HLTF
entrez
6596
canonical
uniprot
Q14527
canonical
ensembl
ENSG00000071794
resolver
ensp
ENSP00000308944
resolver
ensp
ENSP00000376644
resolver
ensp
ENSP00000420429
resolver
ensp
ENSP00000420745
resolver
enst
ENST00000465259
resolver
genesymbol
HLTF
resolver
genesymbol_syn
HIP116A
resolver
genesymbol_syn
RNF80
resolver
genesymbol_syn
SMARCA3
resolver
genesymbol_syn
SNF2L3
resolver
genesymbol_syn
ZBU1
resolver
hgnc
HGNC:11099
resolver
uniprot
A0A0C4DGA6
resolver
uniprot
A8K5B6
resolver
uniprot
D3DNH3
resolver
uniprot
Q05BZ6
resolver
uniprot
Q14536
resolver
uniprot
Q16051
resolver
uniprot
Q7KYJ6
resolver
uniprot
Q86YA5
resolver
uniprot
Q92652
resolver
uniprot
Q96KM9
resolver
uniprot_entry
A0A0C4DGA6_HUMAN
resolver
uniprot_entry
A8K5B6_HUMAN
resolver
uniprot_entry
HLTF_HUMAN
resolver
uniprot_entry
Q05BZ6_HUMAN
resolver
uniprot_sec
D3DNH3
resolver
uniprot_sec
Q14536
resolver
uniprot_sec
Q16051
resolver
uniprot_sec
Q7KYJ6
resolver
uniprot_sec
Q86YA5
resolver
uniprot_sec
Q92652
resolver
uniprot_sec
Q96KM9
resolver
amino_acid_sequence
MSWMFKRDPVWKYLQTVQYGVHGNFPRLSYPTFFPRFEFQDVIPPDDFLTSDEEVDSVLFGSLRGHVVGLRYYTGVVNNNEMVALQRDPNNPYDKNAIKVNNVNGNQVGHLKKELAGALAYIMDNKLAQIEGVVPFGANNAFTMPLHMTFWGKEENRKAVSDQLKKHGFKLGPAPKTLGFNLESGWGSGRAGPSYSMPVHAAVQMTTEQLKTEFDKLFEDLKEDDKTHEMEPAEAIETPLLPHQKQALAWMVSRENSKELPPFWEQRNDLYYNTITNFSEKDRPENVHGGILADDMGLGKTLTAIAVILTNFHDGRPLPIERVKKNLLKKEYNVNDDSMKLGGNNTSEKADGLSKDASRCSEQPSISDIKEKSKFRMSELSSSRPKRRKTAVQYIESSDSEEIETSELPQKMKGKLKNVQSETKGRAKAGSSKVIEDVAFACALTSSVPTTKKKMLKKGACAVEGSKKTDVEERPRTTLIICPLSVLSNWIDQFGQHIKSDVHLNFYVYYGPDRIREPALLSKQDIVLTTYNILTHDYGTKGDSPLHSIRWLRVILDEGHAIRNPNAQQTKAVLDLESERRWVLTGTPIQNSLKDLWSLLSFLKLKPFIDREWWHRTIQRPVTMGDEGGLRRLQSLIKNITLRRTKTSKIKGKPVLELPERKVFIQHITLSDEERKIYQSVKNEGRATIGRYFNEGTVLAHYADVLGLLLRLRQICCHTYLLTNAVSSNGPSGNDTPEELRKKLIRKMKLILSSGSDEECAICLDSLTVPVITHCAHVFCKPCICQVIQNEQPHAKCPLCRNDIHEDNLLECPPEELARDSEKKSDMEWTSSSKINALMHALTDLRKKNPNIKSLVVSQFTTFLSLIEIPLKASGFVFTRLDGSMAQKKRVESIQCFQNTEAGSPTIMLLSLKAGGVGLNLSAASRVFLMDPAWNPAAEDQCFDRCHRLGQKQEVIITKFIVKDSVEENMLKIQNKKRELAAGAFGTKKPNADEMKQAKINEIRTLIDL
uniprot
proteins
ec_number
2.3.2.27
uniprot
proteins
ec_number
3.6.4.-
uniprot
proteins
function
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). {ECO:0000269|PubMed:10391891, ECO:0000269|PubMed:18316726, ECO:0000269|PubMed:18719106, ECO:0000269|PubMed:1994885, ECO:0000269|PubMed:21795603, ECO:0000269|PubMed:26051180, ECO:0000269|PubMed:31960921, ECO:0000269|PubMed:39142279, ECO:0000269|PubMed:40680746, ECO:0000269|PubMed:9126292}.
uniprot
proteins
mass_dalton
113929
uniprot
proteins
mutagenesis
MUTAGEN 71; /note="R->E: No effect on suppression of G4 accumulation. Loss of ssDNA-binding. No effect on ATPase activity. Decreases DNA fork regression activity."; /evidence="ECO:0000269|PubMed:26051180, ECO:0000269|PubMed:39142279"; MUTAGEN 72; /note="Y->A: Decreases ssDNA-binding, no effect on ATPase activity and decreases DNA fork regression activity.; when associated with A-93."; /evidence="ECO:0000269|PubMed:26051180"; MUTAGEN 91; /note="N->A: Strongly decreases ssDNA-binding."; /evidence="ECO:0000269|PubMed:26051180"; MUTAGEN 93; /note="Y->A: Decreases ssDNA-binding, no effect on ATPase activity and decreases DNA fork regression activity; when associated with A-72."; /evidence="ECO:0000269|PubMed:26051180"; MUTAGEN 94; /note="D->A: Strongly decreases ssDNA-binding. No effect on ATPase activity. Decreases DNA fork regression activity."; /evidence="ECO:0000269|PubMed:26051180"; MUTAGEN 110; /note="H->A: Strongly decreases ssDNA-binding. No effect on ATPase activity. Decreases DNA fork regression activity."; /evidence="ECO:0000269|PubMed:26051180"; MUTAGEN 113; /note="K->E: Strongly decreases ssDNA-binding."; /evidence="ECO:0000269|PubMed:26051180"; MUTAGEN 142; /note="F->A: Loss of dsDNA-binding. Decreases ssDNA-binding."; /evidence="ECO:0000269|PubMed:26051180, ECO:0000269|PubMed:31960921"; MUTAGEN 557..558; /note="DE->AA: Loss of ATPase activity. Loss of DNA fork regression activity. Impairs replication fork restart after DNA damage. Abolished ability to mediate histone H3 ubiquitination."; /evidence="ECO:0000269|PubMed:1994885, ECO:0000269|PubMed:21795603, ECO:0000269|PubMed:26051180, ECO:0000269|PubMed:40680746"; MUTAGEN 760; /note="C->S: Abolished E3 ubiquitin-protein ligase activity. Impairs replication fork restart after DNA damage. No effect on suppression of G4 accumulation. Abolished ability to mediate histone H3 ubiquitination."; /evidence="ECO:0000269|PubMed:1994885, ECO:0000269|PubMed:39142279, ECO:0000269|PubMed:40680746"; MUTAGEN 890; /note="R->Q: No effect on chromatin-binding. Loss of suppression of G4 accumulation."; /evidence="ECO:0000269|PubMed:39142279
uniprot
proteins
pathway_participation
PATHWAY: Protein modification; protein ubiquitination. {ECO:0000269|PubMed:18316726, ECO:0000269|PubMed:18719106, ECO:0000269|PubMed:40680746}.
uniprot
proteins
protein_family
RAD16 subfamily
uniprot
proteins
protein_family
SNF2/RAD54 helicase family
uniprot
proteins
pubmed
10391891
uniprot
proteins
pubmed
11904375
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
18316726
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
18719106
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
1994885
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21457752
uniprot
proteins
pubmed
21795603
uniprot
proteins
pubmed
24129315
uniprot
proteins
pubmed
26051180
uniprot
proteins
pubmed
28112733
uniprot
proteins
pubmed
31960921
uniprot
proteins
pubmed
39142279
uniprot
proteins
pubmed
40680746
uniprot
proteins
pubmed
7876228
uniprot
proteins
pubmed
8342330
uniprot
proteins
pubmed
8672239
uniprot
proteins
pubmed
9126292
uniprot
proteins
sequence_length
1009
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:8672239}. Chromosome {ECO:0000269|PubMed:39142279, ECO:0000269|PubMed:40680746}.
uniprot
proteins