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Protein

SLAM family member 6

Gene

Slamf6

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 (PubMed:19648922). Triggers cytolytic activity only in natural killer cells (NK) expressing high surface densities of natural cytotoxicity receptors (By similarity). Positive signaling in NK cells implicates phosphorylation of VAV1. NK cell activation seems to depend on SH2D1B and not on SH2D1A (By similarity). 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 (PubMed:18031695). Promotes T cell differentiation into a helper T-cell Th17 phenotype leading to increased IL-17 secretion; the costimulatory activity requires SH2D1A (By similarity). Promotes recruitment of RORC to the IL-17 promoter (By similarity). In conjunction with SLAMF1 and CD84/SLAMF5 may be a negative regulator of the humoral immune response (PubMed:25926831). 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 (PubMed:22683125). However, reported to mediated T-cell adhesion, to participate in stable T-cell:B-cell interactions and to be involved in maintaining B-cell tolerance in germinal centers and in preventing autoimmunity (PubMed:20153220, PubMed:25801429). Involved in regulation of autoimmunity. Isoform 3 may be suppressor of pathogenic T-cell proliferation (PubMed:21422172).By similarity6 Publications

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Adaptive immunity, Immunity, Innate immunity

Enzyme and pathway databases

ReactomeiR-MMU-198933. Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.

Names & Taxonomyi

Protein namesi
Recommended name:
SLAM family member 6
Alternative name(s):
Lymphocyte antigen 108
CD_antigen: CD352
Gene namesi
Name:Slamf6
Synonyms:Ly108
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:1353620. Slamf6.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini31 – 239209ExtracellularSequence analysisAdd
BLAST
Transmembranei240 – 26223HelicalSequence analysisAdd
BLAST
Topological domaini263 – 35189CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • extracellular exosome Source: MGI
  • integral component of plasma membrane Source: MGI
  • plasma membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi295 – 2951Y → F: Decreases inhibitory signaling in germinal center formation (absence of SH2D1A/SAP); when associated with F-319 and F-349. 1 Publication
Mutagenesisi295 – 2951Y → F: Strong inhibitory signaling in germinal center formation (absence of SH2D1A/SAP); when associated with F-335 and F-349. 1 Publication
Mutagenesisi319 – 3191Y → F: Decreases inhibitory signaling in germinal center formation (absence of SH2D1A/SAP); when associated with F-295 and F-349. 1 Publication
Mutagenesisi319 – 3191Y → F: Strong inhibitory signaling in germinal center formation (absence of SH2D1A/SAP); when associated with F-335 and F-349. 1 Publication
Mutagenesisi335 – 3351Y → F: Strong inhibitory signaling in germinal center formation (absence of SH2D1A/SAP); when associated with F-295 and F-349. 1 Publication
Mutagenesisi335 – 3351Y → F: Strong inhibitory signaling in germinal center formation (absence of SH2D1A/SAP); when associated with F-319 and F-349. 1 Publication
Mutagenesisi349 – 3491Y → F: Decreases inhibitory signaling in germinal center formation (absence of SH2D1A/SAP); when associated with F-295 and F-319. 1 Publication
Mutagenesisi349 – 3491Y → F: Strong inhibitory signaling in germinal center formation (absence of SH2D1A/SAP); when associated with F-295 and F-335. 1 Publication
Mutagenesisi349 – 3491Y → F: Strong inhibitory signaling in germinal center formation (absence of SH2D1A/SAP); when associated with F-319 and F-335. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3030Sequence analysisAdd
BLAST
Chaini31 – 351321SLAM family member 6PRO_0000014962Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi82 – 821N-linked (GlcNAc...)Sequence analysis
Glycosylationi101 – 1011N-linked (GlcNAc...)Sequence analysis
Glycosylationi112 – 1121N-linked (GlcNAc...)Sequence analysis
Glycosylationi152 – 1521N-linked (GlcNAc...)Sequence analysis
Glycosylationi159 – 1591N-linked (GlcNAc...)Sequence analysis
Disulfide bondi162 ↔ 229PROSITE-ProRule annotation
Disulfide bondi168 ↔ 210PROSITE-ProRule annotation
Glycosylationi172 – 1721N-linked (GlcNAc...)Sequence analysis
Glycosylationi186 – 1861N-linked (GlcNAc...)Sequence analysis
Glycosylationi193 – 1931N-linked (GlcNAc...)Sequence analysis
Glycosylationi218 – 2181N-linked (GlcNAc...)Sequence analysis
Modified residuei319 – 3191PhosphotyrosineBy similarity

Post-translational modificationi

Phosphorylated.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ9ET39.
MaxQBiQ9ET39.
PaxDbiQ9ET39.
PRIDEiQ9ET39.

PTM databases

iPTMnetiQ9ET39.
PhosphoSiteiQ9ET39.

Expressioni

Tissue specificityi

Expressed on hematopoietic cells. Isoform 3 is expressed in thymocytes and B lymphocytes of C57Bl/6 strain.1 Publication

Gene expression databases

BgeeiQ9ET39.
CleanExiMM_SLAMF6.
ExpressionAtlasiQ9ET39. baseline and differential.
GenevisibleiQ9ET39. MM.

Interactioni

Subunit structurei

Homodimer. Interacts with PTN6 and, upon phosphorylation, with PTN11 and SH2D1A/SAP (By similarity).By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000130610.

Structurei

3D structure databases

ProteinModelPortaliQ9ET39.
SMRiQ9ET39. Positions 39-230.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini36 – 13095Ig-like V-typeAdd
BLAST
Domaini147 – 21064Ig-like C2-typeAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi293 – 2986ITSM 1By similarity
Motifi317 – 3226ITSM 2By similarity

Domaini

The ITSMs (immunoreceptor tyrosine-based switch motifs) with the consensus sequence T-X-Y-X-X-[VI] present in SLAM family receptors have overlapping specificity for activating and inhibitory SH2 domain-containing binding partners. Especially they mediate the interaction with the SH2 domain of SH2D1A and SH2D1B. A 'two-out-of-three-pronged' mechanism is proposed involving threonine (position -2), phosphorylated tyrosine (position 0) and valine/isoleucine (position +3).By similarity

Sequence similaritiesi

Keywords - Domaini

Immunoglobulin domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IWNS. Eukaryota.
ENOG41116VD. LUCA.
GeneTreeiENSGT00530000063114.
HOGENOMiHOG000059581.
HOVERGENiHBG055054.
InParanoidiQ9ET39.
KOiK16852.
OMAiEIHLTCS.
OrthoDBiEOG77HDFC.
PhylomeDBiQ9ET39.
TreeFamiTF334964.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013106. Ig_V-set.
[Graphical view]
PfamiPF07686. V-set. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 1 hit.
PROSITEiPS50835. IG_LIKE. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9ET39-1) [UniParc]FASTAAdd to basket

Also known as: Ly108s

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAVSRAPAPD SACQRMVWLF PLVFCLGSGS EVSQSSSDPQ LMNGVLGESA
60 70 80 90 100
VLPLKLPAGK IANIIIWNYE WEASQVTALV INLSNPESPQ IMNTDVKKRL
110 120 130 140 150
NITQSYSLQI SNLTMADTGS YTAQITTKDS EVITFKYILR VFERLGNLET
160 170 180 190 200
TNYTLLLENG TCQIHLACVL KNQSQTVSVE WQATGNISLG GPNVTIFWDP
210 220 230 240 250
RNSGDQTYVC RAKNAVSNLS VSVSTQSLCK GVLTNPPWNA VWFMTTISII
260 270 280 290 300
SAVILIFVCW SIHVWKRRGS LPLTSQHPES SQSTDGPGSP GNTVYAQVTR
310 320 330 340 350
PMQEMKIPKP IKNDSMTIYS IVNHSREETV ALTGYNQPIT LKVNTLINYN

S
Length:351
Mass (Da):38,638
Last modified:March 1, 2001 - v1
Checksum:iA8DD9EBF650FB431
GO
Isoform 2 (identifier: Q9ET39-2) [UniParc]FASTAAdd to basket

Also known as: Ly108l

The sequence of this isoform differs from the canonical sequence as follows:
     328-331: ETVA → AEYS
     332-351: Missing.

Show »
Length:331
Mass (Da):36,440
Checksum:i7E1A056C8C0A716A
GO
Isoform 3 (identifier: Q9ET39-3) [UniParc]FASTAAdd to basket

Also known as: Ly108-H1

The sequence of this isoform differs from the canonical sequence as follows:
     305-328: Missing.

Note: Found in Slamf-haplotype 1 mice such as C557Bl/6 but not in Slamf-haplotype 2 strains including 129, Balb/c and NOD.1 Publication
Show »
Length:327
Mass (Da):35,825
Checksum:i75540AC056DF9EF8
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei305 – 32824Missing in isoform 3. 1 PublicationVSP_058034Add
BLAST
Alternative sequencei328 – 3314ETVA → AEYS in isoform 2. 1 PublicationVSP_010404
Alternative sequencei332 – 35120Missing in isoform 2. 1 PublicationVSP_010405Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF248635 mRNA. Translation: AAG01737.1.
AF248636 mRNA. Translation: AAG01738.1.
EU591721 mRNA. Translation: ACF05482.1.
AC091523 Genomic DNA. No translation available.
BC030031 mRNA. Translation: AAH30031.1.
CCDSiCCDS15504.1. [Q9ET39-2]
RefSeqiNP_109635.1. NM_030710.2. [Q9ET39-2]
XP_006496948.1. XM_006496885.2. [Q9ET39-1]
XP_006496950.1. XM_006496887.2. [Q9ET39-3]
UniGeneiMm.486404.

Genome annotation databases

EnsembliENSMUST00000171330; ENSMUSP00000130610; ENSMUSG00000015314. [Q9ET39-2]
ENSMUST00000194561; ENSMUSP00000141944; ENSMUSG00000015314. [Q9ET39-3]
ENSMUST00000195656; ENSMUSP00000141448; ENSMUSG00000015314. [Q9ET39-1]
GeneIDi30925.
KEGGimmu:30925.
UCSCiuc007dph.1. mouse. [Q9ET39-1]
uc011wwh.1. mouse.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF248635 mRNA. Translation: AAG01737.1.
AF248636 mRNA. Translation: AAG01738.1.
EU591721 mRNA. Translation: ACF05482.1.
AC091523 Genomic DNA. No translation available.
BC030031 mRNA. Translation: AAH30031.1.
CCDSiCCDS15504.1. [Q9ET39-2]
RefSeqiNP_109635.1. NM_030710.2. [Q9ET39-2]
XP_006496948.1. XM_006496885.2. [Q9ET39-1]
XP_006496950.1. XM_006496887.2. [Q9ET39-3]
UniGeneiMm.486404.

3D structure databases

ProteinModelPortaliQ9ET39.
SMRiQ9ET39. Positions 39-230.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000130610.

PTM databases

iPTMnetiQ9ET39.
PhosphoSiteiQ9ET39.

Proteomic databases

EPDiQ9ET39.
MaxQBiQ9ET39.
PaxDbiQ9ET39.
PRIDEiQ9ET39.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000171330; ENSMUSP00000130610; ENSMUSG00000015314. [Q9ET39-2]
ENSMUST00000194561; ENSMUSP00000141944; ENSMUSG00000015314. [Q9ET39-3]
ENSMUST00000195656; ENSMUSP00000141448; ENSMUSG00000015314. [Q9ET39-1]
GeneIDi30925.
KEGGimmu:30925.
UCSCiuc007dph.1. mouse. [Q9ET39-1]
uc011wwh.1. mouse.

Organism-specific databases

CTDi114836.
MGIiMGI:1353620. Slamf6.

Phylogenomic databases

eggNOGiENOG410IWNS. Eukaryota.
ENOG41116VD. LUCA.
GeneTreeiENSGT00530000063114.
HOGENOMiHOG000059581.
HOVERGENiHBG055054.
InParanoidiQ9ET39.
KOiK16852.
OMAiEIHLTCS.
OrthoDBiEOG77HDFC.
PhylomeDBiQ9ET39.
TreeFamiTF334964.

Enzyme and pathway databases

ReactomeiR-MMU-198933. Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.

Miscellaneous databases

PROiQ9ET39.
SOURCEiSearch...

Gene expression databases

BgeeiQ9ET39.
CleanExiMM_SLAMF6.
ExpressionAtlasiQ9ET39. baseline and differential.
GenevisibleiQ9ET39. MM.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013106. Ig_V-set.
[Graphical view]
PfamiPF07686. V-set. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 1 hit.
PROSITEiPS50835. IG_LIKE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Ly108: a new member of the mouse CD2 family of cell surface proteins."
    Peck S.R., Ruley H.E.
    Immunogenetics 52:63-72(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
    Strain: C57BL/6J.
    Tissue: Spleen.
  2. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, ALTERNATIVE SPLICING, TISSUE SPECIFICITY, INVOLVEMENT IN SYSTEMIC LUPUS ERYTHEMATOSUS.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Thymus.
  5. "Homotypic interactions mediated by Slamf1 and Slamf6 receptors control NKT cell lineage development."
    Griewank K., Borowski C., Rietdijk S., Wang N., Julien A., Wei D.G., Mamchak A.A., Terhorst C., Bendelac A.
    Immunity 27:751-762(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  6. "Essential function for SAP family adaptors in the surveillance of hematopoietic cells by natural killer cells."
    Dong Z., Cruz-Munoz M.E., Zhong M.C., Chen R., Latour S., Veillette A.
    Nat. Immunol. 10:973-980(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  7. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Lung.
  8. "Optimal germinal center responses require a multistage T cell:B cell adhesion process involving integrins, SLAM-associated protein, and CD84."
    Cannons J.L., Qi H., Lu K.T., Dutta M., Gomez-Rodriguez J., Cheng J., Wakeland E.K., Germain R.N., Schwartzberg P.L.
    Immunity 32:253-265(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  9. "The receptor Ly108 functions as a SAP adaptor-dependent on-off switch for T cell help to B cells and NKT cell development."
    Kageyama R., Cannons J.L., Zhao F., Yusuf I., Lao C., Locci M., Schwartzberg P.L., Crotty S.
    Immunity 36:986-1002(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, MUTAGENESIS OF TYR-295; TYR-319; TYR-335 AND TYR-349.
  10. "Negative regulation of humoral immunity due to interplay between the SLAMF1, SLAMF5, and SLAMF6 receptors."
    Wang N., Halibozek P.J., Yigit B., Zhao H., O'Keeffe M.S., Sage P., Sharpe A., Terhorst C.
    Front. Immunol. 6:158-158(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  11. Cited for: FUNCTION.

Entry informationi

Entry nameiSLAF6_MOUSE
AccessioniPrimary (citable) accession number: Q9ET39
Secondary accession number(s): C6ESQ1, Q9ET40
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 24, 2004
Last sequence update: March 1, 2001
Last modified: June 8, 2016
This is version 125 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Isoform 3 ameliorates spontaneous development in a systemic lupus erythematosus transfer model.1 Publication

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.