CLC4E_MOUSE
ID CLC4E_MOUSE Reviewed; 214 AA.
AC Q9R0Q8;
DT 15-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=C-type lectin domain family 4 member E;
DE AltName: Full=C-type lectin superfamily member 9;
DE AltName: Full=Macrophage-inducible C-type lectin {ECO:0000303|PubMed:18776906};
DE Short=Mincle {ECO:0000303|PubMed:18776906, ECO:0000303|PubMed:19171887};
GN Name=Clec4e {ECO:0000312|MGI:MGI:1861232};
GN Synonyms=Clecsf9, Mincle {ECO:0000303|PubMed:18776906,
GN ECO:0000303|PubMed:19171887};
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], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND INDUCTION.
RX PubMed=10528209;
RA Matsumoto M., Shimada T., Kaisho T., Sanjo H., Tanaka T., Copeland N.G.,
RA Gilbert D.J., Jenkins N.A., Akira S.;
RT "A novel LPS-inducible C-type lectin is a transcriptional target of NF-IL6
RT in macrophages.";
RL J. Immunol. 163:5039-5048(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 [3]
RP FUNCTION AS RECEPTOR FOR CANDIDA ALBICANS, AND SUBUNIT.
RX PubMed=18509109; DOI=10.1093/glycob/cwn046;
RA Bugarcic A., Hitchens K., Beckhouse A.G., Wells C.A., Ashman R.B.,
RA Blanchard H.;
RT "Human and mouse macrophage-inducible C-type lectin (Mincle) bind Candida
RT albicans.";
RL Glycobiology 18:679-685(2008).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, INDUCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18490740; DOI=10.4049/jimmunol.180.11.7404;
RA Wells C.A., Salvage-Jones J.A., Li X., Hitchens K., Butcher S.,
RA Murray R.Z., Beckhouse A.G., Lo Y.L., Manzanero S., Cobbold C.,
RA Schroder K., Ma B., Orr S., Stewart L., Lebus D., Sobieszczuk P.,
RA Hume D.A., Stow J., Blanchard H., Ashman R.B.;
RT "The macrophage-inducible C-type lectin, mincle, is an essential component
RT of the innate immune response to Candida albicans.";
RL J. Immunol. 180:7404-7413(2008).
RN [5]
RP INTERACTION WITH FCER1G, INTERACTION WITH SAP130, MUTAGENESIS OF ARG-42,
RP AND FUNCTION.
RX PubMed=18776906; DOI=10.1038/ni.1651;
RA Yamasaki S., Ishikawa E., Sakuma M., Hara H., Ogata K., Saito T.;
RT "Mincle is an ITAM-coupled activating receptor that senses damaged cells.";
RL Nat. Immunol. 9:1179-1188(2008).
RN [6]
RP FUNCTION.
RX PubMed=20008526; DOI=10.1084/jem.20091750;
RA Ishikawa E., Ishikawa T., Morita Y.S., Toyonaga K., Yamada H., Takeuchi O.,
RA Kinoshita T., Akira S., Yoshikai Y., Yamasaki S.;
RT "Direct recognition of the mycobacterial glycolipid, trehalose dimycolate,
RT by C-type lectin Mincle.";
RL J. Exp. Med. 206:2879-2888(2009).
RN [7]
RP DISRUPTION PHENOTYPE, MUTAGENESIS OF GLU-169 AND ASN-171, AND FUNCTION AS A
RP RECEPTOR FOR MALASSEZIA.
RX PubMed=19171887; DOI=10.1073/pnas.0805177106;
RA Yamasaki S., Matsumoto M., Takeuchi O., Matsuzawa T., Ishikawa E.,
RA Sakuma M., Tateno H., Uno J., Hirabayashi J., Mikami Y., Takeda K.,
RA Akira S., Saito T.;
RT "C-type lectin Mincle is an activating receptor for pathogenic fungus,
RT Malassezia.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:1897-1902(2009).
RN [8]
RP FUNCTION, TISSUE SPECIFICITY, SUBUNIT, IDENTIFICATION IN COMPLEX WITH
RP FCER1G, DISRUPTION PHENOTYPE, INDUCTION BY TREHALOSE 6,6'-DIMYCOLATE, AND
RP SUBCELLULAR 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).
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 abnormal self and pathogen-
CC associated molecular patterns (PAMPs) of bacteria and fungi
CC (PubMed:18509109, PubMed:18490740, PubMed:18776906, PubMed:20008526,
CC PubMed:19171887, PubMed:23602766). The PAMPs notably include
CC mycobacterial trehalose 6,6'-dimycolate (TDM), a cell wall glycolipid
CC with potent adjuvant immunomodulatory functions (PubMed:20008526,
CC PubMed:23602766). Interacts with signaling adapter Fc receptor gamma
CC chain/FCER1G to form a functional complex in myeloid cells
CC (PubMed:23602766, PubMed:18776906). Binding of mycobacterial trehalose
CC 6,6'-dimycolate (TDM) to this receptor complex leads to phosphorylation
CC of the immunoreceptor tyrosine-based activation motif (ITAM) of FCER1G,
CC triggering activation of SYK, CARD9 and NF-kappa-B, consequently
CC driving maturation of antigen-presenting cells and shaping antigen-
CC specific priming of T-cells toward effector T-helper 1 (Th1) and T-
CC helper 17 (Th17) cell subtypes (PubMed:23602766). Also recognizes
CC alpha-mannose residues on pathogenic fungi of the genus Malassezia and
CC mediates macrophage activation (PubMed:19171887). Through recognition
CC of DAMPs released upon nonhomeostatic cell death, enables immune
CC sensing of damaged self and promotes inflammatory cell infiltration
CC into the damaged tissue (PubMed:18776906).
CC {ECO:0000269|PubMed:18490740, ECO:0000269|PubMed:18509109,
CC ECO:0000269|PubMed:18776906, ECO:0000269|PubMed:19171887,
CC ECO:0000269|PubMed:20008526, ECO:0000269|PubMed:23602766}.
CC -!- SUBUNIT: Monomer and homodimer (PubMed:18509109). Interacts with
CC signaling adapter Fc receptor gamma chain/FCER1G to form a functional
CC complex; the interaction is direct (PubMed:23602766). Alternatively,
CC acts as a bridge for interaction between CLEC4D and FCER1G. A
CC heterodimer of CLEC4E and CLEC4D associates with FCER1G to form a
CC functional complex (By similarity). Interacts with SAP130 nuclear
CC protein that is released from necrotic cells; the interaction is direct
CC (PubMed:23602766). {ECO:0000250|UniProtKB:Q67EQ1,
CC ECO:0000269|PubMed:18509109, ECO:0000269|PubMed:23602766}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:18490740,
CC ECO:0000305|PubMed:10528209, ECO:0000305|PubMed:23602766}; Single-pass
CC type II membrane protein {ECO:0000305|PubMed:10528209}. Cell
CC projection, phagocytic cup {ECO:0000269|PubMed:18490740}.
CC -!- TISSUE SPECIFICITY: Highly expressed in macrophages in response to
CC stimulation with bacterial glycolipids and pro-inflammatory cytokines
CC (PubMed:10528209). Expressed in dendritic cells (at protein level) in
CC response to stimulation with mycobacterial trehalose 6,6'-dimycolate
CC (TDM) (PubMed:23602766). {ECO:0000269|PubMed:10528209,
CC ECO:0000269|PubMed:23602766}.
CC -!- INDUCTION: Expression is induced upon exposure to bacterial glycolipids
CC including lipopolysaccharide (LPS) and mycobacterial trehalose 6,6'-
CC dimycolate (TDM) and several pro-inflammatory cytokines, including IFNG
CC and TNF (PubMed:10528209, PubMed:23602766). Rapidly induced in thymus
CC in response to whole-body irradiation and excessive cell death
CC (PubMed:18776906). Induced in macrophages in response to C.albicans
CC infection (PubMed:18490740). {ECO:0000269|PubMed:10528209,
CC ECO:0000269|PubMed:18490740, ECO:0000269|PubMed:18776906,
CC ECO:0000269|PubMed:23602766}.
CC -!- DISRUPTION PHENOTYPE: Knockout mice are born at the expected Mendelian
CC rate (PubMed:19171887, PubMed:23602766). When compared to wild-type
CC littermates, deficient mice show resistance to lethal systemic
CC inflammation caused by exposure to mycobacterial cord factor/trehalose
CC 6,6'-dimycolate (TDM) (PubMed:23602766). Mice are also susceptibility
CC to systemic candidiasis (PubMed:18490740).
CC {ECO:0000269|PubMed:18490740, ECO:0000269|PubMed:19171887,
CC ECO:0000269|PubMed:23602766}.
CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - Glycan Binding;
CC Note=Mincle;
CC URL="http://www.functionalglycomics.org/glycomics/GBPServlet?&operationType=view&cbpId=cbp_mou_Ctlect_167";
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DR EMBL; AB024717; BAA83754.1; -; mRNA.
DR EMBL; BC003218; AAH03218.1; -; mRNA.
DR CCDS; CCDS20514.1; -.
DR RefSeq; NP_064332.1; NM_019948.2.
DR AlphaFoldDB; Q9R0Q8; -.
DR SMR; Q9R0Q8; -.
DR STRING; 10090.ENSMUSP00000032239; -.
DR ChEMBL; CHEMBL4105754; -.
DR GlyGen; Q9R0Q8; 1 site.
DR PhosphoSitePlus; Q9R0Q8; -.
DR SwissPalm; Q9R0Q8; -.
DR MaxQB; Q9R0Q8; -.
DR PaxDb; Q9R0Q8; -.
DR PRIDE; Q9R0Q8; -.
DR ProteomicsDB; 285467; -.
DR Antibodypedia; 23066; 317 antibodies from 27 providers.
DR DNASU; 56619; -.
DR Ensembl; ENSMUST00000032239; ENSMUSP00000032239; ENSMUSG00000030142.
DR GeneID; 56619; -.
DR KEGG; mmu:56619; -.
DR UCSC; uc009dqk.1; mouse.
DR CTD; 26253; -.
DR MGI; MGI:1861232; Clec4e.
DR VEuPathDB; HostDB:ENSMUSG00000030142; -.
DR eggNOG; KOG4297; Eukaryota.
DR GeneTree; ENSGT00940000160666; -.
DR InParanoid; Q9R0Q8; -.
DR OMA; NDMTCFF; -.
DR OrthoDB; 1118305at2759; -.
DR PhylomeDB; Q9R0Q8; -.
DR TreeFam; TF333341; -.
DR Reactome; R-MMU-5621480; Dectin-2 family.
DR BioGRID-ORCS; 56619; 0 hits in 72 CRISPR screens.
DR PRO; PR:Q9R0Q8; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q9R0Q8; protein.
DR Bgee; ENSMUSG00000030142; Expressed in granulocyte and 25 other tissues.
DR ExpressionAtlas; Q9R0Q8; baseline and differential.
DR Genevisible; Q9R0Q8; MM.
DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-KW.
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:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0001891; C:phagocytic cup; IEA:UniProtKB-SubCell.
DR GO; GO:0030670; C:phagocytic vesicle membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0030246; F:carbohydrate binding; IBA:GO_Central.
DR GO; GO:0051861; F:glycolipid binding; IPI:UniProtKB.
DR GO; GO:0038187; F:pattern recognition receptor activity; IDA:UniProtKB.
DR GO; GO:0038023; F:signaling receptor activity; IDA:UniProtKB.
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; IMP:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IDA:UniProtKB.
DR GO; GO:0002221; P:pattern recognition receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0001819; P:positive regulation of cytokine production; IDA: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; IPR018378; C-type_lectin_CS.
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; PS00615; C_TYPE_LECTIN_1; 1.
DR PROSITE; PS50041; C_TYPE_LECTIN_2; 1.
PE 1: Evidence at protein level;
KW Calcium; Cell membrane; Cell projection; Disulfide bond; Glycoprotein;
KW Immunity; Innate immunity; Lectin; Membrane; Metal-binding;
KW Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix.
FT CHAIN 1..214
FT /note="C-type lectin domain family 4 member E"
FT /id="PRO_0000046620"
FT TOPO_DOM 1..22
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 23..45
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 46..214
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 87..206
FT /note="C-type lectin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT MOTIF 169..171
FT /note="Confers specificity for glucose/mannose-type
FT carbohydrates"
FT /evidence="ECO:0000250|UniProtKB:Q9ULY5"
FT BINDING 117
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9ULY5"
FT BINDING 123
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9ULY5"
FT BINDING 169
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9ULY5"
FT BINDING 171
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9ULY5"
FT BINDING 193
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9ULY5"
FT BINDING 194
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9ULY5"
FT BINDING 206
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9ULY5"
FT CARBOHYD 107
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 80..91
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT DISULFID 108..205
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT DISULFID 179..197
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT MUTAGEN 42
FT /note="R->I: Abolishes the association with FCER1G."
FT /evidence="ECO:0000269|PubMed:18776906"
FT MUTAGEN 169
FT /note="E->Q: Abrogates Malassezia recognition; when
FT associated with D-171."
FT /evidence="ECO:0000269|PubMed:19171887"
FT MUTAGEN 171
FT /note="N->D: Abrogates Malassezia recognition; when
FT associated with Q-169."
FT /evidence="ECO:0000269|PubMed:19171887"
SQ SEQUENCE 214 AA; 24431 MW; 2FEF318A69BDAFE3 CRC64;
MNSTKSPASH HTERGCFKNS QVLSWTIAGA SILFLSGCFI TRCVVTYRSS QISGQNLQPH
RNIKELSCYS EASGSVKNCC PLNWKHYQSS CYFFSTTTLT WSSSLKNCSD MGAHLVVIDT
QEEQEFLFRT KPKRKEFYIG LTDQVVEGQW QWVDDTPFTE SLSFWDAGEP NNIVLVEDCA
TIRDSSNSRK NWNDIPCFYS MPWICEMPEI SPLD
