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Protein

Protein timeless

Gene

tim

Organism
Drosophila melanogaster (Fruit fly)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Required for the production of circadian rhythms. The biological cycle depends on the rhythmic formation and nuclear localization of the TIM-PER complex. Light induces the degradation of TIM, which promotes elimination of PER. Nuclear activity of the heterodimer coordinatively regulates PER and TIM transcription through a negative feedback loop. Behaves as a negative element in circadian transcriptional loop. Does not appear to bind DNA, suggesting indirect transcriptional inhibition.5 Publications

GO - Molecular functioni

  • protein heterodimerization activity Source: FlyBase
  • transcription factor binding Source: FlyBase

GO - Biological processi

  • cellular response to light stimulus Source: FlyBase
  • circadian behavior Source: FlyBase
  • circadian regulation of heart rate Source: FlyBase
  • circadian rhythm Source: FlyBase
  • circadian temperature homeostasis Source: FlyBase
  • copulation Source: FlyBase
  • eclosion rhythm Source: FlyBase
  • entrainment of circadian clock Source: FlyBase
  • locomotor rhythm Source: FlyBase
  • mating behavior Source: FlyBase
  • negative phototaxis Source: FlyBase
  • negative regulation of transcription from RNA polymerase II promoter Source: FlyBase
  • negative regulation of transcription regulatory region DNA binding Source: FlyBase
  • photoperiodism Source: FlyBase
  • positive regulation of phagocytosis Source: CACAO
  • protein import into nucleus Source: FlyBase
  • regulation of circadian sleep/wake cycle Source: FlyBase
  • regulation of circadian sleep/wake cycle, sleep Source: FlyBase
  • regulation of phagocytosis Source: CACAO
  • regulation of protein import into nucleus Source: FlyBase
  • rhythmic behavior Source: FlyBase
  • sleep Source: FlyBase
Complete GO annotation...

Keywords - Biological processi

Biological rhythms

Names & Taxonomyi

Protein namesi
Recommended name:
Protein timeless
Gene namesi
Name:tim
ORF Names:CG3234
OrganismiDrosophila melanogaster (Fruit fly)
Taxonomic identifieri7227 [NCBI]
Taxonomic lineageiEukaryotaMetazoaEcdysozoaArthropodaHexapodaInsectaPterygotaNeopteraEndopterygotaDipteraBrachyceraMuscomorphaEphydroideaDrosophilidaeDrosophilaSophophora
Proteomesi
  • UP000000803 Componenti: Chromosome 2L

Organism-specific databases

FlyBaseiFBgn0014396. tim.

Subcellular locationi

  • Nucleus 1 Publication
  • Cytoplasmperinuclear region 1 Publication

  • Note: Nuclear at specific periods of the day. First accumulates in the perinuclear region about one hour before translocation into the nucleus. Interaction with per is required for nuclear localization.

GO - Cellular componenti

  • cytoplasm Source: FlyBase
  • nucleus Source: FlyBase
  • perinuclear region of cytoplasm Source: UniProtKB-SubCell
  • protein complex Source: FlyBase
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

Mutant flies show loss of both behavioral circadian rhythms and molecular oscillations of per RNA and protein.2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000225321 – 1398Protein timelessAdd BLAST1398

Post-translational modificationi

Phosphorylated with a circadian rhythmicity.

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP49021.
PRIDEiP49021.

Expressioni

Tissue specificityi

Expressed in head, photoreceptors, lateral neurons and glial cells in the lamina and medulla of the optic lobes. Expression follows a light-dark cycle, levels show a significant decrease at the end of the night and then remain low throughout the light period (at protein level).2 Publications

Gene expression databases

BgeeiFBgn0014396.
ExpressionAtlasiP49021. baseline.
GenevisibleiP49021. DM.

Interactioni

Subunit structurei

Forms a heterodimer with period (PER); the complex then translocates into the nucleus.

GO - Molecular functioni

  • protein heterodimerization activity Source: FlyBase
  • transcription factor binding Source: FlyBase

Protein-protein interaction databases

BioGridi59781. 7 interactors.
DIPiDIP-29425N.
IntActiP49021. 3 interactors.
MINTiMINT-344208.
STRINGi7227.FBpp0305454.

Structurei

3D structure databases

ProteinModelPortaliP49021.
SMRiP49021.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni237 – 268Necessary for normal circadian rhythmAdd BLAST32

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi550 – 560Nuclear localization signalSequence analysisAdd BLAST11

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi360 – 389Asp/Glu-rich (acidic)Add BLAST30
Compositional biasi432 – 437Poly-Pro6

Sequence similaritiesi

Belongs to the timeless family.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG1974. Eukaryota.
ENOG410XQM6. LUCA.
GeneTreeiENSGT00390000015124.
InParanoidiP49021.
KOiK12074.
OMAiLHIPETH.
OrthoDBiEOG091G01UQ.

Family and domain databases

InterProiIPR006906. Timeless.
[Graphical view]
PfamiPF04821. TIMELESS. 1 hit.
[Graphical view]

Sequences (7)i

Sequence statusi: Complete.

This entry describes 7 isoformsi produced by alternative splicing and alternative initiation. AlignAdd to basket

Isoform BImported (identifier: P49021-4) [UniParc]FASTAAdd to basket
Also known as: PImported

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MDWLLATPQL YSAFSSLGCL EGDTYVVNPN ALAILEEINY KLTYEDQTLR
60 70 80 90 100
TFRRAIGFGQ NVRSDLIPLL ENAKDDAVLE SVIRILVNLT VPVECLFSVD
110 120 130 140 150
VMYRTDVGRH TIFELNKLLY TSKEAFTEAR STKSVVEYMK HILESDPKLS
160 170 180 190 200
PHKCDQINNC LLLLRNILHI PETHAHCVMP MMQSMPHGIS MQNTILWNLF
210 220 230 240 250
IQSIDKLLLY LMTCPQRAFW GVTMVQLIAL IYKDQHVSTL QKLLSLWFEA
260 270 280 290 300
SLSESSEDNE SNTSPPKQGS GDSSPMLTSD PTSDSSDNGS NGRGMGGGMR
310 320 330 340 350
EGTAATLQEV SRKGQEYQNA MARVPADKPD GSEEASDMTG NDSEQPGSPE
360 370 380 390 400
QSQPAGESMD DGDYEDQRHR QLNEHGEEDE DEDEVEEEEY LQLGPASEPL
410 420 430 440 450
NLTQQPADKV NNTTNPTSSA PQGCLGNEPF KPPPPLPVRA STSAHAQMQK
460 470 480 490 500
FNESSYASHV SAVKLGQKSP HAGQLQLTKG KCCPQKRECP SSQSELSDCG
510 520 530 540 550
YGTQVENQES ISTSSNDDDG PQGKPQHQKP PCNTKPRNKP RTIMSPMDKK
560 570 580 590 600
ELRRKKLVKR SKSSLINMKG LVQHTPTDDD ISNLLKEFTV DFLLKGYSYL
610 620 630 640 650
VEELHMQLLS NAKVPIDTSH FFWLVTYFLK FAAQLELDME HIDTILTYDV
660 670 680 690 700
LSYLTYEGVS LCEQLELNAR QEGSDLKPYL RRMHLVVTAI REFLQAIDTY
710 720 730 740 750
NKVTHLNEDD KAHLRQLQLQ ISEMSDLRCL FVLLLRRFNP SIHSKQYLQD
760 770 780 790 800
LVVTNHILLL ILDSSAKLGG CQTIRLSEHI TQFATLEVMH YYGILLEDFN
810 820 830 840 850
NNGEFVNDCI FTMMHHIGGD LGQIGVLFQP IILKTYSRIW EADYELCDDW
860 870 880 890 900
SDLIEYVIHK FMNTPPKSPL TIPTTSLTEM TKEHNQEHTV CSWSQEEMDT
910 920 930 940 950
LYWYYVQSKK NNDIVGKIVK LFSNNGNKLK TRISIIQQLL QQDIITLLEY
960 970 980 990 1000
DDLMKFEDAE YQRTLLTTPT SATTESGIEI KECAYGKPSD DVQILLDLII
1010 1020 1030 1040 1050
KENKAQHLLW LQRILIECCF VKLTLRSGLK VPEGDHIMEP VAYHCICKQK
1060 1070 1080 1090 1100
SIPVVQWNNE QSTTMLYQPF VLLLHKLGIQ LPADAGSIFA RIPDYWTPET
1110 1120 1130 1140 1150
MYGLAKKLGP LDKLNLKFDA SELEDATASS PSRYHHTGPR NSLSSVSSLD
1160 1170 1180 1190 1200
VDLGDTEELA LIPEVDAAVE KAHAMASTPS PSEIFAVPKT KHCNSIIRYT
1210 1220 1230 1240 1250
PDPTPPVPNW LQLVMRSKCN HRTGPSGDPS DCIGSSSTTV DDEGFGKSIS
1260 1270 1280 1290 1300
AATSQAASTS MSTVNPTTTL SLNMLNTFMG SHNENSSSSG CGGTVSSLSM
1310 1320 1330 1340 1350
VALMSTGAAG GGGNTSGLEM DVDASMKSSF ERLEVNGSHF SRANNLDQEY
1360 1370 1380 1390
SAMVASVYEK EKELNSDNVS LASDLTRMYV SDEDDRLERT EIRVPHYH
Length:1,398
Mass (Da):156,382
Last modified:May 14, 2014 - v3
Checksum:iE7974EDCF6F94A88
GO
Isoform RImported (identifier: P49021-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     237-268: Missing.

Note: No experimental confirmation available.
Show »
Length:1,366
Mass (Da):152,847
Checksum:i06F0104288A8703F
GO
Isoform OImported (identifier: P49021-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     891-891: C → W
     892-1398: Missing.

Note: No experimental confirmation available.
Show »
Length:891
Mass (Da):100,623
Checksum:iAB62EC51D0F761AD
GO
Isoform NImported (identifier: P49021-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     613-613: Missing.
     891-891: C → W
     892-1398: Missing.

Note: No experimental confirmation available.
Show »
Length:890
Mass (Da):100,495
Checksum:iBC8202CC37F333B3
GO
Isoform SImported (identifier: P49021-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     237-268: Missing.
     1114-1131: LNLKFDASELEDATASSP → RELKSTTEKNNPFVIPQR
     1132-1398: Missing.

Note: No experimental confirmation available.
Show »
Length:1,099
Mass (Da):124,696
Checksum:i80AA3EF3AB03EF6C
GO
Isoform MImported (identifier: P49021-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1114-1131: LNLKFDASELEDATASSP → RELKSTTEKNNPFVIPQR
     1132-1398: Missing.

Note: No experimental confirmation available.
Show »
Length:1,131
Mass (Da):128,231
Checksum:i608FBAE2361C8271
GO
Isoform LImported (identifier: P49021-8) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     613-613: Missing.

Note: No experimental confirmation available.
Show »
Length:1,397
Mass (Da):156,253
Checksum:iCFA4573C81C95F41
GO

Sequence cautioni

The sequence AAC46920 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAL13507 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAN71179 differs from that shown. Intron retention.Curated
The sequence AAN71179 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence ACX54883 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1233I → V in AAB94890 (PubMed:9365248).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_004457237 – 268Missing in isoform R and isoform S. 1 PublicationAdd BLAST32
Alternative sequenceiVSP_054859613Missing in isoform L and isoform N. 1 Publication1
Alternative sequenceiVSP_007693891C → W in isoform N and isoform O. 2 Publications1
Alternative sequenceiVSP_007694892 – 1398Missing in isoform N and isoform O. 2 PublicationsAdd BLAST507
Alternative sequenceiVSP_0548601114 – 1131LNLKF…TASSP → RELKSTTEKNNPFVIPQR in isoform S and isoform M. CuratedAdd BLAST18
Alternative sequenceiVSP_0548611132 – 1398Missing in isoform S and isoform M. CuratedAdd BLAST267

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U37018 mRNA. Translation: AAC46920.1. Different initiation.
AF032401, AF032400 Genomic DNA. Translation: AAB94890.1.
AE014134 Genomic DNA. Translation: AAF51098.4.
AE014134 Genomic DNA. Translation: AAN10371.3.
AE014134 Genomic DNA. Translation: AAN10372.3.
AE014134 Genomic DNA. Translation: AAX52649.2.
AE014134 Genomic DNA. Translation: ABC65862.2.
AE014134 Genomic DNA. Translation: ACL82987.2.
AE014134 Genomic DNA. Translation: ACL82988.2.
AE014134 Genomic DNA. Translation: ADV36936.2.
Y09930 Genomic DNA. No translation available.
Y09931 Genomic DNA. No translation available.
Y09932 Genomic DNA. No translation available.
Y09933 Genomic DNA. No translation available.
Y09934 Genomic DNA. No translation available.
Y09935 Genomic DNA. No translation available.
AY058278 mRNA. Translation: AAL13507.1. Different initiation.
BT001424 mRNA. Translation: AAN71179.1. Sequence problems.
BT024951 mRNA. Translation: ABE01181.1.
BT099999 mRNA. Translation: ACX54883.1. Different initiation.
AF038501 Genomic DNA. Translation: AAB94929.1.
PIRiA57655.
RefSeqiNP_001014463.2. NM_001014463.4. [P49021-6]
NP_001033872.2. NM_001038783.3. [P49021-7]
NP_001137780.2. NM_001144308.3. [P49021-2]
NP_001137781.2. NM_001144309.4. [P49021-3]
NP_001188686.2. NM_001201757.2. [P49021-5]
NP_722912.3. NM_164540.4. [P49021-4]
NP_722913.3. NM_164541.6. [P49021-8]
NP_722914.3. NM_164542.5. [P49021-4]
UniGeneiDm.2663.

Genome annotation databases

EnsemblMetazoaiFBtr0077567; FBpp0077256; FBgn0014396. [P49021-4]
FBtr0333256; FBpp0305454; FBgn0014396. [P49021-4]
GeneIDi33571.
KEGGidme:Dmel_CG3234.
UCSCiCG3234-RA. d. melanogaster. [P49021-4]
CG3234-RE. d. melanogaster.

Keywords - Coding sequence diversityi

Alternative initiation, Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U37018 mRNA. Translation: AAC46920.1. Different initiation.
AF032401, AF032400 Genomic DNA. Translation: AAB94890.1.
AE014134 Genomic DNA. Translation: AAF51098.4.
AE014134 Genomic DNA. Translation: AAN10371.3.
AE014134 Genomic DNA. Translation: AAN10372.3.
AE014134 Genomic DNA. Translation: AAX52649.2.
AE014134 Genomic DNA. Translation: ABC65862.2.
AE014134 Genomic DNA. Translation: ACL82987.2.
AE014134 Genomic DNA. Translation: ACL82988.2.
AE014134 Genomic DNA. Translation: ADV36936.2.
Y09930 Genomic DNA. No translation available.
Y09931 Genomic DNA. No translation available.
Y09932 Genomic DNA. No translation available.
Y09933 Genomic DNA. No translation available.
Y09934 Genomic DNA. No translation available.
Y09935 Genomic DNA. No translation available.
AY058278 mRNA. Translation: AAL13507.1. Different initiation.
BT001424 mRNA. Translation: AAN71179.1. Sequence problems.
BT024951 mRNA. Translation: ABE01181.1.
BT099999 mRNA. Translation: ACX54883.1. Different initiation.
AF038501 Genomic DNA. Translation: AAB94929.1.
PIRiA57655.
RefSeqiNP_001014463.2. NM_001014463.4. [P49021-6]
NP_001033872.2. NM_001038783.3. [P49021-7]
NP_001137780.2. NM_001144308.3. [P49021-2]
NP_001137781.2. NM_001144309.4. [P49021-3]
NP_001188686.2. NM_001201757.2. [P49021-5]
NP_722912.3. NM_164540.4. [P49021-4]
NP_722913.3. NM_164541.6. [P49021-8]
NP_722914.3. NM_164542.5. [P49021-4]
UniGeneiDm.2663.

3D structure databases

ProteinModelPortaliP49021.
SMRiP49021.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi59781. 7 interactors.
DIPiDIP-29425N.
IntActiP49021. 3 interactors.
MINTiMINT-344208.
STRINGi7227.FBpp0305454.

Proteomic databases

PaxDbiP49021.
PRIDEiP49021.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblMetazoaiFBtr0077567; FBpp0077256; FBgn0014396. [P49021-4]
FBtr0333256; FBpp0305454; FBgn0014396. [P49021-4]
GeneIDi33571.
KEGGidme:Dmel_CG3234.
UCSCiCG3234-RA. d. melanogaster. [P49021-4]
CG3234-RE. d. melanogaster.

Organism-specific databases

CTDi107698.
FlyBaseiFBgn0014396. tim.

Phylogenomic databases

eggNOGiKOG1974. Eukaryota.
ENOG410XQM6. LUCA.
GeneTreeiENSGT00390000015124.
InParanoidiP49021.
KOiK12074.
OMAiLHIPETH.
OrthoDBiEOG091G01UQ.

Miscellaneous databases

GenomeRNAii33571.
PROiP49021.

Gene expression databases

BgeeiFBgn0014396.
ExpressionAtlasiP49021. baseline.
GenevisibleiP49021. DM.

Family and domain databases

InterProiIPR006906. Timeless.
[Graphical view]
PfamiPF04821. TIMELESS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTIM_DROME
AccessioniPrimary (citable) accession number: P49021
Secondary accession number(s): A4V040
, B7Z007, B7Z008, C9QPB7, M9MRE9, O44380, Q1WWF5, Q59E16, Q8I037, Q95U67, Q9VQR6, Q9VQR7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: May 14, 2014
Last modified: November 30, 2016
This is version 144 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programDrosophila annotation project

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Drosophila
    Drosophila: entries, gene names and cross-references to FlyBase
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.