CD69_HUMAN
ID CD69_HUMAN Reviewed; 199 AA.
AC Q07108;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1994, sequence version 1.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=Early activation antigen CD69;
DE AltName: Full=Activation inducer molecule;
DE Short=AIM;
DE AltName: Full=BL-AC/P26;
DE AltName: Full=C-type lectin domain family 2 member C;
DE AltName: Full=EA1;
DE AltName: Full=Early T-cell activation antigen p60;
DE AltName: Full=GP32/28;
DE AltName: Full=Leukocyte surface antigen Leu-23;
DE AltName: Full=MLR-3;
DE AltName: CD_antigen=CD69;
GN Name=CD69; Synonyms=CLEC2C;
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].
RC TISSUE=Blood;
RX PubMed=8496594;
RA Hamann J., Fiebig H., Strauss M.;
RT "Expression cloning of the early activation antigen CD69, a type II
RT integral membrane protein with a C-type lectin domain.";
RL J. Immunol. 150:4920-4927(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 96-103; 128-146 AND
RP 189-199.
RC TISSUE=Blood;
RX PubMed=8340758; DOI=10.1084/jem.178.2.537;
RA Lopez-Cabrera M., Santis A.G., Fernandez-Ruiz E., Blacher R., Esch F.,
RA Sanchez-Mateos P., Sanchez-Madrid F.;
RT "Molecular cloning, expression, and chromosomal localization of the human
RT earliest lymphocyte activation antigen AIM/CD69, a new member of the C-type
RT animal lectin superfamily of signal-transmitting receptors.";
RL J. Exp. Med. 178:537-547(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8100776; DOI=10.1002/eji.1830230737;
RA Ziegler S.F., Ramsdell F., Hjerrild K.A., Armitage R.J., Grabstein K.H.,
RA Hennen K.B., Farrah T., Fanslow W.C., Shevach E.M., Alderson M.R.;
RT "Molecular characterization of the early activation antigen CD69: a type II
RT membrane glycoprotein related to a family of natural killer cell activation
RT antigens.";
RL Eur. J. Immunol. 23:1643-1648(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Placenta;
RX PubMed=8026529; DOI=10.1002/eji.1830240735;
RA Santis A., Lopez-Cabrera M., Hamann J., Strauss M., Sanchez-Madrid F.;
RT "Structure of the gene coding for the human early lymphocyte activation
RT antigen CD69: a C-type lectin receptor evolutionarily related with the gene
RT families of natural killer cell-specific receptors.";
RL Eur. J. Immunol. 24:1692-1697(1994).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pancreas;
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 [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.27 ANGSTROMS), SUBUNIT, AND DISULFIDE BONDS.
RX PubMed=11101293; DOI=10.1021/bi0018180;
RA Natarajan K., Sawicki M.W., Margulies D.H., Mariuzza R.A.;
RT "Crystal structure of human CD69: a C-type lectin-like activation marker of
RT hematopoietic cells.";
RL Biochemistry 39:14779-14786(2000).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 82-199, SUBUNIT, AND DISULFIDE
RP BONDS.
RX PubMed=11036086; DOI=10.1074/jbc.m008573200;
RA Llera A.S., Viedma F., Sanchez-Madrid F., Tormo J.;
RT "Crystal structure of the C-type lectin-like domain from the human
RT hematopoietic cell receptor CD69.";
RL J. Biol. Chem. 276:7312-7319(2001).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 82-199, SUBUNIT, AND DISULFIDE
RP BONDS.
RX PubMed=18959746; DOI=10.1111/j.1742-4658.2008.06683.x;
RA Vanek O., Nalezkova M., Kavan D., Borovickova I., Pompach P., Novak P.,
RA Kumar V., Vannucci L., Hudecek J., Hofbauerova K., Kopecky V. Jr.,
RA Brynda J., Kolenko P., Dohnalek J., Kaderavek P., Chmelik J., Gorcik L.,
RA Zidek L., Sklenar V., Bezouska K.;
RT "Soluble recombinant CD69 receptors optimized to have an exceptional
RT physical and chemical stability display prolonged circulation and remain
RT intact in the blood of mice.";
RL FEBS J. 275:5589-5606(2008).
CC -!- FUNCTION: Involved in lymphocyte proliferation and functions as a
CC signal transmitting receptor in lymphocytes, natural killer (NK) cells,
CC and platelets.
CC -!- SUBUNIT: Homodimer; disulfide-linked. {ECO:0000269|PubMed:11036086,
CC ECO:0000269|PubMed:11101293, ECO:0000269|PubMed:18959746}.
CC -!- INTERACTION:
CC Q07108; P27449: ATP6V0C; NbExp=3; IntAct=EBI-2836595, EBI-721179;
CC Q07108; Q6PL45-2: BRICD5; NbExp=3; IntAct=EBI-2836595, EBI-12244618;
CC Q07108; O95832: CLDN1; NbExp=3; IntAct=EBI-2836595, EBI-723889;
CC Q07108; Q15125: EBP; NbExp=3; IntAct=EBI-2836595, EBI-3915253;
CC Q07108; P21145: MAL; NbExp=3; IntAct=EBI-2836595, EBI-3932027;
CC Q07108; Q9NZG7: NINJ2; NbExp=4; IntAct=EBI-2836595, EBI-10317425;
CC Q07108; Q01453: PMP22; NbExp=3; IntAct=EBI-2836595, EBI-2845982;
CC Q07108; Q9NS64: RPRM; NbExp=3; IntAct=EBI-2836595, EBI-1052363;
CC Q07108; P21453: S1PR1; NbExp=2; IntAct=EBI-2836595, EBI-2681920;
CC Q07108; Q8TB61: SLC35B2; NbExp=3; IntAct=EBI-2836595, EBI-1054782;
CC Q07108; P0DN84: STRIT1; NbExp=3; IntAct=EBI-2836595, EBI-12200293;
CC Q07108; Q8WZ59: TMEM190; NbExp=6; IntAct=EBI-2836595, EBI-10278423;
CC Q07108; Q5TGU0: TSPO2; NbExp=3; IntAct=EBI-2836595, EBI-12195249;
CC Q07108; O75841: UPK1B; NbExp=3; IntAct=EBI-2836595, EBI-12237619;
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type II membrane protein.
CC -!- TISSUE SPECIFICITY: Expressed on the surface of activated T-cells, B-
CC cells, natural killer cells, neutrophils, eosinophils, epidermal
CC Langerhans cells and platelets.
CC -!- DEVELOPMENTAL STAGE: Earliest inducible cell surface glycoprotein
CC acquired during lymphoid activation.
CC -!- INDUCTION: By antigens, mitogens or activators of PKC on the surface of
CC T and B-lymphocytes. By interaction of IL-2 with the p75 IL-2R on the
CC surface of NK cells.
CC -!- PTM: Constitutive Ser/Thr phosphorylation in both mature thymocytes and
CC activated T-lymphocytes.
CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - Glycan Binding;
CC Note=CD69;
CC URL="http://www.functionalglycomics.org/glycomics/GBPServlet?&operationType=view&cbpId=cbp_hum_Ctlect_235";
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DR EMBL; L07555; AAB46359.1; -; mRNA.
DR EMBL; Z22576; CAA80298.1; -; mRNA.
DR EMBL; Z30426; CAA83017.1; -; Genomic_DNA.
DR EMBL; Z30430; CAA83017.1; JOINED; Genomic_DNA.
DR EMBL; Z30427; CAA83017.1; JOINED; Genomic_DNA.
DR EMBL; Z30429; CAA83017.1; JOINED; Genomic_DNA.
DR EMBL; Z30428; CAA83017.1; JOINED; Genomic_DNA.
DR EMBL; BC007037; AAH07037.1; -; mRNA.
DR CCDS; CCDS8604.1; -.
DR PIR; JH0822; JH0822.
DR RefSeq; NP_001772.1; NM_001781.2.
DR PDB; 1E87; X-ray; 1.50 A; A=82-199.
DR PDB; 1E8I; X-ray; 1.95 A; A/B=82-199.
DR PDB; 1FM5; X-ray; 2.27 A; A=64-199.
DR PDB; 3CCK; X-ray; 1.80 A; A/B=82-199.
DR PDB; 3HUP; X-ray; 1.37 A; A/B=70-199.
DR PDBsum; 1E87; -.
DR PDBsum; 1E8I; -.
DR PDBsum; 1FM5; -.
DR PDBsum; 3CCK; -.
DR PDBsum; 3HUP; -.
DR AlphaFoldDB; Q07108; -.
DR BMRB; Q07108; -.
DR SMR; Q07108; -.
DR BioGRID; 107407; 24.
DR DIP; DIP-60426N; -.
DR ELM; Q07108; -.
DR IntAct; Q07108; 21.
DR STRING; 9606.ENSP00000228434; -.
DR BindingDB; Q07108; -.
DR ChEMBL; CHEMBL3308911; -.
DR GlyConnect; 2035; 1 N-Linked glycan (1 site).
DR GlyGen; Q07108; 2 sites, 2 N-linked glycans (1 site), 1 O-linked glycan (1 site).
DR iPTMnet; Q07108; -.
DR PhosphoSitePlus; Q07108; -.
DR SwissPalm; Q07108; -.
DR BioMuta; CD69; -.
DR DMDM; 584906; -.
DR jPOST; Q07108; -.
DR MassIVE; Q07108; -.
DR PaxDb; Q07108; -.
DR PeptideAtlas; Q07108; -.
DR PRIDE; Q07108; -.
DR ProteomicsDB; 58505; -.
DR Antibodypedia; 3741; 1229 antibodies from 47 providers.
DR DNASU; 969; -.
DR Ensembl; ENST00000228434.7; ENSP00000228434.3; ENSG00000110848.8.
DR GeneID; 969; -.
DR KEGG; hsa:969; -.
DR MANE-Select; ENST00000228434.7; ENSP00000228434.3; NM_001781.2; NP_001772.1.
DR CTD; 969; -.
DR DisGeNET; 969; -.
DR GeneCards; CD69; -.
DR HGNC; HGNC:1694; CD69.
DR HPA; ENSG00000110848; Group enriched (bone marrow, lymphoid tissue).
DR MIM; 107273; gene.
DR neXtProt; NX_Q07108; -.
DR OpenTargets; ENSG00000110848; -.
DR PharmGKB; PA26233; -.
DR VEuPathDB; HostDB:ENSG00000110848; -.
DR eggNOG; KOG4297; Eukaryota.
DR GeneTree; ENSGT00940000161987; -.
DR InParanoid; Q07108; -.
DR OMA; WFNFTGS; -.
DR OrthoDB; 1289964at2759; -.
DR PhylomeDB; Q07108; -.
DR TreeFam; TF351467; -.
DR PathwayCommons; Q07108; -.
DR SignaLink; Q07108; -.
DR SIGNOR; Q07108; -.
DR BioGRID-ORCS; 969; 14 hits in 1084 CRISPR screens.
DR ChiTaRS; CD69; human.
DR EvolutionaryTrace; Q07108; -.
DR GeneWiki; CD69; -.
DR GenomeRNAi; 969; -.
DR Pharos; Q07108; Tchem.
DR PRO; PR:Q07108; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q07108; protein.
DR Bgee; ENSG00000110848; Expressed in lymph node and 133 other tissues.
DR ExpressionAtlas; Q07108; baseline and differential.
DR Genevisible; Q07108; HS.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0032991; C:protein-containing complex; IDA:CAFA.
DR GO; GO:0030246; F:carbohydrate binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IDA:CAFA.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; TAS:ProtInc.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEA:Ensembl.
DR CDD; cd03593; CLECT_NK_receptors_like; 1.
DR DisProt; DP00306; -.
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; IPR016187; CTDL_fold.
DR InterPro; IPR033992; NKR-like_CTLD.
DR Pfam; PF00059; Lectin_C; 1.
DR SMART; SM00034; CLECT; 1.
DR SUPFAM; SSF56436; SSF56436; 1.
DR PROSITE; PS50041; C_TYPE_LECTIN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Lectin; Membrane; Phosphoprotein; Reference proteome; Signal-anchor;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..199
FT /note="Early activation antigen CD69"
FT /id="PRO_0000046583"
FT TOPO_DOM 1..40
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 41..61
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 62..199
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 92..195
FT /note="C-type lectin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT REGION 1..29
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 166
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 68
FT /note="Interchain"
FT /evidence="ECO:0000305"
FT DISULFID 85..96
FT DISULFID 113..194
FT DISULFID 173..186
FT STRAND 90..92
FT /evidence="ECO:0007829|PDB:3HUP"
FT STRAND 95..99
FT /evidence="ECO:0007829|PDB:3HUP"
FT HELIX 106..114
FT /evidence="ECO:0007829|PDB:3HUP"
FT TURN 115..117
FT /evidence="ECO:0007829|PDB:3HUP"
FT HELIX 126..136
FT /evidence="ECO:0007829|PDB:3HUP"
FT STRAND 141..147
FT /evidence="ECO:0007829|PDB:3HUP"
FT STRAND 153..155
FT /evidence="ECO:0007829|PDB:3HUP"
FT STRAND 168..170
FT /evidence="ECO:0007829|PDB:1E87"
FT STRAND 172..177
FT /evidence="ECO:0007829|PDB:3HUP"
FT STRAND 180..184
FT /evidence="ECO:0007829|PDB:3HUP"
FT STRAND 190..197
FT /evidence="ECO:0007829|PDB:3HUP"
SQ SEQUENCE 199 AA; 22559 MW; 172E2699D2FB8DFB CRC64;
MSSENCFVAE NSSLHPESGQ ENDATSPHFS TRHEGSFQVP VLCAVMNVVF ITILIIALIA
LSVGQYNCPG QYTFSMPSDS HVSSCSEDWV GYQRKCYFIS TVKRSWTSAQ NACSEHGATL
AVIDSEKDMN FLKRYAGREE HWVGLKKEPG HPWKWSNGKE FNNWFNVTGS DKCVFLKNTE
VSSMECEKNL YWICNKPYK
