TISIDB

Summary
Symbol	NCR3
Name	natural cytotoxicity triggering receptor 3
Aliases	1C7; NKp30; CD337; LY117; MALS; NK-p30; activating NK-A1 receptor; activating natural killer receptor p30; n ......
Chromosomal Location	6p21.3
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 [ TOP ]
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 [ TOP ]
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 [ TOP ]
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
Symbol	NCR3
Name	natural cytotoxicity triggering receptor 3
Aliases	1C7; NKp30; CD337; LY117; MALS; NK-p30; activating NK-A1 receptor; activating natural killer receptor p30; n ......
Chromosomal Location	6p21.3
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

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Literatures describing the relation between NCR3 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
26364607	Gastric Carcinoma	Promote 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.
27777574	Colorectal carcinoma	Promote immunity	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.
23192659	Mesothelioma and lung carcinoma; breast carcinoma; colon carcinoma; gastric carcinoma; bladder carcinoma; uterus carcinoma	Promote immunity	Tumor 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.
23580577	Lymphoma	Promote immunity	Marked 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.
23459515	Hodgkin Lymphoma	Promote immunity	Hodgkin 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).
21224372	Melanoma	Promote 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.
22258454	Melanoma	Promote 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).
19934056	Melanoma	Promote 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.
22851709	Lymphoma	Promote immunity	An 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.
21633088	Lymphoid Leukemia	Promote immunity	Differentiation 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.
16237071	Lung Adenocarcinoma	Promote immunity	NK 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.
21841316	Breast Carcinoma	Promote immunity	With 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
Symbol	NCR3
Name	natural cytotoxicity triggering receptor 3
Aliases	1C7; NKp30; CD337; LY117; MALS; NK-p30; activating NK-A1 receptor; activating natural killer receptor p30; n ......
Chromosomal Location	6p21.3
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

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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
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	NCR3
Name	natural cytotoxicity triggering receptor 3
Aliases	1C7; NKp30; CD337; LY117; MALS; NK-p30; activating NK-A1 receptor; activating natural killer receptor p30; n ......
Chromosomal Location	6p21.3
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

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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
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	0	1
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0	1
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0	1
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.513	0.537
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.374	0.764
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.687	0.628
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.653	0.344
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.18	0.873
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	1.131	0.331
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.879	0.266
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	-0.097	0.927
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.224	0.365

> Mutation difference between responders and non-responders

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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	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	0	0	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	0	0	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	4.5	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	1

Summary
Symbol	NCR3
Name	natural cytotoxicity triggering receptor 3
Aliases	1C7; NKp30; CD337; LY117; MALS; NK-p30; activating NK-A1 receptor; activating natural killer receptor p30; n ......
Chromosomal Location	6p21.3
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 [ TOP ]

Summary
Symbol	NCR3
Name	natural cytotoxicity triggering receptor 3
Aliases	1C7; NKp30; CD337; LY117; MALS; NK-p30; activating NK-A1 receptor; activating natural killer receptor p30; n ......
Chromosomal Location	6p21.3
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 [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	NCR3
Name	natural cytotoxicity triggering receptor 3
Aliases	1C7; NKp30; CD337; LY117; MALS; NK-p30; activating NK-A1 receptor; activating natural killer receptor p30; n ......
Chromosomal Location	6p21.3
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 [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	NCR3
Name	natural cytotoxicity triggering receptor 3
Aliases	1C7; NKp30; CD337; LY117; MALS; NK-p30; activating NK-A1 receptor; activating natural killer receptor p30; n ......
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of NCR3 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	NCR3
Name	natural cytotoxicity triggering receptor 3
Aliases	1C7; NKp30; CD337; LY117; MALS; NK-p30; activating NK-A1 receptor; activating natural killer receptor p30; n ......
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between NCR3 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	NCR3
Name	natural cytotoxicity triggering receptor 3
Aliases	1C7; NKp30; CD337; LY117; MALS; NK-p30; activating NK-A1 receptor; activating natural killer receptor p30; n ......
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting NCR3 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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