SIG10_MOUSE
ID SIG10_MOUSE Reviewed; 688 AA.
AC Q80ZE3;
DT 30-AUG-2017, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Sialic acid-binding Ig-like lectin 10;
DE Short=Siglec-10;
DE AltName: Full=Sialic acid-binding Ig-like lectin G;
DE Short=Siglec-G;
DE Short=mSiglec-G;
DE Flags: Precursor;
GN Name=Siglec10; Synonyms=Siglecg;
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].
RC STRAIN=BALB/cJ;
RX PubMed=14559209; DOI=10.1016/s0888-7543(03)00171-x;
RA Aizawa H., Zimmermann N., Carrigan P.E., Lee J.J., Rothenberg M.E.,
RA Bochner B.S.;
RT "Molecular analysis of human Siglec-8 orthologs relevant to mouse
RT eosinophils: identification of mouse orthologs of Siglec-5 (mSiglec-F) and
RT Siglec-10 (mSiglec-G).";
RL Genomics 82:521-530(2003).
RN [2]
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 [3]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=17572677; DOI=10.1038/ni1480;
RA Hoffmann A., Kerr S., Jellusova J., Zhang J., Weisel F., Wellmann U.,
RA Winkler T.H., Kneitz B., Crocker P.R., Nitschke L.;
RT "Siglec-G is a B1 cell-inhibitory receptor that controls expansion and
RT calcium signaling of the B1 cell population.";
RL Nat. Immunol. 8:695-704(2007).
RN [4]
RP FUNCTION, AND INTERACTION WITH CD24 AND HMGB1.
RX PubMed=19264983; DOI=10.1126/science.1168988;
RA Chen G.Y., Tang J., Zheng P., Liu Y.;
RT "CD24 and Siglec-10 selectively repress tissue damage-induced immune
RT responses.";
RL Science 323:1722-1725(2009).
RN [5]
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 [6]
RP FUNCTION.
RX PubMed=20038598; DOI=10.1084/jem.20091873;
RA Duong B.H., Tian H., Ota T., Completo G., Han S., Vela J.L., Ota M.,
RA Kubitz M., Bovin N., Paulson J.C., Paulson J., Nemazee D.;
RT "Decoration of T-independent antigen with ligands for CD22 and Siglec-G can
RT suppress immunity and induce B cell tolerance in vivo.";
RL J. Exp. Med. 207:173-187(2010).
RN [7]
RP FUNCTION.
RX PubMed=23836061; DOI=10.4049/jimmunol.1300921;
RA Pfrengle F., Macauley M.S., Kawasaki N., Paulson J.C.;
RT "Copresentation of antigen and ligands of Siglec-G induces B cell tolerance
RT independent of CD22.";
RL J. Immunol. 191:1724-1731(2013).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=20200274; DOI=10.4049/jimmunol.0902711;
RA Jellusova J., Wellmann U., Amann K., Winkler T.H., Nitschke L.;
RT "CD22 x Siglec-G double-deficient mice have massively increased B1 cell
RT numbers and develop systemic autoimmunity.";
RL J. Immunol. 184:3618-3627(2010).
RN [9]
RP FUNCTION, INTERACTION WITH DDX58; CBL AND PTPN11, AND MUTAGENESIS OF
RP TYR-590; TYR-635; TYR-659 AND TYR-682.
RX PubMed=23374343; DOI=10.1016/j.cell.2013.01.011;
RA Chen W., Han C., Xie B., Hu X., Yu Q., Shi L., Wang Q., Li D., Wang J.,
RA Zheng P., Liu Y., Cao X.;
RT "Induction of Siglec-G by RNA viruses inhibits the innate immune response
RT by promoting RIG-I degradation.";
RL Cell 152:467-478(2013).
RN [10]
RP FUNCTION, MUTAGENESIS OF ARG-120, AND SUBUNIT.
RX PubMed=24790146; DOI=10.4049/jimmunol.1302875;
RA Hutzler S., Oezgoer L., Naito-Matsui Y., Klaesener K., Winkler T.H.,
RA Reth M., Nitschke L.;
RT "The ligand-binding domain of Siglec-G is crucial for its selective
RT inhibitory function on B1 cells.";
RL J. Immunol. 192:5406-5414(2014).
RN [11]
RP FUNCTION, AND INTERACTION WITH PTPN6 AND NCF1.
RX PubMed=27548433; DOI=10.1038/ni.3535;
RA Ding Y., Guo Z., Liu Y., Li X., Zhang Q., Xu X., Gu Y., Zhang Y., Zhao D.,
RA Cao X.;
RT "The lectin Siglec-G inhibits dendritic cell cross-presentation by
RT impairing MHC class I-peptide complex formation.";
RL Nat. Immunol. 17:1167-1175(2016).
CC -!- FUNCTION: Putative adhesion molecule that mediates sialic-acid
CC dependent binding to cells. Preferentially binds to alpha-2,3- or
CC alpha-2,6-linked sialic acid (PubMed:20038598). The sialic acid
CC recognition site may be masked by cis interactions with sialic acids on
CC the same cell surface. In the immune response, seems to act as an
CC inhibitory receptor upon ligand induced tyrosine phosphorylation by
CC recruiting cytoplasmic phosphatase(s) via their SH2 domain(s) that
CC block signal transduction through dephosphorylation of signaling
CC molecules (By similarity). Involved in negative regulation of B-cell
CC antigen receptor signaling and specifically acts on B1 cells to inhibit
CC Ca(2+) signaling, cellular expansion and antibody secretion
CC (PubMed:17572677). The inhibition of B cell activation is dependent on
CC PTPN6/SHP-1 (PubMed:23836061). In association with CD24 may be involved
CC in the selective suppression of the immune response to danger-
CC associated molecular patterns (DAMPs) such as HMGB1, HSP70 and HSP90
CC (PubMed:19264983). In association with CD24 may regulate the immune
CC repsonse of natural killer (NK) cells (By similarity). Plays a role in
CC the control of autoimmunity (PubMed:20200274). During initiation of
CC adaptive immune responses by CD8-alpha(+) dendritic cells inhibits
CC cross-presentation by impairing the formation of MHC class I-peptide
CC complexes. The function seems to implicate recruitment of PTPN6/SHP-1,
CC which dephosphorylates NCF1 of the NADPH oxidase complex consequently
CC promoting phagosomal acidification (PubMed:27548433).
CC {ECO:0000250|UniProtKB:Q96LC7, ECO:0000269|PubMed:17572677,
CC ECO:0000269|PubMed:19264983, ECO:0000269|PubMed:20038598,
CC ECO:0000269|PubMed:20200274, ECO:0000269|PubMed:27548433}.
CC -!- FUNCTION: (Microbial infection) During infection by RNA viruses
CC inhibits DDX58/RIG-I signaling in macrophages by promoting its CBL-
CC dependent ubiquitination and degradation via PTPN11/SHP-2.
CC {ECO:0000269|PubMed:23374343}.
CC -!- SUBUNIT: Interacts with PTPN6/SHP-1 upon phosphorylation. Interacts
CC with NCF1 (PubMed:27548433). Interacts with CD24; the probable
CC CD24:SIGLEC10 complex is proposed to inhibit HGMB1-mediated tissue
CC damage immune response. Interacts with HMGB1; the interaction is
CC dependent on CD24 (PubMed:19264983). Associates with membrane IgM on
CC the B cell surface (PubMed:24790146). Interacts with DDX58, CBL and
CC PTPN11 (PubMed:23374343). {ECO:0000250|UniProtKB:Q96LC7,
CC ECO:0000269|PubMed:19264983, ECO:0000269|PubMed:23374343,
CC ECO:0000269|PubMed:24790146, ECO:0000269|PubMed:27548433}.
CC -!- INTERACTION:
CC Q80ZE3; Q6Q899: Ddx58; NbExp=7; IntAct=EBI-6841023, EBI-6841237;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q96LC7};
CC Single-pass type I membrane protein.
CC -!- TISSUE SPECIFICITY: Expressed in B cells with high levels in pre-B
CC cells and B1a cells of the peritoneal cavity.
CC {ECO:0000269|PubMed:17572677}.
CC -!- DOMAIN: Contains 1 copy of a cytoplasmic motif that is referred to as
CC the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is
CC involved in modulation of cellular responses. The phosphorylated ITIM
CC motif can bind the SH2 domain of several SH2-containing phosphatases.
CC -!- PTM: Phosphorylation of Tyr-659 is involved in binding to PTPN6.
CC {ECO:0000250|UniProtKB:Q96LC7}.
CC -!- DISRUPTION PHENOTYPE: Cd22/Siglec10 double-deficient mice develop
CC autoimmune disease, which is not observed in single-deficient mice.
CC {ECO:0000269|PubMed:20200274}.
CC -!- SIMILARITY: Belongs to the immunoglobulin superfamily. SIGLEC (sialic
CC acid binding Ig-like lectin) family. {ECO:0000305}.
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DR EMBL; AY210400; AAO48273.1; -; mRNA.
DR EMBL; AC149091; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS52221.1; -.
DR RefSeq; NP_766488.2; NM_172900.3.
DR AlphaFoldDB; Q80ZE3; -.
DR SMR; Q80ZE3; -.
DR IntAct; Q80ZE3; 5.
DR STRING; 10090.ENSMUSP00000005592; -.
DR GlyGen; Q80ZE3; 2 sites.
DR iPTMnet; Q80ZE3; -.
DR PhosphoSitePlus; Q80ZE3; -.
DR MaxQB; Q80ZE3; -.
DR PaxDb; Q80ZE3; -.
DR PRIDE; Q80ZE3; -.
DR ProteomicsDB; 257177; -.
DR DNASU; 243958; -.
DR Ensembl; ENSMUST00000005592; ENSMUSP00000005592; ENSMUSG00000030468.
DR GeneID; 243958; -.
DR KEGG; mmu:243958; -.
DR UCSC; uc009gmo.1; mouse.
DR CTD; 243958; -.
DR MGI; MGI:2443630; Siglecg.
DR VEuPathDB; HostDB:ENSMUSG00000030468; -.
DR eggNOG; ENOG502S41V; Eukaryota.
DR GeneTree; ENSGT01040000240469; -.
DR HOGENOM; CLU_024444_5_1_1; -.
DR InParanoid; Q80ZE3; -.
DR OMA; CEAWNTH; -.
DR OrthoDB; 1124645at2759; -.
DR PhylomeDB; Q80ZE3; -.
DR TreeFam; TF332441; -.
DR Reactome; R-MMU-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR Reactome; R-MMU-2172127; DAP12 interactions.
DR BioGRID-ORCS; 243958; 1 hit in 72 CRISPR screens.
DR ChiTaRS; Siglecg; mouse.
DR PRO; PR:Q80ZE3; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q80ZE3; protein.
DR Bgee; ENSMUSG00000030468; Expressed in mesenteric lymph node and 43 other tissues.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0030246; F:carbohydrate binding; IEA:UniProtKB-KW.
DR GO; GO:0019902; F:phosphatase binding; ISO:MGI.
DR GO; GO:0042169; F:SH2 domain binding; ISO:MGI.
DR GO; GO:0033691; F:sialic acid binding; ISO:MGI.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0007155; P:cell adhesion; IBA:GO_Central.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IMP:MGI.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0050849; P:negative regulation of calcium-mediated signaling; IGI:ARUK-UCL.
DR GO; GO:0002638; P:negative regulation of immunoglobulin production; IGI:ARUK-UCL.
DR GO; GO:0106015; P:negative regulation of inflammatory response to wounding; IPI:UniProtKB.
DR GO; GO:0030888; P:regulation of B cell proliferation; IMP:ARUK-UCL.
DR GO; GO:0050776; P:regulation of immune response; IGI:ARUK-UCL.
DR Gene3D; 2.60.40.10; -; 4.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR013098; Ig_I-set.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR013106; Ig_V-set.
DR Pfam; PF07679; I-set; 1.
DR Pfam; PF07686; V-set; 1.
DR SMART; SM00409; IG; 4.
DR SMART; SM00408; IGc2; 2.
DR SUPFAM; SSF48726; SSF48726; 4.
DR PROSITE; PS50835; IG_LIKE; 3.
PE 1: Evidence at protein level;
KW Adaptive immunity; Cell adhesion; Cell membrane; Disulfide bond;
KW Glycoprotein; Immunity; Immunoglobulin domain; Innate immunity; Lectin;
KW Membrane; Phosphoprotein; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT CHAIN 18..688
FT /note="Sialic acid-binding Ig-like lectin 10"
FT /evidence="ECO:0000255"
FT /id="PRO_5010508953"
FT TOPO_DOM 18..543
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 544..564
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 565..688
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 26..138
FT /note="Ig-like V-type"
FT DOMAIN 145..228
FT /note="Ig-like C2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DOMAIN 250..334
FT /note="Ig-like C2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DOMAIN 339..436
FT /note="Ig-like C2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT REGION 602..656
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 588..593
FT /note="ITIM motif 1"
FT /evidence="ECO:0000250|UniProtKB:Q96LC7"
FT MOTIF 657..662
FT /note="ITIM motif 2"
FT /evidence="ECO:0000250|UniProtKB:Q96LC7"
FT COMPBIAS 619..633
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 638..652
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 120
FT /ligand="N-acetylneuraminate"
FT /ligand_id="ChEBI:CHEBI:35418"
FT /evidence="ECO:0000250"
FT MOD_RES 659
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q96LC7"
FT CARBOHYD 195
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 246
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 37..172
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 42..102
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 163..214
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 271..318
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 375..420
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT MUTAGEN 120
FT /note="R->E: Decreases interaction with membrane IgM (with
FT greater effect in B1a than in B2 cells)."
FT /evidence="ECO:0000269|PubMed:24790146"
FT MUTAGEN 590
FT /note="Y->F: Decreases interaction with DDX58; when
FT associated with F-635, F-659 and F-682."
FT /evidence="ECO:0000269|PubMed:23374343"
FT MUTAGEN 635
FT /note="Y->F: Decreases interaction with DDX58; when
FT associated with F-590, F-659 and F-682."
FT /evidence="ECO:0000269|PubMed:23374343"
FT MUTAGEN 659
FT /note="Y->F: Decreases interaction with DDX58; when
FT associated with F-590,F-635 and F-682."
FT /evidence="ECO:0000269|PubMed:23374343"
FT MUTAGEN 682
FT /note="Y->F: Decreases interaction with DDX58; when
FT associated with F-590, F-635 and F-659."
FT /evidence="ECO:0000269|PubMed:23374343"
SQ SEQUENCE 688 AA; 76884 MW; 21A619E1500BFA76 CRC64;
MSLLLFLLSF LLDGPQGQME SYFLQVQRIV KAQEGLCIFV PCSFSSPEGK WLNRSPLYGY
WFKGIRKPSL SFPVATNNKD KVLEWEARGR FQLLGDISKK NCSLLIKDVQ WGDSTNYFFR
MERGFERFSF KEEFRLQVEA LTQKPDIFIP EVLEPGEPVT VVCLFSWTFN QCPAPSFSWM
GDAVSFQESR PHTSNYSVLS FIPGLQHHDT ELTCQLDFSR MSTQRTVRLR VAYAPRSLAI
SIFHDNVSVP DLHENPSHLE VQQGQSLRLL CTADSQPPAT LSWVLEDQVL SWSSPVGSRT
LALELPWVKA GDSGHYTCQA ENRLGSQQHT LDLSVLYPPQ DLRVTVSQAN RTVLEILRNA
ISLPVLEGQS LCLVCVTYSN PPANVSWAWV TQTLIPIQSS EPGVLELPLV QREHEGEFTC
AAQNPLGAQR ISLSLSVHYP PQMSSPSCSW EAKGLHCNCS SRAWPAPSLR WRLGEGLLEG
NSSNASFTVT FSSLGPWVNS SLSLLQELGP SLWLSCESWN THGAQTTSVL LLPDKDSATA
FSKGAVLGFG ITALLALCLI VVIVKTLQKK GTQEEPSRPK LSRGSTILDY INVVPKTRSL
ARNWKAEPDA PSRSSPLDTH FPKPKKKQKD PHFTYPGCPD PTSSSQVPVS ENNPEELHYA
ALNFSRLRLQ ETQDPQDTYS DYTEVRVH
