Q96DU3 · SLAF6_HUMAN
- ProteinSLAM family member 6
- GeneSLAMF6
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids332 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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:16920955, PubMed:22184727).
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).
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:16920955, PubMed:22184727).
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).
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | external side of plasma membrane | |
Cellular Component | extracellular exosome | |
Cellular Component | plasma membrane | |
Biological Process | innate immune response | |
Biological Process | positive regulation of interleukin-17 production | |
Biological Process | positive regulation of natural killer cell mediated cytotoxicity | |
Biological Process | positive regulation of type II interferon production | |
Biological Process | T cell activation | |
Biological Process | T-helper 17 cell lineage commitment |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameSLAM family member 6
- Alternative names
- CD Antigen Name
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ96DU3
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Single-pass type I membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 22-226 | Extracellular | ||||
Sequence: QSSLTPLMVNGILGESVTLPLEFPAGEKVNFITWLFNETSLAFIVPHETKSPEIHVTNPKQGKRLNFTQSYSLQLSNLKMEDTGSYRAQISTKTSAKLSSYTLRILRQLRNIQVTNHSQLFQNMTCELHLTCSVEDADDNVSFRWEALGNTLSSQPNLTVSWDPRISSEQDYTCIAENAVSNLSFSVSAQKLCEDVKIQYTDTKM | ||||||
Transmembrane | 227-247 | Helical | ||||
Sequence: ILFMVSGICIVFGFIILLLLV | ||||||
Topological domain | 248-331 | Cytoplasmic | ||||
Sequence: LRKRRDSLSLSTQRTQGPAESARNLEYVSVSPTNNTVYASVTHSNRETEIWTPRENDTITIYSTINHSKESKPTFSRATALDNV |
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 108 | Inhibits dimerization. | ||||
Sequence: R → A | ||||||
Mutagenesis | 110 | Inhibits dimerization. | ||||
Sequence: Q → A | ||||||
Mutagenesis | 112 | Inhibits dimerization. | ||||
Sequence: S → A | ||||||
Mutagenesis | 274 | Retains reduced SLAMF6-mediated cytotoxity, disrupts interaction with SH2D1A and retains interaction with SH2D1B; when associated with F-309. | ||||
Sequence: Y → F | ||||||
Mutagenesis | 285 | Abolishes SLAMF6-mediated cytotoxity, disrupts interaction with SH2D1B and retains interaction with SH2D1A. | ||||
Sequence: Y → F | ||||||
Mutagenesis | 309 | Reduced SLAMF6-mediated cytotoxity. | ||||
Sequence: Y → F | ||||||
Mutagenesis | 309 | Retains reduced SLAMF6-mediated cytotoxity, disrupts interaction with SH2D1A and retains interaction with SH2D1B; when associated with F-273. | ||||
Sequence: Y → F |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 373 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for signal, chain, glycosylation, disulfide bond, modified residue, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Signal | 1-21 | UniProt | |||||
Sequence: MLWLFQSLLFVFCFGPGNVVS | |||||||
Chain | PRO_0000014961 | 22-332 | UniProt | SLAM family member 6 | |||
Sequence: QSSLTPLMVNGILGESVTLPLEFPAGEKVNFITWLFNETSLAFIVPHETKSPEIHVTNPKQGKRLNFTQSYSLQLSNLKMEDTGSYRAQISTKTSAKLSSYTLRILRQLRNIQVTNHSQLFQNMTCELHLTCSVEDADDNVSFRWEALGNTLSSQPNLTVSWDPRISSEQDYTCIAENAVSNLSFSVSAQKLCEDVKIQYTDTKMILFMVSGICIVFGFIILLLLVLRKRRDSLSLSTQRTQGPAESARNLEYVSVSPTNNTVYASVTHSNRETEIWTPRENDTITIYSTINHSKESKPTFSRATALDNVV | |||||||
Glycosylation | 58 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Glycosylation | 87 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Glycosylation | 137 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Glycosylation | 144 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Disulfide bond | 147↔214 | UniProt | |||||
Sequence: CELHLTCSVEDADDNVSFRWEALGNTLSSQPNLTVSWDPRISSEQDYTCIAENAVSNLSFSVSAQKLC | |||||||
Disulfide bond | 153↔195 | UniProt | |||||
Sequence: CSVEDADDNVSFRWEALGNTLSSQPNLTVSWDPRISSEQDYTC | |||||||
Glycosylation | 161 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Glycosylation | 178 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Glycosylation | 203 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Modified residue | 274 | UniProt | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 274 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 278 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 278 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 283 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 285 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 289 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 309 | UniProt | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 309 | PRIDE | Phosphotyrosine | ||||
Sequence: Y |
Post-translational modification
Phosphorylation in NK cells upon engagment by SLAMF6-expressing target cells is leading to receptor activation.
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
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.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q96DU3 | BRICD5 Q6PL45-2 | 3 | EBI-14058448, EBI-12244618 | |
BINARY | Q96DU3 | CLDN19 Q8N6F1-2 | 3 | EBI-14058448, EBI-12256978 | |
BINARY | Q96DU3 | JAGN1 Q8N5M9 | 3 | EBI-14058448, EBI-10266796 | |
BINARY | Q96DU3 | RABAC1 Q9UI14 | 3 | EBI-14058448, EBI-712367 | |
BINARY | Q96DU3 | SH2D1A O60880 | 12 | EBI-14058448, EBI-6983382 | |
BINARY | Q96DU3 | SH2D1B O14796 | 4 | EBI-14058448, EBI-3923013 | |
BINARY | Q96DU3 | TMBIM6 P55061 | 3 | EBI-14058448, EBI-1045825 | |
BINARY | Q96DU3 | TMPPE Q6ZT21 | 3 | EBI-14058448, EBI-11724433 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 35-120 | Ig-like V-type | ||||
Sequence: GESVTLPLEFPAGEKVNFITWLFNETSLAFIVPHETKSPEIHVTNPKQGKRLNFTQSYSLQLSNLKMEDTGSYRAQISTKTSAKLS | ||||||
Domain | 132-209 | Ig-like C2-type | ||||
Sequence: NIQVTNHSQLFQNMTCELHLTCSVEDADDNVSFRWEALGNTLSSQPNLTVSWDPRISSEQDYTCIAENAVSNLSFSVS | ||||||
Motif | 283-288 | ITSM 1 | ||||
Sequence: TVYASV | ||||||
Motif | 307-312 | ITSM 2 | ||||
Sequence: TIYSTI |
Domain
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).
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
This entry describes 3 isoforms produced by Alternative splicing.
Q96DU3-1
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.
- Name1
- Length332
- Mass (Da)37,345
- Last updated2008-07-22 v3
- Checksum46D8141A0D198091
Q96DU3-2
- Name2
- Differences from canonical
- 266-266: Missing
Q96DU3-3
- Name3
- Differences from canonical
- 18-128: Missing
Features
Showing features for alternative sequence.
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AJ277141 EMBL· GenBank· DDBJ | CAC59749.1 EMBL· GenBank· DDBJ | mRNA | ||
AJ306388 EMBL· GenBank· DDBJ | CAC59750.1 EMBL· GenBank· DDBJ | mRNA | ||
AY358159 EMBL· GenBank· DDBJ | AAQ88526.1 EMBL· GenBank· DDBJ | mRNA | ||
AL832854 EMBL· GenBank· DDBJ | CAI46161.1 EMBL· GenBank· DDBJ | mRNA | ||
AK125624 EMBL· GenBank· DDBJ | BAG54223.1 EMBL· GenBank· DDBJ | mRNA | ||
AK301026 EMBL· GenBank· DDBJ | BAG62642.1 EMBL· GenBank· DDBJ | mRNA | ||
AK313549 EMBL· GenBank· DDBJ | BAG36325.1 EMBL· GenBank· DDBJ | mRNA | ||
AL138930 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471121 EMBL· GenBank· DDBJ | EAW52713.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471121 EMBL· GenBank· DDBJ | EAW52715.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC113893 EMBL· GenBank· DDBJ | AAI13894.1 EMBL· GenBank· DDBJ | mRNA | ||
BC114495 EMBL· GenBank· DDBJ | AAI14496.1 EMBL· GenBank· DDBJ | mRNA |