Affinage

USP6

Ubiquitin carboxyl-terminal hydrolase 6 · UniProt P35125

Length
1406 aa
Mass
158.7 kDa
Annotated
2026-06-11
100 papers in source corpus 15 papers cited in narrative 16 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

USP6 (TRE17) is a deubiquitinating enzyme whose catalytic USP domain drives both oncogenic and physiological programs by stabilizing diverse ubiquitylated substrates (PMID:8247125, PMID:27162353). Through its DUB activity USP6 deubiquitinates and stabilizes Frizzled receptors to amplify Wnt/β-catenin signaling (PMID:27162353), Jak1 to activate STAT3 (PMID:27440725), and c-Jun to drive AP-1–dependent transcription and cell invasion (PMID:29061731), and it counteracts MARCH E3 ligase–mediated ubiquitylation of clathrin-independent endocytic cargo such as MHC class I to control their surface abundance (PMID:25179595). The same catalytic activity underlies USP6 tumorigenicity: USP6 overexpression activates the classical NF-κB pathway via an IKK-dependent, IκB-degradation-independent route involving p65 Ser536 phosphorylation, inducing MMP-9/MMP-10 through RhoA/ROCK, and blocks osteoblast maturation by suppressing BMP-4 while inducing the antagonist Gremlin-1 (PMID:20418905, PMID:20864534, PMID:22081069). Distinct from its DUB function, the N-terminal TBC domain binds GDP-bound Arf6 and promotes Arf6 GTP loading at the plasma membrane rather than acting as a GAP, linking USP6 to actin remodeling, cell migration, and cytokinesis under control of Cdc42/Rac1 and mitogenic signals (PMID:12612085, PMID:15509780, PMID:22188517). In neurons, USP6 deubiquitinates the NMDAR subunit GluN1 to enhance receptor stability, surface delivery, and synaptic plasticity (PMID:31841517). USP6 itself is regulated by Ca2+/calmodulin binding to its TBC domain, which modulates its mono- and polyubiquitination state (PMID:16127172).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1993 Medium

    Established that the Tre-2/USP6 oncogene is a deubiquitinating enzyme, assigning a molecular activity to a previously enigmatic transforming gene.

    Evidence Sequence homology to and functional characterization of the yeast DUB Doa4

    PMID:8247125

    Open questions at the time
    • DUB activity inferred by homology rather than direct enzymatic assay on USP6
    • No substrates identified at this stage
  2. 2003 High

    Linked USP6 to small-GTPase signaling and cytoskeletal dynamics by showing GTPase-dependent regulation of its localization, addressing how USP6 connects to membrane/actin pathways.

    Evidence Co-IP with active Cdc42/Rac1, mitogen-induced relocalization, actin depolymerization, and truncation mutagenesis

    PMID:12612085

    Open questions at the time
    • Did not define the catalytic relationship between localization and DUB activity
    • Direct GTPase substrate or effector role unresolved
  3. 2004 High

    Resolved the function of the TBC domain by showing it binds GDP-Arf6 and promotes Arf6 activation rather than acting as a GAP, redefining TBC-domain function for this protein.

    Evidence GDP/GTP-fixed Arf6 pulldowns, domain mapping, in vivo GTP-loading assay, and siRNA knockdown

    PMID:15509780

    Open questions at the time
    • Mechanism by which TBC facilitates GEF access not structurally defined
    • Did not connect Arf6 activation to specific downstream tumor phenotypes
  4. 2005 Medium

    Demonstrated that the TBC domain lacks canonical Rab-GAP activity, with both the TBC domain and an adjacent C-terminal region responsible, reinforcing the non-GAP nature of the oncoprotein.

    Evidence Yeast complementation of msb3Δ msb4Δ with Tre2/RN-tre chimeras

    PMID:16099424

    Open questions at the time
    • Negative result from heterologous yeast assay
    • Structural basis of GAP inactivity not determined
  5. 2005 High

    Identified Ca2+/calmodulin as a direct regulator of USP6 that controls its own ubiquitination state, establishing an autoregulatory input.

    Evidence Ca2+-dependent CaM Co-IP and in vitro binding, CaM-site point mutants, W7 and A23187 treatment, and ubiquitination assays

    PMID:16127172

    Open questions at the time
    • E3 ligase responsible for USP6 ubiquitination not identified
    • Functional consequence of CaM regulation on substrate DUB activity not tested
  6. 2010 High

    Tied USP6 tumorigenicity to NF-κB-driven MMP induction via RhoA/ROCK, showing the USP catalytic domain (not Arf6 binding) is required for transformation.

    Evidence Stable overexpression, MMP/NF-κB reporter assays, ROCK inhibitor, USP active-site mutant, and xenograft model

    PMID:20418905

    Open questions at the time
    • Direct DUB substrate linking USP6 to NF-κB/RhoA not identified here
    • How RhoA is engaged downstream of USP6 unresolved
  7. 2010 High

    Explained how USP6 blocks bone-cyst-relevant osteoblast differentiation through an autocrine BMP-axis defect, connecting USP6 to aneurysmal bone cyst pathology.

    Evidence Osteoblast differentiation assays, transcriptome analysis, BMP-4 rescue, and USP active-site mutant

    PMID:20864534

    Open questions at the time
    • DUB substrate driving BMP-4/Gremlin-1 dysregulation not identified
    • Autocrine factor mediating the effect not fully defined
  8. 2011 High

    Defined the atypical mechanism of NF-κB activation, showing USP6 binds and augments IKK activity and stimulates p65 Ser536 phosphorylation without IκB degradation.

    Evidence Co-IP, IKK kinase assay, dominant-negative IKK subunits, USP mutant, p65-S536 western, and xenograft with NF-κB inhibitor

    PMID:22081069

    Open questions at the time
    • The ubiquitylated substrate within the IKK complex that USP6 acts on is unknown
    • How IKK is activated independent of IκB degradation not fully mechanistically resolved
  9. 2011 Medium

    Placed USP6 in control of migration and cytokinesis through an Arf6/ACAP1 axis, extending its non-catalytic membrane-trafficking role to cell division.

    Evidence Overexpression/knockdown migration and cytokinesis assays with Arf6 and ACAP1 epistasis

    PMID:22188517

    Open questions at the time
    • Single-lab study without orthogonal mechanistic dissection
    • Whether DUB activity contributes to this phenotype not established
  10. 2014 High

    Revealed a trafficking function whereby USP6 deubiquitylates clathrin-independent endocytic cargo to oppose MARCH-mediated lysosomal targeting, controlling surface receptor abundance.

    Evidence MARCH8 co-expression, ubiquitination assays, surface MHC-I flow cytometry, USP active-site mutant, and lysosomal degradation assays

    PMID:25179595

    Open questions at the time
    • Full repertoire of CIE cargo substrates not defined
    • Relevance to USP6-driven tumors not addressed
  11. 2016 High

    Identified Frizzled receptors as USP6 substrates, explaining how USP6 amplifies Wnt/β-catenin signaling to drive tumor growth.

    Evidence Genome-wide siRNA Wnt screen, deubiquitylation assays, surface receptor quantification, and DKK1/PORCN inhibitor xenograft assays

    PMID:27162353

    Open questions at the time
    • Which specific Frizzled paralogs are preferred substrates not delineated
    • Crosstalk with other USP6 oncogenic pathways unresolved
  12. 2016 High

    Established the Jak1/STAT3 axis as a USP6 effector pathway by showing USP6 directly stabilizes Jak1, with epistasis confirming requirement for tumorigenicity.

    Evidence Co-IP, deubiquitination assay, CRISPR deletion of Jak1/STAT3, Jak inhibitor, xenograft model, and primary patient transcriptomics

    PMID:27440725

    Open questions at the time
    • Site-specific ubiquitin linkage on Jak1 removed by USP6 not characterized
    • Relative contribution versus Wnt/NF-κB axes not quantified
  13. 2017 High

    Identified c-Jun as a USP6 substrate, linking USP6 DUB activity to AP-1 transcription and an invasive phenotype.

    Evidence DUB library screen, reciprocal Co-IP, ubiquitination assay with catalytically inactive mutant, AP-1 reporter, and invasion assay

    PMID:29061731

    Open questions at the time
    • In vivo relevance of c-Jun stabilization not tested
    • Ubiquitin chain type on c-Jun not defined
  14. 2019 High

    Extended USP6 function to the nervous system by showing it deubiquitinates GluN1 to enhance NMDAR surface expression, synaptic plasticity, and learning.

    Evidence Transgenic mice, ubiquitination proteomics, surface biotinylation, LTP/LTD electrophysiology, behavior, and knockdown in human ESC-derived neurons

    PMID:31841517

    Open questions at the time
    • Mechanism of USP6 recruitment to synapses not defined
    • Whether the same substrate logic applies in non-neuronal tissue unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How USP6 substrate selectivity is governed across its many oncogenic and physiological targets, and how its two functional domains (catalytic USP vs Arf6-activating TBC) are coordinated, remains unresolved.
  • No structural model integrating USP and TBC domain functions
  • No unifying determinant of substrate recognition across Fzd, Jak1, c-Jun, GluN1, and CIE cargo
  • Whether Ca2+/CaM regulation tunes substrate-specific DUB activity untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0016787 hydrolase activity 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 2 GO:0005856 cytoskeleton 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-392499 Metabolism of proteins 5 R-HSA-1643685 Disease 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-112316 Neuronal System 1
Partners
ARF6CALM1CDC42CHUKFZDGRIN1JAK1JUN

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 The human Tre-2 (USP6) oncogene encodes a deubiquitinating enzyme, as inferred from its homology to the yeast Doa4 deubiquitinating enzyme, which cleaves ubiquitin from substrate remnants during proteasomal degradation. Sequence homology and functional characterization of yeast ortholog Doa4 Nature Medium 8247125
2003 TRE17 (USP6) oncogene coprecipitates specifically with the active (GTP-bound) forms of Cdc42 and Rac1 in vivo, and its subcellular localization is regulated by these GTPases and by mitogens: under serum starvation TRE17 localizes to filamentous structures, while EGF or activated Cdc42/Rac1 redistribute it to the plasma membrane in an actin polymerization-dependent manner. A C-terminal truncation mutant of TRE17 induces cortical actin accumulation mimicking activated Cdc42. Co-immunoprecipitation, subcellular localization (fluorescence microscopy), dominant-active GTPase expression, actin depolymerization experiments, truncation mutagenesis Molecular and cellular biology High 12612085
2004 The TBC domain of TRE17/USP6 mediates direct binding to Arf6 in its GDP-bound (inactive) state but not in its GTP-bound state. Rather than acting as a GAP, TRE17 promotes Arf6 activation (GTP loading) in vivo by facilitating its access to membrane-associated GEFs, leading to plasma membrane localization of Arf6. siRNA-mediated knockdown of TRE17 attenuates Arf6 activation. Co-immunoprecipitation with GDP- and GTP-fixed Arf6 mutants, domain-mapping pulldown, in vivo GTP-loading assay, siRNA knockdown, fluorescence microscopy Molecular and cellular biology High 15509780
2005 Calmodulin (CaM) binds directly to TRE17/USP6 in a Ca2+-dependent manner in vitro and in vivo. The CaM-binding site maps to two hydrophobic motifs near the C terminus of the TBC domain. TRE17 is monoubiquitinated and promotes its own deubiquitination; CaM-binding-deficient point mutants show significantly reduced monoubiquitination, and the CaM inhibitor W7 also reduces TRE17 monoubiquitination. The calcium ionophore A23187 induces polyubiquitinated TRE17 in a CaM-binding-dependent manner. Co-immunoprecipitation (Ca2+-dependent), in vitro binding assay, point mutagenesis, pharmacological inhibition (W7, A23187), ubiquitination assays The Journal of biological chemistry High 16127172
2005 The TBC domain of the Tre2 oncoprotein lacks Rab-GAP activity; chimeric protein experiments swapping regions N- and C-terminal to the TBC domain between Tre2 and active GAP RN-tre revealed that both the TBC domain itself and a 93-aa region C-terminal to it contribute to the oncoprotein's failure to function as a Rab-GAP. Yeast complementation of msb3Δ msb4Δ double mutant using chimeric Tre2/RN-tre proteins Biochemical and biophysical research communications Medium 16099424
2010 TRE17/USP6 overexpression in cells induces transcription of MMP-9 and MMP-10 through activation of NF-κB, a process requiring USP catalytic activity but not Arf6 binding. RhoA and its effector kinase ROCK are required for NF-κB activation by TRE17. Xenograft studies confirm that tumorigenic activity of TRE17 depends on the USP domain. Stable overexpression, reporter assays, dominant-negative/constitutively active GTPase constructs, ROCK inhibitor, site-directed mutagenesis of USP active site, xenograft mouse model Oncogene High 20418905
2010 TRE17/USP6 potently inhibits maturation of MC3T3 pre-osteoblasts in a USP-dependent, Arf6-independent manner through an autocrine mechanism. Transcriptome analysis reveals dysregulation of BMP signaling: TRE17 simultaneously inhibits BMP-4 expression and upregulates the BMP antagonist Gremlin-1. Addition of exogenous BMP-4 rescues osteoblast maturation in TRE17-expressing cells. Stable overexpression, osteoblast differentiation assay, transcriptome analysis, cytokine rescue experiments, USP active-site mutant The Journal of biological chemistry High 20864534
2011 TRE17/USP6 activates the classical NF-κB pathway through an atypical mechanism that does not involve IκB degradation. TRE17 co-precipitates with IKK, augments IKK activity in a USP-dependent manner, requires both IKKα and IKKβ catalytic subunits (and IKKγ/NEMO) for optimal activity, and stimulates phosphorylation of p65 at serine 536. Inhibition of NF-κB significantly attenuates TRE17-driven tumor formation in NIH3T3 cells. Co-immunoprecipitation, IKK kinase assay, USP active-site mutant, dominant-negative IKK subunits, p65-S536 phosphorylation western blot, xenograft tumorigenesis with NF-κB inhibitor Oncogene High 22081069
2014 TRE17/USP6 deubiquitylates CIE (clathrin-independent endocytosis) cargo proteins, counteracting MARCH E3 ubiquitin ligase-dependent targeting of these cargos to lysosomes. The effect is dependent on USP6 deubiquitylating activity and is specific to CIE cargo (e.g., MHC class I); transferrin receptor (clathrin-dependent cargo) is unaffected. Expression of TRE17 alone stabilizes surface MHC class I. Co-expression with MARCH8, ubiquitination assays, flow cytometry for surface protein levels, USP active-site mutant, lysosomal degradation assays Journal of cell science High 25179595
2016 USP6 deubiquitylates Frizzled (Fzd) receptors, increasing their cell-surface abundance and thereby enhancing Wnt/β-catenin signaling. Genome-wide siRNA screen identified USP6 as a potent Wnt activator. Inhibition of Wnt signaling with DKK1 or a Porcupine inhibitor significantly decreased the growth of USP6-driven xenograft tumors. Genome-wide siRNA screen, deubiquitylation assays, surface receptor quantification, DKK1 and PORCN inhibitor treatment, xenograft tumor assay Proceedings of the National Academy of Sciences of the United States of America High 27162353
2016 USP6 directly deubiquitinates Jak1, leading to its stabilization and activation of STAT3 signaling. CRISPR-mediated deletion of Jak1 or STAT3 significantly attenuates USP6 tumorigenic potential. A Jak family inhibitor also reduces USP6-driven tumor formation. Co-immunoprecipitation, deubiquitination assay, CRISPR-mediated gene deletion, Jak inhibitor treatment, xenograft tumor model, transcriptomic analysis of primary clinical samples Cancer research High 27440725
2017 USP6 interacts with c-Jun and deubiquitinates it in an enzyme-activity-dependent manner, stabilizing c-Jun protein. USP6 overexpression upregulates AP-1-dependent downstream signaling and promotes cell invasion. DUB expression library screen, co-immunoprecipitation, ubiquitination assay with catalytically inactive USP6 mutant, AP-1 reporter assay, invasion assay Molecular and cellular biology High 29061731
2019 USP6 deubiquitinates GluN1 (NMDAR subunit), reducing NMDAR ubiquitination with concomitant elevation of NMDAR expression, stability, and cell-surface distribution. USP6 transgenic mice show enhanced NMDAR-dependent LTP/LTD and improved learning and memory; USP6 knockdown in human ESC-derived neurons impairs focal GluN1 distribution at postsynaptic densities and synaptic function. Transgenic mouse model, proteomic characterization (ubiquitination), cell surface biotinylation, LTP/LTD electrophysiology, behavior assays, siRNA knockdown in human ESC-derived neurons PLoS biology High 31841517
2011 USP6/TRE17 regulates cell migration and cytokinesis. Manipulating USP6 expression levels alters migration ability and progression through cytokinesis, via a pathway involving the small GTPase Arf6 and its GAP ACAP1. Overexpression and knockdown of USP6, migration assays, cytokinesis/proliferation assays, genetic epistasis with Arf6 and ACAP1 Biology of the cell Medium 22188517
2006 The TBC domain GAP region of the Tre2 oncoprotein interacts with two cytoskeletal proteins—the light regulatory chain of myosin II (Myl2) and LOC91256 (ankyrin repeat protein)—as confirmed by GST pulldown, co-immunoprecipitation, and colocalization. Yeast two-hybrid screen, GST pulldown, co-immunoprecipitation, colocalization microscopy Biotechnology letters Low 16555005
2010 The oncogene TRE17/USP6 is identified as the first deubiquitinating enzyme to activate NF-κB (as stated in the paper reporting its mechanism); specifically, it activates the classical NF-κB pathway through an IκB-degradation-independent mechanism requiring IKK. Co-immunoprecipitation, IKK kinase assay, USP active-site mutant (see also PMID 22081069 for detailed mechanism) Oncogene Medium 20418905

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1993 The yeast DOA4 gene encodes a deubiquitinating enzyme related to a product of the human tre-2 oncogene. Nature 350 8247125
2004 USP6 and CDH11 oncogenes identify the neoplastic cell in primary aneurysmal bone cysts and are absent in so-called secondary aneurysmal bone cysts. The American journal of pathology 283 15509545
2011 Nodular fasciitis: a novel model of transient neoplasia induced by MYH9-USP6 gene fusion. Laboratory investigation; a journal of technical methods and pathology 258 21826056
2004 USP6 (Tre2) fusion oncogenes in aneurysmal bone cyst. Cancer research 232 15026324
1997 Hrp1, a sequence-specific RNA-binding protein that shuttles between the nucleus and the cytoplasm, is required for mRNA 3'-end formation in yeast. Genes & development 207 9334319
2005 Aneurysmal bone cyst variant translocations upregulate USP6 transcription by promoter swapping with the ZNF9, COL1A1, TRAP150, and OMD genes. Oncogene 162 15735689
2013 USP6-induced neoplasms: the biologic spectrum of aneurysmal bone cyst and nodular fasciitis. Human pathology 147 23769422
2006 Screening for target Rabs of TBC (Tre-2/Bub2/Cdc16) domain-containing proteins based on their Rab-binding activity. Genes to cells : devoted to molecular & cellular mechanisms 136 16923123
2000 The yeast hnRNP-like protein Hrp1/Nab4 marks a transcript for nonsense-mediated mRNA decay. Molecular cell 132 10882134
2003 The Tre2 (USP6) oncogene is a hominoid-specific gene. Proceedings of the National Academy of Sciences of the United States of America 123 12604796
2010 TRE17/USP6 oncogene translocated in aneurysmal bone cyst induces matrix metalloproteinase production via activation of NF-kappaB. Oncogene 119 20418905
2017 USP6 activation in nodular fasciitis by promoter-swapping gene fusions. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 99 28752842
2016 USP6 oncogene promotes Wnt signaling by deubiquitylating Frizzleds. Proceedings of the National Academy of Sciences of the United States of America 88 27162353
2006 Grabbing the message: structural basis of mRNA 3'UTR recognition by Hrp1. The EMBO journal 78 16794580
2005 The CHD remodeling factor Hrp1 stimulates CENP-A loading to centromeres. Nucleic acids research 74 15908586
2005 Effects of di-(2-ethylhexyl)-phthalate (DEHP) and its metabolites on fatty acid homeostasis regulating proteins in rat placental HRP-1 trophoblast cells. Toxicological sciences : an official journal of the Society of Toxicology 68 15647598
2015 The Evolutionarily Conserved Tre2/Bub2/Cdc16 (TBC), Lysin Motif (LysM), Domain Catalytic (TLDc) Domain Is Neuroprotective against Oxidative Stress. The Journal of biological chemistry 65 26668325
2006 Expression and transport activity of breast cancer resistance protein (Bcrp/Abcg2) in dually perfused rat placenta and HRP-1 cell line. The Journal of pharmacology and experimental therapeutics 65 16809480
2014 USP6 gene rearrangements occur preferentially in giant cell reparative granulomas of the hands and feet but not in gnathic location. Human pathology 64 24742829
2004 The TBC (Tre-2/Bub2/Cdc16) domain protein TRE17 regulates plasma membrane-endosomal trafficking through activation of Arf6. Molecular and cellular biology 64 15509780
1995 Molecular cloning of a cDNA with a novel domain present in the tre-2 oncogene and the yeast cell cycle regulators BUB2 and cdc16. Oncogene 63 7566974
2020 USP6-Associated Neoplasms: A Rapidly Expanding Family of Lesions. International journal of surgical pathology 62 32635781
2016 Anchored multiplex PCR for targeted next-generation sequencing reveals recurrent and novel USP6 fusions and upregulation of USP6 expression in aneurysmal bone cyst. Genes, chromosomes & cancer 60 27910166
2010 TRE17/ubiquitin-specific protease 6 (USP6) oncogene translocated in aneurysmal bone cyst blocks osteoblastic maturation via an autocrine mechanism involving bone morphogenetic protein dysregulation. The Journal of biological chemistry 57 20864534
2011 Atypical mechanism of NF-κB activation by TRE17/ubiquitin-specific protease 6 (USP6) oncogene and its requirement in tumorigenesis. Oncogene 52 22081069
2016 USP6 gene rearrangement in nodular fasciitis and histological mimics. Histopathology 50 27271298
2010 Novel protein-protein contacts facilitate mRNA 3'-processing signal recognition by Rna15 and Hrp1. Journal of molecular biology 50 20600122
2008 Frequency of USP6 rearrangements in myositis ossificans, brown tumor, and cherubism: molecular cytogenetic evidence that a subset of "myositis ossificans-like lesions" are the early phases in the formation of soft-tissue aneurysmal bone cyst. Skeletal radiology 50 18265974
2019 Fibro-osseous pseudotumor of digits and myositis ossificans show consistent COL1A1-USP6 rearrangement: a clinicopathological and genetic study of 27 cases. Human pathology 49 30946936
2003 The TRE17 oncogene encodes a component of a novel effector pathway for Rho GTPases Cdc42 and Rac1 and stimulates actin remodeling. Molecular and cellular biology 49 12612085
2008 A PY-NLS nuclear targeting signal is required for nuclear localization and function of the Saccharomyces cerevisiae mRNA-binding protein Hrp1. The Journal of biological chemistry 47 18343812
2008 Identification and characterization of a novel Tre-2/Bub2/Cdc16 (TBC) protein that possesses Rab3A-GAP activity. Genes to cells : devoted to molecular & cellular mechanisms 47 19077034
2016 PPP6R3-USP6 amplification: Novel oncogenic mechanism in malignant nodular fasciitis. Genes, chromosomes & cancer 45 27113271
2005 Calcium/calmodulin regulates ubiquitination of the ubiquitin-specific protease TRE17/USP6. The Journal of biological chemistry 45 16127172
2019 Recurrent and novel USP6 fusions in cranial fasciitis identified by targeted RNA sequencing. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 42 31827231
2005 Effects of di-(2-ethylhexyl)-phthalate and its metabolites on the lipid profiling in rat HRP-1 trophoblast cells. Archives of toxicology 41 16328440
2016 Jak1-STAT3 Signals Are Essential Effectors of the USP6/TRE17 Oncogene in Tumorigenesis. Cancer research 40 27440725
2018 Fibro-osseous pseudotumor of digits - Expanding the spectrum of clonal transient neoplasms harboring USP6 rearrangement. Annals of diagnostic pathology 37 29787930
2012 The TRE17/USP6 oncogene: a riddle wrapped in a mystery inside an enigma. Frontiers in bioscience (Scholar edition) 37 22202063
2020 Novel ASAP1-USP6, FAT1-USP6, SAR1A-USP6, and TNC-USP6 fusions in primary aneurysmal bone cyst. Genes, chromosomes & cancer 34 32011035
2019 The deubiquitinase USP6 affects memory and synaptic plasticity through modulating NMDA receptor stability. PLoS biology 34 31841517
2022 HucMSC exosomes promoted imatinib-induced apoptosis in K562-R cells via a miR-145a-5p/USP6/GLS1 axis. Cell death & disease 32 35091542
2016 Structural Basis of the Interaction between Tuberous Sclerosis Complex 1 (TSC1) and Tre2-Bub2-Cdc16 Domain Family Member 7 (TBC1D7). The Journal of biological chemistry 32 26893383
2007 Alternative 3' pre-mRNA processing in Saccharomyces cerevisiae is modulated by Nab4/Hrp1 in vivo. PLoS biology 31 17194212
2021 Overexpression of the Ubiquitin Specific Proteases USP43, USP41, USP27x and USP6 in Osteosarcoma Cell Lines: Inhibition of Osteosarcoma Tumor Growth and Lung Metastasis Development by the USP Antagonist PR619. Cells 30 34571917
2019 RNA sequencing identifies a novel USP9X-USP6 promoter swap gene fusion in a primary aneurysmal bone cyst. Genes, chromosomes & cancer 30 30767316
2018 Misses and near misses in diagnosing nodular fasciitis and morphologically related reactive myofibroblastic proliferations: experience of a referral center with emphasis on frequency of USP6 gene rearrangements. Virchows Archiv : an international journal of pathology 30 29623468
2017 Ubiquitin-Specific Protease USP6 Regulates the Stability of the c-Jun Protein. Molecular and cellular biology 30 29061731
2019 Case of mesenchymal tumor with the PPP6R3-USP6 fusion, possible nodular fasciitis with malignant transformation. Pathology international 29 31538390
2010 Protein kinase WNK1 promotes cell surface expression of glucose transporter GLUT1 by regulating a Tre-2/USP6-BUB2-Cdc16 domain family member 4 (TBC1D4)-Rab8A complex. The Journal of biological chemistry 29 20937822
2019 Tre2 (USP6NL) promotes colorectal cancer cell proliferation via Wnt/β-catenin pathway. Cancer cell international 27 31015802
2017 Gene fusions PAFAH1B1-USP6 and RUNX2-USP6 in aneurysmal bone cysts identified by next generation sequencing. Cancer genetics 27 28449806
2000 Fission yeast hrp1, a chromodomain ATPase, is required for proper chromosome segregation and its overexpression interferes with chromatin condensation. Nucleic acids research 27 10756203
2020 Myositis ossificans-like soft tissue aneurysmal bone cyst: a clinical, radiological, and pathological study of seven cases with COL1A1-USP6 fusion and a novel ANGPTL2-USP6 fusion. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 26 32157177
2021 Ubiquitin-specific Peptidase 6 (USP6)-associated Fibroblastic/Myofibroblastic Tumors: Evolving Concepts. Cancer genomics & proteomics 25 33608306
2020 Characterization of novel USP6 gene rearrangements in a subset of so-called cellular fibroma of tendon sheath. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 25 32661296
2021 Diagnostic Utility of a Custom 34-Gene Anchored Multiplex PCR-Based Next-Generation Sequencing Fusion Panel for the Diagnosis of Bone and Soft Tissue Neoplasms With Identification of Novel USP6 Fusion Partners in Aneurysmal Bone Cysts. Archives of pathology & laboratory medicine 24 33147323
2021 Fibroma of tendon sheath is defined by a USP6 gene fusion-morphologic and molecular reappraisal of the entity. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 24 34088995
2021 Nodular fasciitis of the breast: clinicopathologic and molecular characterization with identification of novel USP6 fusion partners. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 23 34099872
2011 The oncogenic TBC domain protein USP6/TRE17 regulates cell migration and cytokinesis. Biology of the cell 22 22188517
1997 Proviral integrations at the Evi5 locus disrupt a novel 90 kDa protein with homology to the Tre2 oncogene and cell-cycle regulatory proteins. Oncogene 22 9070650
2018 Primary aneurysmal bone cyst with a novel SPARC-USP6 translocation identified by next-generation sequencing. Cancer genetics 21 30553465
2014 TRE17/USP6 regulates ubiquitylation and trafficking of cargo proteins that enter cells by clathrin-independent endocytosis. Journal of cell science 21 25179595
2020 Novel EIF5A-USP6 Gene Fusion in Nodular Fasciitis Associated With Unusual Pathologic Features: A Report of a Case and Review of the Literature. The American Journal of dermatopathology 20 31880592
2019 USP6 Gene Rearrangement by FISH Analysis in Cranial Fasciitis: A Report of Three Cases. Head and neck pathology 20 30758758
2021 Novel partners of USP6 gene in a spectrum of bone and soft tissue lesions. Virchows Archiv : an international journal of pathology 19 33558945
1998 Isolation and characterization of hrp1+, a new member of the SNF2/SWI2 gene family from the fission yeast Schizosaccharomyces pombe. Molecular & general genetics : MGG 19 9520266
2015 A spontaneously resolving breast lesion: imaging and cytological findings of nodular fasciitis of the breast with FISH showing USP6 gene rearrangement. BMJ case reports 18 26698206
2008 Fusion of the COL1A1 and USP6 genes in a benign bone tumor. Cancer genetics and cytogenetics 18 18068538
1997 Permeability and metabolic properties of a trophoblast cell line (HRP-1) derived from normal rat placenta. Experimental cell research 18 9223380
1994 PfEMP3 and HRP1: co-expressed genes localized to chromosome 2 of Plasmodium falciparum. Gene 18 8026748
1993 Human TRE17 oncogene is generated from a family of homologous polymorphic sequences by single-base changes. DNA and cell biology 18 8471161
2021 Overexpression of microRNA-130a represses uveal melanoma cell migration and invasion through inactivation of the Wnt/β-catenin signaling pathway by downregulating USP6. Cancer gene therapy 16 34522027
2020 Benign infiltrative myofibroblastic neoplasms of childhood with USP6 gene rearrangement. Histopathology 16 32583473
2020 Atypical nodular fasciitis with a novel PAFAH1B1-USP6 fusion in a 22-month-old boy. Virchows Archiv : an international journal of pathology 16 33161462
1999 Hepatoma-derived growth factor-related protein (HRP)-1 gene in spermatogenesis in mice. Biochemical and biophysical research communications 16 10462493
2022 Histopathogenesis of bone- and soft-tissue tumor spectrum with USP6 gene rearrangement: multiple partners involved in the tissue repair process. Histology and histopathology 15 36205240
2003 The yeast hnRNP-like protein Hrp1/Nab4 sccumulates in the cytoplasm after hyperosmotic stress: a novel Fps1-dependent response. Molecular biology of the cell 15 12972575
2021 Nodular Fasciitis With Malignant Morphology and a COL6A2-USP6 Fusion: A Case Report (of a 10-Year-old Boy). International journal of surgical pathology 14 33625261
2019 Two case reports of intra-articular nodular fasciitis of the knee confirmed by MYH9-USP6 gene fusion expression. Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 14 30611632
2023 Surveillance of 3' mRNA cleavage during transcription termination requires CF IB/Hrp1. Nucleic acids research 13 37351636
2014 [Chromosomal translocation involving USP6 gene in nodular fasciitis]. Zhonghua bing li xue za zhi = Chinese journal of pathology 13 25346123
2020 Pathologic evaluation of the solid variant of aneurysmal bone cysts with USP6 rearrangement with an emphasis on the frequent diagnostic pitfalls. Pathology international 12 32342641
2020 Fusion of the Lumican (LUM) Gene With the Ubiquitin Specific Peptidase 6 (USP6) Gene in an Aneurysmal Bone Cyst Carrying a t(12;17)(q21;p13) Chromosome Translocation. Cancer genomics & proteomics 12 32859633
2018 Pseudosarcomatous myofibroblastic proliferations of the genitourinary tract are genetically different from nodular fasciitis and lack USP6, ROS1 and ETV6 gene rearrangements. Histopathology 12 29617048
2017 USP6 gene rearrangement differentiates primary paranasal sinus solid aneurysmal bone cyst from other giant cell-rich lesions: report of a rare case. Human pathology 12 29217425
2005 At least two regions of the oncoprotein Tre2 are involved in its lack of GAP activity. Biochemical and biophysical research communications 12 16099424
2024 Unusual fusion gene rearrangements in patients with nodular fasciitis: a study of rare and novel USP6 fusion partners with a review of the literature. Journal of clinical pathology 11 36828621
2019 Evaluation of the Expression and Function of the TRE2-like and TRE2 Genes in Ecdysis of Harmonia axyridis. Frontiers in physiology 10 31736789
2017 Mycobacterium tuberculosis hypoxic response protein 1 (Hrp1) augments the pro-inflammatory response and enhances the survival of Mycobacterium smegmatis in murine macrophages. Journal of medical microbiology 10 28671529
2023 Unravelling the USP6 gene: an update. Journal of clinical pathology 9 37328256
2022 Intraneural Nodular Fasciitis of the Femoral Nerve with A Unique CTNNB1::USP6 Gene Fusion: Apropos of a Case and Review of Literature. International journal of surgical pathology 9 35175167
2018 Aneurysmal Bone Cyst of the Maxillary Sinus with USP6 Rearrangement: Case Report of a Rare Entity and Review of the Literature. Head and neck pathology 9 30076509
2011 Unknown partner for USP6 and unusual SS18 rearrangement detected by fluorescence in situ hybridization in a solid aneurysmal bone cyst. Cancer genetics 9 21536237
2006 The Tre2 oncoprotein, implicated in Ewing's sarcoma, interacts with two components of the cytoskeleton. Biotechnology letters 9 16555005
2022 Multimodality imaging features of USP6-associated neoplasms. Skeletal radiology 8 35962835
2020 Increased RNA production in Saccharomyces cerevisiae by simultaneously overexpressing FHL1, IFH1, and SSF2 and deleting HRP1. Applied microbiology and biotechnology 8 32715361
2006 Evidence for involvement of TRE-2 (USP6) oncogene, low-copy repeat and acrocentric heterochromatin in two families with chromosomal translocations. Human genetics 8 16791615
2024 Recurrent USP6 rearrangement in a subset of atypical myofibroblastic tumours of the soft tissues: low-grade myofibroblastic sarcoma or atypical/malignant nodular fasciitis? Histopathology 7 38651320
1993 Identification of novel sequences in the repertoire of hypervariable TRE17 genes from immortalized nonmalignant and malignant human keratinocytes. Gene 7 8406013

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