Affinage

PSMD7

26S proteasome non-ATPase regulatory subunit 7 · UniProt P51665

Length
324 aa
Mass
37.0 kDa
Annotated
2026-06-10
18 papers in source corpus 15 papers cited in narrative 15 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

PSMD7 (Rpn8/Mov34) is a non-catalytic MPN-domain subunit of the 26S proteasome 19S regulatory particle that was originally cloned as the human p40 regulatory subunit homologous to mouse Mov-34 (PMID:7755639). Its defining mechanistic role is to form an obligate heterodimer with the deubiquitinase Rpn11/PSMD14 through two distinct MPN-MPN interfaces, an arrangement resolved by high-resolution crystal structures of the heterodimer (PMID:24463465, PMID:24516147). Although both partners carry MPN domains, the PSMD7 domain lacks the conserved zinc-coordinating residues of catalytically active MPN proteins and therefore contributes structural support rather than isopeptidase activity, with its N-terminal residues required for proper folding and stability (PMID:17559875, PMID:16842755). Full deubiquitylation by the heterodimer is achieved only upon incorporation into the 26S proteasome and is coupled to ATP hydrolysis, with Rpn11 positioned at the ATPase ring where it removes ubiquitin chains from translocating substrates in a linkage-nonspecific manner (PMID:24463465, PMID:24516147). Beyond its core proteasomal function, PSMD7 acts on specific clients: its C-terminal disordered region directly binds and mediates ubiquitin-independent degradation of Pih1 (PMID:27053109), and in cancer cells PSMD7 reduces ubiquitination to stabilize substrates including RAD23B and SOX2 (PMID:34512150, PMID:38494478). PSMD7 is also a target of HIV-1 Vpr, which binds its C-terminal domain and triggers a shift in PSMD7 nucleocytoplasmic distribution linked to G2/M cell cycle arrest (PMID:9520381, PMID:12237292).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1995 Medium

    Established the molecular identity of PSMD7 by cloning it as a regulatory subunit of the human 26S proteasome, anchoring all later mechanistic work to a defined proteasome component.

    Evidence cDNA cloning and biochemical analysis of 26S proteasome subunit composition

    PMID:7755639

    Open questions at the time
    • Did not resolve the subunit's structural role or catalytic status
    • No interaction partners within the proteasome defined
  2. 1998 Medium

    Showed PSMD7 is a direct target of HIV-1 Vpr, connecting a proteasome subunit to viral manipulation of the cell cycle.

    Evidence Yeast two-hybrid, GST pulldown, co-immunoprecipitation, and histone H1 kinase assay linking Vpr binding to G2/M arrest

    PMID:9520381

    Open questions at the time
    • Binding region on PSMD7 not yet mapped
    • Mechanistic link between localization shift and MPF inhibition not resolved
  3. 2000 Low

    Tested whether PSMD7 has RNA-binding capacity, identifying direct binding to the JEV 3' noncoding RNA stem-loop.

    Evidence UV crosslinking, Northwestern blotting, and competition RNA-binding assays with murine Mov34

    PMID:10799585

    Open questions at the time
    • Functional consequence for proteasome biology not established
    • Single lab, no in vivo validation
  4. 2002 Medium

    Mapped the Vpr-binding and shuttling determinant to the PSMD7 C-terminal domain, explaining how Vpr and glucocorticoid signaling redirect PSMD7 localization.

    Evidence Deletion mutant mapping with co-IP, localization imaging, and glucocorticoid receptor signaling assays

    PMID:12237292

    Open questions at the time
    • Cellular consequence of nuclear redistribution incompletely defined
    • Single lab
  5. 2007 High

    Determined the human PSMD7 MPN domain structure and demonstrated it lacks the catalytic zinc-coordination motif, establishing it as a non-catalytic structural subunit.

    Evidence X-ray crystallography (1.96 Å) with size-exclusion chromatography and dynamic light scattering

    PMID:17559875

    Open questions at the time
    • Domain-swapped dimer biological relevance versus heterodimer not resolved
    • No proteasome-context structure
  6. 2014 High

    Resolved the Rpn11-Rpn8 (PSMD14-PSMD7) heterodimer at atomic resolution and explained why the deubiquitinase is promiscuous and ATP-coupled, defining the core mechanism of co-translational chain removal.

    Evidence Two independent crystal structures (2.0 Å; nanobody-stabilized) with mutagenesis, in vitro deubiquitylation assays, and EM density docking

    PMID:24463465 PMID:24516147

    Open questions at the time
    • PSMD7's specific contribution to lid assembly not separately dissected
    • Dynamics of activation upon proteasome incorporation not fully captured
  7. 2016 Medium

    Demonstrated a proteasome-assembly-independent role for the PSMD7 C-terminus in mediating ubiquitin-independent degradation of Pih1, revealing a substrate-recruitment function distinct from the catalytic heterodimer.

    Evidence Truncation mapping with in vitro and in vivo degradation assays in S. cerevisiae

    PMID:27053109

    Open questions at the time
    • Generality of ubiquitin-independent recruitment to other substrates unknown
    • Structural basis of disordered-region binding not resolved
  8. 2021 Medium

    Showed PSMD7 stabilizes RAD23B by reducing its ubiquitination, linking PSMD7 to DNA damage repair via XPC in cancer cells.

    Evidence Co-IP, ubiquitination assay, shRNA knockdown with stability measurement, and xenograft model

    PMID:34512150

    Open questions at the time
    • Whether stabilization is direct deubiquitination by PSMD7 versus indirect not distinguished
    • Single lab
  9. 2024 Medium

    Extended the substrate-stabilization role to SOX2, placing PSMD7 upstream of Notch1 signaling through deubiquitination-dependent SOX2 stabilization.

    Evidence Co-IP, ubiquitination assay, and epistasis rescue in pancreatic cancer cells in vitro and in vivo

    PMID:38494478

    Open questions at the time
    • Direct catalytic mechanism for an MPN domain lacking the JAMM motif not reconciled
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PSMD7, whose MPN domain lacks catalytic residues, mediates substrate-specific stabilization and ubiquitin-independent degradation outside the Rpn11 heterodimer remains mechanistically unresolved.
  • No structural basis for substrate-specific client binding outside the proteasome
  • Unclear whether reported deubiquitination of clients is intrinsic or relies on associated DUBs
  • Relationship between proteasomal and extra-proteasomal pools undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 4 GO:0005198 structural molecule activity 2 GO:0060090 molecular adaptor activity 1
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 1
Pathway
R-HSA-392499 Metabolism of proteins 3
Partners
PIH1PSMD14RAB1ARAD23BSOX2VPR
Complex memberships
26S proteasome 19S regulatory particle

Evidence

Reading pass · 15 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 Crystal structure of the S. cerevisiae Rpn11-Rpn8 (PSMD14-PSMD7) MPN-domain heterodimer solved at 2.0 Å resolution. Rpn8 forms two distinct interfaces with Rpn11. Structural and mutational analyses revealed that Rpn11 lacks a conserved surface for ubiquitin Ile44-patch binding, does not contact the proximal ubiquitin moiety, and shows no ubiquitin-linkage specificity, explaining its function as a promiscuous co-translational deubiquitinase during proteasomal substrate processing. X-ray crystallography (2.0 Å), site-directed mutagenesis, biochemical deubiquitinase assays Nature structural & molecular biology High 24463465
2014 Crystal structure of the Rpn8-Rpn11 (PSMD7-PSMD14) MPN heterodimer solved using a nanobody-stabilized fusion protein. Full deubiquitylation activity requires incorporation into the 26S proteasome and is coupled to ATP hydrolysis. Activation is normally suppressed by low intrinsic ubiquitin affinity, an insertion segment blocking the substrate access channel, and a conformationally unstable catalytic loop in Rpn11. Docking into proteasome EM density shows Rpn11 contacts ATPase subunits that stabilize the active conformation. X-ray crystallography, nanobody co-crystallization, in vitro deubiquitylation assay, EM density docking Proceedings of the National Academy of Sciences of the United States of America High 24516147
2007 Crystal structure of the human PSMD7/Mov34 MPN domain (residues 1–186) solved at 1.96 Å reveals a dimeric architecture via domain swapping. The MPN domain lacks the conserved zinc-coordinating residues present in catalytically active MPN proteins (Rpn11, Csn5), explaining why PSMD7 has no intrinsic isopeptidase activity; the MPN domain therefore serves a structural rather than catalytic role. X-ray crystallography (1.96 Å and 3.0 Å), size-exclusion chromatography, dynamic light scattering Journal of molecular biology High 17559875
2006 The N-terminal eight residues (1–8) of human PSMD7/Mov34 MPN domain are required for proper folding and thermal stability of the domain; truncation mutants lacking residues 1–8 show reduced alpha-helical content and lower expression levels. Protease resistance assay, circular dichroism spectroscopy, thermal stability measurements Biochemical and biophysical research communications Medium 16842755
1995 PSMD7 (p40) was identified and cloned as a regulatory subunit of the human 26S proteasome. The protein contains a C-terminal KEKE motif (alternating Lys/Glu residues) and is homologous to the mouse Mov-34 gene product, establishing it as a novel essential regulatory subunit of the 26S proteasome. cDNA cloning, sequence analysis, biochemical characterization of 26S proteasome subunit composition Biochemical and biophysical research communications Medium 7755639
1998 HIV-1 Vpr directly interacts with hVIP/MOV34 (PSMD7) both in vitro (GST pulldown) and in vivo (co-immunoprecipitation). Vpr-induced cell cycle arrest at G2/M correlates with a change in PSMD7 subcellular localization from nuclear to perinuclear, accompanied by inhibition of maturation-promoting factor (MPF)-associated histone H1 kinase activity. Yeast two-hybrid, in vitro pulldown, co-immunoprecipitation, subcellular localization imaging, histone H1 kinase assay Proceedings of the National Academy of Sciences of the United States of America Medium 9520381
2002 The carboxyl-terminal domain of hVIP/MOV34 (PSMD7) is required for its interaction with HIV-1 Vpr. In the absence of Vpr, full-length PSMD7 is cytoplasmic; expression of Vpr shifts PSMD7 to a nuclear localization. C-terminal deletion mutants do not respond to Vpr or to dexamethasone, indicating that this domain also mediates glucocorticoid receptor-dependent nucleocytoplasmic shuttling of PSMD7. Deletion mutant mapping, co-immunoprecipitation, subcellular localization imaging, glucocorticoid receptor signaling assays The Journal of biological chemistry Medium 12237292
2016 In S. cerevisiae, the C-terminal 30 amino acids of Rpn8 (PSMD7 ortholog) are sufficient for binding to the C terminus of Pih1 (R2TP complex scaffold). This direct interaction mediates ubiquitin-independent proteasomal degradation of Pih1; truncation of the Rpn8 C-terminal disordered region does not affect proteasome assembly but specifically blocks Pih1 degradation both in vivo and in vitro. Co-immunoprecipitation, truncation mutant analysis, in vitro and in vivo degradation assays The Journal of biological chemistry Medium 27053109
2021 PSMD7 deubiquitinase activity stabilizes RAD23B protein in gastric cancer cells. PSMD7 co-immunoprecipitates with RAD23B, and PSMD7 knockdown enhances RAD23B ubiquitination and degradation, reducing XPC levels and impairing DNA damage repair. Co-immunoprecipitation, ubiquitination assay, shRNA knockdown with protein stability measurement, xenograft mouse model International journal of biological sciences Medium 34512150
2024 PSMD7 deubiquitinates and stabilizes SOX2 protein in pancreatic cancer cells, thereby activating Notch1 signaling. Restoration of SOX2 expression rescued the anti-tumor effects of PSMD7 knockdown, placing PSMD7 upstream of SOX2 in the Notch1 pathway. Co-immunoprecipitation, ubiquitination assay, gain/loss-of-function experiments in vitro and in vivo, epistasis rescue experiment Cell & bioscience Medium 38494478
2023 PSMD7 interacts with RAB1A and reduces its ubiquitination, stabilizing RAB1A protein post-translationally in bladder cancer cells. RAB1A functions as a downstream effector of PSMD7 in promoting bladder cancer progression. Co-immunoprecipitation, ubiquitination assay, shRNA knockdown, overexpression rescue experiment Cellular signalling Low 38040402
2020 PSMD7 knockdown in breast cancer cells promotes ubiquitin-dependent degradation of p21 and p27, leading to G0/G1 cell cycle arrest, senescence, and apoptosis, indicating that PSMD7 normally stabilizes these cell cycle inhibitors. shRNA knockdown, cell cycle analysis, protein stability assay American journal of translational research Low 33042429
2021 PSMD7 knockdown in non-small cell lung cancer cells increases p53 protein levels and induces p21 and PUMA expression in a p53-dependent manner, indicating PSMD7 normally promotes p53 degradation via the proteasome. shRNA knockdown, western blot, xenograft mouse model Journal of Cancer Low 34234864
2018 PSMD7 knockdown in esophageal squamous cell carcinoma reduces proteasomal function and suppresses mTOR/p70S6K pathway activity; conversely, PSMD7 overexpression increases phosphorylation of mTOR (Ser2448) and p70S6K (Thr421/Ser424), placing PSMD7 upstream of this pathway. shRNA knockdown, lentiviral overexpression, western blot for pathway phosphorylation, xenograft mouse model FEBS open bio Low 29632807
2000 Murine Mov34 (PSMD7 ortholog) binds the 3'-stem-loop structure of the Japanese encephalitis virus (JEV) 3'-noncoding region RNA, as detected by UV crosslinking, Northwestern blotting, and competition with viral genomic RNA. Gel retardation assay, UV crosslinking, Northwestern blotting, cDNA library screen, competition RNA binding assay Journal of virology Low 10799585

Source papers

Stage 0 corpus · 18 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Structure of the Rpn11-Rpn8 dimer reveals mechanisms of substrate deubiquitination during proteasomal degradation. Nature structural & molecular biology 133 24463465
2014 Crystal structure of the proteasomal deubiquitylation module Rpn8-Rpn11. Proceedings of the National Academy of Sciences of the United States of America 114 24516147
1998 HIV-1 Vpr interacts with a human 34-kDa mov34 homologue, a cellular factor linked to the G2/M phase transition of the mammalian cell cycle. Proceedings of the National Academy of Sciences of the United States of America 91 9520381
2000 Mov34 protein from mouse brain interacts with the 3' noncoding region of Japanese encephalitis virus. Journal of virology 66 10799585
2007 The crystal structure of the human Mov34 MPN domain reveals a metal-free dimer. Journal of molecular biology 41 17559875
2012 Archaeal JAB1/MPN/MOV34 metalloenzyme (HvJAMM1) cleaves ubiquitin-like small archaeal modifier proteins (SAMPs) from protein-conjugates. Molecular microbiology 37 22970855
2021 Deubiquitinase PSMD7 promotes the proliferation, invasion, and cisplatin resistance of gastric cancer cells by stabilizing RAD23B. International journal of biological sciences 29 34512150
2024 Deubiquitinase PSMD7 facilitates pancreatic cancer progression through activating Nocth1 pathway via modifying SOX2 degradation. Cell & bioscience 28 38494478
1995 cDNA cloning of p40, a regulatory subunit of the human 26S proteasome, and a homolog of the Mov-34 gene product. Biochemical and biophysical research communications 28 7755639
2002 Carboxyl terminus of hVIP/mov34 is critical for HIV-1-Vpr interaction and glucocorticoid-mediated signaling. The Journal of biological chemistry 24 12237292
1991 The murine Mov-34 gene: full-length cDNA and genomic organization. Genomics 22 1837787
2018 PSMD7 downregulation induces apoptosis and suppresses tumorigenesis of esophageal squamous cell carcinoma via the mTOR/p70S6K pathway. FEBS open bio 20 29632807
2020 Deubiquitinase PSMD7 regulates cell fate and is associated with disease progression in breast cancer. American journal of translational research 17 33042429
2021 PSMD7 downregulation suppresses lung cancer progression by regulating the p53 pathway. Journal of Cancer 16 34234864
2016 The Proteasome Subunit Rpn8 Interacts with the Small Nucleolar RNA Protein (snoRNP) Assembly Protein Pih1 and Mediates Its Ubiquitin-independent Degradation in Saccharomyces cerevisiae. The Journal of biological chemistry 6 27053109
2023 Deubiquitinating enzyme PSMD7 promotes bladder cancer development: Involvement of RAB1A stabilization. Cellular signalling 5 38040402
2006 Characterization of the human ortholog of Mov34 reveals eight N-terminal residues important for MPN domain stability. Biochemical and biophysical research communications 5 16842755
2025 Drosophila proteasome subunit Rpn8 controls IMD pathway activation via PGRP-SC2 degradation. Insect biochemistry and molecular biology 1 41083131

Missed literature

Know a paper Affinage missed for PSMD7? Flag it for the maintainers and the community.

No submissions yet.