SLAF5_MOUSE
ID SLAF5_MOUSE Reviewed; 329 AA.
AC Q18PI6; Q18PI7; Q3TBT1; Q3U0A2; Q8BFV0; Q9Z178;
DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 25-JUL-2006, sequence version 1.
DT 25-MAY-2022, entry version 112.
DE RecName: Full=SLAM family member 5;
DE AltName: Full=Leukocyte differentiation antigen CD84;
DE AltName: Full=Signaling lymphocytic activation molecule 5;
DE AltName: CD_antigen=CD84;
DE Flags: Precursor;
GN Name=Cd84; Synonyms=Slamf5;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT LYS-293.
RC TISSUE=Peritoneal macrophage;
RX PubMed=10079287; DOI=10.1007/s002510050490;
RA de la Fuente M.A., Tovar V., Pizcueta P., Nadal M., Bosch J., Engel P.;
RT "Molecular cloning, characterization, and chromosomal localization of the
RT mouse homologue of CD84, a member of the CD2 family of cell surface
RT molecules.";
RL Immunogenetics 49:249-255(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT LYS-293.
RC STRAIN=BXSB/MpJ, MRL/MpJ, NZB/BlNJ, and NZW/LacJ;
RA Furukawa H., Ono M.;
RT "Polymorphisms of SLAM family receptor genes.";
RL Submitted (DEC-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3), AND VARIANT
RP LYS-293.
RC STRAIN=NOD;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP INTERACTION WITH SH2D1B.
RX PubMed=11689425; DOI=10.1093/emboj/20.21.5840;
RA Morra M., Lu J., Poy F., Martin M., Sayos J., Calpe S., Gullo C., Howie D.,
RA Rietdijk S., Thompson A., Coyle A.J., Denny C., Yaffe M.B., Engel P.,
RA Eck M.J., Terhorst C.;
RT "Structural basis for the interaction of the free SH2 domain EAT-2 with
RT SLAM receptors in hematopoietic cells.";
RL EMBO J. 20:5840-5852(2001).
RN [5]
RP FUNCTION.
RX PubMed=16037392; DOI=10.1182/blood-2005-01-0333;
RA Nanda N., Andre P., Bao M., Clauser K., Deguzman F., Howie D., Conley P.B.,
RA Terhorst C., Phillips D.R.;
RT "Platelet aggregation induces platelet aggregate stability via SLAM family
RT receptor signaling.";
RL Blood 106:3028-3034(2005).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP FUNCTION.
RX PubMed=20153220; DOI=10.1016/j.immuni.2010.01.010;
RA Cannons J.L., Qi H., Lu K.T., Dutta M., Gomez-Rodriguez J., Cheng J.,
RA Wakeland E.K., Germain R.N., Schwartzberg P.L.;
RT "Optimal germinal center responses require a multistage T cell:B cell
RT adhesion process involving integrins, SLAM-associated protein, and CD84.";
RL Immunity 32:253-265(2010).
RN [8]
RP FUNCTION.
RX PubMed=20962259; DOI=10.4049/jimmunol.1001974;
RA Wang N., Calpe S., Westcott J., Castro W., Ma C., Engel P., Schatzle J.D.,
RA Terhorst C.;
RT "The adapters EAT-2A and -2B are positive regulators of CD244- and CD84-
RT dependent NK cell functions in the C57BL/6 mouse.";
RL J. Immunol. 185:5683-5687(2010).
RN [9]
RP FUNCTION, AND MUTAGENESIS OF TYR-265 AND TYR-300.
RX PubMed=20628063; DOI=10.1189/jlb.1109756;
RA Sintes J., Romero X., de Salort J., Terhorst C., Engel P.;
RT "Mouse CD84 is a pan-leukocyte cell-surface molecule that modulates LPS-
RT induced cytokine secretion by macrophages.";
RL J. Leukoc. Biol. 88:687-697(2010).
RN [10]
RP FUNCTION.
RX PubMed=25801429; DOI=10.4049/jimmunol.1403023;
RA Wong E.B., Soni C., Chan A.Y., Domeier P.P., Shwetank V., Abraham T.,
RA Limaye N., Khan T.N., Elias M.J., Chodisetti S.B., Wakeland E.K.,
RA Rahman Z.S.;
RT "B cell-intrinsic CD84 and Ly108 maintain germinal center B cell
RT tolerance.";
RL J. Immunol. 194:4130-4143(2015).
CC -!- FUNCTION: Self-ligand receptor of the signaling lymphocytic activation
CC molecule (SLAM) family. SLAM receptors triggered by homo- or
CC heterotypic cell-cell interactions are modulating the activation and
CC differentiation of a wide variety of immune cells and thus are involved
CC in the regulation and interconnection of both innate and adaptive
CC immune response. Activities are controlled by presence or absence of
CC small cytoplasmic adapter proteins, SH2D1A/SAP and/or SH2D1B/EAT-2
CC (PubMed:20962259). Can mediate natural killer (NK) cell cytotoxicity
CC dependent on SH2D1A and SH2D1B (PubMed:20962259). Increases
CC proliferative responses of activated T-cells and SH2D1A/SAP does not
CC seen be required for this process. Homophilic interactions enhance
CC interferon gamma/IFNG secretion in lymphocytes and induce platelet
CC stimulation via a SH2D1A/SAP-dependent pathway. May serve as a marker
CC for hematopoietic progenitor cells (By similarity). Required for a
CC prolonged T-cell:B-cell contact, optimal T follicular helper function,
CC and germinal center formation (PubMed:20153220). In germinal centers
CC involved in maintaining B cell tolerance and in preventing autoimmunity
CC (PubMed:25801429). In mast cells negatively regulates high affinity
CC immunoglobulin epsilon receptor signaling; independent of SH2D1A and
CC SH2D1B but implicating FES and PTPN6/SHP-1 (By similarity). In
CC macrophages enhances LPS-induced MAPK phosphorylation and NF-kappaB
CC activation and modulates LPS-induced cytokine secretion; involving ITSM
CC 2 (PubMed:20628063). Positively regulates macroautophagy in primary
CC dendritic cells via stabilization of IRF8; inhibits TRIM21-mediated
CC proteasomal degradation of IRF8 (By similarity).
CC {ECO:0000250|UniProtKB:Q9UIB8, ECO:0000269|PubMed:16037392,
CC ECO:0000269|PubMed:20153220, ECO:0000269|PubMed:20628063,
CC ECO:0000269|PubMed:20962259, ECO:0000269|PubMed:25801429, ECO:0000305}.
CC -!- SUBUNIT: Homodimer; via its extracellular domain. Forms a head to tail
CC dimer with a CD48 molecule from another cell. Interacts with SH2
CC domain-containing proteins SH2D1A/SAP and SH2D1B/EAT-2. Interacts with
CC tyrosine-protein phosphatases PTPN6/SHP-1 and PTPN11/SHP-2 via its
CC phosphorylated cytoplasmic domain, and this interaction is blocked by
CC SH2D1A (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass type I
CC membrane protein {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q18PI6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q18PI6-2; Sequence=VSP_020857, VSP_020858;
CC Name=3;
CC IsoId=Q18PI6-3; Sequence=VSP_020859;
CC -!- TISSUE SPECIFICITY: Predominantly expressed in hematopoietic tissues
CC such as lymph node, spleen, thymus, and bone marrow. Detected also in
CC lung.
CC -!- DOMAIN: The ITSMs (immunoreceptor tyrosine-based switch motifs) with
CC the consensus sequence T-X-Y-X-X-[VI] present in SLAM family receptors
CC have overlapping specificity for activating and inhibitory SH2 domain-
CC containingbinding partners. Especially they mediate the interaction
CC with the SH2 domain of SH2D1A and SH2D1B. A 'two-out-of-three-pronged'
CC mechanism is proposed involving threonine (position -2), phosphorylated
CC tyrosine (position 0) and valine/isoleucine (position +3).
CC {ECO:0000250|UniProtKB:Q13291, ECO:0000250|UniProtKB:Q9UIB8}.
CC -!- PTM: Phosphorylated by tyrosine-protein kinase LCK on tyrosine residues
CC following ligation induced by agonist monoclonal antibody. The
CC association with SH2D1A/SAP is dependent of tyrosine phosphorylation of
CC its cytoplasmic domain. Phosphorylated on Tyr-280 and Tyr-300 following
CC platelet aggregation. Phosphorylated on tyrosine residues upon high
CC affinity immunoglobulin epsilon receptor aggregation in mast cells.
CC {ECO:0000250|UniProtKB:Q9UIB8}.
CC -!- PTM: N-glycosylated. {ECO:0000250}.
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DR EMBL; AF043445; AAD02273.1; -; mRNA.
DR EMBL; AB196812; BAE96315.1; -; mRNA.
DR EMBL; AB196813; BAE96316.1; -; mRNA.
DR EMBL; AB196814; BAE96317.1; -; mRNA.
DR EMBL; AB196815; BAE96318.1; -; mRNA.
DR EMBL; AK037385; BAC29799.1; -; mRNA.
DR EMBL; AK040694; BAC30670.1; -; mRNA.
DR EMBL; AK154834; BAE32863.1; -; mRNA.
DR EMBL; AK156464; BAE33721.1; -; mRNA.
DR EMBL; AK157075; BAE33953.1; -; mRNA.
DR EMBL; AK171067; BAE42226.1; -; mRNA.
DR CCDS; CCDS15503.1; -. [Q18PI6-1]
DR CCDS; CCDS56657.1; -. [Q18PI6-2]
DR CCDS; CCDS69979.1; -. [Q18PI6-3]
DR RefSeq; NP_001239401.1; NM_001252472.1.
DR RefSeq; NP_038517.1; NM_013489.3.
DR AlphaFoldDB; Q18PI6; -.
DR SMR; Q18PI6; -.
DR STRING; 10090.ENSMUSP00000120881; -.
DR GlyGen; Q18PI6; 1 site.
DR iPTMnet; Q18PI6; -.
DR PhosphoSitePlus; Q18PI6; -.
DR CPTAC; non-CPTAC-4062; -.
DR EPD; Q18PI6; -.
DR jPOST; Q18PI6; -.
DR MaxQB; Q18PI6; -.
DR PaxDb; Q18PI6; -.
DR PeptideAtlas; Q18PI6; -.
DR PRIDE; Q18PI6; -.
DR ProteomicsDB; 261070; -. [Q18PI6-1]
DR ProteomicsDB; 261071; -. [Q18PI6-2]
DR ProteomicsDB; 261072; -. [Q18PI6-3]
DR DNASU; 12523; -.
DR GeneID; 12523; -.
DR KEGG; mmu:12523; -.
DR UCSC; uc007dpd.3; mouse. [Q18PI6-2]
DR CTD; 8832; -.
DR MGI; MGI:1336885; Cd84.
DR eggNOG; ENOG502SB7W; Eukaryota.
DR InParanoid; Q18PI6; -.
DR OrthoDB; 990343at2759; -.
DR TreeFam; TF334964; -.
DR Reactome; R-MMU-202733; Cell surface interactions at the vascular wall.
DR BioGRID-ORCS; 12523; 0 hits in 73 CRISPR screens.
DR ChiTaRS; Cd84; mouse.
DR PRO; PR:Q18PI6; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q18PI6; protein.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0032685; P:negative regulation of granulocyte macrophage colony-stimulating factor production; ISO:MGI.
DR GO; GO:0032693; P:negative regulation of interleukin-10 production; IDA:UniProtKB.
DR GO; GO:0032701; P:negative regulation of interleukin-18 production; ISO:MGI.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; IDA:UniProtKB.
DR GO; GO:0033004; P:negative regulation of mast cell activation; ISO:MGI.
DR GO; GO:0043305; P:negative regulation of mast cell degranulation; ISO:MGI.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:UniProtKB.
DR GO; GO:0071639; P:positive regulation of monocyte chemotactic protein-1 production; IDA:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IDA:UniProtKB.
DR GO; GO:0031664; P:regulation of lipopolysaccharide-mediated signaling pathway; IDA:UniProtKB.
DR GO; GO:0043030; P:regulation of macrophage activation; IDA:UniProtKB.
DR GO; GO:2001256; P:regulation of store-operated calcium entry; ISO:MGI.
DR GO; GO:0042110; P:T cell activation; IBA:GO_Central.
DR Gene3D; 2.60.40.10; -; 2.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR SMART; SM00409; IG; 2.
DR SUPFAM; SSF48726; SSF48726; 2.
DR PROSITE; PS50835; IG_LIKE; 1.
PE 1: Evidence at protein level;
KW Adaptive immunity; Alternative splicing; Autophagy; Cell adhesion;
KW Cell membrane; Disulfide bond; Glycoprotein; Immunity;
KW Immunoglobulin domain; Innate immunity; Membrane; Phosphoprotein; Receptor;
KW Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..21
FT /evidence="ECO:0000250"
FT CHAIN 22..329
FT /note="SLAM family member 5"
FT /id="PRO_0000252030"
FT TOPO_DOM 22..221
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 222..242
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 243..329
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 26..129
FT /note="Ig-like V-type"
FT DOMAIN 132..206
FT /note="Ig-like C2-type"
FT MOTIF 263..268
FT /note="ITSM 1"
FT /evidence="ECO:0000250|UniProtKB:Q13291"
FT MOTIF 298..303
FT /note="ITSM 2"
FT /evidence="ECO:0000250|UniProtKB:Q13291"
FT MOD_RES 265
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9UIB8"
FT MOD_RES 280
FT /note="Phosphotyrosine; by LYN"
FT /evidence="ECO:0000250|UniProtKB:Q9UIB8"
FT MOD_RES 300
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9UIB8"
FT CARBOHYD 147
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 152..190
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 128..140
FT /note="RLKTPKITQSLIS -> KLWQHGALDLLLI (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_020857"
FT VAR_SEQ 141..329
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_020858"
FT VAR_SEQ 256
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_020859"
FT VARIANT 293
FT /note="E -> K"
FT /evidence="ECO:0000269|PubMed:10079287,
FT ECO:0000269|PubMed:16141072, ECO:0000269|Ref.2"
FT MUTAGEN 265
FT /note="Y->F: No effect on macrophage cytokine secretion."
FT /evidence="ECO:0000269|PubMed:20628063"
FT MUTAGEN 300
FT /note="Y->F: Modulates macrophage cytokine secretion."
FT /evidence="ECO:0000269|PubMed:20628063"
FT CONFLICT 27
FT /note="M -> V (in Ref. 1; AAD02273 and 3; BAC29799/
FT BAC30670/BAE32863)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 329 AA; 37378 MW; B3BF45FEA7B00FB6 CRC64;
MAQRHLWIWF LCLQTWSEAA GKDADPMVMN GILGESVTFL LNIQEPKKID NIAWTSQSSV
AFIKPGVNKA EVTITQGTYK GRIEIIDQKY DLVIRDLRME DAGTYKADIN EENEETITKI
YYLHIYRRLK TPKITQSLIS SLNNTCNITL TCSVEKEEKD VTYSWSPFGE KSNVLQIVHS
PMDQKLTYTC TAQNPVSNSS DSVTVQQPCT DTPSFHPRHA VLPGGLAVLF LLILIPMLAF
LFRLYKRRRD RIVLEADDVS KKTVYAVVSR NAQPTESRIY DEIPQSKMLS CKEDPVTTIY
SSVQLSEKMK ETNMKDRSLP KALGNEIVV
