ID   TIM_DROHY               Reviewed;         676 AA.
AC   O44431;
DT   15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-1998, sequence version 1.
DT   03-AUG-2022, entry version 55.
DE   RecName: Full=Protein timeless;
DE   Flags: Fragment;
GN   Name=tim;
OS   Drosophila hydei (Fruit fly).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC   Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC   Drosophilidae; Drosophila.
OX   NCBI_TaxID=7224;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=9504927; DOI=10.1093/genetics/148.2.815;
RA   Ousley A., Zafarullah K., Chen Y., Emerson M., Hickman L., Sehgal A.;
RT   "Conserved regions of the timeless (tim) clock gene in Drosophila analyzed
RT   through phylogenetic and functional studies.";
RL   Genetics 148:815-825(1998).
CC   -!- FUNCTION: Required for the production of circadian rhythms. The
CC       biological cycle depends on the rhythmic formation and nuclear
CC       localization of the TIM-PER complex. Light induces the degradation of
CC       TIM, which promotes elimination of PER. Nuclear activity of the
CC       heterodimer coordinatively regulates PER and TIM transcription through
CC       a negative feedback loop. Behaves as a negative element in circadian
CC       transcriptional loop. Does not appear to bind DNA, suggesting indirect
CC       transcriptional inhibition (By similarity). {ECO:0000250}.
CC   -!- SUBUNIT: Forms a heterodimer with period (PER); the complex then
CC       translocates into the nucleus. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm, perinuclear region.
CC       Note=Nuclear at specific periods of the day. First accumulates in the
CC       perinuclear region about one hour before translocation into the
CC       nucleus. Interaction with per is required for nuclear localization (By
CC       similarity). {ECO:0000250}.
CC   -!- DOMAIN: Contains a 32 AA domain highly conserved between species.
CC       Deletion of this domain leads to long-period phenotype and arrhythmia
CC       (By similarity). {ECO:0000250}.
CC   -!- PTM: Phosphorylated with a circadian rhythmicity. {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the timeless family. {ECO:0000305}.
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DR   EMBL; AF038579; AAB92669.1; -; Genomic_DNA.
DR   AlphaFoldDB; O44431; -.
DR   SMR; O44431; -.
DR   PRIDE; O44431; -.
DR   FlyBase; FBgn0023352; Dhyd\tim.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR   InterPro; IPR044998; Timeless.
DR   InterPro; IPR006906; Timeless_N.
DR   PANTHER; PTHR22940; PTHR22940; 1.
DR   Pfam; PF04821; TIMELESS; 1.
PE   3: Inferred from homology;
KW   Biological rhythms; Cytoplasm; Nucleus; Phosphoprotein; Repeat.
FT   CHAIN           <1..>676
FT                   /note="Protein timeless"
FT                   /id="PRO_0000072536"
FT   REGION          77..108
FT                   /note="Necessary for normal circadian rhythm"
FT                   /evidence="ECO:0000250"
FT   REGION          94..145
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          346..398
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           388..398
FT                   /note="Nuclear localization signal"
FT                   /evidence="ECO:0000255"
FT   COMPBIAS        94..135
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        346..379
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   NON_TER         1
FT   NON_TER         676
SQ   SEQUENCE   676 AA;  76023 MW;  73EBBD1E098DDBF6 CRC64;
     MLLRNILHIP ETHAHFLMPV LQSSGGHQVS MQNTILWNLF IQSIDKLLLY LMTCPQRALW
     GVTMVQLIAM IYKDQHVNTL QKLLNLWFEA SLSESSEDNE SNTSPPKKGS GDSSPMLTSD
     PTSDSSDNGS NGGGSSGKKE GCDERRQALR EGTEATLQEV SRKGHDYQNA MARVTADKPD
     ISEVASDSFE VPCSPQQHLN TEEAMDDIDY EEQVQEYEQE AAAVSSEPLN LSQPANNVNY
     TTNAVYASTT ATETQTTSSL CAMTSLCYEP FKPPAPLPTR RNTLSEMLSD NYTSHSHVSA
     VKLGQKSSHA GQLQLTKGKC CPQKRECPSS QSELSDCGYA TQVENPESIS TSSNDDDGPQ
     GKPQHQKPPC NTKPRNKQRT LMSPQDKKEL RRKKLVKRSK SSLINMKGLV QHTPTNYDIS
     NLLKEFTVDF LLKGYNYLVE ELLKQLLTSA KVLIDTSHFF WLVTFFLKLA AQLELDMEHI
     DSILTYDVLS YLTYEGVSLC EQLELNAQQE GSDLQPYLRR MHLVVTAIRE FLQTIETYNK
     VSHLSEDDRL RLHQLQLQIG ATTDLRCLFV LLLRRFNPRI HSKQYLQDLV VTNHILMLIL
     DSAAKLEGGQ TIGLSEHISQ FATLEVMHYY GILLEDFDNN GEFVNDCIFT MMHHIGGDLG
     QIGVLFQPII LKTYSR