SIG12_MOUSE
ID SIG12_MOUSE Reviewed; 467 AA.
AC Q91Y57; E9QMD1;
DT 08-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Sialic acid-binding Ig-like lectin 12;
DE Short=Siglec-12;
DE AltName: Full=Myeloid inhibitory siglec;
DE Short=MIS;
DE AltName: Full=Sialic acid-binding Ig-like lectin 5;
DE Short=Siglec-5;
DE AltName: Full=Sialic acid-binding Ig-like lectin E;
DE Short=Siglec-E;
DE Short=mSiglec-E;
DE AltName: Full=Sialic acid-binding Ig-like lectin-like 1;
DE Short=Siglec-L1;
DE Flags: Precursor;
GN Name=Siglec12; Synonyms=Siglec5, Siglece, Siglecl1;
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], PHOSPHORYLATION AT TYR-432 AND TYR-455,
RP MUTAGENESIS OF TYR-432 AND TYR-455, AND INTERACTION WITH PTPN6 AND PTPN11.
RX PubMed=11171044; DOI=10.1042/0264-6021:3530483;
RA Yu Z., Maoui M., Wu L., Banville D., Shen S.H.;
RT "mSiglec-E, a novel mouse CD33-related siglec (sialic acid-binding
RT immunoglobulin-like lectin) that recruits Src homology 2 (SH2)-domain-
RT containing protein tyrosine phosphatases SHP-1 and SHP-2.";
RL Biochem. J. 353:483-492(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], PHOSPHORYLATION, MUTAGENESIS OF TYR-432 AND
RP TYR-455, AND INTERACTION WITH PTPN6 AND PTPN11.
RC STRAIN=C57BL/6J; TISSUE=Bone marrow;
RX PubMed=11278955; DOI=10.1074/jbc.m011650200;
RA Ulyanova T., Shah D.D., Thomas M.L.;
RT "Molecular cloning of MIS, a myeloid inhibitory siglec, that binds protein
RT tyrosine phosphatases SHP-1 and SHP-2.";
RL J. Biol. Chem. 276:14451-14458(2001).
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).
CC -!- FUNCTION: Putative adhesion molecule that mediates sialic-acid
CC dependent binding to cells. The sialic acid recognition site may be
CC masked by cis interactions with sialic acids on the same cell surface.
CC In the immune response, may act as an inhibitory receptor upon ligand
CC induced tyrosine phosphorylation by recruiting cytoplasmic
CC phosphatase(s) via their SH2 domain(s) that block signal transduction
CC through dephosphorylation of signaling molecules.
CC -!- SUBUNIT: Homodimer; disulfide-linked. Interacts with PTPN6/SHP-1 and
CC PTPN11/SHP-2 upon phosphorylation. {ECO:0000269|PubMed:11171044,
CC ECO:0000269|PubMed:11278955}.
CC -!- INTERACTION:
CC Q91Y57; Q9QUK6: Tlr4; NbExp=3; IntAct=EBI-16826475, EBI-1534575;
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC -!- TISSUE SPECIFICITY: Expressed by monocytic/myeloid lineage cells. Found
CC at higher levels in spleen, liver and heart. Found at lower levels in
CC kidney and lung.
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-432 is required for binding to PTPN6 and
CC PTPN11. Phosphorylation of Tyr-455 is involved in binding to PTPN6.
CC Tyr-432 needs to be phosphorylated prior to Tyr-455.
CC {ECO:0000269|PubMed:11171044, ECO:0000269|PubMed:11278955}.
CC -!- SIMILARITY: Belongs to the immunoglobulin superfamily. SIGLEC (sialic
CC acid binding Ig-like lectin) family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - Glycan Binding;
CC Note=Siglec-E;
CC URL="http://www.functionalglycomics.org/glycomics/GBPServlet?&operationType=view&cbpId=cbp_mou_Itlect_197";
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DR EMBL; AF317298; AAG38598.1; -; mRNA.
DR EMBL; AF329269; AAK49917.1; -; mRNA.
DR EMBL; AC151989; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS21178.1; -.
DR RefSeq; NP_112458.2; NM_031181.2.
DR AlphaFoldDB; Q91Y57; -.
DR SMR; Q91Y57; -.
DR BioGRID; 219910; 5.
DR ELM; Q91Y57; -.
DR IntAct; Q91Y57; 1.
DR STRING; 10090.ENSMUSP00000032667; -.
DR GlyGen; Q91Y57; 10 sites.
DR iPTMnet; Q91Y57; -.
DR PhosphoSitePlus; Q91Y57; -.
DR SwissPalm; Q91Y57; -.
DR MaxQB; Q91Y57; -.
DR PaxDb; Q91Y57; -.
DR PRIDE; Q91Y57; -.
DR ProteomicsDB; 261040; -.
DR DNASU; 83382; -.
DR Ensembl; ENSMUST00000032667; ENSMUSP00000032667; ENSMUSG00000030474.
DR GeneID; 83382; -.
DR KEGG; mmu:83382; -.
DR UCSC; uc009gng.1; mouse.
DR CTD; 83382; -.
DR MGI; MGI:1932475; Siglece.
DR VEuPathDB; HostDB:ENSMUSG00000030474; -.
DR eggNOG; ENOG502S41V; Eukaryota.
DR GeneTree; ENSGT01040000240469; -.
DR HOGENOM; CLU_024444_6_1_1; -.
DR InParanoid; Q91Y57; -.
DR OMA; YPPWNLT; -.
DR OrthoDB; 324083at2759; -.
DR PhylomeDB; Q91Y57; -.
DR TreeFam; TF332441; -.
DR Reactome; R-MMU-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR BioGRID-ORCS; 83382; 3 hits in 75 CRISPR screens.
DR ChiTaRS; Siglece; mouse.
DR PRO; PR:Q91Y57; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q91Y57; protein.
DR Bgee; ENSMUSG00000030474; Expressed in granulocyte and 51 other tissues.
DR ExpressionAtlas; Q91Y57; baseline and differential.
DR Genevisible; Q91Y57; MM.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
DR GO; GO:0016021; C:integral component of membrane; ISS:MGI.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0048029; F:monosaccharide binding; IDA:MGI.
DR GO; GO:0033691; F:sialic acid binding; IDA:MGI.
DR GO; GO:0007155; P:cell adhesion; IDA:MGI.
DR GO; GO:0006954; P:inflammatory response; IMP:MGI.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IMP:MGI.
DR GO; GO:0060101; P:negative regulation of phagocytosis, engulfment; IDA:MGI.
DR GO; GO:0006911; P:phagocytosis, engulfment; IMP:MGI.
DR Gene3D; 2.60.40.10; -; 3.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003006; Ig/MHC_CS.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR013106; Ig_V-set.
DR Pfam; PF07686; V-set; 1.
DR SMART; SM00409; IG; 3.
DR SMART; SM00408; IGc2; 1.
DR SUPFAM; SSF48726; SSF48726; 3.
DR PROSITE; PS50835; IG_LIKE; 3.
DR PROSITE; PS00290; IG_MHC; 1.
PE 1: Evidence at protein level;
KW Cell adhesion; Disulfide bond; Glycoprotein; Immunoglobulin domain; Lectin;
KW Membrane; Phosphoprotein; Reference proteome; Repeat; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..467
FT /note="Sialic acid-binding Ig-like lectin 12"
FT /id="PRO_0000014954"
FT TOPO_DOM 19..353
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 354..374
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 375..467
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 21..141
FT /note="Ig-like V-type"
FT DOMAIN 152..239
FT /note="Ig-like C2-type 1"
FT DOMAIN 242..339
FT /note="Ig-like C2-type 2"
FT MOTIF 430..435
FT /note="ITIM motif"
FT MOTIF 453..458
FT /note="SLAM-like motif"
FT BINDING 126
FT /ligand="N-acetylneuraminate"
FT /ligand_id="ChEBI:CHEBI:35418"
FT /evidence="ECO:0000250"
FT MOD_RES 432
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:11171044"
FT MOD_RES 455
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:11171044"
FT CARBOHYD 46
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 167
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 197
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 216
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 227
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 237
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 244
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 262
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 287
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 294
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 40..176
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 45..108
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 170..219
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 278..323
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT MUTAGEN 432
FT /note="Y->F: Abolishes binding to PTPN6 and PTPN11."
FT /evidence="ECO:0000269|PubMed:11171044,
FT ECO:0000269|PubMed:11278955"
FT MUTAGEN 455
FT /note="Y->F: Reduces binding to PTPN6."
FT /evidence="ECO:0000269|PubMed:11171044,
FT ECO:0000269|PubMed:11278955"
FT CONFLICT 2
FT /note="L -> M (in Ref. 2; AAK49917)"
FT /evidence="ECO:0000305"
FT CONFLICT 24
FT /note="V -> G (in Ref. 2; AAK49917)"
FT /evidence="ECO:0000305"
FT CONFLICT 102
FT /note="D -> E (in Ref. 2; AAK49917)"
FT /evidence="ECO:0000305"
FT CONFLICT 234
FT /note="I -> T (in Ref. 1; AAG38598)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 467 AA; 51901 MW; E220C29755FE21DE CRC64;
MLLLLLLLLL WGIKGVEGQN PQEVFTLNVE RKVVVQEGLC VLVPCNFSYL KKRLTDWTDS
DPVHGFWYRE GTDRRKDSIV ATNNPIRKAV KETRNRFFLL GDPWRNDCSL NIREIRKKDA
GLYFFRLERG KTKYNYMWDK MTLVVTALTN TPQILLPETL EAGHPSNLTC SVPWDCGWTA
PPIFSWTGTS VSFLSTNTTG SSVLTITPQP QDHGTNLTCQ VTLPGTNVST RMTIRLNVSY
APKNLTVTIY QGADSVSTIL KNGSSLPISE GQSLRLICST DSYPPANLSW SWDNLTLCPS
KLSKPGLLEL FPVHLKHGGV YTCQAQHALG SQHISLSLSP QSSATLSEMM MGTFVGSGVT
ALLFLSVCIL LLAVRSYRRK PARPAVVAPH PDALKVSVSQ NPLVESQADD SSEPLPSILE
AAPSSTEEEI HYATLSFHEM KPMNLWGQQD TTTEYSEIKF PQRTAWP
