UniProtKB - Q9R1X4 (TIM_MOUSE)
Protein timeless homolog
Timeless
Functioni
Plays an important role in the control of DNA replication, maintenance of replication fork stability, maintenance of genome stability throughout normal DNA replication, DNA repair and in the regulation of the circadian clock (PubMed:9856465, PubMed:23418588, PubMed:10428031, PubMed:12875843).
Required to stabilize replication forks during DNA replication by forming a complex with TIPIN: 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 (PubMed:12875843).
TIMELESS promotes TIPIN nuclear localization (PubMed:12875843).
Involved in cell survival after DNA damage or replication stress by promoting DNA repair (PubMed:12875843).
In response to double-strand breaks (DSBs), accumulates at DNA damage sites and promotes homologous recombination repair via its interaction with PARP1 (By similarity).
May be specifically required for the ATR-CHEK1 pathway in the replication checkpoint induced by hydroxyurea or ultraviolet light (PubMed:23418588).
Involved in the determination of period length and in the DNA damage-dependent phase advancing of the circadian clock (PubMed:23418588, PubMed:10428031).
Negatively regulates CLOCK|NPAS2-ARTNL/BMAL1|ARTNL2/BMAL2-induced transactivation of PER1 possibly via translocation of PER1 into the nucleus (PubMed:9856465).
May also play an important role in epithelial cell morphogenesis and formation of branching tubules (PubMed:10963667).
By similarity5 PublicationsGO - Molecular functioni
- DNA binding Source: GO_Central
- identical protein binding Source: MGI
GO - Biological processi
- branching involved in ureteric bud morphogenesis Source: MGI
- branching morphogenesis of an epithelial tube Source: MGI
- cell cycle phase transition Source: MGI
- cell division Source: UniProtKB-KW
- cellular response to bleomycin Source: UniProtKB
- cellular response to cisplatin Source: UniProtKB
- cellular response to DNA damage stimulus Source: UniProtKB
- cellular response to hydroxyurea Source: UniProtKB
- circadian rhythm Source: UniProtKB
- DNA repair Source: GO_Central
- DNA replication checkpoint signaling Source: GO_Central
- kidney development Source: MGI
- lung development Source: MGI
- morphogenesis of an epithelium Source: UniProtKB
- negative regulation of transcription, DNA-templated Source: UniProtKB
- negative regulation of transcription by RNA polymerase II Source: MGI
- positive regulation of circadian rhythm Source: MGI
- positive regulation of double-strand break repair Source: UniProtKB
- positive regulation of double-strand break repair via homologous recombination Source: UniProtKB
- regulation of circadian rhythm Source: UniProtKB
- replication fork arrest Source: GO_Central
- replication fork protection Source: GO_Central
Keywordsi
Molecular function | Developmental protein |
Biological process | Biological rhythms, Cell cycle, Cell division, DNA damage, DNA repair, Mitosis, Transcription, Transcription regulation |
Enzyme and pathway databases
Reactomei | R-MMU-5693607, Processing of DNA double-strand break ends |
Names & Taxonomyi
Protein namesi | Recommended name: Protein timeless homologShort name: mTim |
Gene namesi | |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1321393, Timeless |
VEuPathDBi | HostDB:ENSMUSG00000039994 |
Subcellular locationi
Nucleus
- Nucleus 4 Publications
Other locations
- Chromosome By similarity
Note: In response to double-strand breaks (DSBs), accumulates at DNA damage sites via its interaction with PARP1.By similarity
Nucleus
- nucleoplasm Source: MGI
- nucleus Source: UniProtKB
- replication fork protection complex Source: GO_Central
Other locations
- chromatin Source: MGI
- site of double-strand break Source: UniProtKB
Keywords - Cellular componenti
Chromosome, NucleusPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000072539 | 1 – 1197 | Protein timeless homologAdd BLAST | 1197 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 281 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1071 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1084 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1086 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 1165 | PhosphoserineBy similarity | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
MaxQBi | Q9R1X4 |
PaxDbi | Q9R1X4 |
PeptideAtlasi | Q9R1X4 |
PRIDEi | Q9R1X4 |
ProteomicsDBi | 262789 [Q9R1X4-1] 262790 [Q9R1X4-2] 262791 [Q9R1X4-3] 262792 [Q9R1X4-4] 262793 [Q9R1X4-5] 262794 [Q9R1X4-6] |
PTM databases
iPTMneti | Q9R1X4 |
PhosphoSitePlusi | Q9R1X4 |
Expressioni
Tissue specificityi
Developmental stagei
Inductioni
Gene expression databases
Bgeei | ENSMUSG00000039994, Expressed in primary oocyte and 249 other tissues |
Genevisiblei | Q9R1X4, MM |
Interactioni
Subunit structurei
Homodimer or homomultimer (PubMed:12875843, PubMed:23418588).
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 (PubMed:9856465).
Interacts directly with PER2; the interaction with PER2 is via its second PAS domain (PubMed:14564007).
Interacts directly with PER1 and PER3 (PubMed:9856465, PubMed:10231394, PubMed:14564007).
Interacts with CRY1 (PubMed:10428031, PubMed:23418588, PubMed:24489120).
Interacts with CRY2 (PubMed:10428031).
Interacts with CHEK1, ATR and ATRIP (By similarity).
Interacts with CLSPN (By similarity).
Interacts with TIPIN (PubMed:12875843).
Interacts with DDX11; this interaction increases recruitment of both proteins onto chromatin in response to replication stress induction by hydroxyurea (By similarity).
Interacts with PARP1; interaction is direct and independent of poly-ADP-ribose (By similarity).
By similarity7 PublicationsBinary interactionsi
Q9R1X4
With | #Exp. | IntAct |
---|---|---|
Per1 [O35973] | 3 | EBI-1793117,EBI-1266764 |
GO - Molecular functioni
- identical protein binding Source: MGI
Protein-protein interaction databases
BioGRIDi | 204198, 42 interactors |
IntActi | Q9R1X4, 26 interactors |
STRINGi | 10090.ENSMUSP00000058021 |
Miscellaneous databases
RNActi | Q9R1X4, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 309 | Required for homodimerization and for interaction with CRY1 and CHEK11 PublicationAdd BLAST | 309 | |
Regioni | 647 – 674 | DisorderedSequence analysisAdd BLAST | 28 | |
Regioni | 943 – 1002 | DisorderedSequence analysisAdd BLAST | 60 | |
Regioni | 997 – 1095 | Interaction with PARP1By similarityAdd BLAST | 99 | |
Regioni | 1079 – 1197 | Required for nuclear localization1 PublicationAdd BLAST | 119 | |
Regioni | 1088 – 1197 | DisorderedSequence analysisAdd BLAST | 110 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 657 – 674 | Acidic residuesSequence analysisAdd BLAST | 18 | |
Compositional biasi | 964 – 986 | Acidic residuesSequence analysisAdd BLAST | 23 | |
Compositional biasi | 988 – 1002 | Polar residuesSequence analysisAdd BLAST | 15 | |
Compositional biasi | 1116 – 1144 | Basic and acidic residuesSequence analysisAdd BLAST | 29 | |
Compositional biasi | 1151 – 1165 | Basic and acidic residuesSequence analysisAdd BLAST | 15 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG1974, Eukaryota |
GeneTreei | ENSGT00390000015124 |
InParanoidi | Q9R1X4 |
OMAi | QGPEECG |
OrthoDBi | 839367at2759 |
PhylomeDBi | Q9R1X4 |
TreeFami | TF312802 |
Family and domain databases
InterProi | View protein in InterPro IPR044998, Timeless IPR007725, TIMELESS_C IPR006906, Timeless_N |
PANTHERi | PTHR22940, PTHR22940, 1 hit |
Pfami | View protein in Pfam PF04821, TIMELESS, 1 hit PF05029, TIMELESS_C, 1 hit |
s (6+)i Sequence
Sequence statusi: Complete.
This entry describes 6 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 6 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
PKDSSVRHHF LQVLTYLQAY KEAFASEKAF GVLSETLYEL LQLGWEDRQE
160 170 180 190 200
EDNLLIERIL LLVRNILHVP ANLEQEKSID DDASIHDRLL WAIHLSGMDD
210 220 230 240 250
LLLFLSSSSA EQQWSLHVLE IISLMFRDQT PEQLAGVGQG RLAQERSTDV
260 270 280 290 300
AELEVLRQRE MAEKRARALQ RGNRHSRFGG SYIVQGLKSI GEKDVVFHKG
310 320 330 340 350
LHNLQNYSSD LGKQPRRVPK RRQAAQELSV HRRSVLNVRL FLRDFCSEFL
360 370 380 390 400
ENCYNPLMGA VKDHLLRERA QQHDETYYMW AMAFFMAFNR AATFRPGLVS
410 420 430 440 450
ETLSIRTFHF VEQNLTNYYE MMLTDRKEAA SWARRMHLAL KAYQELLATV
460 470 480 490 500
NEMDMCPDEA VRESSRIIKN NIFYMMEYRE LFLALFRKFD ERYHPRSFLR
510 520 530 540 550
DLVETTHLFL KMLERFCRSR GNLMVQNKRK KRKKKKKVQD QGVAFSQSPG
560 570 580 590 600
ELEAMWPALA EQLLQCAQDP ELSVDPVVPF DAASEVPVEE QRVEAMVRIQ
610 620 630 640 650
DCLTAGQAPQ ALALLRSARE VWPEGNAFGS PVISPGEEMQ LLKQILSTPL
660 670 680 690 700
PRQQEPEEGD AEEEEEEEEE EELQVVQVSE KEFNFLEYLK RFASSTIVRA
710 720 730 740 750
YVLLLRSYRQ NSAHTNHCIA KMLHRLAHGL GMEALLFQLS LFCLFNRLLS
760 770 780 790 800
DPAAAAYKEL VTFAKYIIGK FFALAAVNQK AFVELLFWKN TAVVREMTQG
810 820 830 840 850
YGSLDSGSSS HRAPLWSPEE EAQLQELYLA HKDVEGQDVV ETILAHLKVV
860 870 880 890 900
PRTRKQVIHH LVRMGLADSV KEFQKRKGTQ IVLWTEDQEL ELQRLFEEFR
910 920 930 940 950
DSDDVLGQIM KNITAKRSRA RVVDKLLALG LVSERRQLYK KRRKKLAPSC
960 970 980 990 1000
MQNGEKSPRD PWQEDPEEED EHLPEDESED EESEEGLPSG QGQGSSSLSA
1010 1020 1030 1040 1050
ENLGESLRQE GLSAPLLWLQ SSLIRAANDR EEDGCSQAIP LVPLTEENEE
1060 1070 1080 1090 1100
AMENEQFQHL LRKLGIRPPS SGQETFWRIP AKLSSTQLRR VAASLSQQEN
1110 1120 1130 1140 1150
EEEREEEPEP GVPGEQGPSE EHRTEALRAL LSARKRKAGL GPTEEEATGE
1160 1170 1180 1190
EEWNSAPKKR QLLDSDEEED DEGRRQAVSG TPRVHRKKRF QIEDEDD
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketH7BX89 | H7BX89_MOUSE | Protein timeless homolog | Timeless | 534 | Annotation score: | ||
E9Q302 | E9Q302_MOUSE | Protein timeless homolog | Timeless | 122 | Annotation score: |
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 179 | I → V in AAH64788 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 298 | H → R in AAH64788 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 317 | R → G in AAH64788 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 583 | A → V in BAA76390 (PubMed:10231394).Curated | 1 | |
Sequence conflicti | 744 | L → H in AAD24467 (PubMed:10963667).Curated | 1 | |
Sequence conflicti | 846 | H → Y in AAD24467 (PubMed:10963667).Curated | 1 | |
Sequence conflicti | 956 | K → R in AAD24467 (PubMed:10963667).Curated | 1 | |
Sequence conflicti | 1068 | P → L in AAD24467 (PubMed:10963667).Curated | 1 | |
Sequence conflicti | 1190 | F → L in BAA76390 (PubMed:10231394).Curated | 1 | |
Sequence conflicti | 1196 | D → G in BAA76390 (PubMed:10231394).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_051694 | 1 – 721 | Missing in isoform 4 and isoform 5. 2 PublicationsAdd BLAST | 721 | |
Alternative sequenceiVSP_051695 | 952 | Missing in isoform 2, isoform 3 and isoform 4. 2 Publications | 1 | |
Alternative sequenceiVSP_051696 | 967 – 1104 | Missing in isoform 3. 1 PublicationAdd BLAST | 138 | |
Alternative sequenceiVSP_051697 | 1177 | Missing in isoform 6. 1 Publication | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB015598 mRNA Translation: BAA36500.1 AF098161 mRNA Translation: AAC80010.1 AF071506 mRNA Translation: AAC79687.1 AB019001 mRNA Translation: BAA76390.2 AF126480 mRNA Translation: AAD24467.1 BC026526 mRNA Translation: AAH26526.1 BC052884 mRNA Translation: AAH52884.1 Sequence problems. BC058641 mRNA Translation: AAH58641.1 BC064788 mRNA Translation: AAH64788.1 Sequence problems. BC082770 mRNA Translation: AAH82770.1 |
CCDSi | CCDS24266.1 [Q9R1X4-1] CCDS48724.1 [Q9R1X4-6] CCDS48725.1 [Q9R1X4-2] |
PIRi | T13956 |
RefSeqi | NP_001129554.1, NM_001136082.2 [Q9R1X4-2] NP_001157552.1, NM_001164080.1 [Q9R1X4-6] NP_001157553.1, NM_001164081.1 [Q9R1X4-1] NP_035719.1, NM_011589.2 [Q9R1X4-1] XP_006513646.1, XM_006513583.3 [Q9R1X4-1] |
Genome annotation databases
Ensembli | ENSMUST00000055539; ENSMUSP00000058021; ENSMUSG00000039994 [Q9R1X4-1] ENSMUST00000105242; ENSMUSP00000100876; ENSMUSG00000039994 [Q9R1X4-2] ENSMUST00000105244; ENSMUSP00000100878; ENSMUSG00000039994 [Q9R1X4-6] ENSMUST00000105245; ENSMUSP00000100879; ENSMUSG00000039994 [Q9R1X4-1] |
GeneIDi | 21853 |
KEGGi | mmu:21853 |
UCSCi | uc007hlv.2, mouse [Q9R1X4-1] uc007hlw.2, mouse [Q9R1X4-2] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB015598 mRNA Translation: BAA36500.1 AF098161 mRNA Translation: AAC80010.1 AF071506 mRNA Translation: AAC79687.1 AB019001 mRNA Translation: BAA76390.2 AF126480 mRNA Translation: AAD24467.1 BC026526 mRNA Translation: AAH26526.1 BC052884 mRNA Translation: AAH52884.1 Sequence problems. BC058641 mRNA Translation: AAH58641.1 BC064788 mRNA Translation: AAH64788.1 Sequence problems. BC082770 mRNA Translation: AAH82770.1 |
CCDSi | CCDS24266.1 [Q9R1X4-1] CCDS48724.1 [Q9R1X4-6] CCDS48725.1 [Q9R1X4-2] |
PIRi | T13956 |
RefSeqi | NP_001129554.1, NM_001136082.2 [Q9R1X4-2] NP_001157552.1, NM_001164080.1 [Q9R1X4-6] NP_001157553.1, NM_001164081.1 [Q9R1X4-1] NP_035719.1, NM_011589.2 [Q9R1X4-1] XP_006513646.1, XM_006513583.3 [Q9R1X4-1] |
3D structure databases
SMRi | Q9R1X4 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 204198, 42 interactors |
IntActi | Q9R1X4, 26 interactors |
STRINGi | 10090.ENSMUSP00000058021 |
PTM databases
iPTMneti | Q9R1X4 |
PhosphoSitePlusi | Q9R1X4 |
Proteomic databases
MaxQBi | Q9R1X4 |
PaxDbi | Q9R1X4 |
PeptideAtlasi | Q9R1X4 |
PRIDEi | Q9R1X4 |
ProteomicsDBi | 262789 [Q9R1X4-1] 262790 [Q9R1X4-2] 262791 [Q9R1X4-3] 262792 [Q9R1X4-4] 262793 [Q9R1X4-5] 262794 [Q9R1X4-6] |
Protocols and materials databases
Antibodypediai | 15850, 204 antibodies from 31 providers |
DNASUi | 21853 |
Genome annotation databases
Ensembli | ENSMUST00000055539; ENSMUSP00000058021; ENSMUSG00000039994 [Q9R1X4-1] ENSMUST00000105242; ENSMUSP00000100876; ENSMUSG00000039994 [Q9R1X4-2] ENSMUST00000105244; ENSMUSP00000100878; ENSMUSG00000039994 [Q9R1X4-6] ENSMUST00000105245; ENSMUSP00000100879; ENSMUSG00000039994 [Q9R1X4-1] |
GeneIDi | 21853 |
KEGGi | mmu:21853 |
UCSCi | uc007hlv.2, mouse [Q9R1X4-1] uc007hlw.2, mouse [Q9R1X4-2] |
Organism-specific databases
CTDi | 8914 |
MGIi | MGI:1321393, Timeless |
VEuPathDBi | HostDB:ENSMUSG00000039994 |
Phylogenomic databases
eggNOGi | KOG1974, Eukaryota |
GeneTreei | ENSGT00390000015124 |
InParanoidi | Q9R1X4 |
OMAi | QGPEECG |
OrthoDBi | 839367at2759 |
PhylomeDBi | Q9R1X4 |
TreeFami | TF312802 |
Enzyme and pathway databases
Reactomei | R-MMU-5693607, Processing of DNA double-strand break ends |
Miscellaneous databases
BioGRID-ORCSi | 21853, 24 hits in 66 CRISPR screens |
ChiTaRSi | Timeless, mouse |
PROi | PR:Q9R1X4 |
RNActi | Q9R1X4, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000039994, Expressed in primary oocyte and 249 other tissues |
Genevisiblei | Q9R1X4, MM |
Family and domain databases
InterProi | View protein in InterPro IPR044998, Timeless IPR007725, TIMELESS_C IPR006906, Timeless_N |
PANTHERi | PTHR22940, PTHR22940, 1 hit |
Pfami | View protein in Pfam PF04821, TIMELESS, 1 hit PF05029, TIMELESS_C, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | TIM_MOUSE | |
Accessioni | Q9R1X4Primary (citable) accession number: Q9R1X4 Secondary accession number(s): Q63ZX9 Q9Z0E7 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | March 15, 2005 |
Last sequence update: | March 15, 2005 | |
Last modified: | February 23, 2022 | |
This is version 150 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families