CLC4D_MOUSE
ID CLC4D_MOUSE Reviewed; 219 AA.
AC Q9Z2H6; Q8C212;
DT 15-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=C-type lectin domain family 4 member D;
DE AltName: Full=C-type lectin superfamily member 8;
DE AltName: Full=Dendritic cell-associated C-type lectin 3 {ECO:0000303|PubMed:23911656};
DE Short=DC-associated C-type lectin 3 {ECO:0000303|PubMed:23911656};
DE Short=Dectin-3 {ECO:0000303|PubMed:23911656};
DE AltName: Full=Macrophage-restricted C-type lectin;
DE AltName: CD_antigen=CD368;
GN Name=Clec4d {ECO:0000303|PubMed:23602766, ECO:0000312|MGI:MGI:1298389};
GN Synonyms=Clecsf8, Mcl {ECO:0000303|PubMed:23602766};
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], AND TISSUE SPECIFICITY.
RX PubMed=9660840; DOI=10.1074/jbc.273.29.18656;
RA Balch S.G., McKnight A.J., Seldin M.F., Gordon S.;
RT "Cloning of a novel C-type lectin expressed by murine macrophages.";
RL J. Biol. Chem. 273:18656-18664(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J;
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 FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE, AND SUBCELLULAR
RP LOCATION.
RX PubMed=23602766; DOI=10.1016/j.immuni.2013.03.010;
RA Miyake Y., Toyonaga K., Mori D., Kakuta S., Hoshino Y., Oyamada A.,
RA Yamada H., Ono K., Suyama M., Iwakura Y., Yoshikai Y., Yamasaki S.;
RT "C-type lectin MCL is an FcRgamma-coupled receptor that mediates the
RT adjuvanticity of mycobacterial cord factor.";
RL Immunity 38:1050-1062(2013).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=23911656; DOI=10.1016/j.immuni.2013.05.017;
RA Zhu L.L., Zhao X.Q., Jiang C., You Y., Chen X.P., Jiang Y.Y., Jia X.M.,
RA Lin X.;
RT "C-type lectin receptors Dectin-3 and Dectin-2 form a heterodimeric
RT pattern-recognition receptor for host defense against fungal infection.";
RL Immunity 39:324-334(2013).
CC -!- FUNCTION: Calcium-dependent lectin that acts as a pattern recognition
CC receptor (PRR) of the innate immune system: recognizes damage-
CC associated molecular patterns (DAMPs) of pathogen-associated molecular
CC patterns (PAMPs) of bacteria and fungi. The PAMPs include alpha-mannans
CC on C.albicans hypheas and mycobacterial trehalose 6,6'-dimycolate (TDM)
CC (PubMed:23602766, PubMed:23911656). Interacts with signaling adapter Fc
CC receptor gamma chain/FCER1G, likely via CLEC4E, to form a functional
CC complex in myeloid cells (By similarity). Binding of mycobacterial TDM
CC or C.albicans alpha-mannans to this receptor complex leads to
CC phosphorylation of the immunoreceptor tyrosine-based activation motif
CC (ITAM) of FCER1G, triggering activation of SYK, CARD9 and NF-kappa-B,
CC consequently driving maturation of antigen-presenting cells and shaping
CC antigen-specific priming of T-cells toward effector T-helper 1 and T-
CC helper 17 cell subtypes (PubMed:23602766, PubMed:23911656). The
CC heterodimer formed with CLEC6A is active against fungal infection (By
CC similarity). Functions as an endocytic receptor (By similarity). May be
CC involved in antigen uptake at the site of infection, either for
CC clearance of the antigen, or for processing and further presentation to
CC T-cells (By similarity). {ECO:0000250|UniProtKB:Q69FH1,
CC ECO:0000250|UniProtKB:Q8WXI8, ECO:0000269|PubMed:23602766,
CC ECO:0000269|PubMed:23911656}.
CC -!- SUBUNIT: Heterodimer with CLEC4E; disulfide-linked. CLEC4E acts as a
CC bridge for interaction between CLEC4D and FCER1G to form a functional
CC complex (By similarity). Heterodimer with CLEC6A; this heterodimer
CC forms a pattern recognition receptor (PRR) against fungal infection (By
CC similarity). {ECO:0000250|UniProtKB:Q69FH1,
CC ECO:0000250|UniProtKB:Q8WXI8}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305|PubMed:23602766};
CC Single-pass type II membrane protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Constitutively expressed in myeloid cells including
CC dendritic cells (at protein level) (PubMed:23602766). Expressed in the
CC macrophage populations of bone marrow, spleen, lung and lymph nodes
CC (PubMed:9660840). {ECO:0000269|PubMed:23602766,
CC ECO:0000269|PubMed:9660840}.
CC -!- DISRUPTION PHENOTYPE: Knockout mice are born at the expected Mendelian
CC rate (PubMed:23602766). When compared to wild-type littermates,
CC deficient mice show resistance to lethal systemic inflammation caused
CC by exposure to mycobacterial cord factor/trehalose 6,6'-dimycolate
CC (TDM) (PubMed:23602766). Mice are also susceptibility to C.albicans
CC infections (PubMed:23911656). {ECO:0000269|PubMed:23602766,
CC ECO:0000269|PubMed:23911656}.
CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - Glycan Binding;
CC Note=MCL;
CC URL="http://www.functionalglycomics.org/glycomics/GBPServlet?&operationType=view&cbpId=cbp_mou_Ctlect_161";
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DR EMBL; AF061272; AAD05125.1; -; mRNA.
DR EMBL; AK089500; BAC40905.1; -; mRNA.
DR CCDS; CCDS20513.1; -.
DR RefSeq; NP_001156633.1; NM_001163161.1.
DR RefSeq; NP_034949.3; NM_010819.4.
DR AlphaFoldDB; Q9Z2H6; -.
DR SMR; Q9Z2H6; -.
DR STRING; 10090.ENSMUSP00000032240; -.
DR GlyGen; Q9Z2H6; 2 sites.
DR iPTMnet; Q9Z2H6; -.
DR PhosphoSitePlus; Q9Z2H6; -.
DR MaxQB; Q9Z2H6; -.
DR PaxDb; Q9Z2H6; -.
DR PRIDE; Q9Z2H6; -.
DR ProteomicsDB; 279104; -.
DR Antibodypedia; 1467; 290 antibodies from 30 providers.
DR DNASU; 17474; -.
DR Ensembl; ENSMUST00000032240; ENSMUSP00000032240; ENSMUSG00000030144.
DR GeneID; 17474; -.
DR KEGG; mmu:17474; -.
DR UCSC; uc009dqg.2; mouse.
DR CTD; 338339; -.
DR MGI; MGI:1298389; Clec4d.
DR VEuPathDB; HostDB:ENSMUSG00000030144; -.
DR eggNOG; KOG4297; Eukaryota.
DR GeneTree; ENSGT00940000162400; -.
DR HOGENOM; CLU_049894_7_5_1; -.
DR InParanoid; Q9Z2H6; -.
DR OMA; WAWNDVP; -.
DR OrthoDB; 1269095at2759; -.
DR PhylomeDB; Q9Z2H6; -.
DR TreeFam; TF333341; -.
DR Reactome; R-MMU-5621480; Dectin-2 family.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR BioGRID-ORCS; 17474; 0 hits in 73 CRISPR screens.
DR PRO; PR:Q9Z2H6; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q9Z2H6; protein.
DR Bgee; ENSMUSG00000030144; Expressed in stroma of bone marrow and 50 other tissues.
DR ExpressionAtlas; Q9Z2H6; baseline and differential.
DR Genevisible; Q9Z2H6; MM.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0030246; F:carbohydrate binding; IBA:GO_Central.
DR GO; GO:0034987; F:immunoglobulin receptor binding; IPI:MGI.
DR GO; GO:0005537; F:mannose binding; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0038187; F:pattern recognition receptor activity; ISS:UniProtKB.
DR GO; GO:0002250; P:adaptive immune response; IMP:MGI.
DR GO; GO:0061760; P:antifungal innate immune response; IMP:UniProtKB.
DR GO; GO:0042742; P:defense response to bacterium; IMP:MGI.
DR GO; GO:0038094; P:Fc-gamma receptor signaling pathway; IDA:MGI.
DR GO; GO:0006955; P:immune response; IBA:GO_Central.
DR GO; GO:0045087; P:innate immune response; IMP:MGI.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IMP:UniProtKB.
DR GO; GO:0030887; P:positive regulation of myeloid dendritic cell activation; IMP:UniProtKB.
DR GO; GO:0002292; P:T cell differentiation involved in immune response; IMP:MGI.
DR CDD; cd03590; CLECT_DC-SIGN_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; IPR033989; CD209-like_CTLD.
DR InterPro; IPR016187; CTDL_fold.
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 Adaptive immunity; Calcium; Cell membrane; Disulfide bond; Glycoprotein;
KW Immunity; Innate immunity; Lectin; Membrane; Metal-binding; Receptor;
KW Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix.
FT CHAIN 1..219
FT /note="C-type lectin domain family 4 member D"
FT /id="PRO_0000046617"
FT TOPO_DOM 1..20
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 21..43
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 44..219
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 90..207
FT /note="C-type lectin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT BINDING 172
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q8WXI8"
FT BINDING 194
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q8WXI8"
FT BINDING 195
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q8WXI8"
FT CARBOHYD 101
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 110
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 83..94
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT DISULFID 111..206
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT DISULFID 181..198
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT CONFLICT 70
FT /note="E -> G (in Ref. 2; BAC40905)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 219 AA; 25619 MW; 1801A65F4B69BC40 CRC64;
MWLEESQMKS KGTRHPQLIP CVFAVVSISF LSACFISTCL VTHHYFLRWT RGSVVKLSDY
HTRVTCIREE PQPGATGGTW TCCPVSWRAF QSNCYFPLND NQTWHESERN CSGMSSHLVT
INTEAEQNFV TQLLDKRFSY FLGLADENVE GQWQWVDKTP FNPHTVFWEK GESNDFMEED
CVVLVHVHEK WVWNDFPCHF EVRRICKLPG ITFNWKPSK
