CWO_DROME
ID CWO_DROME Reviewed; 698 AA.
AC Q9VGZ5; C8VV96; Q9U450;
DT 15-FEB-2017, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 2.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Transcription factor cwo {ECO:0000305};
DE AltName: Full=Protein clockwork orange {ECO:0000303|PubMed:17555964};
GN Name=cwo {ECO:0000312|FlyBase:FBgn0259938};
GN ORFNames=CG17100 {ECO:0000312|FlyBase:FBgn0259938};
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 {ECO:0000312|Proteomes:UP000000803};
RN [1] {ECO:0000312|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
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 [2] {ECO:0000312|Proteomes:UP000000803}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
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 [3] {ECO:0000312|EMBL:ACW83550.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:ACW83550.1};
RA Carlson J., Booth B., Frise E., Park S., Wan K., Yu C., Celniker S.;
RL Submitted (SEP-2009) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0000312|EMBL:AAF24476.1}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-610, AND TISSUE SPECIFICITY.
RX PubMed=11102367; DOI=10.1093/genetics/156.4.1691;
RA Prokopenko S.N., He Y., Lu Y., Bellen H.J.;
RT "Mutations affecting the development of the peripheral nervous system in
RT Drosophila: a molecular screen for novel proteins.";
RL Genetics 156:1691-1715(2000).
RN [5] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=17555964; DOI=10.1016/j.cub.2007.05.039;
RA Lim C., Chung B.Y., Pitman J.L., McGill J.J., Pradhan S., Lee J.,
RA Keegan K.P., Choe J., Allada R.;
RT "Clockwork orange encodes a transcriptional repressor important for
RT circadian-clock amplitude in Drosophila.";
RL Curr. Biol. 17:1082-1089(2007).
RN [6] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=17578907; DOI=10.1101/gad.1552607;
RA Kadener S., Stoleru D., McDonald M., Nawathean P., Rosbash M.;
RT "Clockwork Orange is a transcriptional repressor and a new Drosophila
RT circadian pacemaker component.";
RL Genes Dev. 21:1675-1686(2007).
RN [7] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=17578908; DOI=10.1101/gad.1552207;
RA Matsumoto A., Ukai-Tadenuma M., Yamada R.G., Houl J., Uno K.D.,
RA Kasukawa T., Dauwalder B., Itoh T.Q., Takahashi K., Ueda R., Hardin P.E.,
RA Tanimura T., Ueda H.R.;
RT "A functional genomics strategy reveals clockwork orange as a
RT transcriptional regulator in the Drosophila circadian clock.";
RL Genes Dev. 21:1687-1700(2007).
RN [8] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=18375860; DOI=10.1177/0748730407313817;
RA Richier B., Michard-Vanhee C., Lamouroux A., Papin C., Rouyer F.;
RT "The clockwork orange Drosophila protein functions as both an activator and
RT a repressor of clock gene expression.";
RL J. Biol. Rhythms 23:103-116(2008).
RN [9] {ECO:0000305}
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=27814361; DOI=10.1371/journal.pgen.1006430;
RA Zhou J., Yu W., Hardin P.E.;
RT "CLOCKWORK ORANGE enhances PERIOD mediated rhythms in transcriptional
RT repression by antagonizing E-box binding by CLOCK-CYCLE.";
RL PLoS Genet. 12:E1006430-E1006430(2016).
CC -!- FUNCTION: Plays a role in the regulation of circadian rhythms
CC (PubMed:17555964, PubMed:17578907, PubMed:17578908, PubMed:27814361).
CC Transcriptional repressor which inhibits Clock-mediated transcriptional
CC activation by binding to E boxes in the promoters of Clock target genes
CC and repressing their transcription (PubMed:17555964, PubMed:17578907,
CC PubMed:17578908, PubMed:27814361). E box binding activity is time-
CC dependent with higher binding activity seen in the early morning
CC (zeitgeber time 2) than early evening (zeitgeber time 14) and is
CC dependent on the presence of the circadian protein per
CC (PubMed:27814361). It is likely that per binds to Clock-cycle
CC heterodimers, reducing their affinity for E box binding and allowing
CC cwo to bind instead (PubMed:27814361). Negatively regulates its own
CC expression (PubMed:17578908, PubMed:18375860).
CC {ECO:0000269|PubMed:17555964, ECO:0000269|PubMed:17578907,
CC ECO:0000269|PubMed:17578908, ECO:0000269|PubMed:18375860,
CC ECO:0000269|PubMed:27814361}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255,
CC ECO:0000269|PubMed:17578908, ECO:0000269|PubMed:18375860}.
CC -!- TISSUE SPECIFICITY: Expressed in adult brain where it is detected in
CC the dorsal lateral neurons, small and large ventral lateral neurons and
CC dorsal neurons 1, 2 and 3 (at protein level) (PubMed:17578908).
CC Expressed at constant levels in a 12 hour light/12 hour day cycle (at
CC protein level) (PubMed:27814361). Strongly expressed in pacemaker
CC neurons (PubMed:17578907). In adults, mRNA expression oscillates in a
CC circadian manner with a peak at around 14 h Zeitgeber time
CC (PubMed:17578907). mRNA levels oscillate in a rhythmic manner in both
CC 12 hour light/12 hour dark and constant dark conditions with a morning
CC peak around the time of lights-on and an evening peak around the time
CC of lights-off in light/dark conditions (PubMed:17555964,
CC PubMed:17578908, PubMed:18375860). During stage 8 of embryonic
CC development, expressed in the anterior and posterior midgut primordia
CC and expression in the gut continues throughout embryonic development
CC (PubMed:11102367). During germ band retraction, expression is initiated
CC in many tissues in a prominent segmentally repeated pattern
CC (PubMed:11102367). Later, expression is ubiquitous but has higher
CC levels in segmentally repeated clusters of cells (PubMed:11102367).
CC Expression is also found in cells of the amnioserosa, in the head
CC region, in posterior spiracles and in tracheal trees (PubMed:11102367).
CC {ECO:0000269|PubMed:11102367, ECO:0000269|PubMed:17555964,
CC ECO:0000269|PubMed:17578907, ECO:0000269|PubMed:17578908,
CC ECO:0000269|PubMed:18375860, ECO:0000269|PubMed:27814361}.
CC -!- DISRUPTION PHENOTYPE: Strong circadian locomotor phenotype with most
CC mutants being arrhythmic after 4 days in constant darkness and
CC displaying a long period in both light/dark and constant dark
CC conditions (PubMed:17578907). Delayed evening activity peak in
CC light/dark conditions and robust 26.5 hour rhythms for at least 10 days
CC in constant darkness (PubMed:18375860). Reduced circadian oscillation
CC of Clk target genes per, tim, vri and Pdp1 (PubMed:17578907,
CC PubMed:18375860). RNAi-mediated knockdown results in a lengthened
CC circadian period (PubMed:17555964, PubMed:17578908).
CC {ECO:0000269|PubMed:17555964, ECO:0000269|PubMed:17578907,
CC ECO:0000269|PubMed:17578908, ECO:0000269|PubMed:18375860}.
CC -!- MISCELLANEOUS: The name 'clockwork orange' is based on the Anthony
CC Burgess novel of the same name and derives from the potential clock
CC function and the presence of an Orange domain.
CC {ECO:0000303|PubMed:17555964}.
CC -!- CAUTION: Contains a degenerate basic motif not likely to bind DNA.
CC {ECO:0000255|PROSITE-ProRule:PRU00981}.
CC -!- SEQUENCE CAUTION:
CC Sequence=ACW83550.1; Type=Erroneous translation; Note=Wrong choice of frame.; Evidence={ECO:0000305};
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DR EMBL; AE014297; AAF54527.2; -; Genomic_DNA.
DR EMBL; BT099842; ACW83550.1; ALT_SEQ; mRNA.
DR EMBL; AF203477; AAF24476.1; -; mRNA.
DR RefSeq; NP_524775.1; NM_080036.3.
DR AlphaFoldDB; Q9VGZ5; -.
DR IntAct; Q9VGZ5; 1.
DR STRING; 7227.FBpp0081723; -.
DR PaxDb; Q9VGZ5; -.
DR EnsemblMetazoa; FBtr0082246; FBpp0081723; FBgn0259938.
DR GeneID; 44669; -.
DR KEGG; dme:Dmel_CG17100; -.
DR UCSC; CG17100-RA; d. melanogaster.
DR CTD; 44669; -.
DR FlyBase; FBgn0259938; cwo.
DR VEuPathDB; VectorBase:FBgn0259938; -.
DR eggNOG; KOG4304; Eukaryota.
DR GeneTree; ENSGT00940000173160; -.
DR HOGENOM; CLU_412381_0_0_1; -.
DR InParanoid; Q9VGZ5; -.
DR PhylomeDB; Q9VGZ5; -.
DR Reactome; R-DME-432408; Transcription regulation of cwo gene.
DR SignaLink; Q9VGZ5; -.
DR BioGRID-ORCS; 44669; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 44669; -.
DR PRO; PR:Q9VGZ5; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0259938; Expressed in capitellum (Drosophila) and 43 other tissues.
DR ExpressionAtlas; Q9VGZ5; baseline and differential.
DR Genevisible; Q9VGZ5; DM.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:FlyBase.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IBA:GO_Central.
DR GO; GO:0032922; P:circadian regulation of gene expression; IMP:FlyBase.
DR GO; GO:0048813; P:dendrite morphogenesis; IMP:FlyBase.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:FlyBase.
DR GO; GO:0042752; P:regulation of circadian rhythm; IMP:FlyBase.
DR GO; GO:0050767; P:regulation of neurogenesis; IBA:GO_Central.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISS:FlyBase.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR InterPro; IPR003650; Orange_dom.
DR Pfam; PF07527; Hairy_orange; 1.
DR Pfam; PF00010; HLH; 1.
DR SMART; SM00353; HLH; 1.
DR SMART; SM00511; ORANGE; 1.
DR SUPFAM; SSF47459; SSF47459; 1.
DR PROSITE; PS50888; BHLH; 1.
DR PROSITE; PS51054; ORANGE; 1.
PE 1: Evidence at protein level;
KW Biological rhythms; DNA-binding; Nucleus; Reference proteome; Repressor;
KW Transcription; Transcription regulation.
FT CHAIN 1..698
FT /note="Transcription factor cwo"
FT /id="PRO_0000438924"
FT DOMAIN 62..117
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT DOMAIN 128..159
FT /note="Orange"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00380"
FT REGION 62..75
FT /note="Basic motif; degenerate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 76..117
FT /note="Helix-loop-helix motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 257..319
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 349..369
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 284..319
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 698 AA; 75106 MW; 028BDB435ABA8683 CRC64;
MEPYWNETNG HAAHPVKYES EAAVSSFPYC TESSLNFSTS ATAYSEDDAE YATGRRNKTS
RQDPLSHRII EKRRRDRMNS CLADLSRLIP PQYQRKGRGR IEKTEIIEMA IRHLKHLQSE
CQQKESDYRS GYMDCMKEAA KFLYDVHMQD FCHRLLGRLQ EHIDEMFKTD CYKSTRSCHM
PDNVSASSGS PHQAYHPPLC HLRDMLATSA SDVEHSQDHN DVKDLSFRNH LNQLQRSQQA
AAAAAVAAAA VAVANGSSPA SNAGVDSKVP LTNGGGTGGA PPAADNVPSN STGSGSAAAC
AGGNSNSSGS NSSNAASSTI CPPAGGSCPA KVTPLAAHQQ PHQAPVITST APHHHHHHTD
SSHHDFESSR EPILHTDTSN MHSPPPRDLL LQQHPHLAHS HHTQDSLMSV RMRNYSESSH
EIEHNNNYKY KNHIKERFVH ELHDEETSSE HCPVAAHLQS DHSHLQALSE HSKDGTEPEI
APIMAKKRKL AEAAANGEIP LEVHTESSNA GASSANRLDK PSPSFNFSDI KDIKAELHNG
NSNSSPLLAK LSAVAAAGGQ LSTPSSTTAP LPPRHTFTVP IFALHGQGNY YVPLNVDYNA
LVPFLNGMDL LEKSYTSMPV VHPININVNF MPSSPSASLL AAAAAAAVAV GKQQQQQAVV
AAGAGLPLST NSAAAQAAAV AAAAVAKAKL EQAMNQSW
