Search Results

Overview

Uniprot IDQ14527
Protein NameDNA-dependent ATPase/E3 ubiquitin-protein ligase HLTF
Gene NameHLTF
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
355 EKADGLSKDASRCSE
372 SISDIKEKSKFRMSE
374 SDIKEKSKFRMSELS
417 QKMKGKLKNVQSETK
424 KNVQSETKGRAKAGS
452 TSSVPTTKKKMLKKG
453 SSVPTTKKKMLKKGA
454 SVPTTKKKMLKKGAC
458 TKKKMLKKGACAVEG

Function

Functions as a DNA-dependent ATPase and E3 ubiquitin-protein ligase involved in chromatin regulation and DNA damage tolerance (DDT) (PubMed:18316726, PubMed:18719106, PubMed:26051180, PubMed:31960921, PubMed:39142279, PubMed:40680746). Catalyzes 'Lys-63'-linked polyubiquitination of monoubiquitinated PCNA at 'Lys-164' in response to genotoxic stress, promoting error-free postreplication repair via template switching (PubMed:18316726, PubMed:18719106). Acts as an epigenetic regulator by promoting recruitment of DNMT1, thereby ensuring DNA methylation inheritance: specifically binds histone H3 trimethylated at 'Lys-9' (H3K9me3) and mediates histone H3 'Lys-23' polyubiquitination (H3K23ub), a docking site for DNMT1, leading to DNMT1 recruitment and replication-coupled DNA methylation maintenance (PubMed:40680746). Catalyzes formation of H3K23ub in two steps: first mediates monoubiquitination together with UBE2E1 and UBE2D2, and then extends ubiquitin chains via 'Lys-63'-linked ubiquitination together with UBE2N and UBE2V2 (PubMed:40680746). Also acts as a chromatin redodeling factor, thereby regulating transcription (PubMed:10391891, PubMed:1994885, PubMed:9126292). Exhibits ATP-dependent double-stranded DNA (dsDNA) translocase activity but lacks classical helicase activity; mediates replication fork reversal by concertedly unwinding and annealing nascent and parental strands, thereby suppressing DNA synthesis and maintaining genomic stability (PubMed:1994885). Resolves G-quadruplex (G4) DNA structures in cooperation with MSH2, limiting replication stress and G4 accumulation across the cell cycle (PubMed:39142279). Contributes to nucleotide excision repair by evicting lesion-containing oligonucleotides using its HIRAN and ATPase domains (PubMed:26051180). Can displace single-stranded DNA from triplex structures through ATP-dependent dsDNA translocation (PubMed:26051180, PubMed:31960921). Also has protein clearing activity at the stalled replication fork, facilitating restart of DNA replication (PubMed:21795603)

Protein Sequence

10 MSWMFKRDPV 20 WKYLQTVQYG 30 VHGNFPRLSY 40 PTFFPRFEFQ 50 DVIPPDDFLT 60 SDEEVDSVLF 70 GSLRGHVVGL 80 RYYTGVVNNN 90 EMVALQRDPN 100 NPYDKNAIKV 110 NNVNGNQVGH 120 LKKELAGALA 130 YIMDNKLAQI 140 EGVVPFGANN 150 AFTMPLHMTF 160 WGKEENRKAV 170 SDQLKKHGFK 180 LGPAPKTLGF 190 NLESGWGSGR 200 AGPSYSMPVH 210 AAVQMTTEQL 220 KTEFDKLFED 230 LKEDDKTHEM 240 EPAEAIETPL 250 LPHQKQALAW 260 MVSRENSKEL 270 PPFWEQRNDL 280 YYNTITNFSE 290 KDRPENVHGG 300 ILADDMGLGK 310 TLTAIAVILT 320 NFHDGRPLPI 330 ERVKKNLLKK 340 EYNVNDDSMK 350 LGGNNTSEKA 360 DGLSKDASRC 370 SEQPSISDIK 380 EKSKFRMSEL 390 SSSRPKRRKT 400 AVQYIESSDS 410 EEIETSELPQ 420 KMKGKLKNVQ 430 SETKGRAKAG 440 SSKVIEDVAF 450 ACALTSSVPT 460 TKKKMLKKGA 470 CAVEGSKKTD 480 VEERPRTTLI 490 ICPLSVLSNW 500 IDQFGQHIKS 510 DVHLNFYVYY 520 GPDRIREPAL 530 LSKQDIVLTT 540 YNILTHDYGT 550 KGDSPLHSIR 560 WLRVILDEGH 570 AIRNPNAQQT 580 KAVLDLESER 590 RWVLTGTPIQ 600 NSLKDLWSLL 610 SFLKLKPFID 620 REWWHRTIQR 630 PVTMGDEGGL 640 RRLQSLIKNI 650 TLRRTKTSKI 660 KGKPVLELPE 670 RKVFIQHITL 680 SDEERKIYQS 690 VKNEGRATIG 700 RYFNEGTVLA 710 HYADVLGLLL 720 RLRQICCHTY 730 LLTNAVSSNG 740 PSGNDTPEEL 750 RKKLIRKMKL 760 ILSSGSDEEC 770 AICLDSLTVP 780 VITHCAHVFC 790 KPCICQVIQN 800 EQPHAKCPLC 810 RNDIHEDNLL 820 ECPPEELARD 830 SEKKSDMEWT 840 SSSKINALMH 850 ALTDLRKKNP 860 NIKSLVVSQF 870 TTFLSLIEIP 880 LKASGFVFTR 890 LDGSMAQKKR 900 VESIQCFQNT 910 EAGSPTIMLL 920 SLKAGGVGLN 930 LSAASRVFLM 940 DPAWNPAAED 950 QCFDRCHRLG 960 QKQEVIITKF 970 IVKDSVEENM 980 LKIQNKKREL 990 AAGAFGTKKP 1000 NADEMKQAKI NEIRTLIDL

Gene Ontology

Classification GO ID Description
Cellular Component GO:0000785 chromatin
Cellular Component GO:0016020 membrane
Cellular Component GO:0016363 nuclear matrix
Cellular Component GO:0043596 nuclear replication fork
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:0005886 plasma membrane
Molecular Function GO:0005524 ATP binding
Molecular Function GO:0016887 ATP hydrolysis activity
Molecular Function GO:0008094 ATP-dependent activity, acting on DNA
Molecular Function GO:0140658 ATP-dependent chromatin remodeler activity
Molecular Function GO:0015616 DNA translocase activity
Molecular Function GO:0160225 G-quadruplex unwinding activity
Molecular Function GO:0140234 histone H3K23 ubiquitin ligase activity
Molecular Function GO:0062072 histone H3K9me2/3 reader activity
Molecular Function GO:0003723 RNA binding
Molecular Function GO:0003697 single-stranded DNA binding
Molecular Function GO:0061630 ubiquitin protein ligase activity
Molecular Function GO:0031625 ubiquitin protein ligase binding
Molecular Function GO:0008270 zinc ion binding
Biological Process GO:0141119 chromosomal DNA methylation maintenance following DNA replication
Biological Process GO:0006974 DNA damage response
Biological Process GO:0006281 DNA repair
Biological Process GO:0042789 mRNA transcription by RNA polymerase II
Biological Process GO:0045944 positive regulation of transcription by RNA polymerase II
Biological Process GO:0070534 protein K63-linked ubiquitination
Biological Process GO:0071168 protein localization to chromatin
Biological Process GO:0000209 protein polyubiquitination
Biological Process GO:0016567 protein ubiquitination
Biological Process GO:0050767 regulation of neurogenesis
Biological Process GO:0071932 replication fork reversal

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] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[3] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.

[4] 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.