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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)DescriptionActionsGraphical viewLength
Topological domaini31 – 239ExtracellularSequence analysisAdd BLAST209
Transmembranei240 – 262HelicalSequence analysisAdd BLAST23
Topological domaini263 – 351CytoplasmicSequence analysisAdd BLAST89

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)DescriptionActionsGraphical viewLength
Mutagenesisi295Y → F: Decreases inhibitory signaling in germinal center formation (absence of SH2D1A/SAP); when associated with F-319 and F-349. 1 Publication1
Mutagenesisi295Y → F: Strong inhibitory signaling in germinal center formation (absence of SH2D1A/SAP); when associated with F-335 and F-349. 1 Publication1
Mutagenesisi319Y → F: Decreases inhibitory signaling in germinal center formation (absence of SH2D1A/SAP); when associated with F-295 and F-349. 1 Publication1
Mutagenesisi319Y → F: Strong inhibitory signaling in germinal center formation (absence of SH2D1A/SAP); when associated with F-335 and F-349. 1 Publication1
Mutagenesisi335Y → F: Strong inhibitory signaling in germinal center formation (absence of SH2D1A/SAP); when associated with F-295 and F-349. 1 Publication1
Mutagenesisi335Y → F: Strong inhibitory signaling in germinal center formation (absence of SH2D1A/SAP); when associated with F-319 and F-349. 1 Publication1
Mutagenesisi349Y → F: Decreases inhibitory signaling in germinal center formation (absence of SH2D1A/SAP); when associated with F-295 and F-319. 1 Publication1
Mutagenesisi349Y → F: Strong inhibitory signaling in germinal center formation (absence of SH2D1A/SAP); when associated with F-295 and F-335. 1 Publication1
Mutagenesisi349Y → F: Strong inhibitory signaling in germinal center formation (absence of SH2D1A/SAP); when associated with F-319 and F-335. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 30Sequence analysisAdd BLAST30
ChainiPRO_000001496231 – 351SLAM family member 6Add BLAST321

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi82N-linked (GlcNAc...)Sequence analysis1
Glycosylationi101N-linked (GlcNAc...)Sequence analysis1
Glycosylationi112N-linked (GlcNAc...)Sequence analysis1
Glycosylationi152N-linked (GlcNAc...)Sequence analysis1
Glycosylationi159N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi162 ↔ 229PROSITE-ProRule annotation
Disulfide bondi168 ↔ 210PROSITE-ProRule annotation
Glycosylationi172N-linked (GlcNAc...)Sequence analysis1
Glycosylationi186N-linked (GlcNAc...)Sequence analysis1
Glycosylationi193N-linked (GlcNAc...)Sequence analysis1
Glycosylationi218N-linked (GlcNAc...)Sequence analysis1
Modified residuei319PhosphotyrosineBy similarity1

Post-translational modificationi

Phosphorylated.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ9ET39.
PaxDbiQ9ET39.
PRIDEiQ9ET39.

PTM databases

iPTMnetiQ9ET39.
PhosphoSitePlusiQ9ET39.

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

BgeeiENSMUSG00000015314.
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.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini36 – 130Ig-like V-typeAdd BLAST95
Domaini147 – 210Ig-like C2-typeAdd BLAST64

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi293 – 298ITSM 1By similarity6
Motifi317 – 322ITSM 2By similarity6

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.
OrthoDBiEOG091G0KKU.
PhylomeDBiQ9ET39.
TreeFamiTF334964.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
[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)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_058034305 – 328Missing in isoform 3. 1 PublicationAdd BLAST24
Alternative sequenceiVSP_010404328 – 331ETVA → AEYS in isoform 2. 1 Publication4
Alternative sequenceiVSP_010405332 – 351Missing in isoform 2. 1 PublicationAdd BLAST20

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_006496885.3. [Q9ET39-1]
XP_006496950.1. XM_006496887.3. [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_006496885.3. [Q9ET39-1]
XP_006496950.1. XM_006496887.3. [Q9ET39-3]
UniGeneiMm.486404.

3D structure databases

ProteinModelPortaliQ9ET39.
SMRiQ9ET39.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000130610.

PTM databases

iPTMnetiQ9ET39.
PhosphoSitePlusiQ9ET39.

Proteomic databases

EPDiQ9ET39.
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.
OrthoDBiEOG091G0KKU.
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

BgeeiENSMUSG00000015314.
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.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 1 hit.
PROSITEiPS50835. IG_LIKE. 1 hit.
[Graphical view]
ProtoNetiSearch...

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: November 30, 2016
This is version 129 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.