SIG12_HUMAN
ID SIG12_HUMAN Reviewed; 595 AA.
AC Q96PQ1; Q8IYH7;
DT 08-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Sialic acid-binding Ig-like lectin 12;
DE Short=Siglec-12;
DE AltName: Full=Sialic acid-binding Ig-like lectin-like 1;
DE Short=Siglec-L1;
DE Flags: Precursor;
GN Name=SIGLEC12; Synonyms=SIGLECL1, SLG; ORFNames=UNQ9215/PRO34042;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS LONG AND SHORT).
RC TISSUE=Bone marrow;
RX PubMed=11409877; DOI=10.1006/bbrc.2001.5052;
RA Foussias G., Taylor S.M., Yousef G.M., Tropak M.B., Ordon M.H.,
RA Diamandis E.P.;
RT "Cloning and molecular characterization of two splice variants of a new
RT putative member of the Siglec-3-like subgroup of Siglecs.";
RL Biochem. Biophys. Res. Commun. 284:887-899(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
RX PubMed=11546777; DOI=10.1074/jbc.m105926200;
RA Angata T., Varki N.M., Varki A.;
RT "A second uniquely human mutation affecting sialic acid biology.";
RL J. Biol. Chem. 276:40282-40287(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
RC TISSUE=Blood;
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).
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 -!- INTERACTION:
CC Q96PQ1; Q96CM8: ACSF2; NbExp=3; IntAct=EBI-17640454, EBI-2876502;
CC Q96PQ1; Q15848: ADIPOQ; NbExp=3; IntAct=EBI-17640454, EBI-10827839;
CC Q96PQ1; P18859: ATP5PF; NbExp=3; IntAct=EBI-17640454, EBI-2606700;
CC Q96PQ1; O14735: CDIPT; NbExp=3; IntAct=EBI-17640454, EBI-358858;
CC Q96PQ1; Q6UXB4: CLEC4G; NbExp=3; IntAct=EBI-17640454, EBI-2114729;
CC Q96PQ1; Q96LL9: DNAJC30; NbExp=3; IntAct=EBI-17640454, EBI-8639143;
CC Q96PQ1; Q01638-2: IL1RL1; NbExp=3; IntAct=EBI-17640454, EBI-12838366;
CC Q96PQ1; P10620: MGST1; NbExp=3; IntAct=EBI-17640454, EBI-2691601;
CC Q96PQ1; Q8IY26: PLPP6; NbExp=3; IntAct=EBI-17640454, EBI-11721828;
CC Q96PQ1; Q96GM1: PLPPR2; NbExp=3; IntAct=EBI-17640454, EBI-12955265;
CC Q96PQ1; Q59EV6: PPGB; NbExp=3; IntAct=EBI-17640454, EBI-14210385;
CC Q96PQ1; Q13635-3: PTCH1; NbExp=3; IntAct=EBI-17640454, EBI-14199621;
CC Q96PQ1; Q9NRS4: TMPRSS4; NbExp=3; IntAct=EBI-17640454, EBI-10313040;
CC Q96PQ1; Q9Y548: YIPF1; NbExp=3; IntAct=EBI-17640454, EBI-7850136;
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long; Synonyms=SLG-L;
CC IsoId=Q96PQ1-1; Sequence=Displayed;
CC Name=Short; Synonyms=SLG-S;
CC IsoId=Q96PQ1-2; Sequence=VSP_002566;
CC -!- TISSUE SPECIFICITY: Isoform Short is highly expressed in spleen, small
CC intestine and adrenal gland; it is lower expressed in thyroid,
CC placenta, brain, stomach, bone marrow, spinal cord and breast. Isoform
CC Long is highly expressed in spleen, small intestine and bone marrow; it
CC is lower expressed in thyroid, placenta, thymus, trachea, stomach,
CC lung, adrenal gland, fetal brain and testis.
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 -!- 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-L1;
CC URL="http://www.functionalglycomics.org/glycomics/GBPServlet?&operationType=view&cbpId=cbp_hum_Itlect_276";
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DR EMBL; AF277806; AAK51233.1; -; Genomic_DNA.
DR EMBL; AF277806; AAK51234.1; -; Genomic_DNA.
DR EMBL; AF282256; AAK71521.1; -; mRNA.
DR EMBL; AY358140; AAQ88507.1; -; mRNA.
DR EMBL; BC035809; AAH35809.2; -; mRNA.
DR CCDS; CCDS12833.1; -. [Q96PQ1-1]
DR CCDS; CCDS59416.1; -. [Q96PQ1-2]
DR RefSeq; NP_201586.1; NM_033329.2. [Q96PQ1-2]
DR RefSeq; NP_443729.1; NM_053003.3. [Q96PQ1-1]
DR RefSeq; XP_011525743.1; XM_011527441.2. [Q96PQ1-2]
DR AlphaFoldDB; Q96PQ1; -.
DR BioGRID; 124623; 72.
DR IntAct; Q96PQ1; 22.
DR STRING; 9606.ENSP00000291707; -.
DR GlyGen; Q96PQ1; 7 sites.
DR iPTMnet; Q96PQ1; -.
DR PhosphoSitePlus; Q96PQ1; -.
DR BioMuta; SIGLEC12; -.
DR DMDM; 25009264; -.
DR MassIVE; Q96PQ1; -.
DR PaxDb; Q96PQ1; -.
DR PeptideAtlas; Q96PQ1; -.
DR PRIDE; Q96PQ1; -.
DR ProteomicsDB; 77728; -. [Q96PQ1-1]
DR ProteomicsDB; 77729; -. [Q96PQ1-2]
DR Antibodypedia; 52796; 210 antibodies from 26 providers.
DR DNASU; 89858; -.
DR Ensembl; ENST00000291707.8; ENSP00000291707.3; ENSG00000254521.7. [Q96PQ1-1]
DR Ensembl; ENST00000598614.1; ENSP00000472873.1; ENSG00000254521.7. [Q96PQ1-2]
DR GeneID; 89858; -.
DR KEGG; hsa:89858; -.
DR MANE-Select; ENST00000291707.8; ENSP00000291707.3; NM_053003.4; NP_443729.1.
DR UCSC; uc002pww.3; human. [Q96PQ1-1]
DR CTD; 89858; -.
DR DisGeNET; 89858; -.
DR GeneCards; SIGLEC12; -.
DR HGNC; HGNC:15482; SIGLEC12.
DR HPA; ENSG00000254521; Group enriched (intestine, lymphoid tissue).
DR MIM; 606094; gene.
DR neXtProt; NX_Q96PQ1; -.
DR OpenTargets; ENSG00000254521; -.
DR PharmGKB; PA37966; -.
DR VEuPathDB; HostDB:ENSG00000254521; -.
DR eggNOG; ENOG502S41V; Eukaryota.
DR GeneTree; ENSGT01040000240469; -.
DR HOGENOM; CLU_024444_6_1_1; -.
DR InParanoid; Q96PQ1; -.
DR OMA; IDMEGAN; -.
DR OrthoDB; 324083at2759; -.
DR PhylomeDB; Q96PQ1; -.
DR PathwayCommons; Q96PQ1; -.
DR Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR SignaLink; Q96PQ1; -.
DR BioGRID-ORCS; 89858; 6 hits in 1068 CRISPR screens.
DR GeneWiki; Sialic_acid-binding_Ig-like_lectin_12; -.
DR GenomeRNAi; 89858; -.
DR Pharos; Q96PQ1; Tbio.
DR PRO; PR:Q96PQ1; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q96PQ1; protein.
DR Bgee; ENSG00000254521; Expressed in spleen and 71 other tissues.
DR ExpressionAtlas; Q96PQ1; baseline and differential.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0030246; F:carbohydrate binding; IEA:UniProtKB-KW.
DR GO; GO:0033691; F:sialic acid binding; IBA:GO_Central.
DR GO; GO:0007155; P:cell adhesion; IBA:GO_Central.
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; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR013106; Ig_V-set.
DR Pfam; PF07686; V-set; 2.
DR SMART; SM00409; IG; 4.
DR SMART; SM00408; IGc2; 3.
DR SUPFAM; SSF48726; SSF48726; 4.
DR PROSITE; PS50835; IG_LIKE; 3.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell adhesion; Disulfide bond; Glycoprotein;
KW Immunoglobulin domain; Lectin; Membrane; Phosphoprotein;
KW Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..595
FT /note="Sialic acid-binding Ig-like lectin 12"
FT /id="PRO_0000014953"
FT TOPO_DOM 19..481
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 482..502
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 503..595
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 19..142
FT /note="Ig-like V-type 1"
FT DOMAIN 143..269
FT /note="Ig-like V-type 2"
FT DOMAIN 275..358
FT /note="Ig-like C2-type 1"
FT DOMAIN 365..462
FT /note="Ig-like C2-type 2"
FT REGION 512..560
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 563..568
FT /note="ITIM motif"
FT MOTIF 586..591
FT /note="SLAM-like motif"
FT MOD_RES 565
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q91Y57"
FT MOD_RES 588
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q91Y57"
FT CARBOHYD 140
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 179
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 230
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 290
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 360
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 367
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 385
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 44..104
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 166..299
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 171..231
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 293..342
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 401..446
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 4..141
FT /note="LLLLLPPLLCGRVGAKEQKDYLLTMQKSVTVQEGLCVSVLCSFSYPQNGWTA
FT SDPVHGYWFRAGDHVSRNIPVATNNPARAVQEETRDRFHLLGDPQNKDCTLSIRDTRES
FT DAGTYVFCVERGNMKWNYKYDQLSVNV -> PLLWANEERDSGGWADPRFS (in
FT isoform Short)"
FT /evidence="ECO:0000305"
FT /id="VSP_002566"
FT VARIANT 81
FT /note="P -> H (in dbSNP:rs2034891)"
FT /id="VAR_049931"
FT VARIANT 81
FT /note="P -> T (in dbSNP:rs2034891)"
FT /id="VAR_014259"
FT VARIANT 82
FT /note="A -> V (in dbSNP:rs3810110)"
FT /id="VAR_049932"
FT VARIANT 217
FT /note="H -> Q (in dbSNP:rs6509544)"
FT /id="VAR_024501"
FT VARIANT 218
FT /note="G -> R (in dbSNP:rs6509544)"
FT /id="VAR_049933"
FT VARIANT 398
FT /note="H -> Y (in dbSNP:rs11668530)"
FT /id="VAR_049934"
FT VARIANT 478
FT /note="T -> M (in dbSNP:rs3829658)"
FT /id="VAR_020088"
FT VARIANT 494
FT /note="Y -> S (in dbSNP:rs3752135)"
FT /id="VAR_020089"
FT VARIANT 546
FT /note="P -> Q (in dbSNP:rs57043266)"
FT /id="VAR_061327"
FT VARIANT 586
FT /note="Y -> C (in dbSNP:rs7245807)"
FT /id="VAR_049935"
FT CONFLICT 528
FT /note="R -> W (in Ref. 3; AAQ88507)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 595 AA; 64984 MW; D05662176274C5C3 CRC64;
MLLLLLLLPP LLCGRVGAKE QKDYLLTMQK SVTVQEGLCV SVLCSFSYPQ NGWTASDPVH
GYWFRAGDHV SRNIPVATNN PARAVQEETR DRFHLLGDPQ NKDCTLSIRD TRESDAGTYV
FCVERGNMKW NYKYDQLSVN VTASQDLLSR YRLEVPESVT VQEGLCVSVP CSVLYPHYNW
TASSPVYGSW FKEGADIPWD IPVATNTPSG KVQEDTHGRF LLLGDPQTNN CSLSIRDARK
GDSGKYYFQV ERGSRKWNYI YDKLSVHVTA LTHMPTFSIP GTLESGHPRN LTCSVPWACE
QGTPPTITWM GASVSSLDPT ITRSSMLSLI PQPQDHGTSL TCQVTLPGAG VTMTRAVRLN
ISYPPQNLTM TVFQGDGTAS TTLRNGSALS VLEGQSLHLV CAVDSNPPAR LSWTWGSLTL
SPSQSSNLGV LELPRVHVKD EGEFTCRAQN PLGSQHISLS LSLQNEYTGK MRPISGVTLG
AFGGAGATAL VFLYFCIIFV VVRSCRKKSA RPAVGVGDTG MEDANAVRGS ASQGPLIESP
ADDSPPHHAP PALATPSPEE GEIQYASLSF HKARPQYPQE QEAIGYEYSE INIPK
