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 24-JAN-2024, entry version 172. 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 hour 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 CC morning peak around the time of lights-on and an evening peak around CC the time 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 7227-FBpp0081723; -. DR EnsemblMetazoa; FBtr0082246; FBpp0081723; FBgn0259938. DR GeneID; 44669; -. DR KEGG; dme:Dmel_CG17100; -. DR UCSC; CG17100-RA; d. melanogaster. DR AGR; FB:FBgn0259938; -. 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 OMA; RFSQDTH; -. DR OrthoDB; 2968390at2759; -. 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 cell types or 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:0007623; P:circadian rhythm; 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:0006355; P:regulation of DNA-templated transcription; ISS: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 CDD; cd11440; bHLH-O_Cwo_like; 1. DR Gene3D; 4.10.280.10; Helix-loop-helix DNA-binding domain; 1. DR InterPro; IPR011598; bHLH_dom. DR InterPro; IPR036638; HLH_DNA-bd_sf. DR InterPro; IPR003650; Orange_dom. DR PANTHER; PTHR10985; BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTOR, HES-RELATED; 1. DR PANTHER; PTHR10985:SF141; TRANSCRIPTION FACTOR CWO; 1. DR Pfam; PF07527; Hairy_orange; 1. DR Pfam; PF00010; HLH; 1. DR SMART; SM00353; HLH; 1. DR SMART; SM00511; ORANGE; 1. DR SUPFAM; SSF47459; HLH, helix-loop-helix DNA-binding domain; 1. DR SUPFAM; SSF158457; Orange domain-like; 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 //