CLC9A_HUMAN
ID CLC9A_HUMAN Reviewed; 241 AA.
AC Q6UXN8; B0ZBM2;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=C-type lectin domain family 9 member A;
DE AltName: CD_antigen=CD370;
GN Name=CLEC9A; ORFNames=UNQ9341/PRO34046;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBUNIT, PHOSPHORYLATION, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, AND GLYCOSYLATION.
RX PubMed=18408006; DOI=10.1074/jbc.m709923200;
RA Huysamen C., Willment J.A., Dennehy K.M., Brown G.D.;
RT "CLEC9A is a novel activation C-type lectin-like receptor expressed on
RT BDCA3+ dendritic cells and a subset of monocytes.";
RL J. Biol. Chem. 283:16693-16701(2008).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [3]
RP TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=18497879; DOI=10.1172/jci34584;
RA Sancho D., Mourao-Sa D., Joffre O.P., Schulz O., Rogers N.C.,
RA Pennington D.J., Carlyle J.R., Reis e Sousa C.;
RT "Tumor therapy in mice via antigen targeting to a novel, DC-restricted C-
RT type lectin.";
RL J. Clin. Invest. 118:2098-2110(2008).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.64 ANGSTROMS) OF 110-241, FUNCTION, DISULFIDE
RP BONDS, SUBUNIT, AND MUTAGENESIS OF TRP-131 AND TRP-227.
RX PubMed=22483802; DOI=10.1016/j.immuni.2012.03.009;
RA Zhang J.G., Czabotar P.E., Policheni A.N., Caminschi I., Wan S.S.,
RA Kitsoulis S., Tullett K.M., Robin A.Y., Brammananth R., van Delft M.F.,
RA Lu J., O'Reilly L.A., Josefsson E.C., Kile B.T., Chin W.J., Mintern J.D.,
RA Olshina M.A., Wong W., Baum J., Wright M.D., Huang D.C., Mohandas N.,
RA Coppel R.L., Colman P.M., Nicola N.A., Shortman K., Lahoud M.H.;
RT "The dendritic cell receptor Clec9A binds damaged cells via exposed actin
RT filaments.";
RL Immunity 36:646-657(2012).
CC -!- FUNCTION: Functions as an endocytic receptor on a small subset of
CC myeloid cells specialized for the uptake and processing of material
CC from dead cells. Recognizes filamentous form of actin in association
CC with particular actin-binding domains of cytoskeletal proteins,
CC including spectrin, exposed when cell membranes are damaged, and
CC mediate the cross-presentation of dead-cell associated antigens in a
CC Syk-dependent manner. {ECO:0000269|PubMed:18497879,
CC ECO:0000269|PubMed:22483802}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:18408006,
CC ECO:0000269|PubMed:22483802}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:18408006}; Single-
CC pass type II membrane protein {ECO:0000269|PubMed:18408006}.
CC -!- TISSUE SPECIFICITY: In peripheral blood highly restricted on the
CC surface of BDCA31(+) dendritic cells and on a small subset of CD14(+)
CC and CD16(-) monocytes. {ECO:0000269|PubMed:18408006,
CC ECO:0000269|PubMed:18497879}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:18408006}.
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DR EMBL; EU339276; ABZ04557.1; -; mRNA.
DR EMBL; AY358265; AAQ88632.1; -; mRNA.
DR CCDS; CCDS8611.1; -.
DR RefSeq; NP_997228.1; NM_207345.3.
DR PDB; 3VPP; X-ray; 1.64 A; A/B=110-241.
DR PDBsum; 3VPP; -.
DR AlphaFoldDB; Q6UXN8; -.
DR SMR; Q6UXN8; -.
DR BioGRID; 129557; 1.
DR STRING; 9606.ENSP00000348074; -.
DR GlyGen; Q6UXN8; 2 sites.
DR iPTMnet; Q6UXN8; -.
DR PhosphoSitePlus; Q6UXN8; -.
DR BioMuta; CLEC9A; -.
DR DMDM; 73917794; -.
DR MassIVE; Q6UXN8; -.
DR PaxDb; Q6UXN8; -.
DR PeptideAtlas; Q6UXN8; -.
DR PRIDE; Q6UXN8; -.
DR ABCD; Q6UXN8; 59 sequenced antibodies.
DR Antibodypedia; 23221; 455 antibodies from 29 providers.
DR DNASU; 283420; -.
DR Ensembl; ENST00000355819.6; ENSP00000348074.1; ENSG00000197992.7.
DR GeneID; 283420; -.
DR KEGG; hsa:283420; -.
DR MANE-Select; ENST00000355819.6; ENSP00000348074.1; NM_207345.4; NP_997228.1.
DR UCSC; uc001qxa.4; human.
DR CTD; 283420; -.
DR DisGeNET; 283420; -.
DR GeneCards; CLEC9A; -.
DR HGNC; HGNC:26705; CLEC9A.
DR HPA; ENSG00000197992; Tissue enhanced (lymphoid).
DR MIM; 612252; gene.
DR neXtProt; NX_Q6UXN8; -.
DR OpenTargets; ENSG00000197992; -.
DR PharmGKB; PA142672093; -.
DR VEuPathDB; HostDB:ENSG00000197992; -.
DR eggNOG; KOG4297; Eukaryota.
DR GeneTree; ENSGT00940000161796; -.
DR HOGENOM; CLU_049894_9_0_1; -.
DR InParanoid; Q6UXN8; -.
DR OMA; SCIFCMG; -.
DR OrthoDB; 1201127at2759; -.
DR PhylomeDB; Q6UXN8; -.
DR TreeFam; TF336674; -.
DR PathwayCommons; Q6UXN8; -.
DR SignaLink; Q6UXN8; -.
DR BioGRID-ORCS; 283420; 9 hits in 1063 CRISPR screens.
DR ChiTaRS; CLEC9A; human.
DR GenomeRNAi; 283420; -.
DR Pharos; Q6UXN8; Tbio.
DR PRO; PR:Q6UXN8; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q6UXN8; protein.
DR Bgee; ENSG00000197992; Expressed in lymph node and 96 other tissues.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0030246; F:carbohydrate binding; IEA:UniProtKB-KW.
DR GO; GO:0001819; P:positive regulation of cytokine production; IDA:UniProtKB.
DR GO; GO:0006898; P:receptor-mediated endocytosis; IDA:UniProtKB.
DR CDD; cd03593; CLECT_NK_receptors_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; IPR043315; CLEC9A.
DR InterPro; IPR016187; CTDL_fold.
DR InterPro; IPR033992; NKR-like_CTLD.
DR PANTHER; PTHR47727; PTHR47727; 1.
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 3D-structure; Disulfide bond; Endocytosis; Glycoprotein; Lectin; Membrane;
KW Receptor; Reference proteome; Signal-anchor; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..241
FT /note="C-type lectin domain family 9 member A"
FT /id="PRO_0000046637"
FT TOPO_DOM 1..35
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 36..56
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 57..241
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 120..233
FT /note="C-type lectin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT MOTIF 5..10
FT /note="ITAM-like"
FT CARBOHYD 81
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 223
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 113..124
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040,
FT ECO:0000269|PubMed:22483802"
FT DISULFID 141..232
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040,
FT ECO:0000269|PubMed:22483802"
FT DISULFID 211..224
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040,
FT ECO:0000269|PubMed:22483802"
FT VARIANT 107
FT /note="A -> G (in dbSNP:rs11831360)"
FT /id="VAR_050112"
FT MUTAGEN 131
FT /note="W->A: Abolishes binding to damaged cells; when
FT associated with A-227."
FT /evidence="ECO:0000269|PubMed:22483802"
FT MUTAGEN 227
FT /note="W->A: Abolishes binding to damaged cells; when
FT associated with A-131."
FT /evidence="ECO:0000269|PubMed:22483802"
FT STRAND 118..120
FT /evidence="ECO:0007829|PDB:3VPP"
FT STRAND 123..127
FT /evidence="ECO:0007829|PDB:3VPP"
FT HELIX 134..143
FT /evidence="ECO:0007829|PDB:3VPP"
FT HELIX 154..164
FT /evidence="ECO:0007829|PDB:3VPP"
FT STRAND 167..169
FT /evidence="ECO:0007829|PDB:3VPP"
FT STRAND 172..179
FT /evidence="ECO:0007829|PDB:3VPP"
FT TURN 181..183
FT /evidence="ECO:0007829|PDB:3VPP"
FT STRAND 186..188
FT /evidence="ECO:0007829|PDB:3VPP"
FT STRAND 210..215
FT /evidence="ECO:0007829|PDB:3VPP"
FT STRAND 218..226
FT /evidence="ECO:0007829|PDB:3VPP"
FT STRAND 228..235
FT /evidence="ECO:0007829|PDB:3VPP"
SQ SEQUENCE 241 AA; 27324 MW; 6158B3AC44EEC9C3 CRC64;
MHEEEIYTSL QWDSPAPDTY QKCLSSNKCS GACCLVMVIS CVFCMGLLTA SIFLGVKLLQ
VSTIAMQQQE KLIQQERALL NFTEWKRSCA LQMKYCQAFM QNSLSSAHNS SPCPNNWIQN
RESCYYVSEI WSIWHTSQEN CLKEGSTLLQ IESKEEMDFI TGSLRKIKGS YDYWVGLSQD
GHSGRWLWQD GSSPSPGLLP AERSQSANQV CGYVKSNSLL SSNCSTWKYF ICEKYALRSS
V
