CLC4A_RAT
ID CLC4A_RAT Reviewed; 240 AA.
AC Q67EQ0;
DT 15-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 100.
DE RecName: Full=C-type lectin domain family 4 member A;
DE AltName: Full=C-type lectin superfamily member 6;
DE AltName: Full=Dendritic cell inhibitory receptor;
DE AltName: CD_antigen=CD367;
GN Name=Clec4a; Synonyms=Clecsf6, Dcir;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=PVG;
RX PubMed=15368084; DOI=10.1007/s00251-004-0714-x;
RA Flornes L.M., Bryceson Y.T., Spurkland A., Lorentzen J.C., Dissen E.,
RA Fossum S.;
RT "Identification of lectin-like receptors expressed by antigen presenting
RT cells and neutrophils and their mapping to a novel gene complex.";
RL Immunogenetics 56:506-517(2004).
CC -!- FUNCTION: C-type lectin receptor that binds carbohydrates mannose and
CC fucose but also weakly interacts with N-acetylglucosamine (GlcNAc) in a
CC Ca(2+)-dependent manner. Involved in regulating immune reactivity. Once
CC triggered by antigen, it is internalized by clathrin-dependent
CC endocytosis and delivers its antigenic cargo into the antigen
CC presentation pathway resulting in cross-priming of CD8(+) T cells. This
CC cross-presentation and cross-priming are enhanced by TLR7 and TLR8
CC agonists with increased expansion of the CD8(+) T cells, high
CC production of IFNG and TNF with reduced levels of IL4, IL5 and IL13. In
CC plasmacytoid dendritic cells, inhibits TLR9-mediated IFNA and TNF
CC production. May be involved via its ITIM motif (immunoreceptor
CC tyrosine-based inhibitory motifs) in the inhibition of B-cell-receptor-
CC mediated calcium mobilization and protein tyrosine phosphorylation.
CC {ECO:0000250|UniProtKB:Q9UMR7}.
CC -!- SUBUNIT: May interact with PTPN6 via its ITIM site.
CC {ECO:0000250|UniProtKB:Q9UMR7}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Single-pass type II
CC membrane protein {ECO:0000305}; Extracellular side
CC {ECO:0000250|UniProtKB:Q9UMR7}.
CC -!- TISSUE SPECIFICITY: Expressed by myeloid cells (dendritic cells,
CC macrophages, and neutrophils) and B-cells.
CC {ECO:0000269|PubMed:15368084}.
CC -!- DOMAIN: Contains 1 copy of a cytoplasmic motif that is referred to as
CC the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is
CC involved in modulation of cellular responses. The phosphorylated ITIM
CC motif can bind the SH2 domain of several SH2-containing phosphatases.
CC {ECO:0000250|UniProtKB:Q9UMR7}.
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DR EMBL; AY363176; AAR18686.1; -; mRNA.
DR AlphaFoldDB; Q67EQ0; -.
DR SMR; Q67EQ0; -.
DR STRING; 10116.ENSRNOP00000037071; -.
DR GlyGen; Q67EQ0; 1 site.
DR PaxDb; Q67EQ0; -.
DR UCSC; RGD:1359662; rat.
DR RGD; 1359662; Clec4a.
DR eggNOG; KOG4297; Eukaryota.
DR InParanoid; Q67EQ0; -.
DR PhylomeDB; Q67EQ0; -.
DR PRO; PR:Q67EQ0; -.
DR Proteomes; UP000002494; Unplaced.
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; ISO:RGD.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0030246; F:carbohydrate binding; ISS:UniProtKB.
DR GO; GO:0005537; F:mannose binding; ISS:UniProtKB.
DR GO; GO:0038187; F:pattern recognition receptor activity; ISO:RGD.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0061760; P:antifungal innate immune response; ISO:RGD.
DR GO; GO:0042590; P:antigen processing and presentation of exogenous peptide antigen via MHC class I; ISS:UniProtKB.
DR GO; GO:0036037; P:CD8-positive, alpha-beta T cell activation; ISS:UniProtKB.
DR GO; GO:0050832; P:defense response to fungus; ISO:RGD.
DR GO; GO:0001879; P:detection of yeast; ISO:RGD.
DR GO; GO:0006955; P:immune response; IBA:GO_Central.
DR GO; GO:0045087; P:innate immune response; ISO:RGD.
DR GO; GO:0001818; P:negative regulation of cytokine production; ISS:UniProtKB.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; ISS:UniProtKB.
DR GO; GO:0002470; P:plasmacytoid dendritic cell antigen processing and presentation; ISS:UniProtKB.
DR GO; GO:0001819; P:positive regulation of cytokine production; ISO:RGD.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISO:RGD.
DR GO; GO:1902533; P:positive regulation of intracellular signal transduction; ISO:RGD.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISO:RGD.
DR GO; GO:2000318; P:positive regulation of T-helper 17 type immune response; ISO:RGD.
DR GO; GO:0001878; P:response to yeast; ISO:RGD.
DR GO; GO:0002223; P:stimulatory C-type lectin receptor signaling pathway; ISO:RGD.
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 2: Evidence at transcript level;
KW Adaptive immunity; Calcium; Cell membrane; Disulfide bond; Glycoprotein;
KW Immunity; Innate immunity; Lectin; Membrane; Metal-binding;
KW Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix.
FT CHAIN 1..240
FT /note="C-type lectin domain family 4 member A"
FT /id="PRO_0000046614"
FT TOPO_DOM 1..48
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 49..69
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 70..240
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 129..235
FT /note="C-type lectin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT REGION 18..38
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 5..10
FT /note="ITIM motif"
FT BINDING 149
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9UMR7"
FT BINDING 155
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9UMR7"
FT BINDING 200..202
FT /ligand="alpha-D-mannopyranose"
FT /ligand_id="ChEBI:CHEBI:28729"
FT /evidence="ECO:0000250|UniProtKB:Q9UMR7"
FT BINDING 200
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9UMR7"
FT BINDING 202
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9UMR7"
FT BINDING 206
FT /ligand="alpha-D-mannopyranose"
FT /ligand_id="ChEBI:CHEBI:28729"
FT /evidence="ECO:0000250|UniProtKB:Q9UMR7"
FT BINDING 206
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9UMR7"
FT BINDING 211..213
FT /ligand="N-acetyl-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:506227"
FT /evidence="ECO:0000250|UniProtKB:Q9UMR7"
FT BINDING 221
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9UMR7"
FT BINDING 222
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9UMR7"
FT CARBOHYD 190
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 107..118
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT DISULFID 140..233
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT DISULFID 208..225
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
SQ SEQUENCE 240 AA; 27404 MW; 7C3FD5DAEDD8D52B CRC64;
MASEITYAEV RIKNESNSSV TYSGSPAAPR EKPTRHLSKP GSLLVPFTSL MVLLLLLAIT
FLVAFIIYFQ KYSQFLEEKK AIKGITHKEL NCIKNVLLME EKSWSCCPKN WKPFGSHCYW
VTKHTSTYSK ASWSESEKNC FSMGAHLLVI HSKEEQDFIT GILNRDAAYF IGLWDSGHRQ
WQWVSQTPYN ASATFWHKGE PSSDDEKCVI INHLNSGWGW NDIPCSGKQQ SVCQMKKIQL
