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Protein

SLAM family member 7

Gene

SLAMF7

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. Isoform 1 mediates NK cell activation through a SH2D1A-independent extracellular signal-regulated ERK-mediated pathway (PubMed:11698418). Positively regulates NK cell functions by a mechanism dependent on phosphorylated SH2D1B. Downstream signaling implicates PLCG1, PLCG2 and PI3K (PubMed:16339536). In addition to heterotypic NK cells-target cells interactions also homotypic interactions between NK cells may contribute to activation. However, in the absence of SH2D1B, inhibits NK cell function. Acts also inhibitory in T-cells (By similarity). May play a role in lymphocyte adhesion (PubMed:11802771). In LPS-activated monocytes negatively regulates production of proinflammatory cytokines (PubMed:23695528).By similarity5 Publications
Isoform 3 does not mediate any NK cell activation.

Miscellaneous

Proposed to be involved in systemic lupus erythematosus (SLE) disease process.1 Publication

Caution

GO - Molecular functioni

  • identical protein binding Source: IntAct

GO - Biological processi

  • adaptive immune response Source: UniProtKB-KW
  • cell adhesion Source: UniProtKB
  • natural killer cell activation Source: UniProtKB
  • natural killer cell mediated cytotoxicity Source: UniProtKB
  • regulation of immune response Source: Reactome

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 7
Alternative name(s):
CD2 subset 1
CD2-like receptor-activating cytotoxic cells
Short name:
CRACC
Membrane protein FOAP-12
Novel Ly9
Protein 19A
CD_antigen: CD319
Gene namesi
Name:SLAMF7
Synonyms:CS1
ORF Names:UNQ576/PRO1138
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000026751.16
HGNCiHGNC:21394 SLAMF7
MIMi606625 gene
neXtProtiNX_Q9NQ25

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 domaini23 – 226ExtracellularSequence analysisAdd BLAST204
Transmembranei227 – 247HelicalSequence analysisAdd BLAST21
Topological domaini248 – 335CytoplasmicSequence analysisAdd BLAST88

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi57823
OpenTargetsiENSG00000026751
PharmGKBiPA134977110

Chemistry databases

ChEMBLiCHEMBL3559386
DrugBankiDB06317 Elotuzumab
GuidetoPHARMACOLOGYi2850

Polymorphism and mutation databases

DMDMi66774034

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 221 PublicationAdd BLAST22
ChainiPRO_000001496323 – 335SLAM family member 7Add BLAST313

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi98N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi142N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi145 ↔ 215PROSITE-ProRule annotation
Glycosylationi148N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi151 ↔ 195PROSITE-ProRule annotation
Glycosylationi172N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi176N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi204N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiQ9NQ25
PaxDbiQ9NQ25
PeptideAtlasiQ9NQ25
PRIDEiQ9NQ25
TopDownProteomicsiQ9NQ25-2 [Q9NQ25-2]

PTM databases

iPTMnetiQ9NQ25
PhosphoSitePlusiQ9NQ25

Expressioni

Tissue specificityi

Expressed in spleen, lymph node, peripheral blood leukocytes, bone marrow, small intestine, stomach, appendix, lung and trachea. Expression was detected in NK cells, activated B-cells, NK-cell line but not in promyelocytic, B-, or T-cell lines. Expressed in monocytes. Isoform 3 is expressed at much lower level than isoform 1.5 Publications

Gene expression databases

BgeeiENSG00000026751
CleanExiHS_SLAMF7
ExpressionAtlasiQ9NQ25 baseline and differential
GenevisibleiQ9NQ25 HS

Organism-specific databases

HPAiCAB015445
HPA055945
HPA061654

Interactioni

Subunit structurei

Isoform 1 binds to SH2D1A when its cytoplasmic tail is phosphorylated in the presence of FYN (in vitro); low affinity binding, the physiological relevance of the interaction is questioned. Interacts with SH2D1B; in NK cells (PubMed:16339536). Interacts (via ITSM phosphorylated on Tyr-302) with SH2D1B, PTPN6/SHP-1, PTPN11/SHP-2, INPP5D/SHIP1, CSK and FYN (By similarity).By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself2EBI-3916159,EBI-3916159

GO - Molecular functioni

  • identical protein binding Source: IntAct

Protein-protein interaction databases

BioGridi12178216 interactors.
ELMiQ9NQ25
IntActiQ9NQ25 6 interactors.
STRINGi9606.ENSP00000357022

Structurei

3D structure databases

ProteinModelPortaliQ9NQ25
SMRiQ9NQ25
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini23 – 124Ig-like V-typeAdd BLAST102
Domaini131 – 206Ig-like C2-typeAdd BLAST76

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni278 – 296Interaction with FYN when phosphorylated at Tyr-284By similarityAdd BLAST19

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi302 – 307ITSMBy 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 '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

eggNOGiENOG410IJW6 Eukaryota
ENOG41117FX LUCA
GeneTreeiENSGT00530000063114
HOGENOMiHOG000013065
HOVERGENiHBG079189
InParanoidiQ9NQ25
KOiK06733
OMAiEDVTYSW
OrthoDBiEOG091G0KKU
PhylomeDBiQ9NQ25
TreeFamiTF334964

Family and domain databases

Gene3Di2.60.40.102 hits
InterProiView protein in InterPro
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
SUPFAMiSSF48726 SSF48726, 2 hits
PROSITEiView protein in PROSITE
PS50835 IG_LIKE, 1 hit

Sequences (7)i

Sequence statusi: Complete.

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

This entry describes 7 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9NQ25-1) [UniParc]FASTAAdd to basket
Also known as: 19A, CS1-L

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
MAGSPTCLTL IYILWQLTGS AASGPVKELV GSVGGAVTFP LKSKVKQVDS
60 70 80 90 100
IVWTFNTTPL VTIQPEGGTI IVTQNRNRER VDFPDGGYSL KLSKLKKNDS
110 120 130 140 150
GIYYVGIYSS SLQQPSTQEY VLHVYEHLSK PKVTMGLQSN KNGTCVTNLT
160 170 180 190 200
CCMEHGEEDV IYTWKALGQA ANESHNGSIL PISWRWGESD MTFICVARNP
210 220 230 240 250
VSRNFSSPIL ARKLCEGAAD DPDSSMVLLC LLLVPLLLSL FVLGLFLWFL
260 270 280 290 300
KRERQEEYIE EKKRVDICRE TPNICPHSGE NTEYDTIPHT NRTILKEDPA
310 320 330
NTVYSTVEIP KKMENPHSLL TMPDTPRLFA YENVI
Length:335
Mass (Da):37,421
Last modified:October 1, 2000 - v1
Checksum:iD09ABBCFF74BE8D4
GO
Isoform 2 (identifier: Q9NQ25-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     19-125: Missing.

Note: No experimental confirmation available.
Show »
Length:228
Mass (Da):25,831
Checksum:i2B01DB70E7BBFC14
GO
Isoform 3 (identifier: Q9NQ25-3) [UniParc]FASTAAdd to basket
Also known as: 19A24, CS1-S

The sequence of this isoform differs from the canonical sequence as follows:
     258-296: YIEEKKRVDI...IPHTNRTILK → NNPKGRSSKY...DARHTKAICL

Show »
Length:335
Mass (Da):37,026
Checksum:i3CD49C30FF3367B0
GO
Isoform 4 (identifier: Q9NQ25-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     127-165: HLSKPKVTMG...GEEDVIYTWK → NNPKGRSSKY...DARHTKAICL
     166-335: Missing.

Note: No experimental confirmation available.
Show »
Length:165
Mass (Da):17,945
Checksum:iE70079B2E27C5978
GO
Isoform 5 (identifier: Q9NQ25-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     258-335: YIEEKKRVDI...PRLFAYENVI → NNPKGRSSKY...DARHTKAICL

Note: No experimental confirmation available.
Show »
Length:296
Mass (Da):32,581
Checksum:iE85D277192494EEC
GO
Isoform 6 (identifier: Q9NQ25-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     126-256: Missing.

Note: No experimental confirmation available.
Show »
Length:204
Mass (Da):22,785
Checksum:iE7DEE14130014CD5
GO
Isoform 7 (identifier: Q9NQ25-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     19-125: Missing.
     217-256: Missing.

Note: No experimental confirmation available.
Show »
Length:188
Mass (Da):21,316
Checksum:i76BA8CF2C70B4663
GO

Sequence cautioni

The sequence CAB76561 differs from that shown. Reason: Frameshift at several positions.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti135M → L in CAB81950 (PubMed:11802771).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_049938175H → Y. Corresponds to variant dbSNP:rs35325048Ensembl.1
Natural variantiVAR_049939302T → M. Corresponds to variant dbSNP:rs2295617Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_01378119 – 125Missing in isoform 2 and isoform 7. 2 PublicationsAdd BLAST107
Alternative sequenceiVSP_055292126 – 256Missing in isoform 6. 1 PublicationAdd BLAST131
Alternative sequenceiVSP_054540127 – 165HLSKP…IYTWK → NNPKGRSSKYGLLHCGNTEK DGKSPLTAHDARHTKAICL in isoform 4. 1 PublicationAdd BLAST39
Alternative sequenceiVSP_054541166 – 335Missing in isoform 4. 1 PublicationAdd BLAST170
Alternative sequenceiVSP_055293217 – 256Missing in isoform 7. 1 PublicationAdd BLAST40
Alternative sequenceiVSP_054542258 – 335YIEEK…YENVI → NNPKGRSSKYGLLHCGNTEK DGKSPLTAHDARHTKAICL in isoform 5. CuratedAdd BLAST78
Alternative sequenceiVSP_013782258 – 296YIEEK…RTILK → NNPKGRSSKYGLLHCGNTEK DGKSPLTAHDARHTKAICL in isoform 3. 2 PublicationsAdd BLAST39

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF291815 mRNA Translation: AAK11549.1
AF390894 mRNA Translation: AAL26989.1
AJ271869 mRNA Translation: CAB76561.1 Frameshift.
AJ276429 mRNA Translation: CAB81950.2
AB027233 mRNA Translation: BAB61022.1
AY358512 mRNA Translation: AAQ88876.1
AK290706 mRNA Translation: BAF83395.1
AK298499 mRNA Translation: BAG60706.1
AK298548 mRNA Translation: BAG60745.1
AK301438 mRNA Translation: BAG62965.1
AL834424 mRNA Translation: CAD39085.1
AL121985 Genomic DNA No translation available.
CH471121 Genomic DNA Translation: EAW52704.1
BC027867 mRNA Translation: AAH27867.1
CCDSiCCDS1209.1 [Q9NQ25-1]
CCDS60321.1 [Q9NQ25-5]
CCDS60322.1 [Q9NQ25-6]
CCDS60323.1 [Q9NQ25-4]
CCDS60324.1 [Q9NQ25-2]
CCDS60325.1 [Q9NQ25-7]
RefSeqiNP_001269517.1, NM_001282588.1 [Q9NQ25-4]
NP_001269518.1, NM_001282589.1 [Q9NQ25-6]
NP_001269519.1, NM_001282590.1 [Q9NQ25-2]
NP_001269520.1, NM_001282591.1 [Q9NQ25-7]
NP_001269521.1, NM_001282592.1 [Q9NQ25-5]
NP_001269524.1, NM_001282595.1
NP_067004.3, NM_021181.4 [Q9NQ25-1]
UniGeneiHs.517265

Genome annotation databases

EnsembliENST00000359331; ENSP00000352281; ENSG00000026751 [Q9NQ25-5]
ENST00000368042; ENSP00000357021; ENSG00000026751 [Q9NQ25-2]
ENST00000368043; ENSP00000357022; ENSG00000026751 [Q9NQ25-1]
ENST00000441662; ENSP00000405605; ENSG00000026751 [Q9NQ25-6]
ENST00000444090; ENSP00000416592; ENSG00000026751 [Q9NQ25-4]
ENST00000458602; ENSP00000409965; ENSG00000026751 [Q9NQ25-7]
GeneIDi57823
KEGGihsa:57823
UCSCiuc001fwq.5 human [Q9NQ25-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiSLAF7_HUMAN
AccessioniPrimary (citable) accession number: Q9NQ25
Secondary accession number(s): A8K3U1
, B4DPU4, B4DPY3, B4DWA3, Q8N6Y8, Q8ND32, Q9NY08, Q9NY23
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 24, 2005
Last sequence update: October 1, 2000
Last modified: February 28, 2018
This is version 148 of the entry and version 1 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

Complete proteome, Direct protein sequencing, Reference proteome