CLC4A_MOUSE
ID CLC4A_MOUSE Reviewed; 238 AA.
AC Q9QZ15; Q4VA33;
DT 15-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 144.
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 immunoreceptor;
DE AltName: CD_antigen=CD367;
GN Name=Clec4a; Synonyms=Clec4a2, Clecsf6, Dcir;
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].
RC TISSUE=Lymph node;
RX PubMed=10438934;
RA Bates E.E.M., Fournier N., Garcia E., Valladeau J., Durand I., Pin J.-J.,
RA Zurawski S.M., Patel S., Abrams J.S., Lebecque S., Garrone P., Saeland S.;
RT "APCs express DCIR, a novel C-type lectin surface receptor containing an
RT immunoreceptor tyrosine-based inhibitory motif.";
RL J. Immunol. 163:1973-1983(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, MUTAGENESIS OF
RP TYR-7, AND DOMAIN.
RC STRAIN=BALB/cJ;
RX PubMed=11841542; DOI=10.1046/j.0022-202x.2001.01633.x;
RA Kanazawa N., Okazaki T., Nishimura H., Tashiro K., Inaba K., Miyachi Y.;
RT "DCIR acts as an inhibitory receptor depending on its immunoreceptor
RT tyrosine-based inhibitory motif.";
RL J. Invest. Dermatol. 118:261-266(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Cerebellum;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Jaw, Limb, and Mammary gland;
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
CC -!- FUNCTION: May be involved in regulating immune reactivity. May play a
CC role in modulating dendritic cells (DC) differentiation and/or
CC maturation (By similarity). May be involved in the inhibition of B-
CC cell-receptor-mediated calcium mobilization and protein tyrosine
CC phosphorylation. {ECO:0000250, ECO:0000269|PubMed:11841542}.
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 (By similarity). May be involved via its ITIM motif
CC (immunoreceptor tyrosine-based inhibitory motifs) in the inhibition of
CC B-cell-receptor-mediated calcium mobilization and protein tyrosine
CC phosphorylation (PubMed:11841542). {ECO:0000250|UniProtKB:Q9UMR7,
CC ECO:0000269|PubMed:11841542}.
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:0000250|UniProtKB:Q9UMR7}; Extracellular side
CC {ECO:0000250|UniProtKB:Q9UMR7}.
CC -!- TISSUE SPECIFICITY: Expressed in splenic antigen-presenting cells
CC including B-cells, monocytes/macrophages, and dendritic cells (at
CC protein level). Expressed in spleen and lymph node and slightly
CC increased with dendritic cell maturation.
CC {ECO:0000269|PubMed:11841542}.
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:0000269|PubMed:11841542}.
CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - Glycan Binding;
CC Note=DCIR1;
CC URL="http://www.functionalglycomics.org/glycomics/GBPServlet?&operationType=view&cbpId=cbp_mou_Ctlect_160";
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DR EMBL; AJ133533; CAB57870.1; -; mRNA.
DR EMBL; AF387099; AAM22402.1; -; mRNA.
DR EMBL; AK049002; BAC33509.1; -; mRNA.
DR EMBL; BC075729; AAH75729.1; -; mRNA.
DR EMBL; BC096565; AAH96565.1; -; mRNA.
DR CCDS; CCDS20510.1; -.
DR RefSeq; NP_001163803.1; NM_001170332.1.
DR RefSeq; NP_001163804.1; NM_001170333.1.
DR RefSeq; NP_036129.1; NM_011999.4.
DR AlphaFoldDB; Q9QZ15; -.
DR SMR; Q9QZ15; -.
DR STRING; 10090.ENSMUSP00000032248; -.
DR GlyConnect; 2239; 1 N-Linked glycan (1 site).
DR GlyGen; Q9QZ15; 3 sites, 1 N-linked glycan (1 site).
DR iPTMnet; Q9QZ15; -.
DR PhosphoSitePlus; Q9QZ15; -.
DR MaxQB; Q9QZ15; -.
DR PRIDE; Q9QZ15; -.
DR DNASU; 26888; -.
DR Ensembl; ENSMUST00000041779; ENSMUSP00000045781; ENSMUSG00000030148.
DR Ensembl; ENSMUST00000161365; ENSMUSP00000124615; ENSMUSG00000030148.
DR GeneID; 26888; -.
DR KEGG; mmu:26888; -.
DR UCSC; uc009dqa.1; mouse.
DR CTD; 26888; -.
DR MGI; MGI:1349412; Clec4a2.
DR VEuPathDB; HostDB:ENSMUSG00000030148; -.
DR eggNOG; KOG4297; Eukaryota.
DR GeneTree; ENSGT00940000162867; -.
DR HOGENOM; CLU_049894_7_5_1; -.
DR InParanoid; Q9QZ15; -.
DR OMA; MINSARG; -.
DR OrthoDB; 1378771at2759; -.
DR PhylomeDB; Q9QZ15; -.
DR BioGRID-ORCS; 26888; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Clec4a2; mouse.
DR PRO; PR:Q9QZ15; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q9QZ15; protein.
DR Bgee; ENSMUSG00000030148; Expressed in granulocyte and 112 other tissues.
DR ExpressionAtlas; Q9QZ15; baseline and differential.
DR Genevisible; Q9QZ15; 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:0016020; C:membrane; TAS:MGI.
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:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0061760; P:antifungal innate immune response; IBA:GO_Central.
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:0006955; P:immune response; IBA:GO_Central.
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 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; 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..238
FT /note="C-type lectin domain family 4 member A"
FT /id="PRO_0000046613"
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..238
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 126..233
FT /note="C-type lectin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT MOTIF 5..10
FT /note="ITIM motif"
FT BINDING 146
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9UMR7"
FT BINDING 152
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9UMR7"
FT BINDING 197..199
FT /ligand="alpha-D-mannopyranose"
FT /ligand_id="ChEBI:CHEBI:28729"
FT /evidence="ECO:0000250|UniProtKB:Q9UMR7"
FT BINDING 197
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9UMR7"
FT BINDING 199
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9UMR7"
FT BINDING 203
FT /ligand="alpha-D-mannopyranose"
FT /ligand_id="ChEBI:CHEBI:28729"
FT /evidence="ECO:0000250|UniProtKB:Q9UMR7"
FT BINDING 203
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9UMR7"
FT BINDING 209..211
FT /ligand="N-acetyl-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:506227"
FT /evidence="ECO:0000250|UniProtKB:Q9UMR7"
FT BINDING 219
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9UMR7"
FT BINDING 220
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9UMR7"
FT CARBOHYD 91
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 131
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 136
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 107..118
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT DISULFID 137..231
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT DISULFID 205..223
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT MUTAGEN 7
FT /note="Y->F: Loss of inhibition of B-cell calcium
FT mobilization."
FT /evidence="ECO:0000269|PubMed:11841542"
SQ SEQUENCE 238 AA; 27323 MW; 2DB8AE0E11B18A56 CRC64;
MASEITYAEV KFKNESNSLH TYSESPAAPR EKPIRDLRKP GSPSLLLTSL MLLLLLLAIT
FLVAFIIYFQ KYSQLLEEKK AAKNIMHNEL NCTKSVSPME DKVWSCCPKD WRLFGSHCYL
VPTVSSSASW NKSEENCSRM GAHLVVIQSQ EEQDFITGIL DTHAAYFIGL WDTGHRQWQW
VDQTPYEESI TFWHNGEPSS GNEKCATIIY RWKTGWGWND ISCSLKQKSV CQMKKINL
