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

    Gene ID: 114836, updated on 2-Nov-2024

    Summary

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    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

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    See SLAMF6 in Genome Data Viewer
    Location:
    1q23.2-q23.3
    Exon count:
    9
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (160485036..160523255, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (159622119..159660340, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (160454826..160493045, complement)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105371466 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:160379091-160379966 Neighboring gene Sharpr-MPRA regulatory region 8449 Neighboring gene VANGL planar cell polarity protein 2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1923 Neighboring gene uncharacterized LOC105371467 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1924 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1925 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1926 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1927 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1928 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr1:160460168-160461367 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1929 Neighboring gene uncharacterized LOC105371468 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1930 Neighboring gene Sharpr-MPRA regulatory region 7182 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1931 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1461 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1932 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1933 Neighboring gene CD84 molecule Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1934 Neighboring gene NANOG hESC enhancer GRCh37_chr1:160567464-160567965 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1935 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1936 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1937 Neighboring gene signaling lymphocytic activation molecule family member 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1938 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1939 Neighboring gene uncharacterized LOC107985220

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues 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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    Related articles in PubMed

    1. SLAMF6 is associated with the susceptibility and severity of rheumatoid arthritis in the Chinese population. Xia G, et al. J Orthop Surg Res, 2022 Jan 11. PMID 35016729, Free PMC Article
    2. Natural killer-like function of activated T lymphocytes: differential blocking effects of monoclonal antibodies specific for a 90-kDa clonotypic structure. Hercend T, et al. Cell Immunol, 1984 Jul. PMID 6610481
    3. A novel complex, p40/42, is constitutively associated with the B cell antigen receptor and phosphorylated upon receptor stimulation. Lee YJ, et al. J Immunol, 1996 Nov 1. PMID 8892612
    4. NTB-A, a new activating receptor in T cells that regulates autoimmune disease. Valdez PA, et al. J Biol Chem, 2004 Apr 30. PMID 14988414
    5. NTB-A receptor crystal structure: insights into homophilic interactions in the signaling lymphocytic activation molecule receptor family. Cao E, et al. Immunity, 2006 Oct. PMID 17045824

    See all (58) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. 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.
    2. 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.
    3. 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.
    4. 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.
    5. 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.
    6. 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.
    7. 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.
    8. 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.
    9. 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.
    10. 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

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    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

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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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

    Homology

    Clone Names

    • FLJ50657, MGC104953

    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 IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in immune response IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    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 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 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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    NEW Try the new Transcript table

    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)

    1. 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

    2. 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

    3. 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

    4. 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_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      160485036..160523255 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

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

      UniProtKB/TrEMBL
      B4E1U5

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

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      159622119..159660340 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054334140.1 → XP_054190115.1  SLAM family member 6 isoform X2

    2. XM_054334139.1 → XP_054190114.1  SLAM family member 6 isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q96DU3.3 GenPept UniProtKB/Swiss-Prot:Q96DU3

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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