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   05-FEB-2025, entry version 142.
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   UniLectin; Q6UXN8; -.
DR   GlyCosmos; Q6UXN8; 2 sites, No reported glycans.
DR   GlyGen; Q6UXN8; 2 sites.
DR   iPTMnet; Q6UXN8; -.
DR   PhosphoSitePlus; Q6UXN8; -.
DR   BioMuta; CLEC9A; -.
DR   DMDM; 73917794; -.
DR   MassIVE; Q6UXN8; -.
DR   PaxDb; 9606-ENSP00000348074; -.
DR   PeptideAtlas; Q6UXN8; -.
DR   ProteomicsDB; 67640; -.
DR   ABCD; Q6UXN8; 59 sequenced antibodies.
DR   Antibodypedia; 23221; 529 antibodies from 30 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   AGR; HGNC:26705; -.
DR   CTD; 283420; -.
DR   DisGeNET; 283420; -.
DR   GeneCards; CLEC9A; -.
DR   HGNC; HGNC:26705; CLEC9A.
DR   HPA; ENSG00000197992; Tissue enhanced (brain, lymphoid tissue).
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; WDSPAPN; -.
DR   OrthoDB; 6337382at2759; -.
DR   PhylomeDB; Q6UXN8; -.
DR   TreeFam; TF336674; -.
DR   PathwayCommons; Q6UXN8; -.
DR   SignaLink; Q6UXN8; -.
DR   BioGRID-ORCS; 283420; 11 hits in 1141 CRISPR screens.
DR   ChiTaRS; CLEC9A; human.
DR   EvolutionaryTrace; Q6UXN8; -.
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 male germ line stem cell (sensu Vertebrata) in testis and 97 other cell types or tissues.
DR   GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
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   FunFam; 3.10.100.10:FF:000075; C-type lectin domain family 9 member A; 1.
DR   Gene3D; 3.10.100.10; Mannose-Binding Protein A, subunit A; 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; C-TYPE LECTIN DOMAIN FAMILY 9 MEMBER A; 1.
DR   PANTHER; PTHR47727:SF1; C-TYPE LECTIN DOMAIN FAMILY 9 MEMBER A; 1.
DR   Pfam; PF00059; Lectin_C; 1.
DR   SMART; SM00034; CLECT; 1.
DR   SUPFAM; SSF56436; C-type lectin-like; 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   Proteomics identification; Receptor; Reference proteome; Signal-anchor;
KW   Transmembrane; 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
//