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Protein

Protein timeless homolog

Gene

Timeless

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Plays an important role in the control of DNA replication, maintenance of replication fork stability, maintenance of genome stability throughout normal DNA replication and in the regulation of the circadian clock. Involved in the determination of period length and in the DNA damage-dependent phase advancing of the circadian clock. Negatively regulates CLOCK|NPAS2-ARTNL/BMAL1|ARTNL2/BMAL2-induced transactivation of PER1 possibly via translocation of PER1 into the nucleus. Forms a complex with TIPIN and this complex regulates DNA replication processes under both normal and stress conditions, stabilizes replication forks and influences both CHEK1 phosphorylation and the intra-S phase checkpoint in response to genotoxic stress. Timeless promotes TIPIN nuclear localization. Involved in cell survival after DNA damage or replication stress. May be specifically required for the ATR-CHEK1 pathway in the replication checkpoint induced by hydroxyurea or ultraviolet light. May also play an important role in epithelial cell morphogenesis and formation of branching tubules.1 Publication

GO - Biological processi

  • branching involved in ureteric bud morphogenesis Source: MGI
  • cell division Source: UniProtKB-KW
  • cellular response to DNA damage stimulus Source: UniProtKB
  • circadian rhythm Source: UniProtKB
  • kidney development Source: RGD
  • mitotic nuclear division Source: UniProtKB-KW
  • morphogenesis of an epithelium Source: UniProtKB
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of circadian rhythm Source: RGD
  • regulation of circadian rhythm Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Biological rhythms, Cell cycle, Cell division, DNA damage, Mitosis, Transcription, Transcription regulation

Names & Taxonomyi

Protein namesi
Recommended name:
Protein timeless homolog
Short name:
rTIM
Alternative name(s):
Timeless-like protein
Short name:
rTLP
Gene namesi
Name:TimelessImported
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi620939. Timeless.

Subcellular locationi

GO - Cellular componenti

  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 12051205Protein timeless homologPRO_0000072540Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1169 – 11691PhosphoserineCombined sources
Modified residuei1174 – 11741PhosphothreonineCombined sources

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ9Z2Y1.
PRIDEiQ9Z2Y1.

PTM databases

iPTMnetiQ9Z2Y1.

Expressioni

Tissue specificityi

Expressed in all tissues examined including brain, eye, lung, heart, liver, kidney, pancreas, placenta and testis. Highest levels of expression in eye, lung, liver, placenta and kidney. Expressed throughout the suprachiasmatic nucleus (SCN).2 Publications

Inductioni

In both brain and pancreas, no circadian oscillation was detected.2 Publications

Interactioni

Subunit structurei

Homodimer or homomultimer. Component of the circadian core oscillator, which includes the CRY proteins, CLOCK or NPAS2, ARTNL/BMAL1 or ARTNL2/BMAL2, CSKN1D and/or CSNK1E, TIMELESS, and the PER proteins. Interacts directly with PER1, PER2 and PER3; the interaction with PER2 is via its second PAS domain. Interacts with CRY1, CRY2, CHEK1, ATR and ATRIP. Interacts with CLSPN and TIPIN.1 Publication

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000043366.

Structurei

3D structure databases

ProteinModelPortaliQ9Z2Y1.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 309309Required for homodimerization and for interaction with CRY1 and CHEK1By similarityAdd
BLAST
Regioni1081 – 1205125Required for nuclear localizationBy similarityAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi655 – 68531Glu-richAdd
BLAST
Compositional biasi966 – 1178213Glu-richAdd
BLAST

Sequence similaritiesi

Belongs to the timeless family.Curated

Phylogenomic databases

eggNOGiKOG1974. Eukaryota.
ENOG410XQM6. LUCA.
HOVERGENiHBG079258.
InParanoidiQ9Z2Y1.
KOiK03155.
PhylomeDBiQ9Z2Y1.

Family and domain databases

InterProiIPR006906. Timeless.
IPR007725. TIMELESS_C.
[Graphical view]
PfamiPF04821. TIMELESS. 1 hit.
PF05029. TIMELESS_C. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9Z2Y1-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDLYMMNCEL LATCSALGYL EGGTYHKEPD CLESVKDLIR YLRHEDETRD
60 70 80 90 100
VRQQLGAAQI LQSDLLPILT QHRQDKPLFD AVIRLMVNLT QPALLCFGSV
110 120 130 140 150
PKDPTVRHHF LQVLTYLQAY KEAFASEKAF GVLSETLYEL LQLGWEDRQE
160 170 180 190 200
EDNLLIERIL LLVRNILHVP ANLEQEKRID DDASIHDRLL WAIHLSGMDD
210 220 230 240 250
LLLFLSSSSA EQQWSLHVLE IISLMFRDQK PEQLAGVGQG RLAQERSTDL
260 270 280 290 300
AELEVLRQRE VAEKRARALQ RGNRHSRFGG SYVVQGLKSI GERDVVFHKG
310 320 330 340 350
LHNLQNYSSD LGKQPRRVPK RRQAAQELSV HRRSVLNVRL FLRDFCSEFL
360 370 380 390 400
ENCYNPLMGA VKDHLLREKA QQHDETYYMW AMAFFMAFNR AAAFRPGFVS
410 420 430 440 450
ETLSIRTFHF VEQNLTNYYE MMLTDRKEAA SWARRMHLAL KAYQELLATV
460 470 480 490 500
NEMDMCPDDA VRESSRIIKN NIFYMMEYRE LFLALFRKFD ERYHPRSFLC
510 520 530 540 550
DLVETTHLFL KMLERFCRSR GNLMVQNKRK KRKKKKKAQE QGVAFSRSPE
560 570 580 590 600
ELQAMWSALA ERLLQCAQEP ELSVDSIIPF DAASEVPVEE QRVEAMVRIQ
610 620 630 640 650
DCLVAGQAPQ ALALLRSARE VWPEGNVFGS PVISPGEEMQ LLKQILSATL
660 670 680 690 700
PRQQEPVEGD AEEEDEEEEE EEEEELQVVQ VSEKEFKFLD YLKRFACSTI
710 720 730 740 750
VRAYVLLLRS YRQNSAHTNH CIAKMLHRLA HDLGMEALLF QLSLFCLFNQ
760 770 780 790 800
LLSDPAAAAY KELVTFAKYI LGKFFALAAV NQKAFVELLF WKNTSVVREM
810 820 830 840 850
TQGYGSLDSG SCSHRAPVWS SEEEAQLQEL YLAHKDVEGQ DVVETILAHL
860 870 880 890 900
KAVPRTRKQV IHHLVRMGLA DSVKDFQRKG TQIVLWTEDQ ELELQRLFEE
910 920 930 940 950
FQDSDDVLGH IMKNITAKRS RARVVDKLLA LGLVSERRQL HKKRRKKLAP
960 970 980 990 1000
SCMQNGEESQ RDAWQEDPEE EEEKEGLPES EGEENEEDLL AGQVQGSSSL
1010 1020 1030 1040 1050
SAENLRQSLC QDGLSAPLLW LQSSLIRAAD DREEDGCSQA IPLVPLTEEN
1060 1070 1080 1090 1100
EEAMENKQFQ HLLRKLGIRA PCSGQETFWR IPAKLSSTQL RRVAASLSER
1110 1120 1130 1140 1150
ENKEEREEEP EPNPGVPGEQ SPSEEHQVRA PRALLSARKR KAGLVFPKEE
1160 1170 1180 1190 1200
ATGEEEWKSV PKKQQLLDSD EEDTDDERGG QAAVSGTLRI HKEKRFLVED

EDEDY
Length:1,205
Mass (Da):138,565
Last modified:May 1, 1999 - v1
Checksum:iC118B6ACF1DDA03D
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB019576 mRNA. Translation: BAA34400.1.
PIRiT13959.
RefSeqiNP_112630.1. NM_031340.1.
UniGeneiRn.31755.

Genome annotation databases

GeneIDi83508.
KEGGirno:83508.
UCSCiRGD:620939. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB019576 mRNA. Translation: BAA34400.1.
PIRiT13959.
RefSeqiNP_112630.1. NM_031340.1.
UniGeneiRn.31755.

3D structure databases

ProteinModelPortaliQ9Z2Y1.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000043366.

PTM databases

iPTMnetiQ9Z2Y1.

Proteomic databases

PaxDbiQ9Z2Y1.
PRIDEiQ9Z2Y1.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi83508.
KEGGirno:83508.
UCSCiRGD:620939. rat.

Organism-specific databases

CTDi8914.
RGDi620939. Timeless.

Phylogenomic databases

eggNOGiKOG1974. Eukaryota.
ENOG410XQM6. LUCA.
HOVERGENiHBG079258.
InParanoidiQ9Z2Y1.
KOiK03155.
PhylomeDBiQ9Z2Y1.

Miscellaneous databases

PROiQ9Z2Y1.

Family and domain databases

InterProiIPR006906. Timeless.
IPR007725. TIMELESS_C.
[Graphical view]
PfamiPF04821. TIMELESS. 1 hit.
PF05029. TIMELESS_C. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular characterization and nuclear localization of rat timeless-like gene product."
    Sakamoto S., Miyazaki K., Fukui H., Oishi K., Hayasaka N., Okada M., Kamakura M., Taniguchi T., Nagai K., Ishida N.
    Biochem. Biophys. Res. Commun. 279:131-138(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INTERACTION WITH PER2.
    Strain: WistarImported.
    Tissue: Hypothalamus1 Publication.
  2. "A role for Timeless in epithelial morphogenesis during kidney development."
    Li Z., Stuart R.O., Qiao J., Pavlova A., Bush K.T., Pohl M., Sakurai H., Nigam S.K.
    Proc. Natl. Acad. Sci. U.S.A. 97:10038-10043(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  3. "Indication of circadian oscillations in the rat pancreas."
    Muehlbauer E., Wolgast S., Finckh U., Peschke D., Peschke E.
    FEBS Lett. 564:91-96(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, INDUCTION.
  4. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
    Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
    Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1169 AND THR-1174, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiTIM_RAT
AccessioniPrimary (citable) accession number: Q9Z2Y1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 15, 2005
Last sequence update: May 1, 1999
Last modified: June 8, 2016
This is version 86 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 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.