CLC5A_HUMAN
ID CLC5A_HUMAN Reviewed; 188 AA.
AC Q9NY25; Q52M11; Q9UKQ0;
DT 15-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=C-type lectin domain family 5 member A;
DE AltName: Full=C-type lectin superfamily member 5;
DE AltName: Full=Myeloid DAP12-associating lectin 1;
DE Short=MDL-1;
GN Name=CLEC5A; Synonyms=CLECSF5, MDL1;
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] (ISOFORM 2), FUNCTION, TISSUE SPECIFICITY,
RP INTERACTION WITH TYROBP, AND MUTAGENESIS OF LYS-16.
RX PubMed=10449773; DOI=10.1073/pnas.96.17.9792;
RA Bakker A.B.H., Baker E., Sutherland G.R., Phillips J.H., Lanier L.L.;
RT "Myeloid DAP12-associating lectin (MDL)-1 is a cell surface receptor
RT involved in the activation of myeloid cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:9792-9796(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Mueller A., Merz H., Feller A.C.;
RT "Expression of MDL-1 in human blood and cell lines.";
RL Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [5]
RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH DENGUE VIRUS ENVELOPE
RP PROTEIN E.
RX PubMed=18496526; DOI=10.1038/nature07013;
RA Chen S.T., Lin Y.L., Huang M.T., Wu M.F., Cheng S.C., Lei H.Y., Lee C.K.,
RA Chiou T.W., Wong C.H., Hsieh S.L.;
RT "CLEC5A is critical for dengue-virus-induced lethal disease.";
RL Nature 453:672-676(2008).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=20212065; DOI=10.1084/jem.20090516;
RA Joyce-Shaikh B., Bigler M.E., Chao C.C., Murphy E.E., Blumenschein W.M.,
RA Adamopoulos I.E., Heyworth P.G., Antonenko S., Bowman E.P.,
RA McClanahan T.K., Phillips J.H., Cua D.J.;
RT "Myeloid DAP12-associating lectin (MDL)-1 regulates synovial inflammation
RT and bone erosion associated with autoimmune arthritis.";
RL J. Exp. Med. 207:579-589(2010).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 71-187, SUBUNIT, SUBCELLULAR
RP LOCATION, FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH DENGUE VIRUS
RP ENVELOPE PROTEIN E.
RX PubMed=21566123; DOI=10.1074/jbc.m111.226142;
RA Watson A.A., Lebedev A.A., Hall B.A., Fenton-May A.E., Vagin A.A.,
RA Dejnirattisai W., Felce J., Mongkolsapaya J., Palma A.S., Liu Y., Feizi T.,
RA Screaton G.R., Murshudov G.N., O'Callaghan C.A.;
RT "Structural flexibility of the macrophage dengue virus receptor CLEC5A:
RT Implications for ligand binding and signaling.";
RL J. Biol. Chem. 286:24208-24218(2011).
CC -!- FUNCTION: Functions as a positive regulator of osteoclastogenesis (By
CC similarity). Cell surface receptor that signals via TYROBP
CC (PubMed:10449773). Regulates inflammatory responses (By similarity).
CC {ECO:0000250|UniProtKB:Q9R007, ECO:0000269|PubMed:10449773}.
CC -!- FUNCTION: (Microbial infection) Critical macrophage receptor for dengue
CC virus serotypes 1-4 (PubMed:18496526, PubMed:21566123). The binding of
CC dengue virus to CLEC5A triggers signaling through the phosphorylation
CC of TYROBP (PubMed:18496526). This interaction does not result in viral
CC entry, but stimulates pro-inflammatory cytokine release
CC (PubMed:18496526). {ECO:0000269|PubMed:18496526,
CC ECO:0000269|PubMed:21566123}.
CC -!- SUBUNIT: Monomer (PubMed:21566123). Homodimer (PubMed:21566123). The
CC majority of CLEC5A is expressed as a monomeric form on macrophages
CC (PubMed:21566123). Interacts with TYROBP/DAP12 (PubMed:10449773). The
CC interaction with TYROBP is required for CLEC5A cell surface expression
CC (PubMed:10449773). Interacts with HCST/DAP10 (By similarity). Forms a
CC CLEC5A/TYROBP/HCST trimolecular complex depending almost solely on
CC TYROBP (By similarity). {ECO:0000250|UniProtKB:Q9R007,
CC ECO:0000269|PubMed:10449773, ECO:0000269|PubMed:21566123}.
CC -!- SUBUNIT: (Microbial infection) Interacts with dengue virus envelope
CC protein E (PubMed:18496526, PubMed:21566123).
CC {ECO:0000269|PubMed:18496526, ECO:0000269|PubMed:21566123}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21566123};
CC Single-pass type II membrane protein {ECO:0000269|PubMed:21566123}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9NY25-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NY25-2; Sequence=VSP_012839;
CC -!- TISSUE SPECIFICITY: Highly expressed in bone marrow with lower levels
CC in synovium, lung and bronchus (PubMed:20212065). Expressed in
CC peripheral blood monocytes and in the monocyte/macrophage cell lines U-
CC 937 and Mono-Mac-6, but not in cell lines of other origins
CC (PubMed:10449773). Expression is down-regulated when monocytes
CC differentiate into dendritic cells (PubMed:10449773).
CC {ECO:0000269|PubMed:10449773, ECO:0000269|PubMed:20212065}.
CC -!- PTM: N-glycosylated. Contains sialic acid residues.
CC {ECO:0000250|UniProtKB:Q9R007}.
CC -!- MISCELLANEOUS: Acts as a key regulator of synovial injury and bone
CC erosion during autoimmune joint inflammation when its activation leads
CC to enhanced recruitment of inflammatory macrophages and neutrophils to
CC the joints. {ECO:0000250|UniProtKB:Q9R007}.
CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - Glycan Binding;
CC Note=MDL-1;
CC URL="http://www.functionalglycomics.org/glycomics/GBPServlet?&operationType=view&cbpId=cbp_hum_Ctlect_244";
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DR EMBL; AF139768; AAF02491.1; -; mRNA.
DR EMBL; AJ271684; CAB71334.1; -; mRNA.
DR EMBL; AC073647; AAS07444.1; -; Genomic_DNA.
DR EMBL; BC093714; AAH93714.1; -; mRNA.
DR EMBL; BC112099; AAI12100.1; -; mRNA.
DR EMBL; BC113098; AAI13099.1; -; mRNA.
DR CCDS; CCDS5870.1; -. [Q9NY25-1]
DR RefSeq; NP_037384.1; NM_013252.2. [Q9NY25-1]
DR PDB; 2YHF; X-ray; 1.90 A; A/B/C/D/E/F/G/H/I=70-187.
DR PDBsum; 2YHF; -.
DR AlphaFoldDB; Q9NY25; -.
DR SMR; Q9NY25; -.
DR BioGRID; 117135; 30.
DR DIP; DIP-60627N; -.
DR IntAct; Q9NY25; 15.
DR STRING; 9606.ENSP00000449999; -.
DR UniLectin; Q9NY25; -.
DR GlyGen; Q9NY25; 4 sites.
DR BioMuta; CLEC5A; -.
DR DMDM; 59797971; -.
DR EPD; Q9NY25; -.
DR jPOST; Q9NY25; -.
DR MassIVE; Q9NY25; -.
DR PaxDb; Q9NY25; -.
DR PeptideAtlas; Q9NY25; -.
DR PRIDE; Q9NY25; -.
DR ProteomicsDB; 83151; -. [Q9NY25-1]
DR ProteomicsDB; 83152; -. [Q9NY25-2]
DR Antibodypedia; 50228; 246 antibodies from 27 providers.
DR DNASU; 23601; -.
DR Ensembl; ENST00000546910.6; ENSP00000449999.1; ENSG00000258227.7. [Q9NY25-1]
DR GeneID; 23601; -.
DR KEGG; hsa:23601; -.
DR MANE-Select; ENST00000546910.6; ENSP00000449999.1; NM_013252.3; NP_037384.1.
DR UCSC; uc003vwv.1; human. [Q9NY25-1]
DR CTD; 23601; -.
DR DisGeNET; 23601; -.
DR GeneCards; CLEC5A; -.
DR HGNC; HGNC:2054; CLEC5A.
DR HPA; ENSG00000258227; Tissue enriched (bone).
DR MIM; 604987; gene.
DR neXtProt; NX_Q9NY25; -.
DR OpenTargets; ENSG00000258227; -.
DR PharmGKB; PA26583; -.
DR VEuPathDB; HostDB:ENSG00000258227; -.
DR eggNOG; KOG4297; Eukaryota.
DR GeneTree; ENSGT00910000144330; -.
DR InParanoid; Q9NY25; -.
DR OMA; WHWIDNS; -.
DR PhylomeDB; Q9NY25; -.
DR TreeFam; TF337735; -.
DR PathwayCommons; Q9NY25; -.
DR Reactome; R-HSA-2172127; DAP12 interactions.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SignaLink; Q9NY25; -.
DR BioGRID-ORCS; 23601; 8 hits in 1063 CRISPR screens.
DR ChiTaRS; CLEC5A; human.
DR EvolutionaryTrace; Q9NY25; -.
DR GeneWiki; CLEC5A; -.
DR GenomeRNAi; 23601; -.
DR Pharos; Q9NY25; Tbio.
DR PRO; PR:Q9NY25; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q9NY25; protein.
DR Bgee; ENSG00000258227; Expressed in bone marrow and 100 other tissues.
DR ExpressionAtlas; Q9NY25; baseline and differential.
DR Genevisible; Q9NY25; HS.
DR GO; GO:0009986; C:cell surface; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0035579; C:specific 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:0001618; F:virus receptor activity; IDA:UniProtKB.
DR GO; GO:0006968; P:cellular defense response; TAS:ProtInc.
DR GO; GO:0045087; P:innate immune response; IDA:UniProtKB.
DR GO; GO:0030099; P:myeloid cell differentiation; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0033033; P:negative regulation of myeloid cell apoptotic process; IEA:Ensembl.
DR GO; GO:0002076; P:osteoblast development; ISS:UniProtKB.
DR GO; GO:0001819; P:positive regulation of cytokine production; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR CDD; cd03593; CLECT_NK_receptors_like; 1.
DR Gene3D; 3.10.100.10; -; 1.
DR InterPro; IPR001304; C-type_lectin-like.
DR InterPro; IPR016186; C-type_lectin-like/link_sf.
DR InterPro; IPR016187; CTDL_fold.
DR InterPro; IPR033992; NKR-like_CTLD.
DR Pfam; PF00059; Lectin_C; 1.
DR SMART; SM00034; CLECT; 1.
DR SUPFAM; SSF56436; SSF56436; 1.
DR PROSITE; PS50041; C_TYPE_LECTIN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Disulfide bond;
KW Glycoprotein; Host cell receptor for virus entry; Host-virus interaction;
KW Immunity; Innate immunity; Lectin; Membrane; Receptor; Reference proteome;
KW Signal-anchor; Transmembrane; Transmembrane helix.
FT CHAIN 1..188
FT /note="C-type lectin domain family 5 member A"
FT /id="PRO_0000046632"
FT TOPO_DOM 1..4
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 5..27
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 28..188
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 78..184
FT /note="C-type lectin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT CARBOHYD 32
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 93
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 144
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 151
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 71..82
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT DISULFID 99..183
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT DISULFID 161..175
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT VAR_SEQ 116
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10449773"
FT /id="VSP_012839"
FT VARIANT 141
FT /note="R -> H (in dbSNP:rs35942193)"
FT /id="VAR_050110"
FT MUTAGEN 16
FT /note="K->I: Abolishes interaction with TYROBP."
FT /evidence="ECO:0000269|PubMed:10449773"
FT STRAND 76..78
FT /evidence="ECO:0007829|PDB:2YHF"
FT STRAND 81..85
FT /evidence="ECO:0007829|PDB:2YHF"
FT HELIX 92..100
FT /evidence="ECO:0007829|PDB:2YHF"
FT TURN 101..103
FT /evidence="ECO:0007829|PDB:2YHF"
FT HELIX 112..122
FT /evidence="ECO:0007829|PDB:2YHF"
FT STRAND 127..133
FT /evidence="ECO:0007829|PDB:2YHF"
FT TURN 135..137
FT /evidence="ECO:0007829|PDB:2YHF"
FT STRAND 138..142
FT /evidence="ECO:0007829|PDB:2YHF"
FT TURN 143..145
FT /evidence="ECO:0007829|PDB:2YHF"
FT STRAND 152..154
FT /evidence="ECO:0007829|PDB:2YHF"
FT STRAND 161..173
FT /evidence="ECO:0007829|PDB:2YHF"
FT STRAND 179..186
FT /evidence="ECO:0007829|PDB:2YHF"
SQ SEQUENCE 188 AA; 21521 MW; 94A2DBD520DC1985 CRC64;
MNWHMIISGL IVVVLKVVGM TLFLLYFPQI FNKSNDGFTT TRSYGTVSQI FGSSSPSPNG
FITTRSYGTV CPKDWEFYQA RCFFLSTSES SWNESRDFCK GKGSTLAIVN TPEKLKFLQD
ITDAEKYFIG LIYHREEKRW RWINNSVFNG NVTNQNQNFN CATIGLTKTF DAASCDISYR
RICEKNAK
