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Protein

SLAM family member 5

Gene

Cd84

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:20962259). Can mediate natural killer (NK) cell cytotoxicity dependent on SH2D1A and SH2D1B (PubMed:20962259). Increases proliferative responses of activated T-cells and SH2D1A/SAP does not seen be required for this process. Homophilic interactions enhance interferon gamma/IFNG secretion in lymphocytes and induce platelet stimulation via a SH2D1A/SAP-dependent pathway. May serve as a marker for hematopoietic progenitor cells (By similarity). Required for a prolonged T-cell:B-cell contact, optimal T follicular helper function, and germinal center formation (PubMed:20153220). In germinal centers involved in maintaining B cell tolerance and in preventing autoimmunity (PubMed:25801429). In mast cells negatively regulates high affinity immunoglobulin epsilon receptor signaling; independent of SH2D1A and SH2D1B but implicating FES and PTPN6/SHP-1 (By similarity). In macrophages enhances LPS-induced MAPK phosphorylation and NF-kappaB activation and modulates LPS-induced cytokine secretion; involving ITSM 2 (PubMed:20628063).By similarityCurated5 Publications

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Adaptive immunity, Cell adhesion, Immunity, Innate immunity

Names & Taxonomyi

Protein namesi
Recommended name:
SLAM family member 5
Alternative name(s):
Leukocyte differentiation antigen CD84
Signaling lymphocytic activation molecule 5
CD_antigen: CD84
Gene namesi
Name:Cd84
Synonyms:Slamf5
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1336885. Cd84.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini22 – 221200ExtracellularSequence analysisAdd
BLAST
Transmembranei222 – 24221HelicalSequence analysisAdd
BLAST
Topological domaini243 – 32987CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi265 – 2651Y → F: No effect on macrophage cytokine secretion. 1 Publication
Mutagenesisi300 – 3001Y → F: Modulates macrophage cytokine secretion. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2121By similarityAdd
BLAST
Chaini22 – 329308SLAM family member 5PRO_0000252030Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi147 – 1471N-linked (GlcNAc...)Sequence analysis
Disulfide bondi152 ↔ 190PROSITE-ProRule annotation
Modified residuei280 – 2801Phosphotyrosine; by LYNBy similarity
Modified residuei300 – 3001PhosphotyrosineBy similarity

Post-translational modificationi

Phosphorylated by tyrosine-protein kinase LCK on tyrosine residues following ligation induced by agonist monoclonal antibody. The association with SH2D1A/SAP is dependent of tyrosine phosphorylation of its cytoplasmic domain. Phosphorylated on Tyr-280 and Tyr-300 following platelet aggregation. Phosphorylated on tyrosine residues upon high affinity immunoglobulin epsilon receptor aggregation in mast cells.By similarity
N-glycosylated.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ18PI6.
MaxQBiQ18PI6.
PaxDbiQ18PI6.
PRIDEiQ18PI6.

PTM databases

iPTMnetiQ18PI6.
PhosphoSiteiQ18PI6.

Expressioni

Tissue specificityi

Predominantly expressed in hematopoietic tissues such as lymph node, spleen, thymus, and bone marrow. Detected also in lung.

Gene expression databases

BgeeiQ18PI6.
CleanExiMM_CD84.

Interactioni

Subunit structurei

Homodimer; via its extracellular domain. Forms a head to tail dimer with a CD48 molecule from another cell. Interacts with SH2 domain-containing proteins SH2D1A/SAP and SH2D1B/EAT-2. Interacts with tyrosine-protein phosphatases PTPN6/SHP-1 and PTPN11/SHP-2 via its phosphorylated cytoplasmic domain, and this interaction is blocked by SH2D1A (By similarity).By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000047024.

Structurei

3D structure databases

ProteinModelPortaliQ18PI6.
SMRiQ18PI6. Positions 26-209.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini26 – 129104Ig-like V-typeAdd
BLAST
Domaini132 – 20675Ig-like C2-typeAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi263 – 2686ITSM 1By similarity
Motifi298 – 3036ITSM 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-containingbinding 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, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IVV0. Eukaryota.
ENOG410Z5M6. LUCA.
HOGENOMiHOG000013065.
HOVERGENiHBG093961.
InParanoidiQ18PI6.
KOiK06511.
OrthoDBiEOG77HDFC.
TreeFamiTF334964.

Family and domain databases

Gene3Di2.60.40.10. 2 hits.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
[Graphical view]
SMARTiSM00409. IG. 2 hits.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 2 hits.
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: Q18PI6-1) [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
MAQRHLWIWF LCLQTWSEAA GKDADPMVMN GILGESVTFL LNIQEPKKID
60 70 80 90 100
NIAWTSQSSV AFIKPGVNKA EVTITQGTYK GRIEIIDQKY DLVIRDLRME
110 120 130 140 150
DAGTYKADIN EENEETITKI YYLHIYRRLK TPKITQSLIS SLNNTCNITL
160 170 180 190 200
TCSVEKEEKD VTYSWSPFGE KSNVLQIVHS PMDQKLTYTC TAQNPVSNSS
210 220 230 240 250
DSVTVQQPCT DTPSFHPRHA VLPGGLAVLF LLILIPMLAF LFRLYKRRRD
260 270 280 290 300
RIVLEADDVS KKTVYAVVSR NAQPTESRIY DEIPQSKMLS CKEDPVTTIY
310 320
SSVQLSEKMK ETNMKDRSLP KALGNEIVV
Length:329
Mass (Da):37,378
Last modified:July 25, 2006 - v1
Checksum:iB3BF45FEA7B00FB6
GO
Isoform 2 (identifier: Q18PI6-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     128-140: RLKTPKITQSLIS → KLWQHGALDLLLI
     141-329: Missing.

Show »
Length:140
Mass (Da):16,174
Checksum:iEB487F113EF3868D
GO
Isoform 3 (identifier: Q18PI6-3) [UniParc]FASTAAdd to basket

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

Show »
Length:328
Mass (Da):37,307
Checksum:i95E1FA3C07E0FB77
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti27 – 271M → V in AAD02273 (PubMed:10079287).Curated
Sequence conflicti27 – 271M → V in BAC29799 (PubMed:16141072).Curated
Sequence conflicti27 – 271M → V in BAC30670 (PubMed:16141072).Curated
Sequence conflicti27 – 271M → V in BAE32863 (PubMed:16141072).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti293 – 2931E → K.3 Publications

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei128 – 14013RLKTP…QSLIS → KLWQHGALDLLLI in isoform 2. 1 PublicationVSP_020857Add
BLAST
Alternative sequencei141 – 329189Missing in isoform 2. 1 PublicationVSP_020858Add
BLAST
Alternative sequencei256 – 2561Missing in isoform 3. 1 PublicationVSP_020859

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF043445 mRNA. Translation: AAD02273.1.
AB196812 mRNA. Translation: BAE96315.1.
AB196813 mRNA. Translation: BAE96316.1.
AB196814 mRNA. Translation: BAE96317.1.
AB196815 mRNA. Translation: BAE96318.1.
AK037385 mRNA. Translation: BAC29799.1.
AK040694 mRNA. Translation: BAC30670.1.
AK154834 mRNA. Translation: BAE32863.1.
AK156464 mRNA. Translation: BAE33721.1.
AK157075 mRNA. Translation: BAE33953.1.
AK171067 mRNA. Translation: BAE42226.1.
CCDSiCCDS15503.1. [Q18PI6-1]
CCDS56657.1. [Q18PI6-2]
CCDS69979.1. [Q18PI6-3]
RefSeqiNP_001239401.1. NM_001252472.1.
NP_038517.1. NM_013489.3.
UniGeneiMm.259115.

Genome annotation databases

GeneIDi12523.
KEGGimmu:12523.
UCSCiuc007dpd.3. mouse. [Q18PI6-2]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF043445 mRNA. Translation: AAD02273.1.
AB196812 mRNA. Translation: BAE96315.1.
AB196813 mRNA. Translation: BAE96316.1.
AB196814 mRNA. Translation: BAE96317.1.
AB196815 mRNA. Translation: BAE96318.1.
AK037385 mRNA. Translation: BAC29799.1.
AK040694 mRNA. Translation: BAC30670.1.
AK154834 mRNA. Translation: BAE32863.1.
AK156464 mRNA. Translation: BAE33721.1.
AK157075 mRNA. Translation: BAE33953.1.
AK171067 mRNA. Translation: BAE42226.1.
CCDSiCCDS15503.1. [Q18PI6-1]
CCDS56657.1. [Q18PI6-2]
CCDS69979.1. [Q18PI6-3]
RefSeqiNP_001239401.1. NM_001252472.1.
NP_038517.1. NM_013489.3.
UniGeneiMm.259115.

3D structure databases

ProteinModelPortaliQ18PI6.
SMRiQ18PI6. Positions 26-209.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000047024.

PTM databases

iPTMnetiQ18PI6.
PhosphoSiteiQ18PI6.

Proteomic databases

EPDiQ18PI6.
MaxQBiQ18PI6.
PaxDbiQ18PI6.
PRIDEiQ18PI6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi12523.
KEGGimmu:12523.
UCSCiuc007dpd.3. mouse. [Q18PI6-2]

Organism-specific databases

CTDi8832.
MGIiMGI:1336885. Cd84.

Phylogenomic databases

eggNOGiENOG410IVV0. Eukaryota.
ENOG410Z5M6. LUCA.
HOGENOMiHOG000013065.
HOVERGENiHBG093961.
InParanoidiQ18PI6.
KOiK06511.
OrthoDBiEOG77HDFC.
TreeFamiTF334964.

Miscellaneous databases

PROiQ18PI6.
SOURCEiSearch...

Gene expression databases

BgeeiQ18PI6.
CleanExiMM_CD84.

Family and domain databases

Gene3Di2.60.40.10. 2 hits.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
[Graphical view]
SMARTiSM00409. IG. 2 hits.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 2 hits.
PROSITEiPS50835. IG_LIKE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning, characterization, and chromosomal localization of the mouse homologue of CD84, a member of the CD2 family of cell surface molecules."
    de la Fuente M.A., Tovar V., Pizcueta P., Nadal M., Bosch J., Engel P.
    Immunogenetics 49:249-255(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT LYS-293.
    Tissue: Peritoneal macrophage.
  2. "Polymorphisms of SLAM family receptor genes."
    Furukawa H., Ono M.
    Submitted (DEC-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT LYS-293.
    Strain: BXSB/MpJ, MRL/MpJ, NZB/BlNJ and NZW/LacJ.
  3. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3), VARIANT LYS-293.
    Strain: NOD.
  4. "Structural basis for the interaction of the free SH2 domain EAT-2 with SLAM receptors in hematopoietic cells."
    Morra M., Lu J., Poy F., Martin M., Sayos J., Calpe S., Gullo C., Howie D., Rietdijk S., Thompson A., Coyle A.J., Denny C., Yaffe M.B., Engel P., Eck M.J., Terhorst C.
    EMBO J. 20:5840-5852(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SH2D1B.
  5. "Platelet aggregation induces platelet aggregate stability via SLAM family receptor signaling."
    Nanda N., Andre P., Bao M., Clauser K., Deguzman F., Howie D., Conley P.B., Terhorst C., Phillips D.R.
    Blood 106:3028-3034(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  6. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Spleen.
  7. "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.
  8. "The adapters EAT-2A and -2B are positive regulators of CD244- and CD84-dependent NK cell functions in the C57BL/6 mouse."
    Wang N., Calpe S., Westcott J., Castro W., Ma C., Engel P., Schatzle J.D., Terhorst C.
    J. Immunol. 185:5683-5687(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  9. "Mouse CD84 is a pan-leukocyte cell-surface molecule that modulates LPS-induced cytokine secretion by macrophages."
    Sintes J., Romero X., de Salort J., Terhorst C., Engel P.
    J. Leukoc. Biol. 88:687-697(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, MUTAGENESIS OF TYR-265 AND TYR-300.
  10. Cited for: FUNCTION.

Entry informationi

Entry nameiSLAF5_MOUSE
AccessioniPrimary (citable) accession number: Q18PI6
Secondary accession number(s): Q18PI7
, Q3TBT1, Q3U0A2, Q8BFV0, Q9Z178
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 3, 2006
Last sequence update: July 25, 2006
Last modified: June 8, 2016
This is version 78 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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.