DCO_DROME
ID DCO_DROME Reviewed; 440 AA.
AC O76324; A4V3P5; Q0KHY4; Q9V462;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2005, sequence version 2.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Discs overgrown protein kinase;
DE EC=2.7.11.1;
DE AltName: Full=Protein double-time;
GN Name=dco; Synonyms=dbt; ORFNames=CG2048;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND INTERACTION WITH PER.
RX PubMed=9674431; DOI=10.1016/s0092-8674(00)81225-8;
RA Kloss B., Price J.L., Saez L., Blau J., Rothenfluh A., Wesley C.S.,
RA Young M.W.;
RT "The Drosophila clock gene double-time encodes a protein closely related to
RT human casein kinase I epsilon.";
RL Cell 94:97-107(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=10556065; DOI=10.1242/dev.126.23.5409;
RA Zilian O., Frei E., Burke R., Brentrup D., Gutjahr T., Bryant P.J.,
RA Noll M.;
RT "Double-time is identical to discs overgrown, which is required for cell
RT survival, proliferation and growth arrest in Drosophila imaginal discs.";
RL Development 126:5409-5420(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [4]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Embryo;
RX PubMed=10731138; DOI=10.1126/science.287.5461.2222;
RA Rubin G.M., Hong L., Brokstein P., Evans-Holm M., Frise E., Stapleton M.,
RA Harvey D.A.;
RT "A Drosophila complementary DNA resource.";
RL Science 287:2222-2224(2000).
RN [6]
RP MUTAGENESIS, AND FUNCTION.
RX PubMed=9674430; DOI=10.1016/s0092-8674(00)81224-6;
RA Price J.L., Blau J., Rothenfluh A., Abodeely M., Kloss B., Young M.W.;
RT "Double-time is a novel Drosophila clock gene that regulates PERIOD protein
RT accumulation.";
RL Cell 94:83-95(1998).
RN [7]
RP FUNCTION.
RX PubMed=16326393; DOI=10.1016/j.devcel.2005.10.006;
RA Jia J., Zhang L., Zhang Q., Tong C., Wang B., Hou F., Amanai K., Jiang J.;
RT "Phosphorylation by double-time/CKIepsilon and CKIalpha targets cubitus
RT interruptus for Slimb/beta-TRCP-mediated proteolytic processing.";
RL Dev. Cell 9:819-830(2005).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-333 AND SER-334, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Embryo;
RX PubMed=18327897; DOI=10.1021/pr700696a;
RA Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL J. Proteome Res. 7:1675-1682(2008).
RN [9]
RP INTERACTION WITH DLISH.
RX PubMed=27692068; DOI=10.7554/elife.16624;
RA Zhang Y., Wang X., Matakatsu H., Fehon R., Blair S.S.;
RT "The novel SH3 domain protein Dlish/CG10933 mediates fat signaling in
RT Drosophila by binding and regulating Dachs.";
RL Elife 5:E16624-E16624(2016).
RN [10]
RP ERRATUM OF PUBMED:27692068.
RX PubMed=27824307; DOI=10.7554/elife.22672;
RA Zhang Y., Wang X., Matakatsu H., Fehon R., Blair S.S.;
RL Elife 5:E22672-E22672(2016).
CC -!- FUNCTION: Involved in circadian rhythms, viability and molecular
CC oscillations of the clock genes period (per) and timeless (tim). Dbt
CC reduces the stability and thus the accumulation of monomeric per
CC proteins, probably through phosphorylation. No evident circadian
CC oscillation is detected in head. Together with CkIalpha, regulates
CC processing of ci by phosphorylating it which promotes its binding to
CC slmb, the F-box recognition component of the SCF(slmb) E3 ubiquitin-
CC protein ligase (PubMed:16326393). {ECO:0000269|PubMed:10556065,
CC ECO:0000269|PubMed:16326393, ECO:0000269|PubMed:9674430,
CC ECO:0000269|PubMed:9674431}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1;
CC -!- SUBUNIT: Forms a complex with per (PubMed:9674431). Interacts with
CC Dlish (PubMed:27692068). {ECO:0000269|PubMed:27692068,
CC ECO:0000269|PubMed:9674431}.
CC -!- TISSUE SPECIFICITY: Expressed in photoreceptor cells of the eyes as
CC well as in the region situated between the optic lobe and the central
CC brain. {ECO:0000269|PubMed:10556065}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CK1 Ser/Thr
CC protein kinase family. Casein kinase I subfamily. {ECO:0000305}.
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DR EMBL; AF055583; AAC39134.1; -; mRNA.
DR EMBL; AF192484; AAF27346.1; -; Genomic_DNA.
DR EMBL; AE014297; AAF57109.1; -; Genomic_DNA.
DR EMBL; AE014297; AAF57110.1; -; Genomic_DNA.
DR EMBL; AF132558; AAD27857.1; -; mRNA.
DR RefSeq; NP_001263132.1; NM_001276203.1.
DR RefSeq; NP_524602.1; NM_079863.3.
DR RefSeq; NP_733414.1; NM_170535.2.
DR RefSeq; NP_733415.1; NM_170536.3.
DR AlphaFoldDB; O76324; -.
DR SMR; O76324; -.
DR BioGRID; 68523; 39.
DR DIP; DIP-46048N; -.
DR IntAct; O76324; 4.
DR STRING; 7227.FBpp0085104; -.
DR iPTMnet; O76324; -.
DR PaxDb; O76324; -.
DR PRIDE; O76324; -.
DR EnsemblMetazoa; FBtr0085742; FBpp0085104; FBgn0002413.
DR EnsemblMetazoa; FBtr0085743; FBpp0085105; FBgn0002413.
DR EnsemblMetazoa; FBtr0085744; FBpp0085106; FBgn0002413.
DR EnsemblMetazoa; FBtr0334548; FBpp0306615; FBgn0002413.
DR EnsemblMetazoa; FBtr0473370; FBpp0422974; FBgn0002413.
DR GeneID; 43673; -.
DR KEGG; dme:Dmel_CG2048; -.
DR UCSC; CG2048-RC; d. melanogaster.
DR CTD; 43673; -.
DR FlyBase; FBgn0002413; dco.
DR VEuPathDB; VectorBase:FBgn0002413; -.
DR eggNOG; KOG1164; Eukaryota.
DR GeneTree; ENSGT00940000153536; -.
DR HOGENOM; CLU_019279_2_0_1; -.
DR InParanoid; O76324; -.
DR OMA; IFDWTFL; -.
DR OrthoDB; 1097975at2759; -.
DR PhylomeDB; O76324; -.
DR BRENDA; 2.7.11.1; 1994.
DR Reactome; R-DME-201688; WNT mediated activation of DVL.
DR Reactome; R-DME-209155; Phosphorylation of AXN and APC.
DR Reactome; R-DME-209159; Assembly of the CI containing complexes.
DR Reactome; R-DME-209190; Phosphorylation of CI.
DR Reactome; R-DME-209214; Phosphorylation of SMO.
DR Reactome; R-DME-209360; Ubiquitination and proteolysis of phosphorylated CI.
DR Reactome; R-DME-209396; Phosphorylation of ARM.
DR Reactome; R-DME-209413; Assembly of the 'destruction complex'.
DR Reactome; R-DME-209440; Recruitment of the 'destruction complex' to the receptor complex, the degradation of AXN and release of ARM.
DR Reactome; R-DME-209461; Ubiquitination and degradation of phosphorylated ARM.
DR Reactome; R-DME-390023; Subcellular localisation of D.
DR Reactome; R-DME-390150; DS ligand bound to FT receptor.
DR Reactome; R-DME-432395; Degradation of TIM.
DR Reactome; R-DME-432490; Nuclear import of PER and TIM.
DR Reactome; R-DME-432501; Transcription repression by PER and activation by PDP1.
DR Reactome; R-DME-432524; Degradation of PER.
DR Reactome; R-DME-432553; Phosphorylation of PER and TIM.
DR Reactome; R-DME-432620; Dephosphorylation of PER.
DR Reactome; R-DME-538898; Dephosphorylation of TIM.
DR SignaLink; O76324; -.
DR BioGRID-ORCS; 43673; 1 hit in 3 CRISPR screens.
DR ChiTaRS; dco; fly.
DR GenomeRNAi; 43673; -.
DR PRO; PR:O76324; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0002413; Expressed in ovary and 55 other tissues.
DR ExpressionAtlas; O76324; baseline and differential.
DR Genevisible; O76324; DM.
DR GO; GO:0044297; C:cell body; IDA:FlyBase.
DR GO; GO:0005737; C:cytoplasm; IDA:FlyBase.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:FlyBase.
DR GO; GO:0048148; P:behavioral response to cocaine; IMP:FlyBase.
DR GO; GO:0007154; P:cell communication; IMP:FlyBase.
DR GO; GO:0071482; P:cellular response to light stimulus; IDA:FlyBase.
DR GO; GO:0007623; P:circadian rhythm; IDA:FlyBase.
DR GO; GO:0006897; P:endocytosis; IBA:GO_Central.
DR GO; GO:0007446; P:imaginal disc growth; IMP:FlyBase.
DR GO; GO:0045475; P:locomotor rhythm; IMP:FlyBase.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:FlyBase.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IMP:UniProtKB.
DR GO; GO:0045879; P:negative regulation of smoothened signaling pathway; IMP:FlyBase.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0016310; P:phosphorylation; IDA:FlyBase.
DR GO; GO:0030838; P:positive regulation of actin filament polymerization; IMP:UniProtKB.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IMP:FlyBase.
DR GO; GO:0051781; P:positive regulation of cell division; IMP:FlyBase.
DR GO; GO:0030307; P:positive regulation of cell growth; IMP:FlyBase.
DR GO; GO:0035332; P:positive regulation of hippo signaling; IMP:FlyBase.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:FlyBase.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; IDA:FlyBase.
DR GO; GO:0045880; P:positive regulation of smoothened signaling pathway; IGI:FlyBase.
DR GO; GO:0030177; P:positive regulation of Wnt signaling pathway; IGI:FlyBase.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:FlyBase.
DR GO; GO:0006468; P:protein phosphorylation; IDA:FlyBase.
DR GO; GO:0042752; P:regulation of circadian rhythm; IMP:FlyBase.
DR GO; GO:0007555; P:regulation of ecdysteroid secretion; IMP:FlyBase.
DR GO; GO:0090175; P:regulation of establishment of planar polarity; IGI:FlyBase.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Biological rhythms; Kinase; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase.
FT CHAIN 1..440
FT /note="Discs overgrown protein kinase"
FT /id="PRO_0000192849"
FT DOMAIN 9..277
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 376..440
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 376..401
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 128
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 15..23
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 38
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 333
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 334
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MUTAGEN 47
FT /note="P->S: In dbtS; shortens the behavioral period."
FT /evidence="ECO:0000269|PubMed:9674430"
FT MUTAGEN 80
FT /note="M->I: In dbtL; lengthens the behavioral period."
FT /evidence="ECO:0000269|PubMed:9674430"
FT CONFLICT 353
FT /note="A -> R (in Ref. 1; AAC39134)"
FT /evidence="ECO:0000305"
FT CONFLICT 428
FT /note="P -> Q (in Ref. 1; AAC39134)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 440 AA; 47958 MW; 0B67B83E44213902 CRC64;
MELRVGNKYR LGRKIGSGSF GDIYLGTTIN TGEEVAIKLE CIRTKHPQLH IESKFYKTMQ
GGIGIPRIIW CGSEGDYNVM VMELLGPSLE DLFNFCSRRF SLKTVLLLAD QMISRIDYIH
SRDFIHRDIK PDNFLMGLGK KGNLVYIIDF GLAKKFRDAR SLKHIPYREN KNLTGTARYA
SINTHLGIEQ SRRDDLESLG YVLMYFNLGA LPWQGLKAAN KRQKYERISE KKLSTSIVVL
CKGFPSEFVN YLNFCRQMHF DQRPDYCHLR KLFRNLFHRL GFTYDYVFDW NLLKFGGPRN
PQAIQQAQDG ADGQAGHDAV AAAAAVAAAA AASSHQQQQH KVNAALGGGG GSAAQQQLQG
GQTLAMLGGN GGGNGSQLIG GNGLNMDDSM AATNSSRPPY DTPERRPSIR MRQGGGGGGG
GVGVGGMPSG GGGGGVGNAK
