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 25-OCT-2017, entry version 135. 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; OC Pterygota; Neoptera; Holometabola; Diptera; Brachycera; Muscomorpha; OC Ephydroidea; 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., RA Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., RA Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., RA Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., RA Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., RA Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., RA Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., RA Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., RA Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., RA de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., RA Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., RA Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., RA Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., RA 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., RA Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., RA Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., RA Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., RA Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., RA Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., RA Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., RA Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., RA Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., RA Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., RA Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., RA 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., RA Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., RA Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., RA Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., RA Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., RA Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., RA Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., 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., RA Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., RA Lewis S.E.; RT "Annotation of the Drosophila melanogaster euchromatic genome: a RT systematic 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; RA Prokopenko S.N., He Y., Lu Y., Bellen H.J.; RT "Mutations affecting the development of the peripheral nervous system RT in 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., RA Hardin P.E., 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 RT activator and 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, CC PubMed:27814361). Transcriptional repressor which inhibits Clock- CC mediated transcriptional activation by binding to E boxes in the CC promoters of Clock target genes and repressing their transcription CC (PubMed:17555964, PubMed:17578907, PubMed:17578908, CC PubMed:27814361). E box binding activity is time-dependent with CC higher binding activity seen in the early morning (zeitgeber time CC 2) than early evening (zeitgeber time 14) and is dependent on the CC presence of the circadian protein per (PubMed:27814361). It is CC likely that per binds to Clock-cycle heterodimers, reducing their CC affinity for E box binding and allowing cwo to bind instead CC (PubMed:27814361). Negatively regulates its own expression CC (PubMed:17578908, PubMed:18375860). {ECO:0000269|PubMed:17555964, CC ECO:0000269|PubMed:17578907, ECO:0000269|PubMed:17578908, CC ECO:0000269|PubMed:18375860, ECO:0000269|PubMed:27814361}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|SAAS:SAAS00573650, CC ECO:0000269|PubMed:17578908, ECO:0000269|PubMed:18375860}. CC -!- TISSUE SPECIFICITY: Expressed in adult brain where it is detected CC in the dorsal lateral neurons, small and large ventral lateral CC neurons and dorsal neurons 1, 2 and 3 (at protein level) CC (PubMed:17578908). Expressed at constant levels in a 12 hour CC light/12 hour day cycle (at protein level) (PubMed:27814361). CC Strongly expressed in pacemaker neurons (PubMed:17578907). In CC adults, mRNA expression oscillates in a circadian manner with a CC peak at around 14 h Zeitgeber time (PubMed:17578907). mRNA levels CC oscillate in a rhythmic manner in both 12 hour light/12 hour dark CC and constant dark conditions with a morning peak around the time CC of lights-on and an evening peak around the time of lights-off in CC light/dark conditions (PubMed:17555964, PubMed:17578908, CC PubMed:18375860). During stage 8 of embryonic development, CC expressed in the anterior and posterior midgut primordia and CC expression in the gut continues throughout embryonic development CC (PubMed:11102367). During germ band retraction, expression is CC initiated in many tissues in a prominent segmentally repeated CC pattern (PubMed:11102367). Later, expression is ubiquitous but has CC higher levels in segmentally repeated clusters of cells CC (PubMed:11102367). Expression is also found in cells of the CC amnioserosa, in the head region, in posterior spiracles and in CC tracheal trees (PubMed:11102367). {ECO:0000269|PubMed:11102367, CC ECO:0000269|PubMed:17555964, ECO:0000269|PubMed:17578907, CC ECO:0000269|PubMed:17578908, ECO:0000269|PubMed:18375860, CC ECO:0000269|PubMed:27814361}. CC -!- DISRUPTION PHENOTYPE: Strong circadian locomotor phenotype with CC most mutants being arrhythmic after 4 days in constant darkness CC and 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 CC days in constant darkness (PubMed:18375860). Reduced circadian CC oscillation of Clk target genes per, tim, vri and Pdp1 CC (PubMed:17578907, PubMed:18375860). RNAi-mediated knockdown CC results in a lengthened circadian period (PubMed:17555964, CC PubMed:17578908). {ECO:0000269|PubMed:17555964, CC ECO:0000269|PubMed:17578907, ECO:0000269|PubMed:17578908, CC 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 CC clock 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 UniGene; Dm.11736; -. DR ProteinModelPortal; Q9VGZ5; -. DR IntAct; Q9VGZ5; 1. DR STRING; 7227.FBpp0081723; -. DR PaxDb; Q9VGZ5; -. DR PRIDE; 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 eggNOG; KOG4304; Eukaryota. DR eggNOG; ENOG4111F0X; LUCA. DR GeneTree; ENSGT00700000104130; -. DR InParanoid; Q9VGZ5; -. DR OMA; KSTRSCH; -. DR OrthoDB; EOG091G0V2P; -. DR PhylomeDB; Q9VGZ5; -. DR GenomeRNAi; 44669; -. DR PRO; PR:Q9VGZ5; -. DR Proteomes; UP000000803; Chromosome 3R. DR Bgee; FBgn0259938; -. DR ExpressionAtlas; Q9VGZ5; differential. DR Genevisible; Q9VGZ5; DM. DR GO; GO:0005634; C:nucleus; IDA:FlyBase. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro. DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; IDA:FlyBase. 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 from RNA polymerase II promoter; IDA:FlyBase. DR GO; GO:0042752; P:regulation of circadian rhythm; IMP:FlyBase. DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISS:FlyBase. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR CDD; cd00083; HLH; 1. 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; Complete proteome; DNA-binding; Nucleus; KW Reference proteome; Repressor; Transcription; KW Transcription regulation. FT CHAIN 1 698 Transcription factor cwo. FT /FTId=PRO_0000438924. FT DOMAIN 62 117 bHLH. {ECO:0000255|PROSITE- FT ProRule:PRU00981}. FT DOMAIN 128 159 Orange. {ECO:0000255|PROSITE- FT ProRule:PRU00380}. FT REGION 62 75 Basic motif; degenerate. FT {ECO:0000255|PROSITE-ProRule:PRU00981}. FT REGION 76 117 Helix-loop-helix motif. FT {ECO:0000255|PROSITE-ProRule:PRU00981}. FT COMPBIAS 240 263 Ala-rich. {ECO:0000255|PROSITE- FT ProRule:PRU00001}. FT COMPBIAS 338 471 His-rich. {ECO:0000255|PROSITE- FT ProRule:PRU00009}. FT COMPBIAS 637 688 Ala-rich. {ECO:0000255|PROSITE- FT ProRule:PRU00001}. 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 //