CLC6A_MOUSE
ID CLC6A_MOUSE Reviewed; 209 AA.
AC Q9JKF4; Q9JKF2; Q9JKF3;
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 6 member A;
DE AltName: Full=C-type lectin superfamily member 10;
DE AltName: Full=Dendritic cell-associated C-type lectin 2 {ECO:0000303|PubMed:17050534};
DE Short=DC-associated C-type lectin 2 {ECO:0000303|PubMed:17050534};
DE Short=Dectin-2 {ECO:0000303|PubMed:17050534};
GN Name=Clec6a {ECO:0000312|MGI:MGI:1861231};
GN Synonyms=Clec4n, Clecsf10, Dectin2 {ECO:0000303|PubMed:17050534};
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] (ISOFORMS 1; 2 AND 3), AND TISSUE SPECIFICITY.
RC STRAIN=BALB/cJ;
RX PubMed=10766825; DOI=10.1074/jbc.275.16.11957;
RA Ariizumi K., Shen G.-L., Shikano S., Ritter R. III, Zukas P., Edelbaum D.,
RA Morita A., Takashima A.;
RT "Cloning of a second dendritic cell-associated C-type lectin (dectin-2) and
RT its alternatively spliced isoforms.";
RL J. Biol. Chem. 275:11957-11963(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=FVB/N-3; 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, INTERACTION WITH FCER1G, AND MUTAGENESIS OF ARG-17.
RX PubMed=17050534; DOI=10.1074/jbc.m606542200;
RA Sato K., Yang X.L., Yudate T., Chung J.S., Wu J., Luby-Phelps K.,
RA Kimberly R.P., Underhill D., Cruz P.D. Jr., Ariizumi K.;
RT "Dectin-2 is a pattern recognition receptor for fungi that couples with the
RT Fc receptor gamma chain to induce innate immune responses.";
RL J. Biol. Chem. 281:38854-38866(2006).
RN [4]
RP FUNCTION.
RX PubMed=19703985; DOI=10.1084/jem.20082818;
RA Robinson M.J., Osorio F., Rosas M., Freitas R.P., Schweighoffer E.,
RA Gross O., Verbeek J.S., Ruland J., Tybulewicz V., Brown G.D., Moita L.F.,
RA Taylor P.R., Reis e Sousa C.;
RT "Dectin-2 is a Syk-coupled pattern recognition receptor crucial for Th17
RT responses to fungal infection.";
RL J. Exp. Med. 206:2037-2051(2009).
RN [5]
RP FUNCTION.
RX PubMed=19124755; DOI=10.4049/jimmunol.182.2.1119;
RA Barrett N.A., Maekawa A., Rahman O.M., Austen K.F., Kanaoka Y.;
RT "Dectin-2 recognition of house dust mite triggers cysteinyl leukotriene
RT generation by dendritic cells.";
RL J. Immunol. 182:1119-1128(2009).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=20493731; DOI=10.1016/j.immuni.2010.05.001;
RA Saijo S., Ikeda S., Yamabe K., Kakuta S., Ishigame H., Akitsu A.,
RA Fujikado N., Kusaka T., Kubo S., Chung S.H., Komatsu R., Miura N.,
RA Adachi Y., Ohno N., Shibuya K., Yamamoto N., Kawakami K., Yamasaki S.,
RA Saito T., Akira S., Iwakura Y.;
RT "Dectin-2 recognition of alpha-mannans and induction of Th17 cell
RT differentiation is essential for host defense against Candida albicans.";
RL Immunity 32:681-691(2010).
RN [8]
RP FUNCTION.
RX PubMed=21059925; DOI=10.1073/pnas.1010337107;
RA Ritter M., Gross O., Kays S., Ruland J., Nimmerjahn F., Saijo S.,
RA Tschopp J., Layland L.E., Prazeres da Costa C.;
RT "Schistosoma mansoni triggers Dectin-2, which activates the Nlrp3
RT inflammasome and alters adaptive immune responses.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:20459-20464(2010).
RN [9]
RP FUNCTION.
RX PubMed=32358020; DOI=10.4049/jimmunol.1900793;
RA Campuzano A., Zhang H., Ostroff G.R., Dos Santos Dias L., Wuethrich M.,
RA Klein B.S., Yu J.J., Lara H.H., Lopez-Ribot J.L., Hung C.Y.;
RT "CARD9-associated Dectin-1 and Dectin-2 are required for protective
RT immunity of a multivalent vaccine against coccidioides posadasii
RT infection.";
RL J. Immunol. 204:3296-3306(2020).
CC -!- FUNCTION: Calcium-dependent lectin that acts as a pattern recognition
CC receptor (PRR) of the innate immune system: specifically recognizes and
CC binds alpha-mannans on C.albicans hypheas (PubMed:17050534,
CC PubMed:19703985, PubMed:20493731). Binding of C.albicans alpha-mannans
CC to this receptor complex leads to phosphorylation of the immunoreceptor
CC tyrosine-based activation motif (ITAM) of FCER1G, triggering activation
CC of SYK, CARD9 and NF-kappa-B, consequently driving maturation of
CC antigen-presenting cells and shaping antigen-specific priming of T-
CC cells toward effector T-helper 1 and T-helper 17 cell subtypes
CC (PubMed:17050534, PubMed:19703985, PubMed:20493731, PubMed:32358020).
CC Recognizes also, in a mannose-dependent manner, allergens from house
CC dust mite and fungi, by promoting cysteinyl leukotriene production
CC (PubMed:19124755). Recognizes soluble elements from the eggs of
CC Shistosoma mansoni altering adaptive immune responses
CC (PubMed:21059925). {ECO:0000269|PubMed:17050534,
CC ECO:0000269|PubMed:19124755, ECO:0000269|PubMed:19703985,
CC ECO:0000269|PubMed:20493731, ECO:0000269|PubMed:21059925,
CC ECO:0000269|PubMed:32358020}.
CC -!- SUBUNIT: Associated with FCER1G (PubMed:17050534). Heterodimer with
CC CLEC4D; this heterodimer forms a pattern recognition receptor (PRR)
CC against fungal infection (By similarity).
CC {ECO:0000250|UniProtKB:Q6EIG7, ECO:0000269|PubMed:17050534}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q6EIG7};
CC Single-pass type II membrane protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=Alpha;
CC IsoId=Q9JKF4-1; Sequence=Displayed;
CC Name=2; Synonyms=Beta;
CC IsoId=Q9JKF4-2; Sequence=VSP_012846;
CC Name=3; Synonyms=Gamma;
CC IsoId=Q9JKF4-3; Sequence=VSP_012847;
CC -!- TISSUE SPECIFICITY: Expressed by the XS52 DC (dendritic cell) line (at
CC protein level). Expressed constitutively by the epidermis, and skin
CC resident DC appear to be the major source of this expression. Expressed
CC in the spleen and thymus. Expression was undetectable in non-DC lines,
CC including macrophage lines (J774 and Raw), T-cell lines (7-17, HDK-1,
CC and D10), B-cell hybridoma (5C5), a keratinocyte line (Pam 212), and a
CC fibroblast line (NS01). {ECO:0000269|PubMed:10766825}.
CC -!- DOMAIN: A short stretch of the intracellular domain (AA 8-14) proximal
CC to the transmembrane domain is required for association with Fc
CC receptor gamma chain. {ECO:0000269|PubMed:17050534}.
CC -!- DISRUPTION PHENOTYPE: Deficient mice are healthy, fertile, with normal
CC lymphoid cells, but show reduced survival after intravenous Candida
CC albicans infection (PubMed:20493731). In deficient mice fungal burden
CC is higher in kidneys of mutant and in response to yeast antigen
CC inflammatory cytokines and Th17 cells are reduced (PubMed:20493731).
CC {ECO:0000269|PubMed:20493731}.
CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - Glycan Binding;
CC Note=Dectin-2;
CC URL="http://www.functionalglycomics.org/glycomics/GBPServlet?&operationType=view&cbpId=cbp_mou_Ctlect_361";
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DR EMBL; AF240357; AAF67177.1; -; mRNA.
DR EMBL; AF240358; AAF67178.1; -; mRNA.
DR EMBL; AF240359; AAF67179.1; -; mRNA.
DR EMBL; BC023008; AAH23008.1; -; mRNA.
DR CCDS; CCDS20512.1; -. [Q9JKF4-1]
DR CCDS; CCDS51895.1; -. [Q9JKF4-2]
DR RefSeq; NP_001177250.1; NM_001190321.1. [Q9JKF4-2]
DR RefSeq; NP_064385.1; NM_020001.2. [Q9JKF4-1]
DR AlphaFoldDB; Q9JKF4; -.
DR SMR; Q9JKF4; -.
DR STRING; 10090.ENSMUSP00000024118; -.
DR GlyGen; Q9JKF4; 1 site.
DR iPTMnet; Q9JKF4; -.
DR PhosphoSitePlus; Q9JKF4; -.
DR MaxQB; Q9JKF4; -.
DR PaxDb; Q9JKF4; -.
DR PRIDE; Q9JKF4; -.
DR Antibodypedia; 23055; 463 antibodies from 30 providers.
DR DNASU; 56620; -.
DR Ensembl; ENSMUST00000024118; ENSMUSP00000024118; ENSMUSG00000023349. [Q9JKF4-1]
DR Ensembl; ENSMUST00000112554; ENSMUSP00000108173; ENSMUSG00000023349. [Q9JKF4-2]
DR GeneID; 56620; -.
DR KEGG; mmu:56620; -.
DR UCSC; uc009dqe.2; mouse. [Q9JKF4-1]
DR UCSC; uc009dqf.2; mouse. [Q9JKF4-2]
DR CTD; 56620; -.
DR MGI; MGI:1861231; Clec4n.
DR VEuPathDB; HostDB:ENSMUSG00000023349; -.
DR eggNOG; KOG4297; Eukaryota.
DR GeneTree; ENSGT00940000162938; -.
DR HOGENOM; CLU_049894_7_5_1; -.
DR InParanoid; Q9JKF4; -.
DR OMA; EKNVRFW; -.
DR PhylomeDB; Q9JKF4; -.
DR TreeFam; TF333341; -.
DR Reactome; R-MMU-5621480; Dectin-2 family.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR BioGRID-ORCS; 56620; 1 hit in 75 CRISPR screens.
DR PRO; PR:Q9JKF4; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q9JKF4; protein.
DR Bgee; ENSMUSG00000023349; Expressed in stroma of bone marrow and 96 other tissues.
DR ExpressionAtlas; Q9JKF4; baseline and differential.
DR Genevisible; Q9JKF4; 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; ISS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0030246; F:carbohydrate binding; IDA:UniProtKB.
DR GO; GO:0005537; F:mannose binding; ISS:UniProtKB.
DR GO; GO:0038187; F:pattern recognition receptor activity; IMP:ARUK-UCL.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0061760; P:antifungal innate immune response; IMP:UniProtKB.
DR GO; GO:0050832; P:defense response to fungus; IDA:UniProtKB.
DR GO; GO:0001879; P:detection of yeast; IMP:ARUK-UCL.
DR GO; GO:0006955; P:immune response; IBA:GO_Central.
DR GO; GO:0045087; P:innate immune response; IDA:UniProtKB.
DR GO; GO:0001819; P:positive regulation of cytokine production; IDA:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IDA:UniProtKB.
DR GO; GO:1902533; P:positive regulation of intracellular signal transduction; IMP:ARUK-UCL.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IMP:ARUK-UCL.
DR GO; GO:2000318; P:positive regulation of T-helper 17 type immune response; IMP:UniProtKB.
DR GO; GO:0001878; P:response to yeast; IMP:ARUK-UCL.
DR GO; GO:0002223; P:stimulatory C-type lectin receptor signaling pathway; IMP:ARUK-UCL.
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 Adaptive immunity; Alternative splicing; Calcium; Cell membrane;
KW Disulfide bond; Glycoprotein; Immunity; Innate immunity; Lectin; Membrane;
KW Metal-binding; Reference proteome; Signal-anchor; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..209
FT /note="C-type lectin domain family 6 member A"
FT /id="PRO_0000046636"
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..209
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 86..203
FT /note="C-type lectin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT BINDING 116
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q6EIG7"
FT BINDING 118
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q6EIG7"
FT BINDING 122
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q6EIG7"
FT BINDING 168..170
FT /ligand="alpha-D-mannopyranose"
FT /ligand_id="ChEBI:CHEBI:28729"
FT /evidence="ECO:0000250|UniProtKB:Q6EIG7"
FT BINDING 168
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q6EIG7"
FT BINDING 170
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q6EIG7"
FT BINDING 174
FT /ligand="alpha-D-mannopyranose"
FT /ligand_id="ChEBI:CHEBI:28729"
FT /evidence="ECO:0000250|UniProtKB:Q6EIG7"
FT BINDING 174
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q6EIG7"
FT BINDING 182
FT /ligand="alpha-D-mannopyranose"
FT /ligand_id="ChEBI:CHEBI:28729"
FT /evidence="ECO:0000250|UniProtKB:Q6EIG7"
FT BINDING 190..191
FT /ligand="alpha-D-mannopyranose"
FT /ligand_id="ChEBI:CHEBI:28729"
FT /evidence="ECO:0000250|UniProtKB:Q6EIG7"
FT BINDING 190
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q6EIG7"
FT BINDING 191
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q6EIG7"
FT BINDING 203
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q6EIG7"
FT CARBOHYD 131
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 64..78
FT /evidence="ECO:0000250|UniProtKB:Q6EIG7"
FT DISULFID 79..90
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT DISULFID 107..202
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT DISULFID 176..194
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT VAR_SEQ 39..72
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10766825"
FT /id="VSP_012846"
FT VAR_SEQ 142..182
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:10766825"
FT /id="VSP_012847"
FT MUTAGEN 17
FT /note="R->V: Does not affect association with Fc receptor
FT gamma chain."
FT /evidence="ECO:0000269|PubMed:17050534"
SQ SEQUENCE 209 AA; 24324 MW; 7AB8BDC0DB1EA5ED CRC64;
MVQERQSQGK GVCWTLRLWS AAVISMLLLS TCFIASCVVT YQFIMDQPSR RLYELHTYHS
SLTCFSEGTM VSEKMWGCCP NHWKSFGSSC YLISTKENFW STSEQNCVQM GAHLVVINTE
AEQNFITQQL NESLSYFLGL SDPQGNGKWQ WIDDTPFSQN VRFWHPHEPN LPEERCVSIV
YWNPSKWGWN DVFCDSKHNS ICEMKKIYL
