TIMELESS
entrez
8914
canonical
uniprot
Q9UNS1
canonical
ensembl
ENSG00000111602
resolver
ensp
ENSP00000229201
resolver
ensp
ENSP00000450607
resolver
genesymbol
TIMELESS
resolver
genesymbol_syn
TIM
resolver
genesymbol_syn
TIM1
resolver
genesymbol_syn
TIMELESS1
resolver
hgnc
HGNC:11813
resolver
uniprot
B2ZAV0
resolver
uniprot
O94802
resolver
uniprot
Q86VM1
resolver
uniprot
Q8IWH3
resolver
uniprot_entry
TIM_HUMAN
resolver
uniprot_sec
B2ZAV0
resolver
uniprot_sec
O94802
resolver
uniprot_sec
Q86VM1
resolver
uniprot_sec
Q8IWH3
resolver
amino_acid_sequence
MDLHMMNCELLATCSALGYLEGDTYHKEPDCLESVKDLIRYLRHEDETRDVRQQLGAAQILQSDLLPILTQHHQDKPLFDAVIRLMVNLTQPALLCFGNLPKEPSFRHHFLQVLTYLQAYKEAFASEKAFGVLSETLYELLQLGWEERQEEDNLLIERILLLVRNILHVPADLDQEKKIDDDASAHDQLLWAIHLSGLDDLLLFLASSSAEEQWSLHVLEIVSLMFRDQNPEQLAGVGQGRLAQERSADFAELEVLRQREMAEKKTRALQRGNRHSRFGGSYIVQGLKSIGERDLIFHKGLHNLRNYSSDLGKQPKKVPKRRQAARELSIQRRSALNVRLFLRDFCSEFLENCYNRLMGSVKDHLLREKAQQHDETYYMWALAFFMAFNRAASFRPGLVSETLSVRTFHFIEQNLTNYYEMMLTDRKEAASWARRMHLALKAYQELLATVNEMDISPDEAVRESSRIIKNNIFYVMEYRELFLALFRKFDERCQPRSFLRDLVETTHLFLKMLERFCRSRGNLVVQNKQKKRRKKKKKVLDQAIVSGNVPSSPEEVEAVWPALAEQLQCCAQNSELSMDSVVPFDAASEVPVEEQRAEAMVRIQDCLLAGQAPQALTLLRSAREVWPEGDVFGSQDISPEEEIQLLKQILSAPLPRQQGPEERGAEEEEEEEEEEEEELQVVQVSEKEFNFLDYLKRFACSTVVRAYVLLLRSYQQNSAHTNHCIVKMLHRLAHDLKMEALLFQLSVFCLFNRLLSDPAAGAYKELVTFAKYILGKFFALAAVNQKAFVELLFWKNTAVVREMTEGYGSLDDRSSSRRAPTWSPEEEAHLRELYLANKDVEGQDVVEAILAHLNTVPRTRKQIIHHLVQMGLADSVKDFQRKGTHIVLWTGDQELELQRLFEEFRDSDDVLGHIMKNITAKRSRARIVDKLLALGLVAERRELYKKRQKKLASSILPNGAESLKDFCQEDLEEEENLPEEDSEEEEEGGSEAEQVQGSLVLSNENLGQSLHQEGFSIPLLWLQNCLIRAADDREEDGCSQAVPLVPLTEENEEAMENEQFQQLLRKLGVRPPASGQETFWRIPAKLSPTQLRRAAASLSQPEEEQKLQPELQPKVPGEQGSDEEHCKEHRAQALRALLLAHKKKAGLASPEEEDAVGKEPLKAAPKKRQLLDSDEEQEEDEGRNRAPELGAPGIQKKKRYQIEDDEDD
uniprot
proteins
disease_involvement
DISEASE: Advanced sleep phase syndrome, familial, 4 (FASPS4) [MIM:620015]: An autosomal dominant disorder characterized by very early sleep onset and offset. Individuals are 'morning larks' with a 4 hours advance of the sleep, temperature and melatonin rhythms. {ECO:0000269|PubMed:31138685}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: 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:17141802, PubMed:17296725, PubMed:23359676, PubMed:23418588, PubMed:26344098, PubMed:31138685, PubMed:32705708, PubMed:35585232, PubMed:9856465). 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:17141802, PubMed:17296725, PubMed:23359676, PubMed:35585232). During DNA replication, inhibits the CMG complex ATPase activity and activates DNA polymerases catalytic activities, coupling DNA unwinding and DNA synthesis (PubMed:23359676). TIMELESS promotes TIPIN nuclear localization (PubMed:17141802, PubMed:17296725). Plays a role in maintaining processive DNA replication past genomic guanine-rich DNA sequences that form G-quadruplex (G4) structures, possibly together with DDX11 (PubMed:32705708). Involved in cell survival after DNA damage or replication stress by promoting DNA repair (PubMed:17141802, PubMed:17296725, PubMed:26344098, PubMed:30356214). In response to double-strand breaks (DSBs), accumulates at DNA damage sites and promotes homologous recombination repair via its interaction with PARP1 (PubMed:26344098, PubMed:30356214, PubMed:31138685). May be specifically required for the ATR-CHEK1 pathway in the replication checkpoint induced by hydroxyurea or ultraviolet light (PubMed:15798197). Involved in the determination of period length and in the DNA damage-dependent phase advancing of the circadian clock (PubMed:23418588, PubMed:31138685). Negatively regulates CLOCK|NPAS2-ARTNL/BMAL1|ARTNL2/BMAL2-induced transactivation of PER1 possibly via translocation of PER1 into the nucleus (PubMed:31138685, PubMed:9856465). May play a role as destabilizer of the PER2-CRY2 complex (PubMed:31138685). May also play an important role in epithelial cell morphogenesis and formation of branching tubules (By similarity). {ECO:0000250|UniProtKB:Q9R1X4, ECO:0000269|PubMed:15798197, ECO:0000269|PubMed:17141802, ECO:0000269|PubMed:17296725, ECO:0000269|PubMed:23359676, ECO:0000269|PubMed:23418588, ECO:0000269|PubMed:26344098, ECO:0000269|PubMed:30356214, ECO:0000269|PubMed:31138685, ECO:0000269|PubMed:32705708, ECO:0000269|PubMed:35585232, ECO:0000269|PubMed:9856465}.
uniprot
proteins
mass_dalton
138658
uniprot
proteins
mutagenesis
MUTAGEN 1081; /note="R->G: Abolishes interaction with PARP1."; /evidence="ECO:0000269|PubMed:26344098
uniprot
proteins
protein_family
Timeless family
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15798197
uniprot
proteins
pubmed
16541075
uniprot
proteins
pubmed
16959974
uniprot
proteins
pubmed
16964243
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
17102137
uniprot
proteins
pubmed
17116885
uniprot
proteins
pubmed
17141802
uniprot
proteins
pubmed
17296725
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20124417
uniprot
proteins
pubmed
20139726
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
21670590
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23359676
uniprot
proteins
pubmed
23418588
uniprot
proteins
pubmed
26344098
uniprot
proteins
pubmed
26503245
uniprot
proteins
pubmed
28334766
uniprot
proteins
pubmed
30356214
uniprot
proteins
pubmed
31138685
uniprot
proteins
pubmed
32705708
uniprot
proteins
pubmed
34694004
uniprot
proteins
pubmed
34700328
uniprot
proteins
pubmed
35585232
uniprot
proteins
pubmed
9856465
uniprot
proteins
pubmed
9891984
uniprot
proteins
sequence_length
1208
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:17141802, ECO:0000269|PubMed:31138685}. Chromosome {ECO:0000269|PubMed:26344098}. Note=In response to double-strand breaks (DSBs), accumulates at DNA damage sites via its interaction with PARP1. {ECO:0000269|PubMed:26344098}.
uniprot
proteins