SIGL9_HUMAN
ID SIGL9_HUMAN Reviewed; 463 AA.
AC Q9Y336; Q6GTU4; Q9BYI9;
DT 08-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 2.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Sialic acid-binding Ig-like lectin 9;
DE Short=Siglec-9;
DE AltName: Full=CDw329;
DE AltName: Full=Protein FOAP-9;
DE AltName: CD_antigen=CD329;
DE Flags: Precursor;
GN Name=SIGLEC9; ORFNames=UNQ668/PRO1302;
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] (ISOFORM 1).
RC TISSUE=Bone marrow;
RX PubMed=10903842; DOI=10.1006/geno.2000.6208;
RA Foussias G., Yousef G.M., Diamandis E.P.;
RT "Identification and molecular characterization of a novel member of the
RT siglec family (SIGLEC9).";
RL Genomics 67:171-178(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=10801862; DOI=10.1074/jbc.m002788200;
RA Zhang J.Q., Nicoll G., Jones C., Crocker P.R.;
RT "Siglec-9, a novel sialic acid binding member of the immunoglobulin
RT superfamily expressed broadly on human blood leukocytes.";
RL J. Biol. Chem. 275:22121-22126(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND MUTAGENESIS OF ARG-120.
RC TISSUE=Peripheral blood;
RX PubMed=10801860; DOI=10.1074/jbc.m002775200;
RA Angata T., Varki A.;
RT "Cloning, characterization, and phylogenetic analysis of siglec-9, a new
RT member of the CD33-related group of siglecs. Evidence for co-evolution with
RT sialic acid synthesis pathways.";
RL J. Biol. Chem. 275:22127-22135(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT GLU-315.
RA Takayama K., Fujii Y., Turitani K., Naitou K., Kawaguchi A., Ukai Y.,
RA Amemiya C., Yajima Y., Yazaki M.;
RT "Molecular cloning of a novel gene, FOAP-9, which are induced by oxydized
RT LDL in human macrophages.";
RL Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS GLU-100 AND GLU-315.
RC TISSUE=Brain;
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. Preferentially binds to alpha-2,3- or
CC alpha-2,6-linked sialic acid. The sialic acid recognition site may be
CC masked by cis interactions with sialic acids on the same cell surface.
CC -!- INTERACTION:
CC Q9Y336; Q6PL45-2: BRICD5; NbExp=3; IntAct=EBI-12857926, EBI-12244618;
CC Q9Y336; P62166: NCS1; NbExp=3; IntAct=EBI-12857926, EBI-746987;
CC Q9Y336; P11686: SFTPC; NbExp=3; IntAct=EBI-12857926, EBI-10197617;
CC Q9Y336; O00206: TLR4; NbExp=2; IntAct=EBI-12857926, EBI-528701;
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9Y336-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y336-2; Sequence=VSP_054106;
CC -!- TISSUE SPECIFICITY: Expressed by peripheral blood leukocytes
CC (neutrophils and monocytes but not eosinophils). Found in liver, fetal
CC liver, bone marrow, placenta, spleen and in lower levels in skeletal
CC muscle, fetal brain, stomach, lung, thymus, prostate, brain, mammary,
CC adrenal gland, colon, trachea, cerebellum, testis, small intestine and
CC spinal cordon.
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-9;
CC URL="http://www.functionalglycomics.org/glycomics/GBPServlet?&operationType=view&cbpId=cbp_hum_Itlect_275";
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DR EMBL; AF135027; AAD26428.2; -; Genomic_DNA.
DR EMBL; AF247180; AAF87223.1; -; mRNA.
DR EMBL; AF227924; AAF71455.1; -; mRNA.
DR EMBL; AB026265; BAB41100.1; -; mRNA.
DR EMBL; AY358913; AAQ89272.1; -; mRNA.
DR EMBL; AK297043; BAG59570.1; -; mRNA.
DR EMBL; AC011473; AAG23261.1; -; Genomic_DNA.
DR EMBL; BC035365; AAH35365.2; -; mRNA.
DR CCDS; CCDS12825.1; -. [Q9Y336-1]
DR CCDS; CCDS56100.1; -. [Q9Y336-2]
DR RefSeq; NP_001185487.1; NM_001198558.1. [Q9Y336-2]
DR RefSeq; NP_055256.1; NM_014441.2. [Q9Y336-1]
DR AlphaFoldDB; Q9Y336; -.
DR SMR; Q9Y336; -.
DR BioGRID; 118056; 12.
DR IntAct; Q9Y336; 14.
DR STRING; 9606.ENSP00000413861; -.
DR ChEMBL; CHEMBL4105860; -.
DR GlyGen; Q9Y336; 8 sites.
DR iPTMnet; Q9Y336; -.
DR PhosphoSitePlus; Q9Y336; -.
DR BioMuta; SIGLEC9; -.
DR DMDM; 25009270; -.
DR EPD; Q9Y336; -.
DR jPOST; Q9Y336; -.
DR MassIVE; Q9Y336; -.
DR PaxDb; Q9Y336; -.
DR PeptideAtlas; Q9Y336; -.
DR PRIDE; Q9Y336; -.
DR ProteomicsDB; 85970; -. [Q9Y336-1]
DR Antibodypedia; 2416; 603 antibodies from 33 providers.
DR CPTC; Q9Y336; 1 antibody.
DR DNASU; 27180; -.
DR Ensembl; ENST00000250360.8; ENSP00000250360.2; ENSG00000129450.9. [Q9Y336-1]
DR Ensembl; ENST00000440804.7; ENSP00000413861.2; ENSG00000129450.9. [Q9Y336-2]
DR GeneID; 27180; -.
DR KEGG; hsa:27180; -.
DR MANE-Select; ENST00000250360.8; ENSP00000250360.2; NM_014441.3; NP_055256.1.
DR UCSC; uc002pvu.4; human. [Q9Y336-1]
DR CTD; 27180; -.
DR DisGeNET; 27180; -.
DR GeneCards; SIGLEC9; -.
DR HGNC; HGNC:10878; SIGLEC9.
DR HPA; ENSG00000129450; Tissue enhanced (lymphoid).
DR MIM; 605640; gene.
DR neXtProt; NX_Q9Y336; -.
DR OpenTargets; ENSG00000129450; -.
DR PharmGKB; PA35779; -.
DR VEuPathDB; HostDB:ENSG00000129450; -.
DR eggNOG; ENOG502S41V; Eukaryota.
DR GeneTree; ENSGT01040000240469; -.
DR HOGENOM; CLU_024444_6_1_1; -.
DR InParanoid; Q9Y336; -.
DR OMA; LSFQMVK; -.
DR OrthoDB; 324083at2759; -.
DR PhylomeDB; Q9Y336; -.
DR PathwayCommons; Q9Y336; -.
DR Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SignaLink; Q9Y336; -.
DR BioGRID-ORCS; 27180; 18 hits in 1061 CRISPR screens.
DR ChiTaRS; SIGLEC9; human.
DR GeneWiki; SIGLEC9; -.
DR GenomeRNAi; 27180; -.
DR Pharos; Q9Y336; Tbio.
DR PRO; PR:Q9Y336; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9Y336; protein.
DR Bgee; ENSG00000129450; Expressed in monocyte and 99 other tissues.
DR ExpressionAtlas; Q9Y336; baseline and differential.
DR Genevisible; Q9Y336; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; NAS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0030667; C:secretory granule membrane; TAS:Reactome.
DR GO; GO:0030246; F:carbohydrate binding; NAS:UniProtKB.
DR GO; GO:0033691; F:sialic acid binding; IBA:GO_Central.
DR GO; GO:0007155; P:cell adhesion; IBA:GO_Central.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; NAS:UniProtKB.
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; IPR003599; Ig_sub.
DR InterPro; IPR013106; Ig_V-set.
DR Pfam; PF07686; V-set; 1.
DR SMART; SM00409; IG; 3.
DR SUPFAM; SSF48726; SSF48726; 3.
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; Reference proteome; Repeat;
KW Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT CHAIN 18..463
FT /note="Sialic acid-binding Ig-like lectin 9"
FT /id="PRO_0000014949"
FT TOPO_DOM 18..348
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 349..369
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 370..463
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 20..140
FT /note="Ig-like V-type"
FT DOMAIN 146..229
FT /note="Ig-like C2-type 1"
FT DOMAIN 236..336
FT /note="Ig-like C2-type 2"
FT REGION 380..428
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 444..463
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 431..436
FT /note="ITIM motif"
FT MOTIF 454..459
FT /note="SLAM-like motif"
FT COMPBIAS 448..463
FT /note="Basic and acidic 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 CARBOHYD 101
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 138
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 161
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 225
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 231
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 238
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 256
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 334
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 36..170
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 41..102
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 164..213
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 272..320
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 402..463
FT /note="GPLTEPWAEDSPPDQPPPASARSSVGEGELQYASLSFQMVKPWDSRGQEATD
FT TEYSEIKIHR -> ILNHFIGFPTFLGLGFEFLLNLRDLCCHPDSEFYVYHFSHFRLIK
FT NIAGEIVWSLEGKILWLLDVSDFFHWFFLICVG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054106"
FT VARIANT 100
FT /note="K -> E (in dbSNP:rs2075803)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_014254"
FT VARIANT 125
FT /note="S -> N (in dbSNP:rs200658)"
FT /id="VAR_014255"
FT VARIANT 131
FT /note="K -> Q (in dbSNP:rs16988910)"
FT /id="VAR_033621"
FT VARIANT 147
FT /note="N -> K (in dbSNP:rs273687)"
FT /id="VAR_014256"
FT VARIANT 315
FT /note="A -> E (in dbSNP:rs2258983)"
FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.4"
FT /id="VAR_014257"
FT VARIANT 316
FT /note="A -> D (in dbSNP:rs273688)"
FT /id="VAR_014258"
FT VARIANT 349
FT /note="V -> A (in dbSNP:rs273690)"
FT /id="VAR_033622"
FT MUTAGEN 120
FT /note="R->K: Loss of sialic acid binding."
FT /evidence="ECO:0000269|PubMed:10801860"
FT CONFLICT 269
FT /note="R -> H (in Ref. 2; AAF87223)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 463 AA; 50082 MW; 807BDCE0D18191F2 CRC64;
MLLLLLPLLW GRERAEGQTS KLLTMQSSVT VQEGLCVHVP CSFSYPSHGW IYPGPVVHGY
WFREGANTDQ DAPVATNNPA RAVWEETRDR FHLLGDPHTK NCTLSIRDAR RSDAGRYFFR
MEKGSIKWNY KHHRLSVNVT ALTHRPNILI PGTLESGCPQ NLTCSVPWAC EQGTPPMISW
IGTSVSPLDP STTRSSVLTL IPQPQDHGTS LTCQVTFPGA SVTTNKTVHL NVSYPPQNLT
MTVFQGDGTV STVLGNGSSL SLPEGQSLRL VCAVDAVDSN PPARLSLSWR GLTLCPSQPS
NPGVLELPWV HLRDAAEFTC RAQNPLGSQQ VYLNVSLQSK ATSGVTQGVV GGAGATALVF
LSFCVIFVVV RSCRKKSARP AAGVGDTGIE DANAVRGSAS QGPLTEPWAE DSPPDQPPPA
SARSSVGEGE LQYASLSFQM VKPWDSRGQE ATDTEYSEIK IHR
