CLC5A_MOUSE
ID CLC5A_MOUSE Reviewed; 190 AA.
AC Q9R007; Q3SXC9; Q3UV97; Q8BL24;
DT 15-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 28-JUN-2011, sequence version 2.
DT 03-AUG-2022, entry version 151.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, AND
RP INTERACTION WITH TYROBP.
RC STRAIN=BALB/cJ; TISSUE=Myeloid;
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 [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Adipose tissue, and Bone;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
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 TISSUE SPECIFICITY, INTERACTION WITH HCST, SUBCELLULAR LOCATION,
RP GLYCOSYLATION, SIALIC ACID CONTENT, AND INDUCTION.
RX PubMed=19074552; DOI=10.1189/jlb.0508329;
RA Aoki N., Kimura Y., Kimura S., Nagato T., Azumi M., Kobayashi H., Sato K.,
RA Tateno M.;
RT "Expression and functional role of MDL-1 (CLEC5A) in mouse myeloid lineage
RT cells.";
RL J. Leukoc. Biol. 85:508-517(2009).
RN [6]
RP INTERACTION WITH HCST, GLYCOSYLATION, AND FUNCTION.
RX PubMed=19251634; DOI=10.1073/pnas.0900463106;
RA Inui M., Kikuchi Y., Aoki N., Endo S., Maeda T., Sugahara-Tobinai A.,
RA Fujimura S., Nakamura A., Kumanogoh A., Colonna M., Takai T.;
RT "Signal adaptor DAP10 associates with MDL-1 and triggers osteoclastogenesis
RT in cooperation with DAP12.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:4816-4821(2009).
RN [7]
RP FUNCTION, TISSUE SPECIFICITY, INDUCTION, AND DISRUPTION PHENOTYPE.
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 [8]
RP INVOLVEMENT IN JAPANESE ENCEPHALITIS VIRUS INFECTION.
RX PubMed=20637688; DOI=10.1016/j.jcv.2010.06.009;
RA Gupta N., Lomash V., Rao P.V.;
RT "Expression profile of Japanese encephalitis virus induced
RT neuroinflammation and its implication in disease severity.";
RL J. Clin. Virol. 49:4-10(2010).
CC -!- FUNCTION: Functions as a positive regulator of osteoclastogenesis
CC (PubMed:19251634). Cell surface receptor that signals via TYROBP
CC (PubMed:10449773). Regulates inflammatory responses (PubMed:20212065).
CC {ECO:0000269|PubMed:10449773, ECO:0000269|PubMed:19251634,
CC ECO:0000269|PubMed:20212065}.
CC -!- SUBUNIT: Monomer (By similarity). Homodimer (By similarity). The
CC majority of CLEC5A is expressed as a monomeric form on macrophages (By
CC similarity). Interacts with TYROBP/DAP12 (PubMed:10449773). The
CC interaction with TYROBP is required for CLEC5 cell surface expression
CC (PubMed:10449773). Interacts with HCST/DAP10 (PubMed:19074552,
CC PubMed:19251634). Forms a CLEC5A/TYROBP/HCST trimolecular complex
CC depending almost solely on TYROBP (PubMed:19251634).
CC {ECO:0000250|UniProtKB:Q9NY25, ECO:0000269|PubMed:10449773,
CC ECO:0000269|PubMed:19074552, ECO:0000269|PubMed:19251634}.
CC -!- INTERACTION:
CC Q9R007; Q9QUJ0: Hcst; NbExp=3; IntAct=EBI-15761206, EBI-15761243;
CC Q9R007; O54885: Tyrobp; NbExp=3; IntAct=EBI-15761206, EBI-15687058;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:19074552};
CC Single-pass type II membrane protein {ECO:0000269|PubMed:19074552}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=3;
CC IsoId=Q9R007-3; Sequence=Displayed;
CC Name=1;
CC IsoId=Q9R007-1; Sequence=VSP_041577;
CC Name=2;
CC IsoId=Q9R007-2; Sequence=VSP_012840;
CC -!- TISSUE SPECIFICITY: Strong expression in bone marrow cells and
CC thioglycollate-induced neutrophils (at protein level)
CC (PubMed:19074552). Expressed on granulocytes and monocytes from bone
CC marrow and peripheral blood (PubMed:20212065). Expressed in macrophage
CC cell line J-774, but not in T-cell lines, B-cell lines, or mast cell
CC lines (PubMed:10449773). {ECO:0000269|PubMed:10449773,
CC ECO:0000269|PubMed:19074552, ECO:0000269|PubMed:20212065}.
CC -!- INDUCTION: By TNF in bone-marrow derived macrophage colony-stimulating
CC factor-dependent macrophages (PubMed:20212065). Up-regulated during the
CC differentiation of myeloid cell line 32Dcl3 into neutrophils
CC (PubMed:19074552). {ECO:0000269|PubMed:19074552,
CC ECO:0000269|PubMed:20212065}.
CC -!- PTM: N-glycosylated (PubMed:19074552, PubMed:19251634). Contains sialic
CC acid residues (PubMed:19074552). {ECO:0000269|PubMed:19074552,
CC ECO:0000269|PubMed:19251634}.
CC -!- DISEASE: Note=Involved in the pathogenetic mechanisms of Japanese
CC encephalitis virus (JEV) infection of the brain. JEV infection of young
CC mice results in increased expression of CLEC5A in spleen and brain with
CC consequent activation of proinflammatory cytokine secretion.
CC {ECO:0000269|PubMed:20637688}.
CC -!- DISRUPTION PHENOTYPE: Mutants are viable, are born in the expected
CC Mendelian ratios and have similar numbers of myeloid and lymphoid cell
CC subsets as wild-type animals (PubMed:20212065). Inhibition of
CC autoimmune joint inflammation and preservation of bone density
CC (PubMed:20212065). {ECO:0000269|PubMed:20212065}.
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:0000269|PubMed:20212065}.
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_mou_Ctlect_177";
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DR EMBL; AF139769; AAF02492.1; -; mRNA.
DR EMBL; AK036697; BAC29537.1; -; mRNA.
DR EMBL; AK046600; BAC32802.1; -; mRNA.
DR EMBL; AK137482; BAE23374.1; -; mRNA.
DR EMBL; CH466533; EDL13570.1; -; Genomic_DNA.
DR EMBL; BC104364; AAI04365.1; -; mRNA.
DR EMBL; BC104365; AAI04366.1; -; mRNA.
DR CCDS; CCDS20036.1; -. [Q9R007-3]
DR CCDS; CCDS20037.1; -. [Q9R007-1]
DR RefSeq; NP_001033693.1; NM_001038604.1. [Q9R007-3]
DR RefSeq; NP_067339.1; NM_021364.2. [Q9R007-1]
DR AlphaFoldDB; Q9R007; -.
DR SMR; Q9R007; -.
DR CORUM; Q9R007; -.
DR DIP; DIP-48775N; -.
DR IntAct; Q9R007; 2.
DR STRING; 10090.ENSMUSP00000121848; -.
DR MEROPS; I63.002; -.
DR GlyGen; Q9R007; 3 sites.
DR MaxQB; Q9R007; -.
DR PaxDb; Q9R007; -.
DR PRIDE; Q9R007; -.
DR ProteomicsDB; 283368; -. [Q9R007-3]
DR ProteomicsDB; 283369; -. [Q9R007-1]
DR ProteomicsDB; 283370; -. [Q9R007-2]
DR Antibodypedia; 50228; 246 antibodies from 27 providers.
DR DNASU; 23845; -.
DR Ensembl; ENSMUST00000101491; ENSMUSP00000099030; ENSMUSG00000029915. [Q9R007-1]
DR Ensembl; ENSMUST00000129948; ENSMUSP00000121848; ENSMUSG00000029915. [Q9R007-3]
DR GeneID; 23845; -.
DR KEGG; mmu:23845; -.
DR UCSC; uc009bna.1; mouse. [Q9R007-3]
DR UCSC; uc009bnb.1; mouse. [Q9R007-1]
DR UCSC; uc009bnc.1; mouse. [Q9R007-2]
DR CTD; 23601; -.
DR MGI; MGI:1345151; Clec5a.
DR VEuPathDB; HostDB:ENSMUSG00000029915; -.
DR eggNOG; KOG4297; Eukaryota.
DR GeneTree; ENSGT00910000144330; -.
DR HOGENOM; CLU_049894_15_0_1; -.
DR InParanoid; Q9R007; -.
DR OMA; WHWIDNS; -.
DR OrthoDB; 1548780at2759; -.
DR PhylomeDB; Q9R007; -.
DR TreeFam; TF337735; -.
DR Reactome; R-MMU-2172127; DAP12 interactions.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR BioGRID-ORCS; 23845; 1 hit in 74 CRISPR screens.
DR PRO; PR:Q9R007; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q9R007; protein.
DR Bgee; ENSMUSG00000029915; Expressed in granulocyte and 49 other tissues.
DR ExpressionAtlas; Q9R007; baseline and differential.
DR Genevisible; Q9R007; MM.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0030246; F:carbohydrate binding; IEA:UniProtKB-KW.
DR GO; GO:0001618; F:virus receptor activity; IDA:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IDA:UniProtKB.
DR GO; GO:0030099; P:myeloid cell differentiation; IGI:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0033033; P:negative regulation of myeloid cell apoptotic process; IDA:MGI.
DR GO; GO:0002076; P:osteoblast development; IDA:UniProtKB.
DR GO; GO:0001819; P:positive regulation of cytokine production; IMP:UniProtKB.
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 Alternative splicing; Cell membrane; Disulfide bond; Glycoprotein;
KW Immunity; Innate immunity; Lectin; Membrane; Reference proteome;
KW Signal-anchor; Transmembrane; Transmembrane helix.
FT CHAIN 1..190
FT /note="C-type lectin domain family 5 member A"
FT /id="PRO_0000046633"
FT TOPO_DOM 1..4
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 5..25
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 26..190
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 80..186
FT /note="C-type lectin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT CARBOHYD 51
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 146
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 153
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 101..185
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT DISULFID 163..177
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT VAR_SEQ 28..57
FT /note="PQVFGKSNDGFVPTESYGTTSVQNVSQIFG -> SQIFG (in isoform
FT 1)"
FT /evidence="ECO:0000303|PubMed:10449773,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_041577"
FT VAR_SEQ 118
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_012840"
SQ SEQUENCE 190 AA; 21696 MW; AB6AACB3A8D36637 CRC64;
MNWHMIISGL IVVVIKVVGM TFFLLYFPQV FGKSNDGFVP TESYGTTSVQ NVSQIFGRND
ESTMPTRSYG TVCPRNWDFH QGKCFFFSFS ESPWKDSMDY CATQGSTLAI VNTPEKLKYL
QDIAGIENYF IGLVRQPGEK KWRWINNSVF NGNVTNQDQN FDCVTIGLTK TYDAASCEVS
YRWICEMNAK
