SLAF6_MOUSE
ID SLAF6_MOUSE Reviewed; 351 AA.
AC Q9ET39; C6ESQ1; Q9ET40;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=SLAM family member 6;
DE AltName: Full=Lymphocyte antigen 108;
DE AltName: CD_antigen=CD352;
DE Flags: Precursor;
GN Name=Slamf6; Synonyms=Ly108;
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] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Spleen;
RX PubMed=11132158; DOI=10.1007/s002510000252;
RA Peck S.R., Ruley H.E.;
RT "Ly108: a new member of the mouse CD2 family of cell surface proteins.";
RL Immunogenetics 52:63-72(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, ALTERNATIVE SPLICING,
RP TISSUE SPECIFICITY, AND INVOLVEMENT IN SYSTEMIC LUPUS ERYTHEMATOSUS.
RX PubMed=21422172; DOI=10.1084/jem.20101653;
RA Keszei M., Detre C., Rietdijk S.T., Munoz P., Romero X., Berger S.B.,
RA Calpe S., Liao G., Castro W., Julien A., Wu Y.Y., Shin D.M., Sancho J.,
RA Zubiaur M., Morse H.C. III, Morel L., Engel P., Wang N., Terhorst C.;
RT "A novel isoform of the Ly108 gene ameliorates murine lupus.";
RL J. Exp. Med. 208:811-822(2011).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Thymus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION.
RX PubMed=18031695; DOI=10.1016/j.immuni.2007.08.020;
RA Griewank K., Borowski C., Rietdijk S., Wang N., Julien A., Wei D.G.,
RA Mamchak A.A., Terhorst C., Bendelac A.;
RT "Homotypic interactions mediated by Slamf1 and Slamf6 receptors control NKT
RT cell lineage development.";
RL Immunity 27:751-762(2007).
RN [6]
RP FUNCTION.
RX PubMed=19648922; DOI=10.1038/ni.1763;
RA Dong Z., Cruz-Munoz M.E., Zhong M.C., Chen R., Latour S., Veillette A.;
RT "Essential function for SAP family adaptors in the surveillance of
RT hematopoietic cells by natural killer cells.";
RL Nat. Immunol. 10:973-980(2009).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung;
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 [8]
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 [9]
RP FUNCTION, AND MUTAGENESIS OF TYR-295; TYR-319; TYR-335 AND TYR-349.
RX PubMed=22683125; DOI=10.1016/j.immuni.2012.05.016;
RA Kageyama R., Cannons J.L., Zhao F., Yusuf I., Lao C., Locci M.,
RA Schwartzberg P.L., Crotty S.;
RT "The receptor Ly108 functions as a SAP adaptor-dependent on-off switch for
RT T cell help to B cells and NKT cell development.";
RL Immunity 36:986-1002(2012).
RN [10]
RP FUNCTION.
RX PubMed=25926831; DOI=10.3389/fimmu.2015.00158;
RA Wang N., Halibozek P.J., Yigit B., Zhao H., O'Keeffe M.S., Sage P.,
RA Sharpe A., Terhorst C.;
RT "Negative regulation of humoral immunity due to interplay between the
RT SLAMF1, SLAMF5, and SLAMF6 receptors.";
RL Front. Immunol. 6:158-158(2015).
RN [11]
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:19648922). Triggers cytolytic activity only in natural killer
CC cells (NK) expressing high surface densities of natural cytotoxicity
CC receptors (By similarity). Positive signaling in NK cells implicates
CC phosphorylation of VAV1. NK cell activation seems to depend on SH2D1B
CC and not on SH2D1A (By similarity). In conjunction with SLAMF1 controls
CC the transition between positive selection and the subsequent expansion
CC and differentiation of the thymocytic natural killer T (NKT) cell
CC lineage (PubMed:18031695). Promotes T cell differentiation into a
CC helper T-cell Th17 phenotype leading to increased IL-17 secretion; the
CC costimulatory activity requires SH2D1A (By similarity). Promotes
CC recruitment of RORC to the IL-17 promoter (By similarity). In
CC conjunction with SLAMF1 and CD84/SLAMF5 may be a negative regulator of
CC the humoral immune response (PubMed:25926831). In the absence of
CC SH2D1A/SAP can transmit negative signals to CD4(+) T-cells and NKT
CC cells. Negatively regulates germinal center formation by inhibiting T-
CC cell:B-cell adhesion; the function probably implicates increased
CC association with PTPN6/SHP-1 via ITSMs in absence of SH2D1A/SAP
CC (PubMed:22683125). However, reported to mediated T-cell adhesion, to
CC participate in stable T-cell:B-cell interactions and to be involved in
CC maintaining B-cell tolerance in germinal centers and in preventing
CC autoimmunity (PubMed:20153220, PubMed:25801429). Involved in regulation
CC of autoimmunity. Isoform 3 may be suppressor of pathogenic T-cell
CC proliferation (PubMed:21422172). {ECO:0000250|UniProtKB:Q96DU3,
CC ECO:0000269|PubMed:18031695, ECO:0000269|PubMed:19648922,
CC ECO:0000269|PubMed:20153220, ECO:0000269|PubMed:21422172,
CC ECO:0000269|PubMed:22683125, ECO:0000269|PubMed:25801429}.
CC -!- SUBUNIT: Homodimer. Interacts with PTN6 and, upon phosphorylation, with
CC PTN11 and SH2D1A/SAP (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Single-pass type I
CC membrane protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=Ly108s;
CC IsoId=Q9ET39-1; Sequence=Displayed;
CC Name=2; Synonyms=Ly108l;
CC IsoId=Q9ET39-2; Sequence=VSP_010404, VSP_010405;
CC Name=3; Synonyms=Ly108-H1;
CC IsoId=Q9ET39-3; Sequence=VSP_058034;
CC -!- TISSUE SPECIFICITY: Expressed on hematopoietic cells. Isoform 3 is
CC expressed in thymocytes and B lymphocytes of C57Bl/6 strain.
CC {ECO:0000269|PubMed:21422172}.
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 containing binding 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}.
CC -!- PTM: Phosphorylated. {ECO:0000250}.
CC -!- MISCELLANEOUS: Isoform 3 ameliorates spontaneous development in a
CC systemic lupus erythematosus transfer model.
CC {ECO:0000269|PubMed:21422172}.
CC -!- MISCELLANEOUS: [Isoform 3]: Found in Slamf-haplotype 1 mice such as
CC C557Bl/6 but not in Slamf-haplotype 2 strains including 129, Balb/c and
CC NOD. {ECO:0000269|PubMed:21422172}.
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DR EMBL; AF248635; AAG01737.1; -; mRNA.
DR EMBL; AF248636; AAG01738.1; -; mRNA.
DR EMBL; EU591721; ACF05482.1; -; mRNA.
DR EMBL; AC091523; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC030031; AAH30031.1; -; mRNA.
DR CCDS; CCDS15504.1; -. [Q9ET39-2]
DR CCDS; CCDS83638.1; -. [Q9ET39-1]
DR CCDS; CCDS83639.1; -. [Q9ET39-3]
DR RefSeq; NP_001334115.1; NM_001347186.1. [Q9ET39-1]
DR RefSeq; NP_001334116.1; NM_001347187.1. [Q9ET39-3]
DR RefSeq; NP_109635.1; NM_030710.2. [Q9ET39-2]
DR AlphaFoldDB; Q9ET39; -.
DR SMR; Q9ET39; -.
DR STRING; 10090.ENSMUSP00000130610; -.
DR TCDB; 8.A.23.1.32; the basigin (basigin) family.
DR GlyGen; Q9ET39; 9 sites.
DR iPTMnet; Q9ET39; -.
DR PhosphoSitePlus; Q9ET39; -.
DR EPD; Q9ET39; -.
DR MaxQB; Q9ET39; -.
DR PaxDb; Q9ET39; -.
DR PRIDE; Q9ET39; -.
DR ProteomicsDB; 261409; -. [Q9ET39-1]
DR ProteomicsDB; 261410; -. [Q9ET39-2]
DR ProteomicsDB; 261411; -. [Q9ET39-3]
DR ABCD; Q9ET39; 3 sequenced antibodies.
DR Antibodypedia; 34279; 470 antibodies from 33 providers.
DR DNASU; 30925; -.
DR Ensembl; ENSMUST00000171330; ENSMUSP00000130610; ENSMUSG00000015314. [Q9ET39-2]
DR Ensembl; ENSMUST00000194561; ENSMUSP00000141944; ENSMUSG00000015314. [Q9ET39-3]
DR Ensembl; ENSMUST00000195656; ENSMUSP00000141448; ENSMUSG00000015314. [Q9ET39-1]
DR GeneID; 30925; -.
DR KEGG; mmu:30925; -.
DR UCSC; uc007dph.1; mouse. [Q9ET39-1]
DR UCSC; uc011wwh.1; mouse.
DR CTD; 114836; -.
DR MGI; MGI:1353620; Slamf6.
DR VEuPathDB; HostDB:ENSMUSG00000015314; -.
DR eggNOG; ENOG502SSRG; Eukaryota.
DR GeneTree; ENSGT01030000234540; -.
DR HOGENOM; CLU_069386_2_0_1; -.
DR InParanoid; Q9ET39; -.
DR OMA; YLDIRWI; -.
DR OrthoDB; 990343at2759; -.
DR PhylomeDB; Q9ET39; -.
DR TreeFam; TF334964; -.
DR Reactome; R-MMU-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR BioGRID-ORCS; 30925; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Slamf6; mouse.
DR PRO; PR:Q9ET39; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q9ET39; protein.
DR Bgee; ENSMUSG00000015314; Expressed in thymus and 38 other tissues.
DR ExpressionAtlas; Q9ET39; baseline and differential.
DR Genevisible; Q9ET39; MM.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0001779; P:natural killer cell differentiation; IMP:UniProtKB.
DR GO; GO:0001787; P:natural killer cell proliferation; IMP:UniProtKB.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; ISO:MGI.
DR GO; GO:0032740; P:positive regulation of interleukin-17 production; ISO:MGI.
DR GO; GO:0045954; P:positive regulation of natural killer cell mediated cytotoxicity; ISO:MGI.
DR GO; GO:0042110; P:T cell activation; IBA:GO_Central.
DR GO; GO:0072540; P:T-helper 17 cell lineage commitment; ISO:MGI.
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; IPR013106; Ig_V-set.
DR Pfam; PF07686; V-set; 1.
DR SUPFAM; SSF48726; SSF48726; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
PE 1: Evidence at protein level;
KW Adaptive immunity; Alternative splicing; Cell membrane; Disulfide bond;
KW Glycoprotein; Immunity; Immunoglobulin domain; Innate immunity; Membrane;
KW Phosphoprotein; Receptor; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..30
FT /evidence="ECO:0000255"
FT CHAIN 31..351
FT /note="SLAM family member 6"
FT /id="PRO_0000014962"
FT TOPO_DOM 31..239
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 240..262
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 263..351
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 36..130
FT /note="Ig-like V-type"
FT DOMAIN 147..210
FT /note="Ig-like C2-type"
FT REGION 272..295
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 293..298
FT /note="ITSM 1"
FT /evidence="ECO:0000250|UniProtKB:Q13291"
FT MOTIF 317..322
FT /note="ITSM 2"
FT /evidence="ECO:0000250|UniProtKB:Q13291"
FT COMPBIAS 273..295
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 319
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q96DU3"
FT CARBOHYD 82
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 101
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 112
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 152
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 159
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 172
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 186
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 193
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 218
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 162..229
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 168..210
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 305..328
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:21422172"
FT /id="VSP_058034"
FT VAR_SEQ 328..331
FT /note="ETVA -> AEYS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11132158"
FT /id="VSP_010404"
FT VAR_SEQ 332..351
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11132158"
FT /id="VSP_010405"
FT MUTAGEN 295
FT /note="Y->F: Decreases inhibitory signaling in germinal
FT center formation (absence of SH2D1A/SAP); when associated
FT with F-319 and F-349."
FT /evidence="ECO:0000269|PubMed:22683125"
FT MUTAGEN 295
FT /note="Y->F: Strong inhibitory signaling in germinal center
FT formation (absence of SH2D1A/SAP); when associated with F-
FT 335 and F-349."
FT /evidence="ECO:0000269|PubMed:22683125"
FT MUTAGEN 319
FT /note="Y->F: Decreases inhibitory signaling in germinal
FT center formation (absence of SH2D1A/SAP); when associated
FT with F-295 and F-349."
FT /evidence="ECO:0000269|PubMed:22683125"
FT MUTAGEN 319
FT /note="Y->F: Strong inhibitory signaling in germinal center
FT formation (absence of SH2D1A/SAP); when associated with F-
FT 335 and F-349."
FT /evidence="ECO:0000269|PubMed:22683125"
FT MUTAGEN 335
FT /note="Y->F: Strong inhibitory signaling in germinal center
FT formation (absence of SH2D1A/SAP); when associated with F-
FT 295 and F-349."
FT /evidence="ECO:0000269|PubMed:22683125"
FT MUTAGEN 335
FT /note="Y->F: Strong inhibitory signaling in germinal center
FT formation (absence of SH2D1A/SAP); when associated with F-
FT 319 and F-349."
FT /evidence="ECO:0000269|PubMed:22683125"
FT MUTAGEN 349
FT /note="Y->F: Decreases inhibitory signaling in germinal
FT center formation (absence of SH2D1A/SAP); when associated
FT with F-295 and F-319."
FT /evidence="ECO:0000269|PubMed:22683125"
FT MUTAGEN 349
FT /note="Y->F: Strong inhibitory signaling in germinal center
FT formation (absence of SH2D1A/SAP); when associated with F-
FT 295 and F-335."
FT /evidence="ECO:0000269|PubMed:22683125"
FT MUTAGEN 349
FT /note="Y->F: Strong inhibitory signaling in germinal center
FT formation (absence of SH2D1A/SAP); when associated with F-
FT 319 and F-335."
FT /evidence="ECO:0000269|PubMed:22683125"
SQ SEQUENCE 351 AA; 38638 MW; A8DD9EBF650FB431 CRC64;
MAVSRAPAPD SACQRMVWLF PLVFCLGSGS EVSQSSSDPQ LMNGVLGESA VLPLKLPAGK
IANIIIWNYE WEASQVTALV INLSNPESPQ IMNTDVKKRL NITQSYSLQI SNLTMADTGS
YTAQITTKDS EVITFKYILR VFERLGNLET TNYTLLLENG TCQIHLACVL KNQSQTVSVE
WQATGNISLG GPNVTIFWDP RNSGDQTYVC RAKNAVSNLS VSVSTQSLCK GVLTNPPWNA
VWFMTTISII SAVILIFVCW SIHVWKRRGS LPLTSQHPES SQSTDGPGSP GNTVYAQVTR
PMQEMKIPKP IKNDSMTIYS IVNHSREETV ALTGYNQPIT LKVNTLINYN S
