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Protein

SLAM family member 6

Gene

SLAMF6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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. 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).By similarity4 Publications

GO - Biological processi

Keywordsi

Molecular functionReceptor
Biological processAdaptive immunity, Immunity, Innate immunity

Enzyme and pathway databases

ReactomeiR-HSA-198933 Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell

Names & Taxonomyi

Protein namesi
Recommended name:
SLAM family member 6
Alternative name(s):
Activating NK receptor
NK-T-B-antigen
Short name:
NTB-A
CD_antigen: CD352
Gene namesi
Name:SLAMF6
Synonyms:KALI
ORF Names:UNQ6123/PRO20080
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000162739.13
HGNCiHGNC:21392 SLAMF6
MIMi606446 gene
neXtProtiNX_Q96DU3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini22 – 226ExtracellularSequence analysisAdd BLAST205
Transmembranei227 – 247HelicalSequence analysisAdd BLAST21
Topological domaini248 – 331CytoplasmicSequence analysisAdd BLAST84

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi108R → A: Inhibits dimerization. 1 Publication1
Mutagenesisi110Q → A: Inhibits dimerization. 1 Publication1
Mutagenesisi112S → A: Inhibits dimerization. 1 Publication1
Mutagenesisi274Y → F: Retains reduced SLAMF6-mediated cytotoxity, disrupts interaction with SH2D1A and retains interaction with SH2D1B; when associated with F-309. 1 Publication1
Mutagenesisi285Y → F: Abolishes SLAMF6-mediated cytotoxity, disrupts interaction with SH2D1B and retains interaction with SH2D1A. 1 Publication1
Mutagenesisi309Y → F: Reduced SLAMF6-mediated cytotoxity. 1 Publication1
Mutagenesisi309Y → F: Retains reduced SLAMF6-mediated cytotoxity, disrupts interaction with SH2D1A and retains interaction with SH2D1B; when associated with F-273. 1 Publication1

Organism-specific databases

DisGeNETi114836
OpenTargetsiENSG00000162739
PharmGKBiPA134959277

Polymorphism and mutation databases

BioMutaiSLAMF6
DMDMi205830927

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 211 PublicationAdd BLAST21
ChainiPRO_000001496122 – 332SLAM family member 6Add BLAST311

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi58N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi87N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi137N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi144N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi147 ↔ 214PROSITE-ProRule annotation1 Publication
Disulfide bondi153 ↔ 195PROSITE-ProRule annotation1 Publication
Glycosylationi161N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi178N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi203N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei274PhosphotyrosineCombined sources1
Modified residuei278PhosphoserineCombined sources1
Modified residuei309PhosphotyrosineCombined sources1

Post-translational modificationi

Phosphorylation in NK cells upon engagment by SLAMF6-expressing target cells is leading to receptor activation.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ96DU3
PaxDbiQ96DU3
PeptideAtlasiQ96DU3
PRIDEiQ96DU3
ProteomicsDBi76325
76326 [Q96DU3-2]
76327 [Q96DU3-3]

PTM databases

iPTMnetiQ96DU3
PhosphoSitePlusiQ96DU3

Expressioni

Tissue specificityi

Expressed by all (resting and activated) natural killer cells (NK), T- and B-lymphocytes (PubMed:11489943). Increased surface expression on T-cells of systemic lupus erythematosus (SLE) patients (PubMed:22184727).2 Publications

Gene expression databases

BgeeiENSG00000162739 Expressed in 99 organ(s), highest expression level in leukocyte
CleanExiHS_SLAMF6
GenevisibleiQ96DU3 HS

Organism-specific databases

HPAiHPA051363
HPA051903

Interactioni

Subunit structurei

Homodimer. Interacts with PTN6. Interacts (phosphorylated) with PTN11. Interacts (phosphorylated on tyrosine residues) with SH2D1A/SAP and SH2D1B/EAT2; SH2D1A and SH2D1B can associate with the same SLAMF6 molecule; interaction with SH2D1B is mediated by ITSM 2.3 Publications

Binary interactionsi

Protein-protein interaction databases

BioGridi125378, 3 interactors
IntActiQ96DU3, 12 interactors
STRINGi9606.ENSP00000357036

Structurei

Secondary structure

1332
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ96DU3
SMRiQ96DU3
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ96DU3

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini35 – 120Ig-like V-typeAdd BLAST86
Domaini132 – 209Ig-like C2-typeAdd BLAST78

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi283 – 288ITSM 1By similarity6
Motifi307 – 312ITSM 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-containingbinding partners. Especially they mediate the 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

Keywords - Domaini

Immunoglobulin domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IWNS Eukaryota
ENOG41116VD LUCA
GeneTreeiENSGT00530000063114
HOGENOMiHOG000059581
HOVERGENiHBG055054
InParanoidiQ96DU3
KOiK16852
OMAiCEIHLTC
OrthoDBiEOG091G0KKU
PhylomeDBiQ96DU3
TreeFamiTF334964

Family and domain databases

Gene3Di2.60.40.10, 2 hits
InterProiView protein in InterPro
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR003599 Ig_sub
IPR013106 Ig_V-set
PfamiView protein in Pfam
PF07686 V-set, 1 hit
SMARTiView protein in SMART
SM00409 IG, 1 hit
SUPFAMiSSF48726 SSF48726, 2 hits
PROSITEiView protein in PROSITE
PS50835 IG_LIKE, 1 hit

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: Q96DU3-1) [UniParc]FASTAAdd to basket

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
MLWLFQSLLF VFCFGPGNVV SQSSLTPLMV NGILGESVTL PLEFPAGEKV
60 70 80 90 100
NFITWLFNET SLAFIVPHET KSPEIHVTNP KQGKRLNFTQ SYSLQLSNLK
110 120 130 140 150
MEDTGSYRAQ ISTKTSAKLS SYTLRILRQL RNIQVTNHSQ LFQNMTCELH
160 170 180 190 200
LTCSVEDADD NVSFRWEALG NTLSSQPNLT VSWDPRISSE QDYTCIAENA
210 220 230 240 250
VSNLSFSVSA QKLCEDVKIQ YTDTKMILFM VSGICIVFGF IILLLLVLRK
260 270 280 290 300
RRDSLSLSTQ RTQGPAESAR NLEYVSVSPT NNTVYASVTH SNRETEIWTP
310 320 330
RENDTITIYS TINHSKESKP TFSRATALDN VV
Length:332
Mass (Da):37,345
Last modified:July 22, 2008 - v3
Checksum:i46D8141A0D198091
GO
Isoform 2 (identifier: Q96DU3-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     266-266: Missing.

Show »
Length:331
Mass (Da):37,274
Checksum:i16E2727CEF8306F4
GO
Isoform 3 (identifier: Q96DU3-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     18-128: Missing.

Note: No experimental confirmation available.
Show »
Length:221
Mass (Da):24,976
Checksum:i71CACAED7B8FDDEC
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04323018 – 128Missing in isoform 3. 1 PublicationAdd BLAST111
Alternative sequenceiVSP_034620266Missing in isoform 2. 3 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ277141 mRNA Translation: CAC59749.1
AJ306388 mRNA Translation: CAC59750.1
AY358159 mRNA Translation: AAQ88526.1
AL832854 mRNA Translation: CAI46161.1
AK125624 mRNA Translation: BAG54223.1
AK301026 mRNA Translation: BAG62642.1
AK313549 mRNA Translation: BAG36325.1
AL138930 Genomic DNA No translation available.
CH471121 Genomic DNA Translation: EAW52713.1
CH471121 Genomic DNA Translation: EAW52715.1
BC113893 mRNA Translation: AAI13894.1
BC114495 mRNA Translation: AAI14496.1
CCDSiCCDS1205.1 [Q96DU3-2]
CCDS53393.1 [Q96DU3-3]
CCDS53394.1 [Q96DU3-1]
RefSeqiNP_001171643.1, NM_001184714.1 [Q96DU3-1]
NP_001171644.1, NM_001184715.1
NP_001171645.1, NM_001184716.1 [Q96DU3-3]
NP_443163.1, NM_052931.4 [Q96DU3-2]
UniGeneiHs.492348

Genome annotation databases

EnsembliENST00000368055; ENSP00000357034; ENSG00000162739 [Q96DU3-3]
ENST00000368057; ENSP00000357036; ENSG00000162739 [Q96DU3-1]
ENST00000368059; ENSP00000357038; ENSG00000162739 [Q96DU3-2]
GeneIDi114836
KEGGihsa:114836
UCSCiuc001fwd.2 human [Q96DU3-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ277141 mRNA Translation: CAC59749.1
AJ306388 mRNA Translation: CAC59750.1
AY358159 mRNA Translation: AAQ88526.1
AL832854 mRNA Translation: CAI46161.1
AK125624 mRNA Translation: BAG54223.1
AK301026 mRNA Translation: BAG62642.1
AK313549 mRNA Translation: BAG36325.1
AL138930 Genomic DNA No translation available.
CH471121 Genomic DNA Translation: EAW52713.1
CH471121 Genomic DNA Translation: EAW52715.1
BC113893 mRNA Translation: AAI13894.1
BC114495 mRNA Translation: AAI14496.1
CCDSiCCDS1205.1 [Q96DU3-2]
CCDS53393.1 [Q96DU3-3]
CCDS53394.1 [Q96DU3-1]
RefSeqiNP_001171643.1, NM_001184714.1 [Q96DU3-1]
NP_001171644.1, NM_001184715.1
NP_001171645.1, NM_001184716.1 [Q96DU3-3]
NP_443163.1, NM_052931.4 [Q96DU3-2]
UniGeneiHs.492348

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2IF7X-ray3.00A/B/C/D24-215[»]
ProteinModelPortaliQ96DU3
SMRiQ96DU3
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi125378, 3 interactors
IntActiQ96DU3, 12 interactors
STRINGi9606.ENSP00000357036

PTM databases

iPTMnetiQ96DU3
PhosphoSitePlusiQ96DU3

Polymorphism and mutation databases

BioMutaiSLAMF6
DMDMi205830927

Proteomic databases

MaxQBiQ96DU3
PaxDbiQ96DU3
PeptideAtlasiQ96DU3
PRIDEiQ96DU3
ProteomicsDBi76325
76326 [Q96DU3-2]
76327 [Q96DU3-3]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000368055; ENSP00000357034; ENSG00000162739 [Q96DU3-3]
ENST00000368057; ENSP00000357036; ENSG00000162739 [Q96DU3-1]
ENST00000368059; ENSP00000357038; ENSG00000162739 [Q96DU3-2]
GeneIDi114836
KEGGihsa:114836
UCSCiuc001fwd.2 human [Q96DU3-1]

Organism-specific databases

CTDi114836
DisGeNETi114836
EuPathDBiHostDB:ENSG00000162739.13
GeneCardsiSLAMF6
HGNCiHGNC:21392 SLAMF6
HPAiHPA051363
HPA051903
MIMi606446 gene
neXtProtiNX_Q96DU3
OpenTargetsiENSG00000162739
PharmGKBiPA134959277
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IWNS Eukaryota
ENOG41116VD LUCA
GeneTreeiENSGT00530000063114
HOGENOMiHOG000059581
HOVERGENiHBG055054
InParanoidiQ96DU3
KOiK16852
OMAiCEIHLTC
OrthoDBiEOG091G0KKU
PhylomeDBiQ96DU3
TreeFamiTF334964

Enzyme and pathway databases

ReactomeiR-HSA-198933 Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell

Miscellaneous databases

EvolutionaryTraceiQ96DU3
GeneWikiiSLAMF6
GenomeRNAii114836
PROiPR:Q96DU3
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000162739 Expressed in 99 organ(s), highest expression level in leukocyte
CleanExiHS_SLAMF6
GenevisibleiQ96DU3 HS

Family and domain databases

Gene3Di2.60.40.10, 2 hits
InterProiView protein in InterPro
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR003599 Ig_sub
IPR013106 Ig_V-set
PfamiView protein in Pfam
PF07686 V-set, 1 hit
SMARTiView protein in SMART
SM00409 IG, 1 hit
SUPFAMiSSF48726 SSF48726, 2 hits
PROSITEiView protein in PROSITE
PS50835 IG_LIKE, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiSLAF6_HUMAN
AccessioniPrimary (citable) accession number: Q96DU3
Secondary accession number(s): A6NMW2
, B2R8X8, Q14CF0, Q5TAS4, Q5TAS6, Q5TAT3, Q96DV0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 24, 2004
Last sequence update: July 22, 2008
Last modified: October 10, 2018
This is version 154 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
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