Browse NCR3

Summary
SymbolNCR3
Namenatural cytotoxicity triggering receptor 3
Aliases 1C7; NKp30; CD337; LY117; MALS; NK-p30; activating NK-A1 receptor; activating natural killer receptor p30; n ......
Chromosomal Location6p21.3
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 I membrane protein
Domain PF07686 Immunoglobulin V-set domain
Function

Cell membrane receptor of natural killer/NK cells that is activated by binding of extracellular ligands including BAG6 and NCR3LG1. Stimulates NK cells cytotoxicity toward neighboring cells producing these ligands. It controls, for instance, NK cells cytotoxicity against tumor cells. Engagement of NCR3 by BAG6 also promotes myeloid dendritic cells (DC) maturation, both through killing DCs that did not acquire a mature phenotype, and inducing the release by NK cells of TNFA and IFNG which promote DC maturation.

> Gene Ontology
 
Biological Process 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:0001913 T cell mediated cytotoxicity
GO:0001914 regulation of T cell mediated cytotoxicity
GO:0001916 positive regulation of T cell mediated cytotoxicity
GO:0002228 natural killer cell mediated immunity
GO:0002250 adaptive immune response
GO:0002347 response to tumor cell
GO:0002418 immune response to tumor cell
GO:0002420 natural killer cell mediated cytotoxicity directed against tumor cell target
GO:0002423 natural killer cell mediated immune response to tumor cell
GO:0002443 leukocyte mediated immunity
GO:0002449 lymphocyte mediated immunity
GO:0002456 T cell mediated immunity
GO:0002460 adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains
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:0002709 regulation of T cell mediated immunity
GO:0002711 positive regulation of T cell mediated immunity
GO:0002715 regulation of natural killer cell mediated immunity
GO:0002717 positive regulation of natural killer cell mediated immunity
GO:0002819 regulation of adaptive immune response
GO:0002821 positive regulation of adaptive immune response
GO:0002822 regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains
GO:0002824 positive regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains
GO:0002831 regulation of response to biotic stimulus
GO:0002833 positive regulation of response to biotic stimulus
GO:0002834 regulation of response to tumor cell
GO:0002836 positive regulation of response to tumor cell
GO:0002837 regulation of immune response to tumor cell
GO:0002839 positive regulation of immune response to tumor cell
GO:0002855 regulation of natural killer cell mediated immune response to tumor cell
GO:0002857 positive regulation of natural killer cell mediated immune response to tumor cell
GO:0002858 regulation of natural killer cell mediated cytotoxicity directed against tumor cell target
GO:0002860 positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target
GO:0007156 homophilic cell adhesion via plasma membrane adhesion molecules
GO:0007157 heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules
GO:0008037 cell recognition
GO:0031341 regulation of cell killing
GO:0031343 positive regulation of cell killing
GO:0031349 positive regulation of defense response
GO:0042267 natural killer cell mediated cytotoxicity
GO:0042269 regulation of natural killer cell mediated cytotoxicity
GO:0042271 susceptibility to natural killer cell mediated cytotoxicity
GO:0045088 regulation of innate immune response
GO:0045089 positive regulation of innate immune response
GO:0045954 positive regulation of natural killer cell mediated cytotoxicity
GO:0060370 susceptibility to T cell mediated cytotoxicity
GO:0098742 cell-cell adhesion via plasma-membrane adhesion molecules
Molecular Function GO:0050839 cell adhesion molecule binding
Cellular Component GO:0005913 cell-cell adherens junction
> KEGG and Reactome Pathway
 
KEGG hsa04650 Natural killer cell mediated cytotoxicity
Reactome R-HSA-1280218: Adaptive Immune System
R-HSA-168256: Immune System
R-HSA-198933: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
Summary
SymbolNCR3
Namenatural cytotoxicity triggering receptor 3
Aliases 1C7; NKp30; CD337; LY117; MALS; NK-p30; activating NK-A1 receptor; activating natural killer receptor p30; n ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between NCR3 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 NCR3 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
26364607Gastric CarcinomaPromote immunity (NK cell function)In contrast, another cell line AGS expressing low levels of HLA-I with activated NKp30/MAPK/IL-12 (interleukin-12) or IL-2 (interleukin-2) pathway was susceptible to NK lysis. Treatment of tumor bearing mice with systemic administration of IL-12 in combination with intratumor injection of anti-HLA-I antibody significantly increased NK cell recruitment into xenograft tumors, which became sensitive to NK killing, resulting in reduced tumor progression.
27777574Colorectal carcinomaPromote immunityCRC-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.
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.
23580577LymphomaPromote immunityMarked elevations in expression of activation receptors, natural cytotoxicity receptors (NKp30, NKp44), and adhesion molecules (CD11a, ICAM-1) were associated with high tumor-lytic capacity, in both in vitro and in vivo models.
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).
21224372MelanomaPromote immunity (T 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.
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).
19934056MelanomaPromote immunity (NK cell function)Thus, both the IL-2-induced up-regulation of the surface expression of NKp44, NKp30, and DNAM-1 triggering receptors and the acquisition of cytolytic granules were inhibited in NK cells. This resulted in an impairment of the NK cell-mediated killing of melanoma target cells.
22851709LymphomaPromote immunityAn NKp30-based chimeric antigen receptor promotes T cell effector functions and antitumor efficacy in vivo. The data show that chimeric NKp30-expressing T cells responded to B7-H6+ tumor cells. NKp30 CAR-expressing T cells produced IFN-γ and killed B7-H6 ligand-expressing tumor cells; this response was dependent upon ligand expression on target cells but not on MHC expression.
21633088Lymphoid LeukemiaPromote immunityDifferentiation of human peripheral blood Vδ1+ T cells expressing the natural cytotoxicity receptor NKp30 for recognition of lymphoid leukemia cells. Specific gain-of-function and loss-of-function experiments demonstrated that NKp30 makes the most important contribution to TCR-independent leukemia cell recognition.
16237071Lung AdenocarcinomaPromote immunityNK cells infiltrating a MHC class I-deficient lung adenocarcinoma display impaired cytotoxic activity toward autologous tumor cells associated with altered NK cell-triggering receptors. The present study indicates that the MHC-I-deficient lung adenocarcinoma had developed mechanisms of escape from the innate immune response based on down-regulation of NCR and ligands required for target cell recognition.
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
Summary
SymbolNCR3
Namenatural cytotoxicity triggering receptor 3
Aliases 1C7; NKp30; CD337; LY117; MALS; NK-p30; activating NK-A1 receptor; activating natural killer receptor p30; n ......
Chromosomal Location6p21.3
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 NCR3 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
SymbolNCR3
Namenatural cytotoxicity triggering receptor 3
Aliases 1C7; NKp30; CD337; LY117; MALS; NK-p30; activating NK-A1 receptor; activating natural killer receptor p30; n ......
Chromosomal Location6p21.3
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 NCR3 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)141201
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)6501
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)8701
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.5130.537
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.3740.764
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.6870.628
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.6530.344
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.180.873
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11121.1310.331
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.8790.266
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 28-0.0970.927
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.2240.365
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of NCR3 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) 27730001
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27590001
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.602.61
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.504.51
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
SymbolNCR3
Namenatural cytotoxicity triggering receptor 3
Aliases 1C7; NKp30; CD337; LY117; MALS; NK-p30; activating NK-A1 receptor; activating natural killer receptor p30; n ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of NCR3. 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
SymbolNCR3
Namenatural cytotoxicity triggering receptor 3
Aliases 1C7; NKp30; CD337; LY117; MALS; NK-p30; activating NK-A1 receptor; activating natural killer receptor p30; n ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of NCR3. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by NCR3.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolNCR3
Namenatural cytotoxicity triggering receptor 3
Aliases 1C7; NKp30; CD337; LY117; MALS; NK-p30; activating NK-A1 receptor; activating natural killer receptor p30; n ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of NCR3. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolNCR3
Namenatural cytotoxicity triggering receptor 3
Aliases 1C7; NKp30; CD337; LY117; MALS; NK-p30; activating NK-A1 receptor; activating natural killer receptor p30; n ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of NCR3 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolNCR3
Namenatural cytotoxicity triggering receptor 3
Aliases 1C7; NKp30; CD337; LY117; MALS; NK-p30; activating NK-A1 receptor; activating natural killer receptor p30; n ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between NCR3 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolNCR3
Namenatural cytotoxicity triggering receptor 3
Aliases 1C7; NKp30; CD337; LY117; MALS; NK-p30; activating NK-A1 receptor; activating natural killer receptor p30; n ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting NCR3 collected from DrugBank database.
> Drugs from DrugBank database
 

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