SIGL5_HUMAN
ID SIGL5_HUMAN Reviewed; 551 AA.
AC O15389;
DT 08-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Sialic acid-binding Ig-like lectin 5;
DE Short=Siglec-5;
DE AltName: Full=CD33 antigen-like 2;
DE AltName: Full=Obesity-binding protein 2;
DE Short=OB-BP2;
DE Short=OB-binding protein 2;
DE AltName: CD_antigen=CD170;
DE Flags: Precursor;
GN Name=SIGLEC5; Synonyms=CD33L2, OBBP2;
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 [MRNA], AND VARIANT TRP-358.
RC TISSUE=Macrophage;
RX PubMed=9731071;
RA Cornish A.L., Freeman S., Forbes G., Ni J., Zhang M., Cepeda M., Gentz R.,
RA Augustus M., Carter K.C., Crocker P.R.;
RT "Characterization of siglec-5, a novel glycoprotein expressed on myeloid
RT cells related to CD33.";
RL Blood 92:2123-2132(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Erythroleukemia;
RX PubMed=10428856; DOI=10.1074/jbc.274.32.22729;
RA Patel N., Brinkman-Van der Linden E.C.M., Altmann S.W., Gish K.C.,
RA Balasubramanian S., Timans J.C., Peterson D., Bell M.P., Bazan J.F.,
RA Varki A., Kastelein R.A.;
RT "OB-BP1/Siglec-6. A leptin- and sialic acid-binding protein of the
RT immunoglobulin superfamily.";
RL J. Biol. Chem. 274:22729-22738(1999).
RN [3]
RP ERRATUM OF PUBMED:10428856.
RA Patel N., Brinkman-Van der Linden E.C.M., Altmann S.W., Gish K.C.,
RA Balasubramanian S., Timans J.C., Peterson D., Bell M.P., Bazan J.F.,
RA Varki A., Kastelein R.A.;
RL J. Biol. Chem. 274:28058-28058(1999).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-499.
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).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 20-233 ALONE AND IN COMPLEX WITH
RP ALPHA-LINKED SIALYLLACTOSES, DISULFIDE BONDS, AND SIALIC ACID BINDING
RP SITES.
RX PubMed=18022638; DOI=10.1016/j.jmb.2007.10.009;
RA Zhuravleva M.A., Trandem K., Sun P.D.;
RT "Structural implications of Siglec-5-mediated sialoglycan recognition.";
RL J. Mol. Biol. 375:437-447(2008).
CC -!- FUNCTION: Putative adhesion molecule that mediates sialic-acid
CC dependent binding to cells. Binds equally to alpha-2,3-linked and
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 O15389; Q9H115: NAPB; NbExp=3; IntAct=EBI-750381, EBI-3921185;
CC O15389; Q9UHI5: SLC7A8; NbExp=3; IntAct=EBI-750381, EBI-13292283;
CC O15389; O00206: TLR4; NbExp=2; IntAct=EBI-750381, EBI-528701;
CC O15389; Q15645: TRIP13; NbExp=4; IntAct=EBI-750381, EBI-358993;
CC O15389; Q08AM6: VAC14; NbExp=6; IntAct=EBI-750381, EBI-2107455;
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC -!- TISSUE SPECIFICITY: Expressed by monocytic/myeloid lineage cells. Found
CC at high levels in peripheral blood leukocytes, spleen, bone marrow and
CC at lower levels in lymph node, lung, appendix, placenta, pancreas and
CC thymus. Expressed by monocytes and neutrophils but absent from leukemic
CC cell lines representing early stages of myelomonocytic differentiation.
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-5;
CC URL="http://www.functionalglycomics.org/glycomics/GBPServlet?&operationType=view&cbpId=cbp_hum_Itlect_272";
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DR EMBL; AF170484; AAD50978.1; -; mRNA.
DR EMBL; U71383; AAB70703.1; -; mRNA.
DR EMBL; AC018755; AAF87846.1; -; Genomic_DNA.
DR EMBL; BC029896; AAH29896.1; -; mRNA.
DR CCDS; CCDS33088.1; -.
DR RefSeq; NP_003821.1; NM_003830.3.
DR PDB; 2ZG1; X-ray; 2.70 A; A=20-233.
DR PDB; 2ZG2; X-ray; 2.85 A; A=20-233.
DR PDB; 2ZG3; X-ray; 3.00 A; A=20-233.
DR PDBsum; 2ZG1; -.
DR PDBsum; 2ZG2; -.
DR PDBsum; 2ZG3; -.
DR AlphaFoldDB; O15389; -.
DR BMRB; O15389; -.
DR SMR; O15389; -.
DR BioGRID; 114308; 29.
DR IntAct; O15389; 24.
DR STRING; 9606.ENSP00000470259; -.
DR UniLectin; O15389; -.
DR GlyConnect; 568; 17 N-Linked glycans.
DR GlyGen; O15389; 9 sites, 33 N-linked glycans (1 site).
DR iPTMnet; O15389; -.
DR PhosphoSitePlus; O15389; -.
DR BioMuta; SIGLEC5; -.
DR EPD; O15389; -.
DR MassIVE; O15389; -.
DR PaxDb; O15389; -.
DR PeptideAtlas; O15389; -.
DR PRIDE; O15389; -.
DR ProteomicsDB; 48625; -.
DR Antibodypedia; 2301; 601 antibodies from 32 providers.
DR DNASU; 8778; -.
DR Ensembl; ENST00000429354.3; ENSP00000415200.2; ENSG00000268500.6.
DR Ensembl; ENST00000534261.3; ENSP00000473238.1; ENSG00000105501.12.
DR Ensembl; ENST00000599649.5; ENSP00000470259.1; ENSG00000268500.6.
DR Ensembl; ENST00000683636.1; ENSP00000507738.1; ENSG00000268500.6.
DR GeneID; 8778; -.
DR KEGG; hsa:8778; -.
DR MANE-Select; ENST00000683636.1; ENSP00000507738.1; NM_003830.4; NP_003821.1.
DR UCSC; uc002pxe.5; human.
DR CTD; 8778; -.
DR DisGeNET; 8778; -.
DR GeneCards; SIGLEC5; -.
DR HGNC; HGNC:10874; SIGLEC5.
DR HPA; ENSG00000105501; Tissue enhanced (bone marrow, lymphoid tissue).
DR MIM; 604200; gene.
DR neXtProt; NX_O15389; -.
DR OpenTargets; ENSG00000105501; -.
DR OpenTargets; ENSG00000268500; -.
DR PharmGKB; PA35775; -.
DR VEuPathDB; HostDB:ENSG00000105501; -.
DR eggNOG; ENOG502S41V; Eukaryota.
DR GeneTree; ENSGT01040000240469; -.
DR HOGENOM; CLU_024444_6_2_1; -.
DR InParanoid; O15389; -.
DR OMA; WNINGSQ; -.
DR OrthoDB; 873673at2759; -.
DR PhylomeDB; O15389; -.
DR TreeFam; TF332441; -.
DR PathwayCommons; O15389; -.
DR Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SignaLink; O15389; -.
DR BioGRID-ORCS; 8778; 12 hits in 1060 CRISPR screens.
DR EvolutionaryTrace; O15389; -.
DR GeneWiki; SIGLEC5; -.
DR GenomeRNAi; 8778; -.
DR Pharos; O15389; Tbio.
DR PRO; PR:O15389; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; O15389; protein.
DR Bgee; ENSG00000105501; Expressed in blood and 85 other tissues.
DR Genevisible; O15389; HS.
DR GO; GO:0101003; C:ficolin-1-rich granule membrane; TAS:Reactome.
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:0030667; C:secretory granule membrane; TAS:Reactome.
DR GO; GO:0070821; C:tertiary granule membrane; TAS:Reactome.
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; 1.
DR SMART; SM00409; IG; 3.
DR SMART; SM00408; IGc2; 1.
DR SUPFAM; SSF48726; SSF48726; 4.
DR PROSITE; PS50835; IG_LIKE; 3.
DR PROSITE; PS00290; IG_MHC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell adhesion; Disulfide bond; Glycoprotein;
KW Immunoglobulin domain; Lectin; Membrane; Reference proteome; Repeat;
KW Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..16
FT /evidence="ECO:0000255"
FT CHAIN 17..551
FT /note="Sialic acid-binding Ig-like lectin 5"
FT /id="PRO_0000014944"
FT TOPO_DOM 17..441
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 442..462
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 463..551
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 19..136
FT /note="Ig-like V-type"
FT DOMAIN 146..229
FT /note="Ig-like C2-type 1"
FT DOMAIN 236..330
FT /note="Ig-like C2-type 2"
FT REGION 189..210
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 469..551
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 518..523
FT /note="ITIM motif"
FT MOTIF 542..547
FT /note="SLAM-like motif"
FT BINDING 119
FT /ligand="N-acetylneuraminate"
FT /ligand_id="ChEBI:CHEBI:35418"
FT /evidence="ECO:0000269|PubMed:18022638"
FT BINDING 127
FT /ligand="N-acetylneuraminate"
FT /ligand_id="ChEBI:CHEBI:35418"
FT /evidence="ECO:0000269|PubMed:18022638"
FT BINDING 129
FT /ligand="N-acetylneuraminate"
FT /ligand_id="ChEBI:CHEBI:35418"
FT /evidence="ECO:0000269|PubMed:18022638"
FT CARBOHYD 100
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 210
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 253
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 328
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 375
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 384
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 393
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 36..170
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:18022638"
FT DISULFID 41..101
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:18022638"
FT DISULFID 164..213
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:18022638"
FT DISULFID 269..314
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VARIANT 72
FT /note="V -> A (in dbSNP:rs1973019)"
FT /id="VAR_014249"
FT VARIANT 215
FT /note="M -> V (in dbSNP:rs1807124)"
FT /id="VAR_014250"
FT VARIANT 322
FT /note="F -> S (in dbSNP:rs2278831)"
FT /id="VAR_014251"
FT VARIANT 358
FT /note="R -> W (in dbSNP:rs8108074)"
FT /evidence="ECO:0000269|PubMed:9731071"
FT /id="VAR_049929"
FT VARIANT 499
FT /note="P -> A (in dbSNP:rs3829655)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_020087"
FT CONFLICT 309
FT /note="E -> K (in Ref. 1; AAD50978)"
FT /evidence="ECO:0000305"
FT CONFLICT 388
FT /note="A -> P (in Ref. 1; AAD50978)"
FT /evidence="ECO:0000305"
FT CONFLICT 403
FT /note="S -> N (in Ref. 1; AAD50978)"
FT /evidence="ECO:0000305"
FT STRAND 22..24
FT /evidence="ECO:0007829|PDB:2ZG1"
FT STRAND 27..32
FT /evidence="ECO:0007829|PDB:2ZG1"
FT STRAND 37..39
FT /evidence="ECO:0007829|PDB:2ZG1"
FT STRAND 42..44
FT /evidence="ECO:0007829|PDB:2ZG1"
FT STRAND 56..62
FT /evidence="ECO:0007829|PDB:2ZG1"
FT HELIX 67..69
FT /evidence="ECO:0007829|PDB:2ZG1"
FT STRAND 72..76
FT /evidence="ECO:0007829|PDB:2ZG1"
FT STRAND 78..80
FT /evidence="ECO:0007829|PDB:2ZG2"
FT TURN 84..89
FT /evidence="ECO:0007829|PDB:2ZG1"
FT STRAND 90..92
FT /evidence="ECO:0007829|PDB:2ZG1"
FT HELIX 96..98
FT /evidence="ECO:0007829|PDB:2ZG1"
FT STRAND 103..105
FT /evidence="ECO:0007829|PDB:2ZG1"
FT HELIX 110..112
FT /evidence="ECO:0007829|PDB:2ZG1"
FT STRAND 114..122
FT /evidence="ECO:0007829|PDB:2ZG1"
FT TURN 123..125
FT /evidence="ECO:0007829|PDB:2ZG1"
FT STRAND 126..129
FT /evidence="ECO:0007829|PDB:2ZG1"
FT STRAND 135..140
FT /evidence="ECO:0007829|PDB:2ZG1"
FT STRAND 147..149
FT /evidence="ECO:0007829|PDB:2ZG1"
FT STRAND 160..165
FT /evidence="ECO:0007829|PDB:2ZG1"
FT STRAND 171..174
FT /evidence="ECO:0007829|PDB:2ZG2"
FT STRAND 177..183
FT /evidence="ECO:0007829|PDB:2ZG1"
FT STRAND 186..188
FT /evidence="ECO:0007829|PDB:2ZG1"
FT TURN 190..193
FT /evidence="ECO:0007829|PDB:2ZG2"
FT STRAND 195..200
FT /evidence="ECO:0007829|PDB:2ZG1"
FT TURN 204..208
FT /evidence="ECO:0007829|PDB:2ZG2"
FT STRAND 210..216
FT /evidence="ECO:0007829|PDB:2ZG1"
FT STRAND 225..229
FT /evidence="ECO:0007829|PDB:2ZG1"
SQ SEQUENCE 551 AA; 60715 MW; 2FEA2B6B341EFEAF CRC64;
MLPLLLLPLL WGGSLQEKPV YELQVQKSVT VQEGLCVLVP CSFSYPWRSW YSSPPLYVYW
FRDGEIPYYA EVVATNNPDR RVKPETQGRF RLLGDVQKKN CSLSIGDARM EDTGSYFFRV
ERGRDVKYSY QQNKLNLEVT ALIEKPDIHF LEPLESGRPT RLSCSLPGSC EAGPPLTFSW
TGNALSPLDP ETTRSSELTL TPRPEDHGTN LTCQMKRQGA QVTTERTVQL NVSYAPQTIT
IFRNGIALEI LQNTSYLPVL EGQALRLLCD APSNPPAHLS WFQGSPALNA TPISNTGILE
LRRVRSAEEG GFTCRAQHPL GFLQIFLNLS VYSLPQLLGP SCSWEAEGLH CRCSFRARPA
PSLCWRLEEK PLEGNSSQGS FKVNSSSAGP WANSSLILHG GLSSDLKVSC KAWNIYGSQS
GSVLLLQGRS NLGTGVVPAA LGGAGVMALL CICLCLIFFL IVKARRKQAA GRPEKMDDED
PIMGTITSGS RKKPWPDSPG DQASPPGDAP PLEEQKELHY ASLSFSEMKS REPKDQEAPS
TTEYSEIKTS K
