Affinage

PSMC3

26S proteasome regulatory subunit 6A · UniProt P17980

Round 2 corrected
Length
439 aa
Mass
49.2 kDa
Annotated
2026-04-28
70 papers in source corpus 22 papers cited in narrative 22 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PSMC3 (Rpt5/TBP-1) is an essential AAA-ATPase subunit of the 19S regulatory particle of the 26S proteasome that drives ATP-dependent unfolding and translocation of ubiquitinated substrates into the 20S core for degradation, with its C-terminal tail mediating both 20S core particle docking and assembly chaperone Nas2/p27 binding (PMID:8811196, PMID:21878651, PMID:24817721). Beyond canonical proteolysis, PSMC3 functions as a molecular chaperone that prevents substrate aggregation, stabilizes p14ARF against ubiquitin-independent 20S degradation, and maintains AGO2 protein levels by facilitating USP14-mediated deubiquitination to sustain RNAi (PMID:23617410, PMID:17334400, PMID:36528617). PSMC3 also participates in transcriptional regulation, being recruited to promoters of CIITA and androgen receptor target genes through its leucine zipper and ATPase domains (PMID:19853614, PMID:19325002). De novo missense variants in PSMC3 cause an autosomal dominant neurodevelopmental syndrome characterized by proteotoxic stress and dysregulated type I interferon signaling via PKR, while biallelic loss-of-function variants produce inner ear and lens developmental anomalies (PMID:37256937, PMID:32500975).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1996 High

    Establishing that PSMC3/Rpt5 is a core ATPase subunit of the 19S regulatory particle resolved the enzymatic basis of substrate recognition and translocation in ubiquitin-dependent proteolysis.

    Evidence Biochemical purification and enzymatic characterization of the 26S proteasome subunits

    PMID:8811196

    Open questions at the time
    • Substrate specificity determinants of individual ATPase subunits were not resolved
    • Structural arrangement of the ATPase ring was unknown
  2. 1997 Medium

    Localization of PSMC3 to spermatid manchettes and identification of its leucine zipper domain suggested non-proteasomal roles in germ cell differentiation, expanding PSMC3 function beyond bulk proteolysis.

    Evidence Immunofluorescence and immunogold electron microscopy in rat spermatids; domain analysis

    PMID:9266764 PMID:9345291

    Open questions at the time
    • Functional consequence of manchette localization was not tested
    • TBPIP interaction validated only by yeast two-hybrid in single study
  3. 1999 Medium

    Demonstration that PSMC3 together with SUG2 forms an activator complex stimulating 20S proteasome activity in an ATP-dependent manner established that individual 19S ATPases can function outside the intact 26S holoenzyme.

    Evidence Purification from bovine red cells and human tissues with in vitro 20S proteasome activity assay

    PMID:10363644

    Open questions at the time
    • Physiological context for a free PSMC3-SUG2 activator complex was not defined
    • Stoichiometry and regulation of the activator complex were not characterized
  4. 2000 High

    Psmc3 knockout in mice demonstrated pre-implantation lethality with defective blastocyst development, proving that PSMC3 is non-redundant with Psmc4 and essential for early embryogenesis.

    Evidence Gene-targeted knockout mice with embryo analysis

    PMID:10945464

    Open questions at the time
    • Whether lethality arises from global proteasome failure versus a specific PSMC3 function was unresolved
    • Cell-type-specific requirements were not addressed
  5. 2007 High

    Showing that PSMC3 protects p14ARF from ubiquitin-independent 20S proteasome degradation revealed a substrate-stabilization function distinct from its role in 26S-dependent proteolysis.

    Evidence In vitro 20S proteasome degradation assay with purified components, co-IP, and deletion mutagenesis

    PMID:17334400

    Open questions at the time
    • Whether p14ARF stabilization occurs through direct binding or steric exclusion from the 20S gate was not resolved
    • In vivo relevance for tumor suppression was not demonstrated
  6. 2009 High

    Two contemporaneous studies established transcription-regulatory roles for PSMC3: it is required for CIITA promoter activation through histone acetylation and transcription factor recruitment, and it enhances androgen receptor transactivation via its leucine zipper and ATPase domains.

    Evidence siRNA knockdown with ChIP and RT-PCR for CIITA; GST pulldown, co-IP, ChIP, and reporter assays with domain mutagenesis for AR

    PMID:19325002 PMID:19853614

    Open questions at the time
    • Whether transcriptional roles require assembled 19S particles or free PSMC3 was not distinguished
    • Genome-wide scope of PSMC3 transcriptional targets was unknown
  7. 2011 High

    Dissection of the Rpt5 C-terminal tail revealed separable functions for 20S core particle docking and Nas2 chaperone binding, establishing how assembly intermediates are guided to the mature holoenzyme.

    Evidence C-terminal truncation mutagenesis in yeast combined with proteasome purification, enzymatic assays, and genetic epistasis with ECM29

    PMID:21878651

    Open questions at the time
    • Structural basis of the C-tail–CP interface at atomic resolution was not obtained
    • How Ecm29 senses faulty proteasomes mechanistically was unclear
  8. 2013 High

    Reconstitution of chaperone activity demonstrated that PSMC3/Rpt5 prevents substrate aggregation and promotes refolding, establishing a triage function between folding and degradation at the proteasome.

    Evidence In vitro aggregation assay with denatured ricin A chain, competition binding, and yeast ATPase-mutant genetic validation

    PMID:23617410

    Open questions at the time
    • Range of endogenous substrates subject to PSMC3-mediated triage was uncharacterized
    • Structural basis of chaperone versus degradation commitment was unknown
  9. 2020 High

    Identification of a pathogenic deep intronic PSMC3 variant causing proteotoxic stress, constitutive TCF11/Nrf1 activation, and inner ear/lens developmental anomalies in humans and zebrafish linked PSMC3 dysfunction to a human sensory-developmental syndrome.

    Evidence Whole-genome sequencing of patients, fibroblast proteostasis assays, and zebrafish PSMC3 knockout phenotyping

    PMID:32500975

    Open questions at the time
    • Whether TCF11/Nrf1 pathway exhaustion is the proximal cause of tissue-specific defects was not tested
    • Genotype-phenotype correlation across different variant types was limited
  10. 2022 High

    Discovery that PSMC3 stabilizes AGO2 by facilitating USP14-mediated deubiquitination revealed a proteasome-independent post-translational mechanism through which PSMC3 sustains RNA interference.

    Evidence Yeast two-hybrid, co-IP, truncation mutagenesis, cycloheximide chase, ubiquitination assay, and EGFP-RNAi reporter

    PMID:36528617

    Open questions at the time
    • Whether PSMC3-AGO2 interaction occurs as free protein or within 19S context was not resolved
    • Impact on specific miRNA pathways or global small RNA populations was not assessed
  11. 2023 High

    Characterization of 15 de novo PSMC3 missense variants established an autosomal dominant neurodevelopmental syndrome and revealed that proteotoxic stress activates PKR-driven type I interferon signaling, identifying a druggable inflammatory axis downstream of proteasome dysfunction.

    Evidence Patient genetics, mouse neuronal morphology, Drosophila behavioral assay, proteomics/transcriptomics, PKR inhibitor treatment in patient T cells

    PMID:37256937

    Open questions at the time
    • Whether PKR activation is specific to PSMC3 variants or generalizable to other proteasome subunit mutations was untested
    • Long-term efficacy of PKR inhibition in vivo was not assessed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: how PSMC3 partitions between proteasomal, transcriptional, and chaperone roles in different cell types; the structural basis for substrate triage at the intact 26S holoenzyme; and whether therapeutic activation of the 20S proteasome via Rpt5-derived peptides can ameliorate neurodegenerative proteinopathies in vivo.
  • No in vivo pharmacological validation of Rpt5 C-terminal peptides in neurodegeneration models
  • Cell-type-specific partitioning of PSMC3 functions is unexplored
  • High-resolution cryo-EM of PSMC3 in chaperone versus degradation states is lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 4 GO:0140657 ATP-dependent activity 4 GO:0098772 molecular function regulator activity 3 GO:0140110 transcription regulator activity 2 GO:0044183 protein folding chaperone 1
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 3 GO:0005856 cytoskeleton 2
Pathway
R-HSA-392499 Metabolism of proteins 8 R-HSA-1266738 Developmental Biology 2 R-HSA-1643685 Disease 2 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-168256 Immune System 1 R-HSA-8953854 Metabolism of RNA 1
Complex memberships
26S proteasome 19S regulatory particlePSMC3-SUG2 proteasome activator complex

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 The 26S proteasome 19S regulatory complex contains multiple ATPase subunits (including PSMC3/Rpt5) that are required for binding and unfolding ubiquitinated protein substrates prior to degradation by the 20S core particle; the ATPases form a ring that drives substrate translocation through the gated channel. Biochemical purification, enzymatic assays, subunit characterization Annual review of biochemistry High 8811196
1997 Rat testis TBP-1 (rtTBP-1, the PSMC3 ortholog) encodes a 49 kDa protein with a leucine zipper domain and conserved ATPase/helicase motifs. By immunofluorescence and immunogold electron microscopy, rtTBP-1 colocalizes with α-tubulin-decorated manchettes of elongating spermatids and is also detected in paraaxonemal mitochondria and outer dense fibers of the developing spermatid tail. Immunofluorescence, immunogold electron microscopy, chromatofocusing fractionation, in situ hybridization Molecular reproduction and development Medium 9266764
1997 PSMC3 (TBP-1/Rpt5) was chromosomally mapped to human chromosome 11p12-p13, and a processed pseudogene locus was identified on chromosome 9p. Fluorescence in situ hybridization (FISH), radiation hybrid mapping Human genetics Medium 9048938
1997 TBPIP (TBP-1-interacting protein) was cloned from mouse and shown to interact with mouse TBP-1 (PSMC3 ortholog) in vivo; TBPIP co-localizes with TBP-1 and synergistically enhances TBP-1's inhibitory action on HIV-1 Tat-mediated transactivation in vitro. Yeast two-hybrid, co-localization, in vitro transactivation assay Biochemical and biophysical research communications Medium 9345291
1998 Mouse TBP-1 (PSMC3) is primarily localized to the nuclei of spermatogonia and spermatocytes in the testis, as demonstrated by immunohistochemistry; expression is also confirmed in CD4+ lymphocytes by RT-PCR, indicating heterogeneous tissue distribution. Immunohistochemistry, in situ hybridization, RT-PCR Biochimica et biophysica acta Medium 9714759
1999 PSMC3 (S6'/TBP-1) is a component of an activator complex (modulator) that, together with S10b (SUG2), stimulates 20S proteasome activity in an ATP- and concentration-dependent manner. This activator complex was isolated from bovine red cells and human tissues (brain, placenta, HEK cells) and also activates 26S proteasomes in a cross-species manner. Biochemical purification, 20S proteasome activity assay, cross-species activation experiments Molecular biology reports Medium 10363644
2000 Mouse Psmc3 gene consists of 12 coding exons with structural similarity to Psmc4; Psmc3 maps to mouse chromosome 2. Gene-targeted Psmc3-deficient mice die before implantation with defective blastocyst development, demonstrating that PSMC3 is essential for early embryogenesis and that Psmc3 and Psmc4 have non-compensatory functions in vivo. Gene targeting (knockout mice), genomic sequencing, embryo analysis Genomics High 10945464
2007 TBP-1 (PSMC3) stabilizes the p14ARF tumor suppressor by protecting it from 20S proteasome-mediated degradation. This stabilization requires an intact N-terminal 39 amino acids of ARF and occurs independently of N-terminal ubiquitination. In vitro, p14ARF can be degraded by the 20S proteasome without ubiquitination, and this degradation is counteracted by TBP-1. In vitro 20S proteasome degradation assay, co-immunoprecipitation, western blotting, deletion mutagenesis Oncogene High 17334400
2009 During rat spermatid development, PSMC3 (a component of the 19S regulatory cap of the 26S proteasome) and the ubiquitin E3 ligase Rnf19a are initially found in Golgi-derived proacrosomal vesicles, then localize along the cytosolic side of acrosomal membranes and the acroplaxome, and subsequently accumulate at the acroplaxome marginal ring-manchette perinuclear ring region and the developing head-tail coupling apparatus, implicating the ubiquitin-proteasome system in acrosome biogenesis and spermatid head shaping. Immunofluorescence, immunogold electron microscopy, cDNA cloning, co-localization studies Developmental dynamics Medium 19517565
2009 The 19S ATPase S6a (TBP-1/PSMC3) is required for cytokine-inducible CIITA transcription: knockdown of S6a reduces recruitment of transcription factors to the CIITA interferon-γ-inducible promoter IV (pIV), decreases histone H3K18 and H4K8 acetylation at that promoter, and impairs CIITA mRNA expression. S6b (another 19S ATPase) binds CIITApIV in an S6a-dependent manner, implicating the 19S ATPase hexamer in transcriptional initiation machinery assembly. siRNA knockdown, chromatin immunoprecipitation (ChIP), RT-PCR, reporter assays Journal of molecular biology Medium 19853614
2009 TBP-1 (PSMC3) directly binds TBPIP through its amino-terminal leucine zipper domain. AR (androgen receptor) is physically associated with TBP-1 and TBPIP both in vitro and in LNCaP cells. TBP-1 augments AR-mediated transcription additively with TBPIP, and the ATPase domain as well as the leucine zipper domain of TBP-1 are required for transcriptional enhancement. TBP-1 is transiently recruited to the proximal androgen response element of the PSA gene promoter in a ligand-dependent manner. Yeast two-hybrid, GST pulldown, co-immunoprecipitation, chromatin immunoprecipitation (ChIP), reporter assay, mutagenesis Endocrinology High 19325002
2011 The C-terminal tail of yeast Rpt5 (PSMC3 ortholog) provides two distinct functions: (1) facilitating the interaction with the proteasome core particle (CP), and (2) enabling binding to the assembly chaperone Nas2/p27. Deletion of the last C-terminal amino acid disrupts CP interaction but not Nas2 binding; deletion of the last three amino acids disrupts both. Proteasomes from rpt5-Δ3 strains are strongly enriched in Ecm29, which inhibits proteasome activity (reduced suc-LLVY-AMC hydrolysis). Deletion of ECM29 rescues the phenotypes of rpt5-Δ3 and nas2Δ in an hsm3Δ background, demonstrating that Ecm29 acts as a negative regulator of faulty proteasomes. Site-directed mutagenesis, proteasome purification, enzymatic activity assay, genetic epistasis, yeast genetics The Journal of biological chemistry High 21878651
2011 Stable knockdown of TBP-1 (PSMC3) in human immortalized fibroblasts increases cell proliferation, migration, and resistance to serum deprivation-induced apoptosis. TBP-1 silencing activates Akt/PKB kinase, and TBP-1 is itself a downstream target of Akt/PKB. MDM2, a known Akt target, plays a major role in this regulation, suggesting a negative feedback loop where Akt/PKB modulates TBP-1 levels in proliferating cells. Stable shRNA knockdown, proliferation assays, migration assays, apoptosis assay, western blotting, kinase pathway analysis PloS one Medium 21991300
2013 The 26S proteasome AAA-ATPase subunit RPT5 (PSMC3 ortholog) acts as a molecular chaperone that prevents aggregation of denatured ricin A chain (RTA) and stimulates recovery of RTA catalytic activity in vitro. Denatured RTA and casein compete for the same binding site on the regulatory particle of the 26S proteasome, but their fates differ: casein is degraded while RTA is not. In vivo, ATPase activity of yeast Rpt5p is required for maximal RTA toxicity after ER dislocation, implicating RPT5 in substrate triage between folding and degradation pathways. In vitro aggregation assay, proteasome binding competition, catalytic activity measurement, yeast genetic analysis The Biochemical journal High 23617410
2014 The N-terminal domain of the assembly chaperone p27 (residues 1-128, mouse) was crystallized alone (1.7 Å resolution, space group P212121) and in complex with the C-terminal ATPase domain of Rpt5/PSMC3 (residues 173-442; 4 Å resolution, space group P222), revealing that the p27 N-terminus directly contacts the Rpt5 ATPase domain and providing structural evidence for their interaction in proteasome assembly. X-ray crystallography, protein purification, co-crystallization Acta crystallographica. Section F, Structural biology communications Medium 24817721
2020 A deep intronic homozygous variant in PSMC3 leads to transcription of a cryptic exon and impaired protein homeostasis in patient fibroblasts, characterized by accumulation of ubiquitinated proteins (proteotoxic stress). The TCF11/Nrf1 transcriptional pathway for proteasome recovery is constitutively activated in patient cells, but upon chemical proteasome inhibition, this compensatory pathway is impaired. Zebrafish knockout of PSMC3 reproduces the human phenotype with inner ear development anomalies and cataracts, demonstrating a critical role for PSMC3/Rpt5 in inner ear, lens, and CNS development. Whole-genome sequencing, patient fibroblast studies, ubiquitination assays, proteasome activity assays, zebrafish knockout modeling, transcriptional pathway analysis EMBO molecular medicine High 32500975
2022 PSMC3 is a novel binding partner of AGO2 (Argonaute 2), interacting via the N-terminal coiled-coil motif of PSMC3 in an RNA-independent manner. PSMC3 depletion decreases AGO2 protein amount by promoting its ubiquitination and subsequent 26S proteasome-mediated degradation, whereas PSMC3 overexpression stabilizes AGO2 post-translationally. Mechanistically, PSMC3 facilitates the interaction of AGO2 with the deubiquitylase USP14, promoting USP14-mediated deubiquitination of AGO2, thereby stabilizing AGO2 and maintaining effective RNAi activity. Yeast two-hybrid screen, co-immunoprecipitation, immunofluorescence, truncation mutagenesis, cycloheximide chase, ubiquitination assay, EGFP-RNAi reporter assay, western blotting Cellular & molecular biology letters High 36528617
2022 VCPIP1 (a deubiquitinating enzyme) recruits PSMC3 to form a ternary complex with the hepatitis B virus X protein (HBx), stabilizing HBx through a ubiquitin-independent pathway. In vitro, purified His-tagged PSMC3 rescues HBx from 20S proteasome-mediated degradation. VCPIP1 synergizes this stabilization in vivo. The ternary VCPIP1-HBx-PSMC3 complex enhances HBx transcriptional transactivation (NF-κB, AP-1, SP-1) and affects cccDNA transcription. Yeast two-hybrid, co-immunoprecipitation, in vitro degradation assay with purified proteins, reporter assay, western blotting Journal of virology High 35695579
2022 Rpt5 (PSMC3) in glial cells reversibly associates with cold-stable microtubules upon cold stress, while other 19S and 20S subunits do not show this redistribution. This relocalization coincides with 26S proteasome partial disassembly and reduced 20S proteolytic activity. Both MAP6 expression and post-translational acetylation of α-tubulin modulate the Rpt5-microtubule association. Immunofluorescence, subcellular fractionation, 20S proteasome activity assay, western blotting, glial cell culture cold stress experiments FEBS letters Medium 35114005
2023 Fifteen de novo missense variants in PSMC3 cause an autosomal dominant neurodevelopmental delay syndrome. Expression of PSMC3 variants in mouse neuronal cultures leads to altered dendrite development. Deletion of the PSMC3 Drosophila ortholog Rpt5 impairs reversal learning. Structural modeling and proteomic/transcriptomic analyses of patient T cells indicate that PSMC3 variants disrupt substrate translocation, induce proteotoxic stress, and dysregulate type I interferon (IFN) signaling through activation of the intracellular stress sensor PKR (protein kinase R). Inhibition of PKR blocks the type I IFN response in patient-derived T cells. Patient genetics, structural modeling, mouse neuronal culture with morphological readout, Drosophila behavioral assay, proteomics, transcriptomics, PKR inhibitor treatment Science translational medicine High 37256937
2024 Procyanidin B1 mediates interaction between PSMC3 and NRF2 to promote ubiquitin-dependent proteasomal degradation of NRF2 in glioblastoma cells, inducing ferroptosis. PSMC3-NRF2 interaction was demonstrated by immunoprecipitation and mass spectrometry; the mechanism involves enhanced H₂O₂ accumulation through NRF2 downregulation. Procyanidin B1 binding to NRF2 was confirmed by surface plasmon resonance and protein-small molecule docking. Protein-small molecule docking, surface plasmon resonance, z-stack laser confocal imaging, immunoprecipitation, mass spectrometry, western blotting, in vivo orthotopic GBM model Phytotherapy research Medium 39293861
2024 Synthetic peptides and peptidomimetics derived from the C-terminus of the Rpt5 (PSMC3) subunit of the 19S regulatory particle efficiently stimulate human 20S proteasome activity in vitro. Cell-penetrating TAT-conjugated versions stimulate proteasome activity in HEK293T cells (measured with cell-permeable substrate TAS3) and enhance degradation of aggregation-prone α-synuclein and Tau-441. Peptide synthesis, in vitro 20S proteasome activity assay, cell-based proteasome activity assay, western blotting for substrate degradation International journal of molecular sciences Medium 38731881

Source papers

Stage 0 corpus · 70 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 Structure and functions of the 20S and 26S proteasomes. Annual review of biochemistry 2108 8811196
2002 Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature 1924 12167863
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
2005 A human protein-protein interaction network: a resource for annotating the proteome. Cell 1704 16169070
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2009 Recognition and processing of ubiquitin-protein conjugates by the proteasome. Annual review of biochemistry 1398 19489727
2009 Defining the human deubiquitinating enzyme interaction landscape. Cell 1282 19615732
2003 Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts. Nature 1236 12808466
2003 DNA deamination mediates innate immunity to retroviral infection. Cell 1150 12809610
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2003 Induction of APOBEC3G ubiquitination and degradation by an HIV-1 Vif-Cul5-SCF complex. Science (New York, N.Y.) 1006 14564014
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2003 The cytidine deaminase CEM15 induces hypermutation in newly synthesized HIV-1 DNA. Nature 912 12808465
2013 Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization. Nature 870 23503661
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2004 A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway. Nature cell biology 841 14743216
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2003 The antiretroviral enzyme APOBEC3G is degraded by the proteasome in response to HIV-1 Vif. Nature medicine 798 14528300
2008 Global analysis of host-pathogen interactions that regulate early-stage HIV-1 replication. Cell 787 18854154
2003 Species-specific exclusion of APOBEC3G from HIV-1 virions by Vif. Cell 763 12859895
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2003 HIV-1 Vif protein binds the editing enzyme APOBEC3G and induces its degradation. Nature medicine 679 14528301
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2006 A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration. Cell 610 16713569
2003 HIV-1 Vif blocks the antiviral activity of APOBEC3G by impairing both its translation and intracellular stability. Molecular cell 607 14527406
2003 Hypermutation of HIV-1 DNA in the absence of the Vif protein. Science (New York, N.Y.) 570 12750511
2005 Specificity and biomineralization activities of Ti-binding peptide-1 (TBP-1). Langmuir : the ACS journal of surfaces and colloids 145 15779989
1993 Cloning and characterization of Neisseria meningitidis genes encoding the transferrin-binding proteins Tbp1 and Tbp2. Gene 134 8344530
2009 The Arabidopsis proteasome RPT5 subunits are essential for gametophyte development and show accession-dependent redundancy. The Plant cell 60 19223514
2020 Proteasome subunit PSMC3 variants cause neurosensory syndrome combining deafness and cataract due to proteotoxic stress. EMBO molecular medicine 53 32500975
2011 Loss of Rpt5 protein interactions with the core particle and Nas2 protein causes the formation of faulty proteasomes that are inhibited by Ecm29 protein. The Journal of biological chemistry 53 21878651
2009 Rnf19a, a ubiquitin protein ligase, and Psmc3, a component of the 26S proteasome, tether to the acrosome membranes and the head-tail coupling apparatus during rat spermatid development. Developmental dynamics : an official publication of the American Association of Anatomists 47 19517565
1997 A protein associated with the manchette during rat spermiogenesis is encoded by a gene of the TBP-1-like subfamily with highly conserved ATPase and protease domains. Molecular reproduction and development 46 9266764
2000 Mouse proteasomal ATPases Psmc3 and Psmc4: genomic organization and gene targeting. Genomics 39 10945464
1994 Identification of a novel mammalian member of the NSF/CDC48p/Pas1p/TBP-1 family through heterologous expression in yeast. FEBS letters 39 8082782
2023 PSMC3 proteasome subunit variants are associated with neurodevelopmental delay and type I interferon production. Science translational medicine 30 37256937
2009 The 19S ATPase S6a (S6'/TBP1) regulates the transcription initiation of class II transactivator. Journal of molecular biology 25 19853614
1992 Isolation of a yeast gene encoding a protein homologous to the human Tat-binding protein TBP-1. DNA and cell biology 25 1388730
2009 Tat-binding protein-1 (TBP-1), an ATPase of 19S regulatory particles of the 26S proteasome, enhances androgen receptor function in cooperation with TBP-1-interacting protein/Hop2. Endocrinology 22 19325002
1993 AFG2, an essential gene in yeast, encodes a new member of the Sec18p, Pas1p, Cdc48p, TBP-1 family of putative ATPases. Yeast (Chichester, England) 22 8109176
2007 TBP-1 protects the human oncosuppressor p14ARF from proteasomal degradation. Oncogene 20 17334400
1997 Molecular cloning and characterization of a novel TBP-1 interacting protein (TBPIP):enhancement of TBP-1 action on Tat by TBPIP. Biochemical and biophysical research communications 20 9345291
2010 Transcriptional activation requires protection of the TATA-binding protein Tbp1 by the ubiquitin-specific protease Ubp3. The Biochemical journal 18 20738257
1995 Structure and expression of LeMA-1, a tomato protein belonging to the SEC18-PAS1-CDC48-TBP-1 protein family of putative Mg(2+)-dependent ATPases. Plant molecular biology 15 7766893
2022 Hepatitis B Virus X Protein Is Stabilized by the Deubiquitinating Enzyme VCPIP1 in a Ubiquitin-Independent Manner by Recruiting the 26S Proteasome Subunit PSMC3. Journal of virology 14 35695579
2013 The proteasome cap RPT5/Rpt5p subunit prevents aggregation of unfolded ricin A chain. The Biochemical journal 14 23617410
1997 Localization of genes encoding two human one-domain members of the AAA family: PSMC5 (the thyroid hormone receptor-interacting protein, TRIP1) and PSMC3 (the Tat-binding protein, TBP1). Human genetics 14 9048938
2020 Circ PSMC3 inhibits prostate cancer cell proliferation by downregulating DGCR8. European review for medical and pharmacological sciences 11 32196577
1998 Cloning and heterogeneous in vivo expression of Tat binding protein-1 (TBP-1) in the mouse. Biochimica et biophysica acta 10 9714759
2024 Procyanidin B1 Promotes PSMC3-NRF2 Ubiquitination to Induce Ferroptosis in Glioblastoma. Phytotherapy research : PTR 8 39293861
2011 A regulatory mechanism involving TBP-1/Tat-Binding Protein 1 and Akt/PKB in the control of cell proliferation. PloS one 5 21991300
2007 TFIIB/SUA7(E202G) is an allele-specific suppressor of TBP1(E186D). The Biochemical journal 5 17680779
2024 Rpt5-Derived Analogs Stimulate Human Proteasome Activity in Cells and Degrade Proteins Forming Toxic Aggregates in Age-Related Diseases. International journal of molecular sciences 4 38731881
2021 Prioritization of human well-being spectrum related GWAS-SNVs using ENCODE-based web-tools predict interplay between PSMC3, ITIH4, and SERPINC1 genes in modulating well-being. Journal of psychiatric research 4 34883412
1997 Expression of a gene for a protein similar to HIV-1 Tat binding protein 1 (TBP1) in floral organs of Brassica rapa. Plant & cell physiology 4 9327593
2024 A Moroccan Pyrenophora teres f. teres Population Defeats Rpt5, the Broadly Effective Resistance on Barley Chromosome 6H. Phytopathology 3 37386751
2023 In Vivo Validation of Novel Synthetic tbp1 Peptide-Based Vaccine Candidates against Haemophilus influenzae Strains in BALB/c Mice. Vaccines 3 38005983
2022 PSMC3 promotes RNAi by maintaining AGO2 stability through USP14. Cellular & molecular biology letters 3 36528617
1999 Activator complexes containing the proteasomal regulatory ATPases S10b (SUG2) and S6 (TBP1) in different tissues and organisms. Molecular biology reports 3 10363644
1998 Distribution of mRNA encoding Tat-binding protein-1 (TBP-1), a component of 26S proteasome, in the rat brain. Brain research. Molecular brain research 3 9473711
1996 Genomic structure of the maize TATA-box binding protein 1 (TBP-1): conserved exon/intron structure in eukaryotic TBP genes. Gene 3 8863736
2022 The 19S proteasome subunit Rpt5 reversibly associates with cold-stable microtubules in glial cells at low temperatures. FEBS letters 1 35114005
2014 Purification, crystallization and preliminary X-ray data collection of the N-terminal domain of the 26S proteasome regulatory subunit p27 and its complex with the ATPase domain of Rpt5 from Mus musculus. Acta crystallographica. Section F, Structural biology communications 1 24817721
1997 Cloning and sequencing of the gene encoding the outer-membrane protein Tbp1 from Actinobacillus pleuropneumoniae. Expression of Tbp1 and Tbp2. Behring Institute Mitteilungen 1 9382765
2026 Neuroimaging PheWAS and molecular phenotyping implicate PSMC3 in Alzheimer's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association 0 41732108
2025 Neuroimaging PheWAS and molecular phenotyping implicate PSMC3 in Alzheimer's Disease. medRxiv : the preprint server for health sciences 0 41001458