Search Results

Overview

Uniprot IDQ9UNS1
Protein NameProtein timeless homolog
Gene NameTIMELESS
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
1144 LLLAHKKKAGLASPE
1196 LGAPGIQKKKRYQIE
1197 GAPGIQKKKRYQIED
299 ERDLIFHKGLHNLRN
313 NYSSDLGKQPKKVPK
950 LYKKRQKKLASSILP

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)

Protein Sequence

10 MDLHMMNCEL 20 LATCSALGYL 30 EGDTYHKEPD 40 CLESVKDLIR 50 YLRHEDETRD 60 VRQQLGAAQI 70 LQSDLLPILT 80 QHHQDKPLFD 90 AVIRLMVNLT 100 QPALLCFGNL 110 PKEPSFRHHF 120 LQVLTYLQAY 130 KEAFASEKAF 140 GVLSETLYEL 150 LQLGWEERQE 160 EDNLLIERIL 170 LLVRNILHVP 180 ADLDQEKKID 190 DDASAHDQLL 200 WAIHLSGLDD 210 LLLFLASSSA 220 EEQWSLHVLE 230 IVSLMFRDQN 240 PEQLAGVGQG 250 RLAQERSADF 260 AELEVLRQRE 270 MAEKKTRALQ 280 RGNRHSRFGG 290 SYIVQGLKSI 300 GERDLIFHKG 310 LHNLRNYSSD 320 LGKQPKKVPK 330 RRQAARELSI 340 QRRSALNVRL 350 FLRDFCSEFL 360 ENCYNRLMGS 370 VKDHLLREKA 380 QQHDETYYMW 390 ALAFFMAFNR 400 AASFRPGLVS 410 ETLSVRTFHF 420 IEQNLTNYYE 430 MMLTDRKEAA 440 SWARRMHLAL 450 KAYQELLATV 460 NEMDISPDEA 470 VRESSRIIKN 480 NIFYVMEYRE 490 LFLALFRKFD 500 ERCQPRSFLR 510 DLVETTHLFL 520 KMLERFCRSR 530 GNLVVQNKQK 540 KRRKKKKKVL 550 DQAIVSGNVP 560 SSPEEVEAVW 570 PALAEQLQCC 580 AQNSELSMDS 590 VVPFDAASEV 600 PVEEQRAEAM 610 VRIQDCLLAG 620 QAPQALTLLR 630 SAREVWPEGD 640 VFGSQDISPE 650 EEIQLLKQIL 660 SAPLPRQQGP 670 EERGAEEEEE 680 EEEEEEEELQ 690 VVQVSEKEFN 700 FLDYLKRFAC 710 STVVRAYVLL 720 LRSYQQNSAH 730 TNHCIVKMLH 740 RLAHDLKMEA 750 LLFQLSVFCL 760 FNRLLSDPAA 770 GAYKELVTFA 780 KYILGKFFAL 790 AAVNQKAFVE 800 LLFWKNTAVV 810 REMTEGYGSL 820 DDRSSSRRAP 830 TWSPEEEAHL 840 RELYLANKDV 850 EGQDVVEAIL 860 AHLNTVPRTR 870 KQIIHHLVQM 880 GLADSVKDFQ 890 RKGTHIVLWT 900 GDQELELQRL 910 FEEFRDSDDV 920 LGHIMKNITA 930 KRSRARIVDK 940 LLALGLVAER 950 RELYKKRQKK 960 LASSILPNGA 970 ESLKDFCQED 980 LEEEENLPEE 990 DSEEEEEGGS 1000 EAEQVQGSLV 1010 LSNENLGQSL 1020 HQEGFSIPLL 1030 WLQNCLIRAA 1040 DDREEDGCSQ 1050 AVPLVPLTEE 1060 NEEAMENEQF 1070 QQLLRKLGVR 1080 PPASGQETFW 1090 RIPAKLSPTQ 1100 LRRAAASLSQ 1110 PEEEQKLQPE 1120 LQPKVPGEQG 1130 SDEEHCKEHR 1140 AQALRALLLA 1150 HKKKAGLASP 1160 EEEDAVGKEP 1170 LKAAPKKRQL 1180 LDSDEEQEED 1190 EGRNRAPELG 1200 APGIQKKKRY QIEDDEDD

Gene Ontology

Classification GO ID Description
Cellular Component GO:0000785 chromatin
Cellular Component GO:0043596 nuclear replication fork
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:0031298 replication fork protection complex
Cellular Component GO:0035861 site of double-strand break
Molecular Function GO:0003677 DNA binding
Molecular Function GO:0008047 enzyme activator activity
Molecular Function GO:0042802 identical protein binding
Biological Process GO:0044770 cell cycle phase transition
Biological Process GO:0051301 cell division
Biological Process GO:1904976 cellular response to bleomycin
Biological Process GO:0072719 cellular response to cisplatin
Biological Process GO:0072711 cellular response to hydroxyurea
Biological Process GO:0007623 circadian rhythm
Biological Process GO:0009582 detection of abiotic stimulus
Biological Process GO:0006974 DNA damage response
Biological Process GO:0006281 DNA repair
Biological Process GO:0000076 DNA replication checkpoint signaling
Biological Process GO:0006351 DNA-templated transcription
Biological Process GO:0031573 mitotic intra-S DNA damage checkpoint signaling
Biological Process GO:0002009 morphogenesis of an epithelium
Biological Process GO:0045892 negative regulation of DNA-templated transcription
Biological Process GO:2000781 positive regulation of double-strand break repair
Biological Process GO:1905168 positive regulation of double-strand break repair via homologous recombination
Biological Process GO:0042752 regulation of circadian rhythm
Biological Process GO:0043111 replication fork arrest
Biological Process GO:0031297 replication fork processing

Reference

[1] Yang D, Yin J, Shan L, Yi X, Zhang W et al.. Identification of lysine-lactylated substrates in gastric cancer cells.. iScience 25(7):104630. 2022 Jul 15. PMID: 35800753.

[2] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.