Search Results

Overview

Uniprot IDQ96T88
Protein NameE3 ubiquitin-protein ligase UHRF1
Gene NameUHRF1
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
385 RESKKKAKMASATSS
399 SSQRDWGKGMACVGR
670 RRTSKKTKVEPYSLT

Function

E3 ubiquitin-protein ligase that acts as a key epigenetic regulator by bridging DNA methylation and chromatin modification (PubMed:10646863, PubMed:15009091, PubMed:19056828, PubMed:23022729, PubMed:24013172, PubMed:27595565, PubMed:30104358, PubMed:30392929, PubMed:30392931, PubMed:39607687). Plays a key role in DNA methylation inheritance by promoting recruitment of DNMT1 to hemimethylated DNA and ensure faithful propagation of the DNA methylation patterns through DNA replication (PubMed:23022729, PubMed:24013172, PubMed:27595565, PubMed:30104358, PubMed:30392929, PubMed:30392931, PubMed:39607687). Acts both as a histone reader and writer: specifically recognizes and binds (1) hemimethylated DNA at replication forks and (2) histone H3 trimethylated at 'Lys-9' and unmethylated at 'Arg-2' (H3K9me3 and H3R2me0, respectively), thereby activating its E3 ubiquitin-protein ligase activity (PubMed:15361834, PubMed:17673620, PubMed:17967883, PubMed:18772889, PubMed:21745816, PubMed:21777816, PubMed:22100450, PubMed:22837395, PubMed:23022729, PubMed:27595565, PubMed:30104358). UHRF1 then mediates histone H3 'Lys-18' monoubiquitination (H3K18ub), a docking site for DNMT1, leading to DNMT1 recruitment and replication-coupled DNA methylation maintenance (PubMed:27595565). Also mediates histone H3 'Lys-14' and 'Lys-23' ubiquitination (H3K14ub and H3K23ub) at lower level (PubMed:24013172, PubMed:27595565). Histone ubiquitin ligase activity also stimulates the methyltransferase activity of SUV39H1 and/or SUV39H2, promoting accumulation of H3K9me3 histone mark to reinformce heterochromatin state (PubMed:39631394). Enriched in pericentric heterochromatin where it recruits different chromatin modifiers required for this chromatin replication. Also localizes to euchromatic regions where it negatively regulates transcription possibly by impacting DNA methylation and histone modifications (PubMed:21777816). Plays a role in DNA repair by cooperating with UHRF2 to ensure recruitment of FANCD2 to interstrand cross-links (ICLs) leading to FANCD2 activation (PubMed:30335751). Also ubiquitinates non-histone proteins, such as histone H3, KIF11 and PML (PubMed:22945642, PubMed:37728657). Acts as a critical player of proper spindle architecture by catalyzing the 'Lys-63'-linked ubiquitination of KIF11, thereby controlling KIF11 localization on the spindle (PubMed:37728657)

Protein Sequence

10 MWIQVRTMDG 20 RQTHTVDSLS 30 RLTKVEELRR 40 KIQELFHVEP 50 GLQRLFYRGK 60 QMEDGHTLFD 70 YEVRLNDTIQ 80 LLVRQSLVLP 90 HSTKERDSEL 100 SDTDSGCCLG 110 QSESDKSSTH 120 GEAAAETDSR 130 PADEDMWDET 140 ELGLYKVNEY 150 VDARDTNMGA 160 WFEAQVVRVT 170 RKAPSRDEPC 180 SSTSRPALEE 190 DVIYHVKYDD 200 YPENGVVQMN 210 SRDVRARART 220 IIKWQDLEVG 230 QVVMLNYNPD 240 NPKERGFWYD 250 AEISRKRETR 260 TARELYANVV 270 LGDDSLNDCR 280 IIFVDEVFKI 290 ERPGEGSPMV 300 DNPMRRKSGP 310 SCKHCKDDVN 320 RLCRVCACHL 330 CGGRQDPDKQ 340 LMCDECDMAF 350 HIYCLDPPLS 360 SVPSEDEWYC 370 PECRNDASEV 380 VLAGERLRES 390 KKKAKMASAT 400 SSSQRDWGKG 410 MACVGRTKEC 420 TIVPSNHYGP 430 IPGIPVGTMW 440 RFRVQVSESG 450 VHRPHVAGIH 460 GRSNDGAYSL 470 VLAGGYEDDV 480 DHGNFFTYTG 490 SGGRDLSGNK 500 RTAEQSCDQK 510 LTNTNRALAL 520 NCFAPINDQE 530 GAEAKDWRSG 540 KPVRVVRNVK 550 GGKNSKYAPA 560 EGNRYDGIYK 570 VVKYWPEKGK 580 SGFLVWRYLL 590 RRDDDEPGPW 600 TKEGKDRIKK 610 LGLTMQYPEG 620 YLEALANRER 630 EKENSKREEE 640 EQQEGGFASP 650 RTGKGKWKRK 660 SAGGGPSRAG 670 SPRRTSKKTK 680 VEPYSLTAQQ 690 SSLIREDKSN 700 AKLWNEVLAS 710 LKDRPASGSP 720 FQLFLSKVEE 730 TFQCICCQEL 740 VFRPITTVCQ 750 HNVCKDCLDR 760 SFRAQVFSCP 770 ACRYDLGRSY 780 AMQVNQPLQT 790 VLNQLFPGYG NGR

Gene Ontology

Classification GO ID Description
Cellular Component GO:0000785 chromatin
Cellular Component GO:0000791 euchromatin
Cellular Component GO:0000792 heterochromatin
Cellular Component GO:0016363 nuclear matrix
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:0005657 replication fork
Cellular Component GO:0005819 spindle
Molecular Function GO:0000987 cis-regulatory region sequence-specific DNA binding
Molecular Function GO:0140612 DNA damage sensor activity
Molecular Function GO:0044729 hemi-methylated DNA-binding
Molecular Function GO:0042393 histone binding
Molecular Function GO:0141055 histone H3 ubiquitin ligase activity
Molecular Function GO:0140851 histone H3K14 ubiquitin ligase activity
Molecular Function GO:0140248 histone H3K18 ubiquitin ligase activity
Molecular Function GO:0140234 histone H3K23 ubiquitin ligase activity
Molecular Function GO:0062072 histone H3K9me2/3 reader activity
Molecular Function GO:0042802 identical protein binding
Molecular Function GO:0008327 methyl-CpG binding
Molecular Function GO:0003676 nucleic acid binding
Molecular Function GO:0061630 ubiquitin protein ligase activity
Molecular Function GO:0004842 ubiquitin-protein transferase activity
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:0006351 DNA-templated transcription
Biological Process GO:0000724 double-strand break repair via homologous recombination
Biological Process GO:0040029 epigenetic regulation of gene expression
Biological Process GO:0031507 heterochromatin formation
Biological Process GO:0035825 homologous recombination
Biological Process GO:0090307 mitotic spindle assembly
Biological Process GO:0044027 negative regulation of gene expression via chromosomal CpG island methylation
Biological Process GO:0000122 negative regulation of transcription by RNA polymerase II
Biological Process GO:0051247 positive regulation of protein metabolic process
Biological Process GO:0045944 positive regulation of transcription by RNA polymerase II
Biological Process GO:0051865 protein autoubiquitination
Biological Process GO:0071168 protein localization to chromatin
Biological Process GO:0016567 protein ubiquitination
Biological Process GO:0050678 regulation of epithelial cell proliferation
Biological Process GO:0006511 ubiquitin-dependent protein catabolic process

Reference

[1] 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.

[2] Bao Q, Wan N, He Z, Cao J, Yuan W et al.. Subcellular Proteomic Mapping of Lysine Lactylation.. J Am Soc Mass Spectrom 35(12):3221-3232. 2024 Dec 4. PMID: 39569522.