Affinage

USP47

Ubiquitin carboxyl-terminal hydrolase 47 · UniProt Q96K76

Length
1375 aa
Mass
157.3 kDa
Annotated
2026-04-28
48 papers in source corpus 33 papers cited in narrative 32 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

USP47 is a cysteine deubiquitylase of the USP family that stabilizes a broad range of substrates by removing ubiquitin chains to prevent their proteasomal degradation, thereby regulating DNA repair, Wnt signaling, MAPK signaling, inflammasome activation, innate immunity, neuronal development, and metabolic homeostasis. Structural studies reveal that its catalytic triad is misaligned in the free state and becomes activated upon ubiquitin binding, a mechanism shared with USP7; full-length USP47 exhibits higher catalytic activity than the isolated catalytic domain, with substrate selectivity conferred by divergent BL1–BL3 loops (PMID:37740002). USP47 stabilizes DNA polymerase β to maintain base excision repair (PMID:21362556), deubiquitylates both β-catenin and the corepressor TLE3/Groucho to promote Wnt pathway output (PMID:26169834, PMID:36749823), counteracts N-end-rule-mediated MAPK degradation (PMID:27552662), deubiquitylates NLRP3/ASC to enable inflammasome assembly (PMID:30206189), removes K63-linked ubiquitin from TRAF3/TRAF6 to attenuate type I interferon signaling (PMID:37001379), and stabilizes katanin-p60 to promote axonal growth (PMID:23904609). USP47 itself is regulated through interaction with the SCFβ-TrCP E3 ligase, which binds USP47 through an atypical degron motif and modulates its ubiquitination status, while ERAP1 can displace β-TrCP from USP47 to redirect Hedgehog signaling (PMID:19966869, PMID:31341163).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2009 High

    Identifying USP47 as a physical partner of SCFβ-TrCP revealed that this DUB is itself subject to E3-ligase-mediated regulation, establishing a regulatory axis rather than a simple enzyme–substrate relationship.

    Evidence Reciprocal co-immunoprecipitation with β-TrCP1/2 WD-repeat point mutants, siRNA knockdown and cell viability in human cancer cells

    PMID:19966869

    Open questions at the time
    • Whether β-TrCP ubiquitylates USP47 for degradation or modulates its activity was not resolved
    • No structural basis for the atypical binding motif
  2. 2011 High

    Demonstrating that USP47 is the principal DUB for cytoplasmic Pol β established a direct connection between deubiquitylation and base excision repair fidelity, the first well-defined physiological substrate pathway for USP47.

    Evidence siRNA knockdown, ubiquitylation assays, and BER functional assays in human cells

    PMID:21362556

    Open questions at the time
    • How USP47 selectively recognizes newly synthesized Pol β over mature nuclear Pol β was unknown
    • Whether other DUBs partially compensate in vivo
  3. 2013 High

    Identification of katanin-p60 as a USP47 substrate linked deubiquitylation to microtubule severing and axonal growth, broadening USP47's roles beyond DNA repair into neuronal biology.

    Evidence Co-IP, ubiquitination assays, siRNA knockdown, and axonal growth assays in rat hippocampal neurons

    PMID:23904609

    Open questions at the time
    • Whether USP47–katanin-p60 axis operates in CNS contexts beyond bFGF stimulation
    • In vivo neuronal phenotype of Usp47 knockout not tested
  4. 2014 High

    Showing that KIFC3 recruits USP47 to adherens junctions to protect E-cadherin from Hakai-mediated degradation established a spatial targeting mechanism for USP47 activity at cell–cell contacts.

    Evidence Co-IP, immunofluorescence localization, E-cadherin ubiquitination and cleavage assays in epithelial cells

    PMID:25253721

    Open questions at the time
    • Whether USP47 directly deubiquitylates E-cadherin or acts indirectly through Hakai was not fully resolved
    • In vivo junctional phenotype not examined
  5. 2015 High

    Demonstrating that USP47 deubiquitylates β-catenin to promote Wnt signaling, conserved from Drosophila to mammals, placed USP47 as a positive Wnt pathway regulator and revealed β-TrCP-mediated autoregulation of USP47 ubiquitination.

    Evidence RNAi screen, Wnt reporter assays, in vivo Drosophila wing phenotypes, ubiquitination assays

    PMID:26169834

    Open questions at the time
    • Whether USP47 acts at the destruction complex or downstream was not distinguished at this stage
  6. 2016 High

    Systematic epistasis screening in Drosophila revealed that USP47 counteracts the N-end rule pathway (UBC6/POE-UBR4/KCMF1) to maintain MAPK protein levels, establishing USP47 as a post-translational stabilizer of RAS–MAPK signaling output.

    Evidence RNAi genetic interaction screen, epistasis analysis, and MAPK stability assays in Drosophila

    PMID:27552662

    Open questions at the time
    • Mammalian validation of the N-end rule mechanism for MAPK was not provided
    • Identity of the specific MAPK ubiquitin chain type was not determined
  7. 2018 High

    Pharmacological and genetic evidence that USP47 (together with USP7) deubiquitylates NLRP3 and is required for ASC speck formation extended USP47's roles to innate immune inflammasome regulation.

    Evidence USP7/USP47 inhibitor, CRISPR knockdown in THP-1 macrophages, ASC oligomerization and IL-1β/IL-18 release assays

    PMID:30206189

    Open questions at the time
    • Individual contributions of USP7 versus USP47 were not fully separated
    • Direct deubiquitylation of ASC by USP47 was not reconstituted in vitro
  8. 2019 High

    Two studies expanded USP47's substrate repertoire to include SATB1 (stabilized for colon cancer transcription programs) and revealed that ERAP1 competes with β-TrCP for USP47 binding to modulate Hedgehog signaling, uncovering a protein-competition regulatory mechanism.

    Evidence Co-IP, ubiquitination assays, xenograft models (SATB1); CRISPR/siRNA, protein stability assays, tumor models (ERAP1–β-TrCP–USP47)

    PMID:30742943 PMID:31341163

    Open questions at the time
    • Structural basis for ERAP1 displacement of β-TrCP from USP47 remains unknown
    • Whether ERAP1 regulation of USP47 operates outside Hedgehog-driven tumors
  9. 2020 High

    Identification of RPL11 deubiquitylation by USP47 connected USP47 to the ribosomal stress–MDM2–p53 axis, demonstrating that USP47 prevents RPL11 nucleolar-to-nucleoplasmic translocation and thereby suppresses p53 activation under basal conditions.

    Evidence Catalytic-dead mutant analysis, ubiquitination assays, p53 pathway reporters, miR-101-3p transfection

    PMID:32370049 PMID:35205710

    Open questions at the time
    • Whether USP47 acts on other ribosomal stress sensors
    • In vivo validation of the RPL11–p53 axis via Usp47 knockout
  10. 2020 Medium

    Demonstrating that USP47 stabilizes IK (spliceosomal component) to maintain proper ATM pre-mRNA splicing linked USP47 for the first time to RNA processing and the DNA damage response via a splicing intermediate.

    Evidence Co-IP, ubiquitination assays, RT-PCR splicing analysis, siRNA knockdown

    PMID:32377397

    Open questions at the time
    • Single-lab finding; independent replication needed
    • Whether USP47 regulates splicing of transcripts beyond ATM
  11. 2021 High

    USP47 stabilization of YBX1 in CML cells, with Usp47 knockout significantly inhibiting CML driven by BCR-ABL and the T315I gatekeeper mutant in mice, established USP47 as a therapeutic vulnerability in drug-resistant leukemia.

    Evidence Usp47 knockout mice, BCR-ABL CML model, shRNA/siRNA, Lin⁻Sca1⁺c-Kit⁺ stem cell analysis

    PMID:33397955

    Open questions at the time
    • Whether USP47 inhibition is tolerated long-term in vivo
    • Whether YBX1 is the sole CML-relevant substrate
  12. 2023 High

    Crystal structures of free and ubiquitin-bound USP47 catalytic domain resolved the activation mechanism: the catalytic triad is misaligned until ubiquitin binding induces conformational rearrangement, explaining substrate-dependent activation analogous to USP7.

    Evidence X-ray crystallography (free and Ub-bound forms), in vitro DUB activity assays comparing full-length vs. catalytic domain

    PMID:37740002

    Open questions at the time
    • No structure of full-length USP47 with regulatory domains
    • Structural basis for substrate selectivity beyond BL loop differences not resolved
  13. 2023 High

    Reconstituted in vitro deubiquitylation of TLE3 by USP47, counteracting XIAP-mediated monoubiquitylation, definitively placed USP47 downstream of the β-catenin destruction complex in Wnt signaling and resolved the earlier ambiguity about its pathway position.

    Evidence In vitro deubiquitylation assay, genome-scale RNAi screen, Xenopus/Drosophila/human cell Wnt reporter validation

    PMID:36749823

    Open questions at the time
    • Whether β-catenin and TLE3 deubiquitylation are independent or coordinated events
    • Quantitative contribution of USP47 versus other Wnt-regulatory DUBs in vivo
  14. 2023 High

    Discovery that USP47 deubiquitylates YTHDF1 to attenuate m6A-dependent c-Myc translation in regulatory T cells revealed a non-degradative function—modifying reader-protein interactions—and linked USP47 to Treg metabolic fitness and immune homeostasis.

    Evidence Treg-specific conditional knockout mice, polyribosome profiling, ubiquitination assays, metabolic assays

    PMID:37788092

    Open questions at the time
    • Whether USP47 regulation of YTHDF1 extends to other m6A targets beyond c-Myc
    • Ubiquitin chain type on YTHDF1 not specified
  15. 2023 Medium

    Showing that USP47 removes K63-linked polyubiquitin from TRAF3 and TRAF6 to dampen type I interferon signaling identified USP47 as a negative regulator of antiviral innate immunity, extending its chain-type specificity beyond K48.

    Evidence K63-linkage-specific ubiquitination assays, dual-luciferase ISRE/IFN-β reporters, overexpression/knockdown in virus infection models

    PMID:37001379

    Open questions at the time
    • In vivo viral challenge in Usp47 knockout mice not performed
    • Direct in vitro cleavage of K63 chains not reconstituted

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis for how full-length USP47's non-catalytic domains regulate activity and substrate selection; the physiological hierarchy among its many reported substrates in different tissues; and whether selective USP47 inhibitors can achieve therapeutic windows in cancer and immune disease.
  • No full-length USP47 structure available
  • No systematic comparison of substrate affinities
  • No clinical-stage USP47 inhibitor with characterized selectivity

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 24
Localization
GO:0005829 cytosol 2 GO:0005886 plasma membrane 1
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-168256 Immune System 4 R-HSA-5357801 Programmed Cell Death 3 R-HSA-73894 DNA Repair 3 R-HSA-392499 Metabolism of proteins 2 R-HSA-1500931 Cell-Cell communication 1
Partners
BTRCCTNNB1KATNA1POLBRPL11TLE3YBX1YTHDF1

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 USP47 is the major deubiquitylating enzyme responsible for deubiquitylation of DNA polymerase β (Pol β) in the cytoplasm, stabilizing newly synthesized Pol β that is used as a source for nuclear Pol β involved in base excision repair (BER). Knockdown of USP47 increases ubiquitylated Pol β, decreases Pol β levels, and causes BER deficiency with accumulation of DNA strand breaks. siRNA knockdown, ubiquitylation assays, BER functional assays, cell viability assays Molecular cell High 21362556
2009 USP47 interacts with SCF(β-TrCP) E3 ubiquitin ligase; both β-TrCP1 and β-TrCP2 bind specifically to USP47, with point mutations in the β-TrCP WD-repeat region abolishing binding, indicating an E3-substrate-type interaction. Depletion of USP47 induces accumulation of Cdc25A, decreases cell survival, and augments cytotoxic effects of anticancer drugs. Co-immunoprecipitation, site-directed mutagenesis, siRNA knockdown, cell viability assays Oncogene High 19966869
2015 USP47 (and its Drosophila counterpart UBP64E) prevents β-catenin ubiquitination to promote Wnt signaling. USP47 inactivation by RNAi increases β-catenin ubiquitination, attenuates Wnt signaling, and represses cancer cell growth. β-TrCP promotes USP47 ubiquitination through interaction with an atypical motif in USP47, while USP47 also deubiquitinates itself. In Drosophila, UBP64E is required for Armadillo stabilization. RNAi library screen, ubiquitination assays, Wnt reporter assays, in vivo Drosophila wing studies Molecular and cellular biology High 26169834
2013 USP47 is a katanin-p60-specific deubiquitinating enzyme that stabilizes katanin-p60 by counteracting CHIP (an E3 ubiquitin ligase that promotes proteasomal degradation of katanin-p60). USP47 promotes axonal growth of rat hippocampal neurons; bFGF treatment increases USP47 and katanin-p60 levels and decreases ubiquitinated katanin-p60, promoting axonal growth. Co-immunoprecipitation, ubiquitination assays, siRNA knockdown, neuronal culture axonal growth assays The Journal of neuroscience High 23904609
2016 In Drosophila, USP47 acts post-translationally to counteract proteasome-mediated degradation of MAPK, thereby maintaining MAPK half-life and signaling output. RNAi genetic interaction screening identified UBC6 (E2) and POE/UBR4 (E3 N-recognin) as enzymes opposing USP47 activity; KCMF1 is another component of this degradation module. USP47 thus counteracts the N-end rule pathway to control MAPK levels. RNAi-based genetic interaction screen (Drosophila), epistasis analysis, protein stability assays PLoS biology High 27552662
2018 USP47 (together with USP7) regulates NLRP3 inflammasome activation in macrophages. Chemical inhibition of USP7/USP47 blocks inflammasome formation by preventing ASC oligomerisation and speck formation, independently of transcription. The ubiquitination status of NLRP3 itself is altered by inhibition of USP7 and USP47. CRISPR/Cas9 knockdown of both USP7 and USP47 in THP-1 cells reduces inflammasome activation and IL-1β/IL-18 release. Pharmacological inhibition, CRISPR/Cas9 knockdown, ASC oligomerization/speck assays, cytokine release assays EMBO reports High 30206189
2019 USP47 interacts with SATB1 and mediates its deubiquitination and stabilization. USP47 deficiency impairs SATB1 transcriptional activity and inhibits colon cancer cell proliferation, migration, and tumorigenesis. SMURF2 functions as an E3 ubiquitin ligase promoting SATB1 degradation, and SMURF2 is negatively regulated by USP47 (USP47 depletion sensitizes cells to 5-FU). Co-immunoprecipitation, ubiquitination assays, siRNA knockdown, mouse xenograft model Cancer letters High 30742943
2019 ERAP1 binds USP47, displaces USP47-associated βTrCP (the substrate-receptor subunit of SCFβTrCP), and promotes βTrCP degradation. This results in modulation of Gli transcription factors and enhancement of Hedgehog pathway activity. Genetic or pharmacological inhibition of ERAP1 suppresses Hh-dependent tumor growth in vitro and in vivo. Co-immunoprecipitation, protein stability assays, genetic inhibition (CRISPR/siRNA), in vivo tumor models Nature communications High 31341163
2014 KIFC3 (a minus end-directed kinesin motor) binds USP47 and recruits it to adherens junctions (AJs). USP47 at AJs prevents ubiquitination and Hakai E3-ligase-mediated degradation of E-cadherin. Depletion of KIFC3 or USP47 promotes cleavage of E-cadherin at a juxtamembrane region, producing a 90-kDa fragment and causing E-cadherin internalization; this process is inhibited by proteasome inhibitors. Co-immunoprecipitation, siRNA knockdown, immunofluorescence localization, proteasome inhibitor treatment, E-cadherin ubiquitination assays Molecular biology of the cell High 25253721
2021 USP47 stabilizes Y-box binding protein 1 (YBX1) to promote DNA damage repair in CML cells. USP47 knockdown represses CML cell proliferation in vitro and in vivo; Usp47 knockout significantly inhibits BCR-ABL and BCR-ABLT315I-induced CML in mice and reduces Lin-Sca1+c-Kit+ CML stem/progenitor cells. siRNA/shRNA knockdown, Usp47 knockout mice, in vitro proliferation assays, CML mouse model Nature communications High 33397955
2020 USP47 deubiquitinates RPL11 (ribosomal protein L11), preventing its interaction with MDM2 under normal conditions. USP47 inhibition or miR-101-3p-mediated suppression leads to RPL11 translocation from nucleolus to nucleoplasm, enabling RPL11-MDM2 binding that suppresses MDM2 and stabilizes p53, inhibiting cancer cell proliferation. The catalytically inactive form of USP47 cannot restore these effects. Co-immunoprecipitation, ubiquitination assays, siRNA knockdown, catalytic mutant analysis, p53 pathway reporter assays, miRNA transfection Cancers / Cancers (multiple papers) High 32370049 35205710
2020 USP47 directly interacts with IK (a spliceosomal component) and stabilizes it through deubiquitination, preventing its proteasomal degradation. IK is required for proper splicing of ATM pre-mRNA; IK depletion leads to retention of intron 1 in ATM pre-mRNA and loss of ATM protein, impairing DNA damage repair. SMU1 absence induces IK ubiquitination; USP47 counteracts this. Co-immunoprecipitation, ubiquitination assays, RT-PCR splicing assays, siRNA knockdown Cell death discovery Medium 32377397
2023 USP47 deubiquitylates the transcriptional corepressor TLE3/Groucho to counteract XIAP-mediated monoubiquitylation of TLE, promoting Wnt-β-catenin signaling. USP47 interacts with TLE3 and XIAP, and inhibits XIAP-mediated ubiquitylation of TLE3 in vitro in a dose-dependent manner. USP47 acts downstream of the β-catenin destruction complex and is required for Wnt signaling in Drosophila, Xenopus, and human cells. Genome-scale RNAi screen (Drosophila cells), in vitro deubiquitylation assay, Co-immunoprecipitation, Wnt reporter assays, Xenopus and Drosophila in vivo assays Science signaling High 36749823
2023 Crystal structures of the USP47 catalytic domain in free and ubiquitin-bound states reveal misaligned catalytic triads that become aligned upon ubiquitin binding (similar to USP7), enabling catalysis. Full-length USP47 shows higher deubiquitinase activity than the catalytic domain alone. BL1, BL2, and BL3 loops differ from USP7 and contribute to substrate selectivity. USP47 depletion inhibits cancer cell growth in a p53-dependent manner, enhanced by simultaneous USP7 knockdown. X-ray crystallography (free and ubiquitin-bound), in vitro DUB activity assays, siRNA knockdown, cancer cell growth assays Communications biology High 37740002
2023 USP47 prevents YTHDF1 ubiquitination to attenuate the association of YTHDF1 with translation initiation machinery, thereby decreasing m6A-based c-Myc translation efficiency in regulatory T cells. USP47 ablation triggers c-Myc protein accumulation and exacerbated hyperglycolysis in Tregs, compromising Treg homeostasis and function. Co-immunoprecipitation, ubiquitination assays, polyribosome/translation assays, Treg-specific conditional knockout mice, metabolic assays The Journal of clinical investigation High 37788092
2023 USP47 removes K63-linked polyubiquitin chains from TRAF3 and TRAF6, attenuating type I interferon signaling downstream of MAVS and upstream of TBK1. USP47 overexpression suppresses virus-induced ISRE and IFN-β activation and enhances viral replication; knockdown has opposite effects. Co-immunoprecipitation, K63-linkage-specific ubiquitination assays, dual-luciferase reporter assays, overexpression/knockdown in virus infection models International immunopharmacology Medium 37001379
2022 USP47 stabilizes BACH1 by direct binding and deubiquitination, promoting the Warburg effect and NSCLC development. USP47 deubiquitination of BACH1 leads to downstream transcriptional upregulation of Hk2 and Gapdh, enhancing glycolysis. Co-immunoprecipitation, ubiquitination assays, siRNA knockdown, in vivo xenograft, glycolysis assays American journal of cancer research Medium 35141006
2022 USP47 regulates mutant EZH2 protein stability; inhibition of USP47 promotes ubiquitination and degradation of mutant EZH2. Targeting USP47 leads to death of mutant EZH2-positive cells in vitro and in vivo. Selectivity profiling, genetic studies (siRNA/KO), animal models, ubiquitination assays Leukemia Medium 35034955
2021 USP47 binds TCEA3 (transcription elongation factor A3) and regulates its deubiquitination and intracellular stability. USP47 ectopic expression increases TCEA3 levels; TCEA3 regulates pro-apoptotic Bax levels, and the USP47-TCEA3 axis modulates doxorubicin-induced pyroptosis and apoptosis in colorectal cancer cells. Co-immunoprecipitation, ubiquitination assays, siRNA knockdown, apoptosis/pyroptosis assays Frontiers in pharmacology Medium 34630087
2024 USP47 stabilizes IRF1 through deubiquitination. IRF1 binds to the CXCL4 promoter to upregulate CXCL4, promoting NLRP3-mediated pyroptosis and impairing cardiac function in myocardial infarction. USP47 silencing increases IRF1 ubiquitination, decreases IRF1 and CXCL4, and reduces pyroptosis. Co-immunoprecipitation, ubiquitination assays, ChIP (IRF1-CXCL4 promoter binding), siRNA knockdown, MI mouse model International immunopharmacology Medium 38850785
2025 USP47 stabilizes c-Myc by preventing its proteasomal degradation through deubiquitination, promoting NSCLC cell proliferation. A selective USP47 inhibitor (K-552) destabilizes c-Myc and enhances the efficacy of Sotorasib (KRASG12C inhibitor) in vitro and in vivo. siRNA knockdown, ubiquitination assays, in vitro/in vivo proliferation assays, virtual screening-derived inhibitor Pharmacological research Medium 40180254
2025 USP47 binds and deubiquitinates GluR1 (AMPAR subunit), inhibiting its degradation and enhancing excitatory postsynaptic transmission and dendritic spine maturation. USP47 knockdown reduces seizure frequency and duration in epileptic mice. Co-immunoprecipitation, ubiquitination assays, electrophysiology, dendritic spine imaging, epilepsy mouse model with USP47 knockdown Neuroscience bulletin Medium 40716012
2025 USP47 binds, deubiquitinates, and stabilizes PRMT5 (protein arginine methyltransferase 5), which in turn upregulates O-GlcNAcase expression, reducing protein O-GlcNAcylation in cardiomyocytes and attenuating Ang II-induced cardiac hypertrophy. Co-immunoprecipitation, ubiquitination assays, adenovirus-mediated gain/loss-of-function, in vitro and in vivo cardiac hypertrophy models Journal of cardiovascular pharmacology Medium 39436323
2025 USP47 deubiquitinates PD-L1 to stabilize its protein expression in hepatocellular carcinoma cells. USP47 deficiency reduces PD-L1 protein without affecting its mRNA. USP47 inhibition combined with anti-PD-1 therapy enhances tumor suppression in HCC mouse models. Co-immunoprecipitation, ubiquitination assays, Western blot, siRNA knockdown, HCC mouse model International immunopharmacology Medium 40494207
2026 USP47 directly interacts with HDAC2, promotes its deubiquitination, and stabilizes its protein. HDAC2 acts as a transcriptional repressor of CYP1A1 by deacetylating H3K9/H3K27 at the CYP1A1 promoter, limiting ROS-driven autophagy and protecting against cigarette smoke-induced skeletal muscle atrophy. Co-immunoprecipitation, ubiquitination assays, ChIP-qPCR, RNA-seq, gain/loss-of-function, CS-induced mouse model Free radical biology & medicine Medium 41529803
2026 USP47 inhibits the ubiquitination and degradation of SIRT1, stabilizing its expression. SIRT1 then increases PPARα expression through deacetylation, promoting lipid metabolism and alleviating metabolic-associated fatty liver disease (MAFLD). Co-immunoprecipitation, ubiquitination assays, adenovirus-mediated overexpression/knockdown, HFD rat model, HepG2 cell model Biochimica et biophysica acta. Molecular basis of disease Medium 41930505
2020 USP47 is upregulated in MCF-10A cells undergoing TGFβ2-induced EMT (as identified by quantitative proteomics), and chemical inhibition of USP47 reduces expression of EMT markers and reverts morphological changes. USP47 acts in SNAIL stabilization during EMT. Quantitative proteomics (MRM), pharmacological inhibition (P5091), Western blot, morphological assays Journal of proteomics Low 32201364
2023 USP47 deubiquitinates NNT (nicotinamide nucleotide transhydrogenase) to protect it from ubiquitin-mediated degradation; loss of USP47 decreases NNT levels, leading to increased mitochondrial ROS and impaired energy production in irradiated skin cells. Usp47 knockout mice show aggravated oxidative skin damage. Usp47 knockout mouse models, proteomic analysis, ubiquitination assays, ROS/mitochondrial function assays Toxicology and applied pharmacology Medium 37924851
2026 NUP85 competitively binds USP47 to ASK1, deubiquitinates ASK1 at lysine residue 805, and regulates ASK1 activation, thereby promoting collagen deposition and endoplasmic reticulum stress in liver fibrosis. USP47 thus deubiquitinates ASK1 as part of the NUP85-USP47-ASK1 pathway. Co-immunoprecipitation, ubiquitination assays (site-specific K805), competitive binding assays, siRNA knockdown, liver fibrosis mouse model Advanced science Medium 41903125
2025 USP47 stabilizes NRP1 (neuropilin-1) by preventing its ubiquitination and degradation, activating the PI3K/Akt signaling pathway and promoting angiogenesis in gastric cancer. Co-immunoprecipitation, ubiquitination assays, siRNA knockdown, angiogenesis assays Biochimica et biophysica acta. Molecular cell research Low 40499689
2024 USP47 deubiquitinates and stabilizes SIRT1, which then enhances Wnt/β-catenin pathway activity by upregulating PPARα. USP47 knockdown suppresses Icariin-induced osteogenic differentiation of bone marrow mesenchymal stem cells. Co-immunoprecipitation, ubiquitination assays, siRNA knockdown, osteogenic differentiation assays Chemical biology & drug design Low 38373741
2018 USP47 promotes β-TrCP stability and phosphorylation of RelA (NF-κB subunit) in gastric cancer cells, contributing to cell viability and chemoresistance. Knockdown of USP47 decreases metabolic activity and induces apoptotic cell death. Immunoblots, MTT assay, Annexin V staining, siRNA knockdown Biomedicines Low 29786670

Source papers

Stage 0 corpus · 48 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 USP7 and USP47 deubiquitinases regulate NLRP3 inflammasome activation. EMBO reports 156 30206189
2012 Selective Dual Inhibitors of the Cancer-Related Deubiquitylating Proteases USP7 and USP47. ACS medicinal chemistry letters 146 24900381
2011 USP47 is a deubiquitylating enzyme that regulates base excision repair by controlling steady-state levels of DNA polymerase β. Molecular cell 103 21362556
2014 MicroRNA-204-5p inhibits gastric cancer cell proliferation by downregulating USP47 and RAB22A. Medical oncology (Northwood, London, England) 94 25429829
2015 Deubiquitinase USP47/UBP64E Regulates β-Catenin Ubiquitination and Degradation and Plays a Positive Role in Wnt Signaling. Molecular and cellular biology 77 26169834
2019 Reversible regulation of SATB1 ubiquitination by USP47 and SMURF2 mediates colon cancer cell proliferation and tumor progression. Cancer letters 73 30742943
2009 The ubiquitin-specific protease USP47 is a novel beta-TRCP interactor regulating cell survival. Oncogene 69 19966869
2021 Targeting USP47 overcomes tyrosine kinase inhibitor resistance and eradicates leukemia stem/progenitor cells in chronic myelogenous leukemia. Nature communications 59 33397955
2019 ERAP1 promotes Hedgehog-dependent tumorigenesis by controlling USP47-mediated degradation of βTrCP. Nature communications 49 31341163
2019 LINC00668 promotes tumorigenesis and progression through sponging miR-188-5p and regulating USP47 in colorectal cancer. European journal of pharmacology 46 31233752
2023 USP47 inhibits m6A-dependent c-Myc translation to maintain regulatory T cell metabolic and functional homeostasis. The Journal of clinical investigation 39 37788092
2013 USP47 and C terminus of Hsp70-interacting protein (CHIP) antagonistically regulate katanin-p60-mediated axonal growth. The Journal of neuroscience : the official journal of the Society for Neuroscience 39 23904609
2016 The Deubiquitinase USP47 Stabilizes MAPK by Counteracting the Function of the N-end Rule ligase POE/UBR4 in Drosophila. PLoS biology 36 27552662
2020 Spatial transcriptomics identifies spatially dysregulated expression of GRM3 and USP47 in amyotrophic lateral sclerosis. Neuropathology and applied neurobiology 35 31925813
2020 Proteomics analysis reveals the role of ubiquitin specific protease (USP47) in Epithelial to Mesenchymal Transition (EMT) induced by TGFβ2 in breast cells. Journal of proteomics 31 32201364
2021 USP47-Mediated Deubiquitination and Stabilization of TCEA3 Attenuates Pyroptosis and Apoptosis of Colorectal Cancer Cells Induced by Chemotherapeutic Doxorubicin. Frontiers in pharmacology 30 34630087
2014 Minus end-directed motor KIFC3 suppresses E-cadherin degradation by recruiting USP47 to adherens junctions. Molecular biology of the cell 28 25253721
2021 USP47 maintains the stemness of colorectal cancer cells and is inhibited by parthenolide. Biochemical and biophysical research communications 27 34030041
2019 MicroRNA-204-5p Inhibits Ovarian Cancer Cell Proliferation by Down-Regulating USP47. Cell transplantation 26 31526052
2022 LncRNA ZNF883-Mediated NLRP3 Inflammasome Activation and Epilepsy Development Involve USP47 Upregulation. Molecular neurobiology 25 35678979
2022 USP47 stabilizes BACH1 to promote the Warburg effect and non-small cell lung cancer development via stimulating Hk2 and Gapdh transcription. American journal of cancer research 22 35141006
2021 E2F7 Transcriptionally Inhibits MicroRNA-199b Expression to Promote USP47, Thereby Enhancing Colon Cancer Tumor Stem Cell Activity and Promoting the Occurrence of Colon Cancer. Frontiers in oncology 22 33489876
2021 Long non‑coding RNA KCNQ1OT1 promotes nasopharyngeal carcinoma cell cisplatin resistance via the miR‑454/USP47 axis. International journal of molecular medicine 22 33576460
2020 USP47 Promotes Tumorigenesis by Negative Regulation of p53 through Deubiquitinating Ribosomal Protein S2. Cancers 22 32370049
2020 Long non-coding RNA DSCAM-AS1 upregulates USP47 expression through sponging miR-101-3p to accelerate osteosarcoma progression. Biochemistry and cell biology = Biochimie et biologie cellulaire 22 32379981
2018 Deubiquitinylase USP47 Promotes RelA Phosphorylation and Survival in Gastric Cancer Cells. Biomedicines 21 29786670
2020 USP47 promotes apoptosis in rat myocardial cells after ischemia/reperfusion injury via NF-κB activation. Biotechnology and applied biochemistry 20 32761659
2022 Inhibition of the deubiquitinating enzyme USP47 as a novel targeted therapy for hematologic malignancies expressing mutant EZH2. Leukemia 19 35034955
2022 MicroRNA-101-3p Suppresses Cancer Cell Growth by Inhibiting the USP47-Induced Deubiquitination of RPL11. Cancers 19 35205710
2020 Gga-miR-30d regulates infectious bronchitis virus infection by targeting USP47 in HD11 cells. Microbial pathogenesis 17 31982568
2020 Deubiquitinase USP47-stabilized splicing factor IK regulates the splicing of ATM pre-mRNA. Cell death discovery 16 32377397
2023 USP47 deubiquitylates Groucho/TLE to promote Wnt-β-catenin signaling. Science signaling 13 36749823
2024 Role of deubiquitinase USP47 in cardiac function alleviation and anti-inflammatory immunity after myocardial infarction by regulating NLRP3 inflammasome-mediated pyroptotic signal pathways. International immunopharmacology 11 38850785
2024 Icariin promotes osteogenic differentiation of human bone marrow mesenchymal stem cells by regulating USP47/SIRT1/Wnt/β-catenin. Chemical biology & drug design 9 38373741
2023 Structural and functional characterization of USP47 reveals a hot spot for inhibitor design. Communications biology 8 37740002
2023 Deubiquitinase USP47 attenuates virus-induced type I interferon signaling. International immunopharmacology 7 37001379
2023 Upregulation of ubiquitin carboxy‑terminal hydrolase 47 (USP47) in papillary thyroid carcinoma ex vivo and reduction of tumor cell malignant behaviors after USP47 knockdown by stabilizing SATB1 expression in vitro. Oncology letters 7 37564825
2025 Targeting USP47 enhances the efficacy of KRAS inhibitor in KRASG12C mutated non-small cell lung cancer by controlling deubiquitination of c-Myc. Pharmacological research 5 40180254
2025 Deubiquitinase USP47 Ameliorates Cardiac Hypertrophy Through Reducing Protein O-GlcNAcylation. Journal of cardiovascular pharmacology 4 39436323
2025 USP47 Regulates Excitatory Synaptic Plasticity and Modulates Seizures in Murine Models by Blocking Ubiquitinated AMPAR Degradation. Neuroscience bulletin 3 40716012
2024 USP47 deficiency in mice modulates tumor infiltrating immune cells and enhances antitumor immune responses in prostate cancer. Cancer immunology, immunotherapy : CII 3 38832955
2023 Ubiquitin-specific peptidase 47 (USP47) regulates cutaneous oxidative injury through nicotinamide nucleotide transhydrogenase (NNT). Toxicology and applied pharmacology 3 37924851
2025 Targeting USP47 enhances immunotherapy in hepatocellular carcinoma by destabilizing PD-L1. International immunopharmacology 2 40494207
2024 [Retracted] Long non‑coding RNA KCNQ1OT1 promotes nasopharyngeal carcinoma cell cisplatin resistance via the miR‑454/USP47 axis. International journal of molecular medicine 1 38334226
2026 USP47 stabilizes HDAC2 to ameliorate cigarette smoke-induced skeletal muscle atrophy by suppressing CYP1A1/ROS-mediated autophagy. Free radical biology & medicine 0 41529803
2026 NUP85 Mediates Endoplasmic Reticulum Stress through the USP47/ASK1 Signaling Pathway to Regulate the Progression of Liver Fibrosis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 0 41903125
2026 USP47 alleviates metabolic-associated fatty liver disease by activating the PPARα signaling pathway through the stabilization of SIRT1. Biochimica et biophysica acta. Molecular basis of disease 0 41930505
2025 USP47 enhances NRP1-mediated angiogenesis to promote gastric cancer progression. Biochimica et biophysica acta. Molecular cell research 0 40499689