TISIDB

Summary
Symbol	SLAMF6
Name	SLAM family member 6
Aliases	KALI; NTBA; KALIb; Ly108; SF2000; NTB-A; CD352; NK-T-B-antigen; NTBA receptor; activating NK receptor; natur ......
Chromosomal Location	1q23.1
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	Self-ligand receptor of the signaling lymphocytic activation molecule (SLAM) family. SLAM receptors triggered by homo- or heterotypic cell-cell interactions are modulating the activation and differentiation of a wide variety of immune cells and thus are involved in the regulation and interconnection of both innate and adaptive immune response. Activities are controlled by presence or absence of small cytoplasmic adapter proteins, SH2D1A/SAP and/or SH2D1B/EAT-2. Triggers cytolytic activity only in natural killer cells (NK) expressing high surface densities of natural cytotoxicity receptors (PubMed:11489943, PubMed:16920955). Positive signaling in NK cells implicates phosphorylation of VAV1. NK cell activation seems to depend on SH2D1B and not on SH2D1A (PubMed:16920955). In conjunction with SLAMF1 controls the transition between positive selection and the subsequent expansion and differentiation of the thymocytic natural killer T (NKT) cell lineage (By similarity). Promotes T-cell differentiation into a helper T-cell Th17 phenotype leading to increased IL-17 secretion; the costimulatory activity requires SH2D1A (PubMed:22184727, PubMed:16920955). Promotes recruitment of RORC to the IL-17 promoter (PubMed:22989874). In conjunction with SLAMF1 and CD84/SLAMF5 may be a negative regulator of the humoral immune response. In the absence of SH2D1A/SAP can transmit negative signals to CD4(+) T-cells and NKT cells. Negatively regulates germinal center formation by inhibiting T-cell:B-cell adhesion; the function probably implicates increased association with PTPN6/SHP-1 via ITSMs in absence of SH2D1A/SAP. However, reported to be involved in maintaining B-cell tolerance in germinal centers and in preventing autoimmunity (By similarity).

> Gene Ontology [ TOP ]
Biological Process	GO:0001779 natural killer cell differentiation GO:0001787 natural killer cell proliferation 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:0002228 natural killer cell mediated immunity GO:0002250 adaptive immune response GO:0002263 cell activation involved in immune response GO:0002285 lymphocyte activation involved in immune response GO:0002286 T cell activation involved in immune response GO:0002287 alpha-beta T cell activation involved in immune response GO:0002292 T cell differentiation involved in immune response GO:0002293 alpha-beta T cell differentiation involved in immune response GO:0002294 CD4-positive, alpha-beta T cell differentiation involved in immune response GO:0002295 T-helper cell lineage commitment GO:0002360 T cell lineage commitment GO:0002363 alpha-beta T cell lineage commitment GO:0002366 leukocyte activation involved in immune response GO:0002443 leukocyte mediated immunity GO:0002449 lymphocyte mediated immunity GO:0002460 adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains GO:0002521 leukocyte differentiation 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:0007159 leukocyte cell-cell adhesion GO:0030098 lymphocyte differentiation GO:0030101 natural killer cell activation GO:0030217 T cell differentiation GO:0031341 regulation of cell killing GO:0031343 positive regulation of cell killing GO:0031349 positive regulation of defense response GO:0032609 interferon-gamma production GO:0032620 interleukin-17 production GO:0032649 regulation of interferon-gamma production GO:0032660 regulation of interleukin-17 production GO:0032729 positive regulation of interferon-gamma production GO:0032740 positive regulation of interleukin-17 production GO:0032943 mononuclear cell proliferation GO:0035710 CD4-positive, alpha-beta T cell activation GO:0042093 T-helper cell differentiation GO:0042110 T cell activation GO:0042267 natural killer cell mediated cytotoxicity GO:0042269 regulation of natural killer cell mediated cytotoxicity GO:0043367 CD4-positive, alpha-beta T cell differentiation GO:0043368 positive T cell selection GO:0043369 CD4-positive or CD8-positive, alpha-beta T cell lineage commitment GO:0043373 CD4-positive, alpha-beta T cell lineage commitment GO:0045058 T cell selection GO:0045088 regulation of innate immune response GO:0045089 positive regulation of innate immune response GO:0045165 cell fate commitment GO:0045954 positive regulation of natural killer cell mediated cytotoxicity GO:0046631 alpha-beta T cell activation GO:0046632 alpha-beta T cell differentiation GO:0046651 lymphocyte proliferation GO:0070486 leukocyte aggregation GO:0070489 T cell aggregation GO:0070661 leukocyte proliferation GO:0071593 lymphocyte aggregation GO:0072538 T-helper 17 type immune response GO:0072539 T-helper 17 cell differentiation GO:0072540 T-helper 17 cell lineage commitment
Molecular Function	-
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
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	SLAMF6
Name	SLAM family member 6
Aliases	KALI; NTBA; KALIb; Ly108; SF2000; NTB-A; CD352; NK-T-B-antigen; NTBA receptor; activating NK receptor; natur ......
Chromosomal Location	1q23.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between SLAMF6 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

[ TOP ]

Literatures describing the relation between SLAMF6 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
29305520	Melanoma	Promote immunity (T/NK cell function); essential for immunotherapy	Soluble SLAMF6 Receptor Induces Strong CD8+ T-cell Effector Function and Improves Anti-Melanoma Activity In Vivo. CD8+ T cells costimulated with seSLAMF6 secreted more IFNγ and displayed augmented cytolytic activity.
24510590	Ovarian Carcinoma	Promote immunity (T and NK cell function)	Most tumor-associated NK cells displayed a CD56(bright) , CD16(neg) or CD56(bright) , CD16(dim) phenotype, and very poor cytolytic activities, despite an increased expression of the activation marker CD69. They also showed downregulation of DNAM-1, 2B4, and NTB-A activating receptors, and an altered chemokine receptor repertoire.
22156347	Melanoma	Promote immunity (T cell function)	Specific blocking of NTB-A on APCs markedly reduced cytokine production by CD8 lymphocytes, pointing to a possible contribution of NTB-A costimulation to T cell functional diversity.

Summary
Symbol	SLAMF6
Name	SLAM family member 6
Aliases	KALI; NTBA; KALIb; Ly108; SF2000; NTB-A; CD352; NK-T-B-antigen; NTBA receptor; activating NK receptor; natur ......
Chromosomal Location	1q23.1
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

[ TOP ]

Statistical results of SLAMF6 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	SLAMF6
Name	SLAM family member 6
Aliases	KALI; NTBA; KALIb; Ly108; SF2000; NTB-A; CD352; NK-T-B-antigen; NTBA receptor; activating NK receptor; natur ......
Chromosomal Location	1q23.1
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

[ TOP ]

Points in the above scatter plot represent the expression difference of SLAMF6 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	-0.008	0.988
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.643	0.504
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.49	0.563
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.041	0.931
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.548	0.624
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.606	0.68
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.924	0.14
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	1.601	0.141
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.202	0.864
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.582	0.0701
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	1.575	0.239
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.019	0.94

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of SLAMF6 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	7.4	4.1	3.3	0.61
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	7.4	5.1	2.3	0.647
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	5.9	-1.1	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	0	12.5	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	9.1	-9.1	0.458
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	0	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	0	4.5	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	7.7	-7.7	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	8.3	-8.3	1

Summary
Symbol	SLAMF6
Name	SLAM family member 6
Aliases	KALI; NTBA; KALIb; Ly108; SF2000; NTB-A; CD352; NK-T-B-antigen; NTBA receptor; activating NK receptor; natur ......
Chromosomal Location	1q23.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of SLAMF6. 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	SLAMF6
Name	SLAM family member 6
Aliases	KALI; NTBA; KALIb; Ly108; SF2000; NTB-A; CD352; NK-T-B-antigen; NTBA receptor; activating NK receptor; natur ......
Chromosomal Location	1q23.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of SLAMF6. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by SLAMF6. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	SLAMF6
Name	SLAM family member 6
Aliases	KALI; NTBA; KALIb; Ly108; SF2000; NTB-A; CD352; NK-T-B-antigen; NTBA receptor; activating NK receptor; natur ......
Chromosomal Location	1q23.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of SLAMF6. 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	SLAMF6
Name	SLAM family member 6
Aliases	KALI; NTBA; KALIb; Ly108; SF2000; NTB-A; CD352; NK-T-B-antigen; NTBA receptor; activating NK receptor; natur ......
Chromosomal Location	1q23.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of SLAMF6 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	SLAMF6
Name	SLAM family member 6
Aliases	KALI; NTBA; KALIb; Ly108; SF2000; NTB-A; CD352; NK-T-B-antigen; NTBA receptor; activating NK receptor; natur ......
Chromosomal Location	1q23.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between SLAMF6 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	SLAMF6
Name	SLAM family member 6
Aliases	KALI; NTBA; KALIb; Ly108; SF2000; NTB-A; CD352; NK-T-B-antigen; NTBA receptor; activating NK receptor; natur ......
Chromosomal Location	1q23.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting SLAMF6 collected from DrugBank database.

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

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