Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBNJUF2)

DOT Name E3 ubiquitin-protein ligase UHRF1
Synonyms
EC 2.3.2.27; Inverted CCAAT box-binding protein of 90 kDa; Nuclear protein 95; Nuclear zinc finger protein Np95; HuNp95; hNp95; RING finger protein 106; RING-type E3 ubiquitin transferase UHRF1; Transcription factor ICBP90; Ubiquitin-like PHD and RING finger domain-containing protein 1; hUHRF1; Ubiquitin-like-containing PHD and RING finger domains protein 1
Gene Name UHRF1
UniProt ID
UHRF1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2FAZ ; 2L3R ; 2LGG ; 2LGK ; 2LGL ; 2PB7 ; 3ASK ; 3ASL ; 3BI7 ; 3CLZ ; 3DB3 ; 3DB4 ; 3DWH ; 3FL2 ; 3SHB ; 3SOU ; 3SOW ; 3SOX ; 3T6R ; 3ZVY ; 3ZVZ ; 4GY5 ; 4QQD ; 5C6D ; 5IAY ; 5XPI ; 5YY9 ; 5YYA ; 6B9M ; 6IIW ; 6VCS ; 6VED ; 6VYJ ; 6W92 ; 7FB7
EC Number
2.3.2.27
Pfam ID
PF00628 ; PF02182 ; PF12148 ; PF00240
Sequence
MWIQVRTMDGRQTHTVDSLSRLTKVEELRRKIQELFHVEPGLQRLFYRGKQMEDGHTLFD
YEVRLNDTIQLLVRQSLVLPHSTKERDSELSDTDSGCCLGQSESDKSSTHGEAAAETDSR
PADEDMWDETELGLYKVNEYVDARDTNMGAWFEAQVVRVTRKAPSRDEPCSSTSRPALEE
DVIYHVKYDDYPENGVVQMNSRDVRARARTIIKWQDLEVGQVVMLNYNPDNPKERGFWYD
AEISRKRETRTARELYANVVLGDDSLNDCRIIFVDEVFKIERPGEGSPMVDNPMRRKSGP
SCKHCKDDVNRLCRVCACHLCGGRQDPDKQLMCDECDMAFHIYCLDPPLSSVPSEDEWYC
PECRNDASEVVLAGERLRESKKKAKMASATSSSQRDWGKGMACVGRTKECTIVPSNHYGP
IPGIPVGTMWRFRVQVSESGVHRPHVAGIHGRSNDGAYSLVLAGGYEDDVDHGNFFTYTG
SGGRDLSGNKRTAEQSCDQKLTNTNRALALNCFAPINDQEGAEAKDWRSGKPVRVVRNVK
GGKNSKYAPAEGNRYDGIYKVVKYWPEKGKSGFLVWRYLLRRDDDEPGPWTKEGKDRIKK
LGLTMQYPEGYLEALANREREKENSKREEEEQQEGGFASPRTGKGKWKRKSAGGGPSRAG
SPRRTSKKTKVEPYSLTAQQSSLIREDKSNAKLWNEVLASLKDRPASGSPFQLFLSKVEE
TFQCICCQELVFRPITTVCQHNVCKDCLDRSFRAQVFSCPACRYDLGRSYAMQVNQPLQT
VLNQLFPGYGNGR
Function
Multidomain protein that acts as a key epigenetic regulator by bridging DNA methylation and chromatin modification. Specifically recognizes and binds hemimethylated DNA at replication forks via its YDG domain and recruits DNMT1 methyltransferase to ensure faithful propagation of the DNA methylation patterns through DNA replication. In addition to its role in maintenance of DNA methylation, also plays a key role in chromatin modification: through its tudor-like regions and PHD-type zinc fingers, specifically recognizes and binds histone H3 trimethylated at 'Lys-9' (H3K9me3) and unmethylated at 'Arg-2' (H3R2me0), respectively, and recruits chromatin proteins. 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. Has E3 ubiquitin-protein ligase activity by mediating the ubiquitination of target proteins such as histone H3 and PML. It is still unclear how E3 ubiquitin-protein ligase activity is related to its role in chromatin in vivo. Plays a role in DNA repair by cooperating with UHRF2 to ensure recruitment of FANCD2 to interstrand cross-links (ICLs) leading to FANCD2 activation. 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.
Tissue Specificity Expressed in thymus, bone marrow, testis, lung and heart. Overexpressed in breast cancer.
Reactome Pathway
Chromatin modifications during the maternal to zygotic transition (MZT) (R-HSA-9821002 )
DNA methylation (R-HSA-5334118 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of E3 ubiquitin-protein ligase UHRF1. [1]
TAK-243 DM4GKV2 Phase 1 TAK-243 increases the sumoylation of E3 ubiquitin-protein ligase UHRF1. [27]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 increases the phosphorylation of E3 ubiquitin-protein ligase UHRF1. [29]
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35 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of E3 ubiquitin-protein ligase UHRF1. [2]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of E3 ubiquitin-protein ligase UHRF1. [3]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of E3 ubiquitin-protein ligase UHRF1. [4]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of E3 ubiquitin-protein ligase UHRF1. [5]
Estradiol DMUNTE3 Approved Estradiol increases the expression of E3 ubiquitin-protein ligase UHRF1. [6]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of E3 ubiquitin-protein ligase UHRF1. [7]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of E3 ubiquitin-protein ligase UHRF1. [8]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of E3 ubiquitin-protein ligase UHRF1. [9]
Testosterone DM7HUNW Approved Testosterone decreases the expression of E3 ubiquitin-protein ligase UHRF1. [9]
Triclosan DMZUR4N Approved Triclosan decreases the expression of E3 ubiquitin-protein ligase UHRF1. [10]
Marinol DM70IK5 Approved Marinol affects the expression of E3 ubiquitin-protein ligase UHRF1. [11]
Zoledronate DMIXC7G Approved Zoledronate decreases the expression of E3 ubiquitin-protein ligase UHRF1. [12]
Menadione DMSJDTY Approved Menadione affects the expression of E3 ubiquitin-protein ligase UHRF1. [13]
Niclosamide DMJAGXQ Approved Niclosamide decreases the expression of E3 ubiquitin-protein ligase UHRF1. [14]
Troglitazone DM3VFPD Approved Troglitazone decreases the expression of E3 ubiquitin-protein ligase UHRF1. [15]
Hydroquinone DM6AVR4 Approved Hydroquinone decreases the expression of E3 ubiquitin-protein ligase UHRF1. [16]
Sodium lauryl sulfate DMLJ634 Approved Sodium lauryl sulfate increases the expression of E3 ubiquitin-protein ligase UHRF1. [17]
Dasatinib DMJV2EK Approved Dasatinib decreases the expression of E3 ubiquitin-protein ligase UHRF1. [18]
Palbociclib DMD7L94 Approved Palbociclib decreases the expression of E3 ubiquitin-protein ligase UHRF1. [19]
Propofol DMB4OLE Approved Propofol increases the expression of E3 ubiquitin-protein ligase UHRF1. [20]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of E3 ubiquitin-protein ligase UHRF1. [21]
Resveratrol DM3RWXL Phase 3 Resveratrol decreases the expression of E3 ubiquitin-protein ligase UHRF1. [22]
Genistein DM0JETC Phase 2/3 Genistein increases the expression of E3 ubiquitin-protein ligase UHRF1. [6]
GSK2110183 DMZHB37 Phase 2 GSK2110183 decreases the expression of E3 ubiquitin-protein ligase UHRF1. [23]
phorbol 12-myristate 13-acetate DMJWD62 Phase 2 phorbol 12-myristate 13-acetate decreases the expression of E3 ubiquitin-protein ligase UHRF1. [24]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the mutagenesis of E3 ubiquitin-protein ligase UHRF1. [25]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of E3 ubiquitin-protein ligase UHRF1. [26]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of E3 ubiquitin-protein ligase UHRF1. [28]
THAPSIGARGIN DMDMQIE Preclinical THAPSIGARGIN decreases the expression of E3 ubiquitin-protein ligase UHRF1. [30]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of E3 ubiquitin-protein ligase UHRF1. [31]
Trichostatin A DM9C8NX Investigative Trichostatin A affects the expression of E3 ubiquitin-protein ligase UHRF1. [32]
Coumestrol DM40TBU Investigative Coumestrol increases the expression of E3 ubiquitin-protein ligase UHRF1. [33]
Deguelin DMXT7WG Investigative Deguelin decreases the expression of E3 ubiquitin-protein ligase UHRF1. [34]
AM251 DMTAWHL Investigative AM251 decreases the expression of E3 ubiquitin-protein ligase UHRF1. [35]
Plumbagin DM9BS50 Investigative Plumbagin decreases the expression of E3 ubiquitin-protein ligase UHRF1. [36]
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⏷ Show the Full List of 35 Drug(s)

References

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20 Propofol suppresses proliferation, migration, invasion, and tumor growth of liver cancer cells via suppressing cancer susceptibility candidate 9/phosphatase and tensin homolog/AKT serine/threonine kinase/mechanistic target of rapamycin kinase axis. Hum Exp Toxicol. 2022 Jan-Dec;41:9603271211065972. doi: 10.1177/09603271211065972.
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36 Plumbagin downregulates UHRF1, p-Akt, MMP-2 and suppresses survival, growth and migration of cervical cancer CaSki cells. Toxicol In Vitro. 2023 Feb;86:105512. doi: 10.1016/j.tiv.2022.105512. Epub 2022 Nov 4.