protein is over expressed in trophoblast cells during the first trimester (Korgun et al., 2006). As an inhibitory ligand for NKp44, extracellular PCNA expression on trophoblast cells would help explain the diminished ability of dNK cells to lyse trophoblasts despite low levels of classical HLA I expression (Vacca et al., 2008). Invasion of trophoblast into decidua facilitates proper placentation and NK cells help govern how far trophoblasts infiltrate (Moffett and Loke, 2006). dNK cells also help reorganize the spiral arteries to facilitate appropriate blood transfer between the mother and fetus at the placenta (Moffett and Loke, 2006; Vacca et al., 2008). Alterations in dNK cells and invasion of fetal trophoblast cells are implicated in pregnancy complications, such as pre-eclampsia and tubal pregnancies (Moffett and Loke, 2006). Since fetal trophoblast and maternal decidual cells express a NKp44 ligand, this receptor constitutively expressed on dNK cell plays a crucial role in proper development of the placenta in pregnancy that requires further study.
Entity name
Spontaneous abortion
Note
NKp44 expression is increased on CD56brightCD16- dNK cells in patients with spontaneous abortion, resulting in increased cytolytic activity of these NK cells (Zhang et al., 2008).
Entity name
Crohns Disease and ankylosing spondylitis
Note
NKp44+ NK cells (CD3-CD56+NKp44+NKp46-RORChighCD122-CD127+) in the intestinal lamina propria are significantly reduced in inflamed mucosa of patients with Crohns Disease (CD) while IFN-γ producing NKp46+ NK cells (CD3-CD56+NKp44-NKp46+RORCdullCD122+CD127-) are dramatically increased (Takayama et al., 2010). IL-22 is produced by NKp44+ NK cells, which is protective in the onset of murine colitis, and possibly implicated in human colitis. Thus the imbalance of the NKp44+/NKp46+ NK cell axis in the intestinal lamina propria may play a role in colitis onset (Takayama et al., 2010). Contrary to CD, NKp44+ NK cells are increased in the inflamed ileum of patients with Ankylosing Spondylitis (AS) (Ciccia et al., 2012). AS Patients over express IL-23 in the intestines which modulates IL-22 production by NKp44+IL-22+ NK cells (Ciccia et al., 2012). IL-22 then promotes mucosal wound healing through increased mucin production by goblet cells.

Bibliography

Pubmed IDLast YearTitleAuthors
126459562003The human TREM gene cluster at 6p21.1 encodes both activating and inhibitory single IgV domain receptors and includes NKp44.Allcock RJ et al
115361662001Recognition of viral hemagglutinins by NKp44 but not by NKp30.Arnon TI et al
127310482003Selective cross-talk among natural cytotoxicity receptors in human natural killer cells.Augugliaro R et al
180920042007Expression analysis of the ligands for the Natural Killer cell receptors NKp30 and NKp44.Byrd A et al
147070612004NKp44 triggers NK cell activation through DAP12 association that is not influenced by a putative cytoplasmic inhibitory sequence.Campbell KS et al
100499421999NKp44, a triggering receptor involved in tumor cell lysis by activated human natural killer cells, is a novel member of the immunoglobulin superfamily.Cantoni C et al
127912602003The three-dimensional structure of the human NK cell receptor NKp44, a triggering partner in natural cytotoxicity.Cantoni C et al
189787712009A human natural killer cell subset provides an innate source of IL-22 for mucosal immunity.Cella M et al
164741302006Recognition of vaccinia virus-infected cells by human natural killer cells depends on natural cytotoxicity receptors.Chisholm SE et al
222131792012Interleukin-22 and interleukin-22-producing NKp44+ natural killer cells in subclinical gut inflammation in ankylosing spondylitis.Ciccia F et al
129382172003The impaired NK cell cytolytic function in viremic HIV-1 infection is associated with a reduced surface expression of natural cytotoxicity receptors (NKp46, NKp30 and NKp44).De Maria A et al
146628962003Evasion from NK cell immunity by MHC class I chain-related molecules expressing colon adenocarcinoma.Doubrovina ES et al
182120802008Direct binding of human NK cell natural cytotoxicity receptor NKp44 to the surfaces of mycobacteria and other bacteria.Esin S et al
235780922013Interaction of Mycobacterium tuberculosis cell wall components with the human natural killer cell receptors NKp44 and Toll-like receptor 2.Esin S et al
206171702010HIV gp41 engages gC1qR on CD4+ T cells to induce the expression of an NK ligand through the PIP3/H2O2 pathway.Fausther-Bovendo H et al
152590292004Significant NK cell activation associated with decreased cytolytic function in peripheral blood of HIV-1-infected patients.Fogli M et al
159419122005Paradoxic inhibition of human natural interferon-producing cells by the activating receptor NKp44.Fuchs A et al
168920622006Decidual NK cells regulate key developmental processes at the human fetal-maternal interface.Hanna J et al
191961842009Natural cytotoxicity receptors NKp30, NKp44 and NKp46 bind to different heparan sulfate/heparin sequences.Hecht ML et al
196359192009NKp44 receptor mediates interaction of the envelope glycoproteins from the West Nile and dengue viruses with NK cells.Hershkovitz O et al
180777182008H5-type influenza virus hemagglutinin is functionally recognized by the natural killer-activating receptor NKp44.Ho JW et al
235272182013Novel interaction between proliferating cell nuclear antigen and HLA I on the surface of tumor cells inhibits NK cell function through NKp44.Horton NC et al
235186912013Natural cytotoxicity receptors: broader expression patterns and functions in innate and adaptive immune cells.Hudspeth K et al
224665662012Unlike natural killer (NK) p30, natural cytotoxicity receptor NKp44 binds to multimeric α2,3-NeuNAc-containing N-glycans.Ito K et al
195157832009Activation of natural killer cells by newcastle disease virus hemagglutinin-neuraminidase.Jarahian M et al
162306312005Human decidual NK cells form immature activating synapses and are not cytotoxic.Kopcow HD et al
164913472006Location of cell cycle regulators cyclin B1, cyclin A, PCNA, Ki67 and cell cycle inhibitors p21, p27 and p57 in human first trimester placenta and deciduas.Korgun ET et al
226749892012Kaposi's sarcoma-associated herpesvirus ORF54/dUTPase downregulates a ligand for the NK activating receptor NKp44.Madrid AS et al
200557912010The unique properties of uterine NK cells.Manaster I et al
146457132003Natural killer cells in HIV-1 infection: dichotomous effects of viremia on inhibitory and activating receptors and their functional correlates.Mavilio D et al
153579472004Coordinated induction by IL15 of a TCR-independent NKG2D signaling pathway converts CTL into lymphokine-activated killer cells in celiac disease.Meresse B et al
168685492006Immunology of placentation in eutherian mammals.Moffett A et al
156571832005Ligands for natural killer cell-activating receptors are expressed upon the maturation of normal myelomonocytic cells but at low levels in acute myeloid leukemias.Nowbakht P et al
222584542012Melanoma cells inhibit natural killer cell function by modulating the expression of activating receptors and cytolytic activity.Pietra G et al
157284722005Tumor-induced apoptosis of human IL-2-activated NK cells: role of natural cytotoxicity receptors.Poggi A et al
220216142011Proliferating cell nuclear antigen is a novel inhibitory ligand for the natural cytotoxicity receptor NKp44.Rosental B et al
111372072000Triggering receptors involved in natural killer cell-mediated cytotoxicity against choriocarcinoma cell lines.Sivori S et al
179515262008Mesenchymal stem cells inhibit natural killer-cell proliferation, cytotoxicity, and cytokine production: role of indoleamine 2,3-dioxygenase and prostaglandin E2.Spaggiari GM et al
206389362010Imbalance of NKp44(+)NKp46(-) and NKp44(-)NKp46(+) natural killer cells in the intestinal mucosa of patients with Crohn's disease.Takayama T et al
188020532008Umbilical cord blood T cells express multiple natural cytotoxicity receptors after IL-15 stimulation, but only NKp30 is functional.Tang Q et al
188151192008Regulatory role of NKp44, NKp46, DNAM-1 and NKG2D receptors in the interaction between NK cells and trophoblast cells. Evidence for divergent functional profiles of decidual versus peripheral NK cells.Vacca P et al
182348552008A vaccine strategy against AIDS: an HIV gp41 peptide immunization prevents NKp44L expression and CD4+ T cell depletion in SHIV-infected macaques.Vieillard V et al
96257661998NKp44, a novel triggering surface molecule specifically expressed by activated natural killer cells, is involved in non-major histocompatibility complex-restricted tumor cell lysis.Vitale M et al
175136172007HIV modulates the expression of ligands important in triggering natural killer cell cytotoxic responses on infected primary T-cell blasts.Ward J et al
180234312008Expressions of natural cytotoxicity receptors and NKG2D on decidual natural killer cells in patients having spontaneous abortions.Zhang Y et al
180531642007The proinflammatory cytokines IL-2, IL-15 and IL-21 modulate the repertoire of mature human natural killer cell receptors.de Rham C et al
167346232006Activated gammadelta T cells express the natural cytotoxicity receptor natural killer p 44 and show cytotoxic activity against myeloma cells.von Lilienfeld-Toal M et al

Other Information

Locus ID:

NCBI: 9436
MIM: 604531
HGNC: 6732
Ensembl: ENSG00000096264

Variants:

dbSNP: 9436
ClinVar: 9436
TCGA: ENSG00000096264
COSMIC: NCR2

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000096264ENST00000373083O95944
ENSG00000096264ENST00000373086O95944
ENSG00000096264ENST00000373089O95944

Expression (GTEx)

0
1
2

Pathways

PathwaySourceExternal ID
Natural killer cell mediated cytotoxicityKEGGko04650
Natural killer cell mediated cytotoxicityKEGGhsa04650
Immune SystemREACTOMER-HSA-168256
Adaptive Immune SystemREACTOMER-HSA-1280218
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cellREACTOMER-HSA-198933
Innate Immune SystemREACTOMER-HSA-168249
DAP12 interactionsREACTOMER-HSA-2172127

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
243520382014Characterization of innate lymphoid cells in human skin and blood demonstrates increase of NKp44+ ILC3 in psoriasis.93
206389362010Imbalance of NKp44(+)NKp46(-) and NKp44(-)NKp46(+) natural killer cells in the intestinal mucosa of patients with Crohn's disease.78
220216142011Proliferating cell nuclear antigen is a novel inhibitory ligand for the natural cytotoxicity receptor NKp44.78
233453272013Human NK cells selective targeting of colon cancer-initiating cells: a role for natural cytotoxicity receptors and MHC class I molecules.73
239589512013Identification of a cellular ligand for the natural cytotoxicity receptor NKp44.64
246585042014Composition of innate lymphoid cell subsets in the human skin: enrichment of NCR(+) ILC3 in lesional skin and blood of psoriasis patients.62
156571832005Ligands for natural killer cell-activating receptors are expressed upon the maturation of normal myelomonocytic cells but at low levels in acute myeloid leukemias.60
196359192009NKp44 receptor mediates interaction of the envelope glycoproteins from the West Nile and dengue viruses with NK cells.56
237916422013RORγt⁺ innate lymphoid cells acquire a proinflammatory program upon engagement of the activating receptor NKp44.54
159419122005Paradoxic inhibition of human natural interferon-producing cells by the activating receptor NKp44.50

Citation

Nathan Horton ; Kelly Bowen ; Porunelloor Mathew

NCR2 (natural cytotoxicity triggering receptor 2)

Atlas Genet Cytogenet Oncol Haematol. 2013-06-01

Online version: http://atlasgeneticsoncology.org/gene/46140/ncr2