SLAMF6 SLAM family member 6 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SLAMF6provided by HGNC
Official Full Name: SLAM family member 6provided by HGNC
Primary source: HGNC:HGNC:21392
See related: Ensembl:ENSG00000162739 MIM:606446; AllianceGenome:HGNC:21392
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: KALI; NTBA; CD352; KALIb; Ly108; NTB-A; SF2000
Summary: The protein encoded by this gene is a type I transmembrane protein, belonging to the CD2 subfamily of the immunoglobulin superfamily. This encoded protein is expressed on Natural killer (NK), T, and B lymphocytes. It undergoes tyrosine phosphorylation and associates with the Src homology 2 domain-containing protein (SH2D1A) as well as with SH2 domain-containing phosphatases (SHPs). It functions as a coreceptor in the process of NK cell activation. It can also mediate inhibitory signals in NK cells from X-linked lymphoproliferative patients. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, May 2010]
Expression: Biased expression in lymph node (RPKM 29.2), spleen (RPKM 15.5) and 7 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1q23.2-q23.3

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (160485036..160523255, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (159622119..159660340, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (160454826..160493045, complement)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Clinical and immunological relevance of SLAMF6 expression in the tumor microenvironment of breast cancer and melanoma.
Title: Clinical and immunological relevance of SLAMF6 expression in the tumor microenvironment of breast cancer and melanoma.
SLAMF6 is associated with the susceptibility and severity of rheumatoid arthritis in the Chinese population.
Title: SLAMF6 is associated with the susceptibility and severity of rheumatoid arthritis in the Chinese population.
Expression and function of SLAMF6 in CD8(+) T lymphocytes of patients with severe aplastic anemia.
Title: Expression and function of SLAMF6 in CD8(+) T lymphocytes of patients with severe aplastic anemia.
SLAMF6 is an important regulator of T cell activation where both its ectodomain and its endodomain contribute differentially to T cell functions.
Title: SLAMF6 clustering is required to augment T cell activation.
Authors found that seSLAMF6 reduced activation-induced cell death and had an antiapoptotic effect on tumor-infiltrating lymphocytes.
Title: Soluble SLAMF6 Receptor Induces Strong CD8(+) T-cell Effector Function and Improves Anti-Melanoma Activity In Vivo.
these results showed that the NTB-A/SAP pathway regulates T-cell activation and restimulation-induced cell death during human tuberculosis
Title: Restimulation-induced T-cell death through NTB-A/SAP signaling pathway is impaired in tuberculosis patients with depressed immune responses.
in addition to its established role in Invariant NKT(iNKT) cell ontogeny, Ly108 regulates iNKT cell function in mice and humans
Title: Invariant NKT Cell Activation Is Potentiated by Homotypic trans-Ly108 Interactions.
In addition to their role in NK cell activation by hematopoietic cells, the SLAM-SAP-SHP1 pathways influence responsiveness toward nonhematopoietic targets by a process akin to NK cell 'education'.
Title: A hematopoietic cell-driven mechanism involving SLAMF6 receptor, SAP adaptors and SHP-1 phosphatase regulates NK cell education.
our data reveal how SAP nucleates a previously unknown signaling complex involving NTB-A and LCK to potentiate restimulation-induced cell death of activated human T cells.
Title: SAP facilitates recruitment and activation of LCK at NTB-A receptors during restimulation-induced cell death.
Together, these results suggest that the reduction of NTB-A from the cell surface is associated with the Vpu-mediated effect on the glycosylation pattern of newly synthesized NTB-A molecules.
Title: HIV-1 Vpu affects the anterograde transport and the glycosylation pattern of NTB-A.

Submit: New GeneRIF Correction See all GeneRIFs (24)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Robust evidence for five new Graves' disease risk loci from a staged genome-wide association analysis. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Nef	nef	HIV-1 (SF2) Nef downregulates SLAMF6 (NTB-A); downregulation is dependent upon a proline rich SH3 binding domain in Nef as shown in A3.01 T cells and HeLa TZM-bl cells	PubMed
Vpu	vpu	HIV-1 (NL4-3) Vpu downregulates SLAMF6 (NTB-A); downregulation is dependent upon serines at positions 52 and 56 in Vpu as shown in A3.01 T cells and HeLa TZM-bl cells	PubMed
	vpu	HIV-1 Vpu downregulates NTB-A on infected T cells. Vpu does not increase NTB-A endocytosis or degradation within lysosomes. Vpu-mediated downregulation of NTB-A protects the HIV infected cell from lysis by NK cells	PubMed
	vpu	HIV-1 (NL4-3) Vpu downregulates SLAMF6 via a cullin-RING E3 ubiquitin ligase complex- independent mechanism	PubMed
	vpu	The second alpha-helix of Vpu is critical to affect the glycosylation and surface expression of NTB-A. Vpu delta-23, Vpu A18H, and Vpu-KKDQ mutants exhibit an attenuated activity on NTB-A glycosylation	PubMed
	vpu	HIV-1 Vpu modulates the glycosylation pattern of NTB-A, which correlates with re-localization of NTB-A from the cell surface to the Golgi-compartment	PubMed
	vpu	HIV-1 Vpu proteins from Cameroonian group N viruses are largely unable to downregulate NTB-A	PubMed
	vpu	A combination of molecular dynamics simulations and docking approaches shows the lowest energy structure of Vpu-NTB-A, indicating that the residues C-235, F-238, I-242, and L-243/245/246 in NTB-A interact with the alanine rim (A-8/11/15/19) of Vpu	PubMed
	vpu	HIV-1 Vpu binds to NK-T- and -B cell antigen (NTB-A) through its transmembrane region (residues 4-28)	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D8S2279 (e-PCR)
- UniSTS:473907

NoName (e-PCR)
- UniSTS:486452

G35510 (e-PCR)
- UniSTS:44150

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in T cell activation	IBA Inferred from Biological aspect of Ancestor more info
involved_in T-helper 17 cell lineage commitment	IBA Inferred from Biological aspect of Ancestor more info
involved_in T-helper 17 cell lineage commitment	IDA Inferred from Direct Assay more info	PubMed
involved_in innate immune response	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of interleukin-17 production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of natural killer cell mediated cytotoxicity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of type II interferon production	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of type II interferon production	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
is_active_in external side of plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular exosome	HDA more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: SLAM family member 6

Names: NK-T-B-antigen; NTBA receptor; activating NK receptor; natural killer-, T- and B-cell antigen

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001184714.2 → NP_001171643.1 SLAM family member 6 isoform 1 precursor

See identical proteins and their annotated locations for NP_001171643.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AK125624, AY358159, DB197632

Consensus CDS

CCDS53394.1

UniProtKB/Swiss-Prot

A6NMW2, B2R8X8, Q14CF0, Q5TAS4, Q5TAS6, Q5TAT3, Q96DU3, Q96DV0

UniProtKB/TrEMBL

B4E1U5

Related

ENSP00000357036.3, ENST00000368057.8

Conserved Domains (1) summary

cd16842
Location:32 → 126

Ig_SLAM-CD84_like_N; N-terminal immunoglobulin (Ig)-like domain of the signaling lymphocyte activation molecule (SLAM) family
NM_001184715.2 → NP_001171644.1 SLAM family member 6 isoform 3 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses multiple alternate splice sites in the coding region, compared to variant 1, which result in an isoform (3) with a shorter extracellular domain than isoform 1.

Source sequence(s)

AJ277141, AK125624, AK303990

UniProtKB/TrEMBL

B4E1U5

Conserved Domains (2) summary

pfam13927
Location:102 → 150

Ig_3; Immunoglobulin domain

cl11960
Location:3 → 78

Ig; Immunoglobulin domain
NM_001184716.2 → NP_001171645.1 SLAM family member 6 isoform 4 precursor

See identical proteins and their annotated locations for NP_001171645.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) lacks an alternate exon in the 5' coding region, compared to variant 1, which result in an isoform (4) with a shorter extracellular domain than isoform 1.

Source sequence(s)

AK125624, AK301026, AW402723, DB197632

Consensus CDS

CCDS53393.1

UniProtKB/Swiss-Prot

Q96DU3

Related

ENSP00000357034.1, ENST00000368055.1
NM_052931.5 → NP_443163.1 SLAM family member 6 isoform 2 precursor

See identical proteins and their annotated locations for NP_443163.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate splice site in the 3' coding region, compared to variant 1, which results in an isoform (2) that is one amino acid shorter than isoform 1.

Source sequence(s)

AK125624, BC113893, DB197632

Consensus CDS

CCDS1205.1

UniProtKB/TrEMBL

B4E1U5

Related

ENSP00000357038.3, ENST00000368059.7

Conserved Domains (3) summary

cd05775
Location:32 → 127

Ig_SLAM-CD84_like_N; N-terminal immunoglobulin (Ig)-like domain of the signaling lymphocyte activation molecule (SLAM) family, CD84_like

smart00410
Location:34 → 126

IG_like; Immunoglobulin like

pfam13927
Location:151 → 199

Ig_3; Immunoglobulin domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000001.11 Reference GRCh38.p14 Primary Assembly

Range

160485036..160523255 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017000216.2 → XP_016855705.1 SLAM family member 6 isoform X2

UniProtKB/TrEMBL

B4E1U5
XM_047443866.1 → XP_047299822.1 SLAM family member 6 isoform X1