TIM_DROVI
ID TIM_DROVI Reviewed; 1343 AA.
AC O17482; O44430; O44785;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 83.
DE RecName: Full=Protein timeless;
GN Name=tim;
OS Drosophila virilis (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila.
OX NCBI_TaxID=7244;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9365248; DOI=10.1093/nar/25.23.4710;
RA Myers M.P., Rothenfluh A., Chang M., Young M.W.;
RT "Comparison of chromosomal DNA composing timeless in Drosophila
RT melanogaster and D. virilis suggests a new conserved structure for the
RT TIMELESS protein.";
RL Nucleic Acids Res. 25:4710-4714(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE OF 1-1194 AND 1196-1343.
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 {ECO:0000250}. Cytoplasm, perinuclear
CC region {ECO:0000250}. Note=Nuclear at specific periods of the day.
CC First accumulates in the perinuclear region about one hour before
CC translocation into the nucleus. Interaction with per is required for
CC nuclear localization (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; AF032403; AAB94891.1; -; Genomic_DNA.
DR EMBL; AF032402; AAB94891.1; JOINED; Genomic_DNA.
DR EMBL; AF038502; AAB94930.1; -; Genomic_DNA.
DR EMBL; AF040096; AAB94942.1; -; mRNA.
DR AlphaFoldDB; O17482; -.
DR SMR; O17482; -.
DR STRING; 7244.FBpp0232018; -.
DR eggNOG; KOG1974; Eukaryota.
DR ChiTaRS; tim; fly.
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; IPR007725; TIMELESS_C.
DR InterPro; IPR006906; Timeless_N.
DR PANTHER; PTHR22940; PTHR22940; 1.
DR Pfam; PF04821; TIMELESS; 1.
DR Pfam; PF05029; TIMELESS_C; 1.
PE 2: Evidence at transcript level;
KW Biological rhythms; Cytoplasm; Nucleus; Phosphoprotein; Repeat.
FT CHAIN 1..1343
FT /note="Protein timeless"
FT /id="PRO_0000072537"
FT REGION 238..270
FT /note="Necessary for normal circadian rhythm"
FT /evidence="ECO:0000250"
FT REGION 256..314
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 453..512
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1247..1270
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 517..527
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 256..291
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 292..314
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 454..488
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1247..1267
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 851
FT /note="Q -> H (in Ref. 2; AAB94930)"
FT /evidence="ECO:0000305"
FT CONFLICT 1180
FT /note="T -> S (in Ref. 2; AAB94930)"
FT /evidence="ECO:0000305"
FT CONFLICT 1223
FT /note="S -> A (in Ref. 2; AAB94942)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1343 AA; 150944 MW; 3FC2F286AC5355F5 CRC64;
MDWLLATPQL QSVFSSLGSL VGGTYVVSPN ALAILEEINH KLTYEDQTLR TFRRAIGFGQ
NVRVDLIPLL ENAKDDAVLE SVIRILVNLT VPVECLFSVD LMYRTEVGRH TIFELNKLLY
NSKEAFTDPK STKSVVEYMK HILESDPKLS PHKCDQINNC LLLLRNILHI PETHAHFLMP
RLQPGSGHQV SMQNTILWNL FIQSIDKLLL YLMTCPQRSL WGVTMVQLIA LIYKDQHVST
LQKLLNLWFE ASLSESSDDN ESNTTPPKQA SGDSSPMLTS DPTSDSSDNG SGGKKESCEE
RRQALREGTD ATLHEVSRKG HEYQNAMASS NAANYILEGP CSAQQPWSDC EMQEYKQMTA
VISEPLNLSQ PADNVNYTTN ANYARTTSTD ILTKTTSLKH EGFKPPAPRR NTLSAILSDN
YAPLSFISAV KLGQKSPHAG QLQLIKGKCC PQKRECPSSQ SEHSDCGYGT QMENPESIST
SSNDDDGPQG KPQHQKPPCS SKHRSKQRIF AVPQDTKDLR RKKLVKRSKS SLINMKGLVL
HTPNDDDISN LLKEFTVDFL LKGYNYLVEE LHSQLLSNAK MPIDTSHFFW LVTFFLKFAA
QLELDMEHID TILTFDVLSF LTYEGVSLCE QLELNARQEG ADLRPYLRRM HLVVTAIREF
LQAIEAYNKV THLSEDDRYR LRQLQLQISA TTDLRCLFVL LLRRFNPSIH SKQYLQDLVV
TNHILLLILD NAAKLEGGQT IGLSEHISQF ATLEVMHYYG ILLEDFSNNG EYVNDCIFTM
MHHIGGDLDQ VGVLYQPIIL KAYSRIWEAD YDICDDWSDL IEYVIHKFLN TPPKSPMAIP
TASLTELTKE QNQEHTACPW SQEDMDSLCW YFVQSKRQND VIGNIAKLFS NNGNKIKTRI
SIIQQLLQQD IITLLEYDDL MKFEDAEYQR TLLATPTSLT TDSGIELKES AYGKPSDDVQ
VLLDLIRKEN KSQHLVWLQK LLLECCYVKM MIKCGSCQTD VEPIMEPVVY HCMFKQKPIP
VVQWNNEQSS TMLYQPFMLL LHKLGIQLPA DAGLIFARIP DFWTPETMYG LAKKLGPLDK
LTLKFDPRDL EDAPPSRHHT GARNSLSSIS SLEADFGDSE GLALIPEVDP AVEKAAAAAS
AIPNNEIFAL PRVKHCNSII RYTPDPTPPV PSWLQLVMRT KCSKRRSPAT DASDCTSTST
MIADDEIKSY ASMAQASHTK LNSGYPTSTL VCMNKLSNCS FAAPPNENSS SSGCGGTASS
MSMPNMPDGN SDALMKTSFE RLAVTGARYL RPSNTDQDYS ALVASVYENE FANSDNVSVA
SDLTRMYVSD EDEKHELQLQ QVE
