SIG15_HUMAN
ID SIG15_HUMAN Reviewed; 328 AA.
AC Q6ZMC9; A8K2Y5; B4DVQ9;
DT 10-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Sialic acid-binding Ig-like lectin 15;
DE Short=Siglec-15;
DE AltName: Full=CD33 antigen-like 3;
DE Flags: Precursor;
GN Name=SIGLEC15; Synonyms=CD33L3;
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 [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Spleen, and Umbilical cord blood;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16177791; DOI=10.1038/nature03983;
RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D.,
RA Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J.,
RA Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L.,
RA Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A.,
RA Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C.,
RA Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 18.";
RL Nature 437:551-555(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION, INTERACTION WITH TYROBP AND HCST, AND MUTAGENESIS OF ARG-143 AND
RP LYS-274.
RX PubMed=17483134; DOI=10.1093/glycob/cwm049;
RA Angata T., Tabuchi Y., Nakamura K., Nakamura M.;
RT "Siglec-15: an immune system Siglec conserved throughout vertebrate
RT evolution.";
RL Glycobiology 17:838-846(2007).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: Binds sialylated glycoproteins.
CC {ECO:0000269|PubMed:17483134}.
CC -!- SUBUNIT: Interacts with TYROBP and HCST. {ECO:0000269|PubMed:17483134}.
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=Q6ZMC9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6ZMC9-2; Sequence=VSP_056817, VSP_056818;
CC -!- TISSUE SPECIFICITY: Expressed in macrophage and/or dendritic cells of
CC spleen and lymph nodes.
CC -!- SIMILARITY: Belongs to the immunoglobulin superfamily. SIGLEC (sialic
CC acid binding Ig-like lectin) family. {ECO:0000305}.
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DR EMBL; AK172835; BAD18800.1; -; mRNA.
DR EMBL; AK290400; BAF83089.1; -; mRNA.
DR EMBL; AK290402; BAF83091.1; -; mRNA.
DR EMBL; AK301189; BAG62771.1; -; mRNA.
DR EMBL; AC087685; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471088; EAX01463.1; -; Genomic_DNA.
DR CCDS; CCDS32819.1; -. [Q6ZMC9-1]
DR RefSeq; NP_998767.1; NM_213602.2. [Q6ZMC9-1]
DR AlphaFoldDB; Q6ZMC9; -.
DR SMR; Q6ZMC9; -.
DR STRING; 9606.ENSP00000374125; -.
DR ChEMBL; CHEMBL4523355; -.
DR GlyGen; Q6ZMC9; 1 site.
DR iPTMnet; Q6ZMC9; -.
DR PhosphoSitePlus; Q6ZMC9; -.
DR BioMuta; SIGLEC15; -.
DR DMDM; 74762385; -.
DR MassIVE; Q6ZMC9; -.
DR PaxDb; Q6ZMC9; -.
DR PeptideAtlas; Q6ZMC9; -.
DR PRIDE; Q6ZMC9; -.
DR ProteomicsDB; 5292; -.
DR ProteomicsDB; 67864; -. [Q6ZMC9-1]
DR ABCD; Q6ZMC9; 1 sequenced antibody.
DR Antibodypedia; 60463; 141 antibodies from 23 providers.
DR DNASU; 284266; -.
DR Ensembl; ENST00000389474.8; ENSP00000374125.2; ENSG00000197046.12. [Q6ZMC9-1]
DR Ensembl; ENST00000546268.5; ENSP00000443509.1; ENSG00000197046.12. [Q6ZMC9-2]
DR GeneID; 284266; -.
DR KEGG; hsa:284266; -.
DR MANE-Select; ENST00000389474.8; ENSP00000374125.2; NM_213602.3; NP_998767.1.
DR UCSC; uc002lbl.2; human. [Q6ZMC9-1]
DR CTD; 284266; -.
DR DisGeNET; 284266; -.
DR GeneCards; SIGLEC15; -.
DR HGNC; HGNC:27596; SIGLEC15.
DR HPA; ENSG00000197046; Tissue enhanced (breast, intestine, urinary bladder).
DR MIM; 618105; gene.
DR neXtProt; NX_Q6ZMC9; -.
DR OpenTargets; ENSG00000197046; -.
DR PharmGKB; PA162403350; -.
DR VEuPathDB; HostDB:ENSG00000197046; -.
DR eggNOG; ENOG502RFMV; Eukaryota.
DR GeneTree; ENSGT01040000240469; -.
DR HOGENOM; CLU_076258_0_0_1; -.
DR InParanoid; Q6ZMC9; -.
DR OMA; HDKYESR; -.
DR OrthoDB; 42984at2759; -.
DR PhylomeDB; Q6ZMC9; -.
DR TreeFam; TF351096; -.
DR PathwayCommons; Q6ZMC9; -.
DR Reactome; R-HSA-2172127; DAP12 interactions.
DR BioGRID-ORCS; 284266; 9 hits in 1065 CRISPR screens.
DR GenomeRNAi; 284266; -.
DR Pharos; Q6ZMC9; Tbio.
DR PRO; PR:Q6ZMC9; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; Q6ZMC9; protein.
DR Bgee; ENSG00000197046; Expressed in jejunal mucosa and 101 other tissues.
DR ExpressionAtlas; Q6ZMC9; 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:0032991; C:protein-containing complex; IEA:Ensembl.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0045124; P:regulation of bone resorption; IBA:GO_Central.
DR GO; GO:2001204; P:regulation of osteoclast development; IBA:GO_Central.
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; IPR003599; Ig_sub.
DR InterPro; IPR013106; Ig_V-set.
DR InterPro; IPR042836; SIG15.
DR PANTHER; PTHR46942; PTHR46942; 1.
DR Pfam; PF07686; V-set; 1.
DR SMART; SM00409; IG; 1.
DR SUPFAM; SSF48726; SSF48726; 2.
DR PROSITE; PS50835; IG_LIKE; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Disulfide bond; Glycoprotein; Immunoglobulin domain;
KW Membrane; Reference proteome; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..328
FT /note="Sialic acid-binding Ig-like lectin 15"
FT /id="PRO_0000294369"
FT TOPO_DOM 20..263
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 264..284
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 285..328
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 40..158
FT /note="Ig-like V-type"
FT DOMAIN 168..251
FT /note="Ig-like C2-type"
FT REGION 289..328
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 299..328
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 143
FT /ligand="N-acetylneuraminate"
FT /ligand_id="ChEBI:CHEBI:35418"
FT /evidence="ECO:0000250"
FT CARBOHYD 172
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 64..142
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 95..104
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 187..237
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 1..12
FT /note="MEKSIWLLACLA -> MTATRAATASGS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056817"
FT VAR_SEQ 13..166
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056818"
FT VARIANT 273
FT /note="F -> L (in dbSNP:rs2919643)"
FT /id="VAR_033174"
FT MUTAGEN 143
FT /note="R->A: Abrogates glycan-binding."
FT /evidence="ECO:0000269|PubMed:17483134"
FT MUTAGEN 274
FT /note="K->A: Abrogates interaction with HCST and TYROBP."
FT /evidence="ECO:0000269|PubMed:17483134"
SQ SEQUENCE 328 AA; 35653 MW; 534D6D2E76F04C8B CRC64;
MEKSIWLLAC LAWVLPTGSF VRTKIDTTEN LLNTEVHSSP AQRWSMQVPP EVSAEAGDAA
VLPCTFTHPH RHYDGPLTAI WRAGEPYAGP QVFRCAAARG SELCQTALSL HGRFRLLGNP
RRNDLSLRVE RLALADDRRY FCRVEFAGDV HDRYESRHGV RLHVTAAPRI VNISVLPSPA
HAFRALCTAE GEPPPALAWS GPALGNSLAA VRSPREGHGH LVTAELPALT HDGRYTCTAA
NSLGRSEASV YLFRFHGASG ASTVALLLGA LGFKALLLLG VLAARAARRR PEHLDTPDTP
PRSQAQESNY ENLSQMNPRS PPATMCSP
