Affinage

ADRM1

Proteasomal ubiquitin receptor ADRM1 · UniProt Q16186

Length
407 aa
Mass
42.2 kDa
Annotated
2026-06-09
73 papers in source corpus 34 papers cited in narrative 35 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ADRM1/Rpn13 is a subunit of the 19S regulatory particle of the 26S proteasome that couples recognition of ubiquitinated substrates to their disassembly and degradation (PMID:18497817, PMID:17139257). It is recruited to the proteasome by direct docking onto the C-terminal tail of RPN2/PSMD1, an interaction mapped to the final ~14 residues of RPN2 binding the Rpn13 Pru domain and further tuned by RPN2 modification — Tyr-950 phosphorylation enhances affinity while SUMOylation of RPN2 adjacent to the docking site regulates Adrm1 association in a manner linked to mitotic exit (PMID:28442575, PMID:31064842, PMID:24910440). Through its N-terminal Pru domain Rpn13 acts as a proteasomal ubiquitin receptor, binding K48-linked diubiquitin with high affinity by engaging both proximal and distal ubiquitin moieties and selecting a defined chain conformation (PMID:18497817, PMID:30962947, PMID:32160516). The Pru domain also captures the ubiquitin-like domains of UBL-UBA shuttle proteins; genetic ablation in mice shows that Rpn13 and Rpn10 are the two main receptors that recruit shuttle factors mHR23B and ubiquilins and that they act redundantly for bulk conjugate handling, with double loss causing massive conjugate accumulation (PMID:18497817, PMID:26222436). Through its C-terminal DEUBAD domain Rpn13 functions as a deubiquitinase adaptor, recruiting UCH37/UCHL5 and allosterically activating it by disrupting an autoinhibitory homodimer and repositioning the enzyme's ULD domain and crossover loop to license substrate binding and catalysis (PMID:16906146, PMID:25702870, PMID:24752541). Rpn13 directs the proteasome toward specific substrates and partners — including iNOS and IκB-α via the Rpn13/UCH37 axis, parkin via high-affinity Ubl-domain docking, and mislocalised membrane proteins delivered by SGTA through a carboxylate-clamp interaction with the C-terminal domain (PMID:20634424, PMID:25666615, PMID:26169395). Its conjugate-binding capacity is itself regulated: under proteotoxic stress the proteasome-associated ligase Ube3c/Hul5 autoubiquitinates Rpn13, an autoinhibitory mechanism that selectively suppresses ubiquitin-conjugate degradation at stalled proteasomes (PMID:24811749). Rpn13 is present asymmetrically in only one of the two 19S caps of double-capped proteasomes (PMID:24429290). Beyond the proteasome, Rpn13 participates in DNA double-strand break end resection, where it inhibits resection and is removed by CRL4WDR70-mediated ubiquitination (PMID:37815873), and its deletion in germ cells disrupts 26S proteasome assembly and blocks meiosis, causing infertility (PMID:40422199).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2006 High

    Established that Adrm1/hRpn13 is a bona fide 19S subunit and the proteasomal recruiter of the deubiquitinase Uch37, defining a physical link between a regulatory particle protein and chain disassembly.

    Evidence Affinity purification, co-IP, in vitro reconstitution and ubiquitin-AMC assays, siRNA knockdown in mammalian cells

    PMID:16815440 PMID:16906146 PMID:17139257

    Open questions at the time
    • Did not resolve the structural basis of Uch37 activation
    • Conflicting reports on whether knockdown affects bulk degradation
  2. 2008 High

    Defined Rpn13's N-terminal Pru domain as a high-affinity K48-polyubiquitin receptor functionally linked to Rpn10, answering how the proteasome recognizes ubiquitinated cargo through a second receptor.

    Evidence NMR, affinity measurements, mutagenesis, yeast genetic epistasis

    PMID:18497817

    Open questions at the time
    • Did not establish in vivo substrate specificity
    • Mode of bivalent diubiquitin engagement not yet resolved at atomic level
  3. 2010 Medium

    Connected Rpn13 to degradation of defined regulatory substrates (iNOS, IκB-α) via the Rpn13/UCH37 complex rather than bulk turnover, indicating a specialized substrate-selective role.

    Evidence siRNA knockdown, co-IP, protein stability assays; plus ChIP-based transcriptional regulation of RPN13 by phospho-ΔNp63α

    PMID:20634424 PMID:20959455 PMID:21191146

    Open questions at the time
    • Substrate selectivity mechanism not structurally defined
    • ΔNp63α/LKB1 link rests on single Co-IP without reciprocal validation
  4. 2014 High

    Resolved the mechanism of UCH37 activation and revealed two layers of regulation — Rpn13-mediated disruption of UCH37 autoinhibitory oligomerization, and stress-induced autoubiquitination of Rpn13 itself that shuts down conjugate binding.

    Evidence NMR/SAXS/TR-SAXS/FRET activity reconstitution; MS site mapping and in vitro ubiquitination with purified 26S proteasomes; AQUA-MS proteasome asymmetry mapping; RPN2 SUMOylation site mapping

    PMID:24429290 PMID:24752541 PMID:24811749 PMID:24910440

    Open questions at the time
    • Physiological triggers of Ube3c/Hul5 autoubiquitination incompletely defined
    • Functional consequence of 19S asymmetry for Rpn13 unresolved
  5. 2015 High

    Genetically established Rpn13 and Rpn10 as the two principal proteasomal receptors for UBL-UBA shuttle proteins, and broadened Rpn13's substrate-targeting repertoire to parkin and SGTA-delivered mislocalised membrane proteins.

    Evidence Liver-specific conditional double-knockout mice with rescue; NMR binding and siRNA functional assays for parkin; carboxylate-clamp NMR/co-IP for SGTA

    PMID:25666615 PMID:26169395 PMID:26222436

    Open questions at the time
    • Relative contribution of Rpn13 vs Rpn10 for individual substrates not fully partitioned
    • SGTA-Rpn13 axis characterized in a single lab
  6. 2015 High

    Provided atomic-level mechanism for both arms of Rpn13: how the DEUBAD domain repositions UCH37 to activate it (versus INO80G's inhibitory mimicry), and how the Pru domain docks onto the RPN2 C-terminus.

    Evidence Crystal structures of UCH-L5:DEUBAD and Pru:RPN2/ubiquitin complexes with mutagenesis and SPR/FP validation

    PMID:25702870 PMID:26466095 PMID:28442575

    Open questions at the time
    • Conformational coupling between RPN2 docking and ubiquitin binding within intact proteasome unresolved
  7. 2017 High

    Defined how RPN2 docking masks the Pru ubiquitin-binding surface and clarified that the RA190 inhibitor binds and inactivates UCH37 rather than disrupting Rpn13-UCH37, refining the drug-target relationship.

    Evidence NMR structure of hRpn13:hRpn2 segment, SPR/FP, CRISPR cell-based assays

    PMID:28598414

    Open questions at the time
    • In-cell selectivity of RA190 not yet resolved at this stage
  8. 2019 High

    Established the structural basis of bivalent K48-diubiquitin recognition and showed that RPN2 Tyr-950 phosphorylation enhances Rpn13 docking, defining how chain selection and proteasome anchoring are tuned.

    Evidence NMR structures with dynamics, smFRET, charge-reversal mutagenesis with cellular conjugate readout; 1.76 Å crystal structure of pTyr-RPN2:Rpn13:ubiquitin

    PMID:30962947 PMID:31064842 PMID:32160516

    Open questions at the time
    • Kinase responsible for RPN2 Tyr-950 phosphorylation not identified in corpus
    • Physiological context selecting open vs compact diubiquitin states unclear
  9. 2020 Medium

    Challenged Rpn13 as the physiologically relevant target of the RA190 inhibitor, showing no in-cell engagement of Rpn13 and Rpn13-independent toxicity.

    Evidence In vitro interaction assays, chemical proteomics in two cell lines, Rpn13-modulation viability assays

    PMID:32857985

    Open questions at the time
    • Directly contradicts earlier CRISPR-based RA190 target assignment
    • True target(s) responsible for RA190 toxicity not defined
  10. 2023 Medium

    Extended Rpn13 function beyond canonical degradation — into substrate-stabilizing deubiquitination (UCH37/ALK5 in cartilage), splice-variant rewiring of deubiquitinase and substrate partners, and a non-proteasomal role restraining DNA end resection.

    Evidence Global/conditional knockout mice and DMM OA model; ubiquitin-array, organoid and xenograft profiling of ADRM1-ΔEx9; co-IP and HR/ubiquitination assays for CDW19S/CRL4WDR70 resection

    PMID:37406898 PMID:37815873 PMID:39788431

    Open questions at the time
    • Each non-canonical role characterized by a single lab
    • How a degradation receptor stabilizes a substrate (ALK5) mechanistically incompletely defined
  11. 2025 Medium

    Demonstrated a physiological requirement for Rpn13 in 26S proteasome assembly during germ-cell development and exploited Rpn13 as the receptor module for ubiquitin-independent targeted degradation.

    Evidence PGC-specific conditional knockout with proteasome assembly and meiosis staging; Protea-Tac chimeric reconstitution with multiple substrates and xenograft validation (preprint)

    PMID:40422199 PMID:bio_10.1101_2025.08.18.670774

    Open questions at the time
    • Molecular basis of Rpn13's assembly requirement not defined
    • Degrader study is a preprint not yet peer-reviewed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How Rpn13's distinct activities — ubiquitin recognition, UCH37 activation, shuttle/substrate recruitment, and non-proteasomal resection control — are spatially and temporally coordinated within a single asymmetric cap remains unresolved.
  • No integrated model linking 19S asymmetry to functional specialization
  • Regulation switching between proteasomal and DNA-repair roles unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0031386 protein tag activity 4 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005829 cytosol 2 GO:0005634 nucleus 1
Pathway
R-HSA-392499 Metabolism of proteins 3 R-HSA-168256 Immune System 2 R-HSA-8953854 Metabolism of RNA 2 R-HSA-73894 DNA Repair 1
Partners
PARK2PSMD1PSMD4RAD23BSGTAUBE3CUCHL5
Complex memberships
26S proteasome 19S regulatory particle

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 Rpn13/ADRM1 was identified as a novel proteasomal ubiquitin receptor that binds ubiquitin through a conserved N-terminal pleckstrin-like receptor for ubiquitin (Pru) domain, binding K48-linked diubiquitin with ~90 nM affinity. Like Rpn10/S5a, Rpn13 also binds UBL domains of UBL-UBA shuttle proteins. In yeast, combining specific ubiquitin-binding mutations in both Rpn10 and Rpn13 produces a synthetic phenotype, indicating functional linkage. Rpn13 also serves as the proteasomal receptor for deubiquitinating enzyme Uch37, suggesting coupling of chain recognition and disassembly. Biochemical binding assays, NMR, mutational analysis, yeast genetic epistasis (synthetic phenotype screen) Nature High 18497817
2006 Uch37 (UCH-L5) is recruited to mammalian PA700 (19S) proteasomes via direct binding to Adrm1/hRpn13, which is itself bound to the S1/Rpn2 subunit of the 19S complex. The C-terminal tail of Uch37 (distinct from its UCH catalytic domain) mediates binding to Adrm1. Adrm1 binding relieves Uch37 autoinhibition and accelerates hydrolysis of ubiquitin-AMC. Full incorporation into the 19S complex (not Uch37-Adrm1 or Uch37-Adrm1-S1 alone) is required for efficient polyubiquitin chain processing. PA700 isopeptidase disassembles K48-linked polyubiquitin from the distal end of the chain. Co-immunoprecipitation, in vitro biochemical reconstitution, ubiquitin-AMC fluorogenic assay, di-ubiquitin hydrolysis assay Nature cell biology High 16906146
2006 ADRM1/hRpn13 is a novel 46-kDa subunit of the 19S regulatory complex whose N-terminal half is homologous to yeast Rpn13 and incorporates into the 26S proteasome, while its C-terminal half binds directly to UCH37 and enhances its isopeptidase activity. Knockdown of hRpn13 in 293T cells increases cellular ubiquitin conjugates and decreases degradation of short-lived proteins. Overproduction of hRpn13 or transfection of the C-terminal half (dominant-negative) also reduces proteolysis and induces cell death. Affinity purification, co-immunoprecipitation, siRNA knockdown, ubiquitin conjugate accumulation assay, protein degradation assay The EMBO journal High 17139257
2006 Adrm1 is a component of the regulatory ATPase complex of the 26S proteasome, present almost exclusively in soluble 26S proteasomes at equimolar amounts with core subunit S6a (Rpn1). A small fraction is membrane-associated. No free pool of Adrm1 exists in cells, but recombinant Adrm1 can bind pre-existing 26S proteasomes in cell extracts. Knockdown of Adrm1 in HeLa cells had no effect on proteasome amount, bulk protein degradation, or polyubiquitinated protein accumulation, indicating a specialized rather than general role in proteasome function. Co-immunoprecipitation, gel-filtration chromatography, non-denaturing PAGE, siRNA knockdown, protein degradation assay Journal of molecular biology Medium 16815440
2013 The bis-benzylidine piperidone RA190 covalently binds to cysteine 88 (C88) of ubiquitin receptor RPN13 in the 19S regulatory particle, inhibiting proteasome function and triggering rapid accumulation of polyubiquitinated proteins, ER stress-related apoptosis. CRISPR/Cas9 Rpn13-knockout abrogates RA190-induced substrate accumulation at proteasomes. Covalent drug binding assay, cell-based proteasome activity assay, CRISPR/Cas9 knockout, western blotting for polyubiquitinated proteins Cancer cell Medium 24332045
2014 During proteotoxic stress or partial proteasome inhibition, the proteasome-associated ubiquitin ligase Ube3c/Hul5 selectively poly-ubiquitinates Rpn13 on the 26S proteasome. This autoubiquitination of Rpn13 strongly decreases the proteasome's ability to bind and degrade ubiquitin-conjugated proteins without affecting activity against peptide substrates, constituting an autoinhibitory mechanism that prevents ubiquitin conjugate binding to stalled or defective proteasomes. Mass spectrometry identification of ubiquitinated sites, in vitro ubiquitination assay with purified 26S proteasomes, cell-based stress treatments, proteasome activity assays The EMBO journal High 24811749
2015 Crystal structures of UCH-L5/Uch37 in complex with the DEUBAD domain of RPN13 reveal that RPN13 activates Uch37 by repositioning its C-terminal ULD domain and crossover loop to promote substrate binding and catalysis. The related DEUBAD domain of INO80G inhibits UCH-L5 by exploiting the same structural elements but driving a radically different conformation and employing molecular mimicry to block ubiquitin docking. Crystal structure determination, mutagenesis, enzymatic activity assays Molecular cell High 25702870
2017 The structure of hRpn13 bound to a segment of hRpn2 (its proteasome docking site) was solved; a proline-rich C-terminal hRpn2 extension stretches across a narrow canyon of the ubiquitin-binding hRpn13 Pru domain, blocking an RA190-binding surface. hRpn13 binds preferentially to hRpn2/proteasomes over RA190. RA190 does not affect the hRpn13-Uch37 interaction but directly binds and inactivates Uch37. hRpn13 deletion from HCT116 cells abrogates RA190-induced substrate accumulation at proteasomes. NMR structure determination, biophysical binding assays (SPR, fluorescence polarization), CRISPR/Cas9 cell-based assays Nature communications High 28598414
2017 Crystal structures of the RPN13 PRU domain in complex with peptides corresponding to the RPN2 C terminus and ubiquitin were determined. The RPN13-binding epitope maps to the C-terminal 14 residues of RPN2. RPN2, ubiquitin, and UCH37 each bind RPN13 with independent energetics. Mutational analysis validated the RPN2-binding interface by SPR and fluorescence polarization. Crystal structure determination, SPR, fluorescence polarization, mutational analysis The Journal of biological chemistry High 28442575
2010 Rpn13 is involved in selective degradation of iNOS and IκB-α via the Rpn13/UCH37 complex. Knockdown of Rpn13 by siRNA does not lead to global ubiquitinated protein accumulation but impairs iNOS interaction with UCH37. IκB-α, whose proteasomal degradation activates NF-κB, is also a substrate for the Rpn13/UCH37 pathway. siRNA knockdown, co-immunoprecipitation, protein stability/degradation assays Proceedings of the National Academy of Sciences of the United States of America Medium 20634424
2014 Uch37 oligomerizes in solution and has very low isopeptidase activity due to autoinhibition in which each catalytic domain in the homodimer blocks the other's ubiquitin-binding site. Rpn13C (residues 270–407) disrupts Uch37 oligomerization by sequestering it in a 1:1 stoichiometric complex, activating Uch37 with ~12-fold higher activity. TR-SAXS and FRET confirmed the mode of autoinhibition and activation mechanism. Mutagenesis, NMR, SAXS, TR-SAXS, FRET, biochemical activity assay Protein & cell High 24752541
2015 Simultaneous liver-specific deletion of both Rpn13 and Rpn10 in mice causes severe liver injury with massive ubiquitin conjugate accumulation, while single deletion causes only modest impairment. In the double knockout, shuttle proteins mHR23B and ubiquilin/Plic-1 and -4 fail to bind the proteasome, establishing Rpn10 and Rpn13 as the two main receptors for UBL-UBA substrate delivery proteins at the proteasome. Conditional knockout mouse (liver-specific), ubiquitin conjugate accumulation assay, co-immunoprecipitation, genetic rescue by re-expression PLoS genetics High 26222436
2015 The N-terminal ubiquitin-like (Ubl) domain of parkin binds directly to the Pru domain of Rpn13/ADRM1 via a hydrophobic patch surrounding Ile-44, with >10-fold higher affinity than ubiquitin for the Pru domain. Knockdown of Rpn13 in cells increases parkin levels, abrogates parkin recruitment to the 26S proteasome, and delays clearance of mitochondrial proteins (TIM23, TIM44, TOM20) while enhancing parkin autoubiquitination. Rpn13 knockdown did not impair parkin recruitment to mitochondria or mitophagy initiation. Co-immunoprecipitation, NMR binding analysis, mutational analysis, siRNA knockdown, mitochondrial protein clearance assay The Journal of biological chemistry High 25666615
2015 The C-terminal region of Rpn13 (DEUBAD domain) binds to the tetratricopeptide repeat (TPR) domain of SGTA via a carboxylate clamp mechanism. SGTA overexpression increases steady-state mislocalised membrane protein (MLP) levels in a manner dependent on SGTA's interaction with Rpn13. Expression of the SGTA-binding region of Rpn13 or TPR domain point mutations inhibit SGTA-Rpn13 binding and substantially reduce MLP levels. Co-immunoprecipitation, NMR structural characterization (carboxylate clamp interaction), mutational analysis, protein stability assays Journal of cell science Medium 26169395
2016 The structural basis for SGTA-Rpn13 interaction was characterized: a region of the Rpn13 C-terminal domain is necessary and sufficient for binding to the TPR domain of SGTA through a carboxylate clamp-mediated molecular recognition event, and the interaction was validated in a cellular context. NMR structural characterization, biophysical binding assays, cellular co-immunoprecipitation Scientific reports Medium 27827410
2014 Although most double-capped 26S proteasomes contain Rpn10/S5a in both 19S particles, only one of the two 19S particles contains Rpn13, defining inherent asymmetry in the 26S proteasome. This was validated in both yeast and mammals using biochemical fractionation and quantitative AQUA-MS methodology. Biochemical fractionation, AQUA-MS quantitation, validation in yeast and mammalian cells The Journal of biological chemistry Medium 24429290
2014 SUMOylation of Psmd1/RPN2 (by PIASy E3 ligase) at a critical lysine immediately adjacent to the Adrm1-binding domain regulates the association of Adrm1 with Psmd1/RPN2. The SUMO deconjugating enzyme xSENP1 specifically interacts with Psmd1, and disruption of xSENP1 targeting delays mitotic exit, linking this SUMOylation-mediated regulation to cell division. SUMOylation site mapping, co-immunoprecipitation, Xenopus extract cell cycle assay, SENP1 targeting experiments Cell reports Medium 24910440
2019 The structure of hRpn13 Pru:hRpn2(940-953):K48-diubiquitin was solved by NMR, revealing that hRpn2-bound hRpn13 selects a dynamic, extended conformation of K48-diubiquitin distinct from previously determined closed crystal structures. hRpn13 exchanges between the two ubiquitins within 100 ms but prefers the proximal ubiquitin due to interactions with the K48 linker region. NMR structure determination, NMR dynamics experiments Structure High 32160516
2019 The structure of Rpn13NTD bound to K48-diubiquitin was determined by NMR; Rpn13NTD simultaneously contacts both proximal and distal Ub subunits of K48-diUb in a compact state. The proximal Ub binds similarly to Ub monomer, while distal Ub engages a largely electrostatic surface of Rpn13NTD. A charge-reversal mutation in Rpn13NTD weakens K48-linked chain binding and causes ubiquitinated protein accumulation. Single-molecule FRET showed K48-diUb fluctuates among conformational states, with the compact state selectively enriched by Rpn13NTD. NMR structure, smFRET, charge-reversal mutagenesis, cell-based ubiquitin conjugate assay Cell discovery High 30962947
2019 Phosphorylation of RPN2 Tyr-950 enhances its binding to RPN13. Crystal structure of the RPN2-RPN13 pTyr-950-ubiquitin complex at 1.76 Å reveals specific interactions with positively charged RPN13 side chains that explain the increased affinity without conformational change. Mutagenesis and SPR/fluorescence polarization validated the crystallographic interface. Crystal structure determination (1.76 Å), SPR, fluorescence polarization, mutagenesis The Journal of biological chemistry High 31064842
2015 An hRpn2-derived 38-amino acid peptide binds the hRpn13 Pru domain with 12 nM affinity. NMR identified the hRpn13-interacting amino acids in this fragment. The peptide immunoprecipitates endogenous Rpn13 from 293T cells and displaces it from the proteasome. Over-expression of the peptide leads to increased ubiquitinated proteins. Conserved F948 and Y950/I951 of hRpn2 are critical for this interaction. NMR binding analysis, Co-immunoprecipitation, mutational analysis, fluorescence polarization PloS one Medium 26466095
2010 Phospho-ΔNp63α interacts with Rpn13 protein in cisplatin-sensitive SCC cells and this interaction leads to proteasome-dependent degradation of phospho-ΔNp63α while protecting LKB1 from degradation. In SCC cells with impaired ATM-dependent ΔNp63α phosphorylation, non-phosphorylated ΔNp63α fails to form complexes with Rpn13, allowing Rpn13 to target LKB1 for proteasome-dependent degradation, modulating cisplatin-induced autophagy. Co-immunoprecipitation, siRNA knockdown, protein stability assays Aging Low 21191146
2010 Phospho-ΔNp63α binds to the RPN13 gene promoter through a TP63-responsive element and, together with co-factors DDIT3/CHOP, NF-Y and NF-κB, activates RPN13 gene transcription. Cisplatin-induced, phospho-ΔNp63α-dependent RPN13 transcription leads to NOS2/iNOS degradation; RPN13 siRNA knockdown rescues NOS2 from this degradation. Chromatin immunoprecipitation, promoter-binding assay, siRNA knockdown, protein degradation assay The Journal of biological chemistry Medium 20959455
2009 Adrm1 interacts with Atp6v0d2 (d2 isoform of vacuolar H+-ATPase V0 domain) as identified by yeast two-hybrid screening and confirmed by co-immunoprecipitation. Adrm1 is required for cell migration and osteoclast maturation. Yeast two-hybrid screen, co-immunoprecipitation, cell migration assay, osteoclast differentiation assay Biochemical and biophysical research communications Low 19818731
2018 Shigella effector IpaH4.5 (an E3 ubiquitin ligase) targets RPN13 and induces its degradation via the ubiquitin-proteasome system. IpaH4.5-mediated RPN13 degradation causes dysfunction of the 19S regulatory particle, inhibiting guidance of ubiquitinated proteins to the 20S core particle and suppressing proteasome-catalyzed peptide splicing. This reduces antigen cross-presentation to CD8+ T cells via MHC class I. In RPN13 knockout MEFs, loss of RPN13 suppressed CD8+ T cell priming during Shigella infection. Bacterial infection model, RPN13 knockout MEFs, antigen presentation assay, T cell activation assay Cellular microbiology Medium 30414351
2023 ADRM1/Rpn13 upregulates UCH37 expression and binds UCH37 to activate its deubiquitination activity. Activated UCH37 enhances deubiquitination of ALK5 (activin receptor-like kinase 5), stabilizing ALK5 expression and maintaining extracellular matrix homeostasis in cartilage. Global knockout of ADRM1 accelerates cartilage degeneration in DMM-induced OA model. Global knockout mouse, conditional overexpression, co-immunoprecipitation, deubiquitination assay, ALK5 stability assay International journal of biological macromolecules Medium 37406898
2019 HDAC8 interacts with the proteasome receptor ADRM1, and inhibition of HDAC8 decreases MGMT protein levels in GBM cell lines in a manner dependent on this interaction. Treatment with TMZ disrupts the HDAC8-ADRM1 interaction exclusively in TMZ-sensitive cells. Co-immunoprecipitation, HDAC8 inhibitor/shRNA knockdown, western blotting for MGMT levels Genes & cancer Low 31798765
2023 A spliced ADRM1 variant lacking exon 9 (ADRM1-ΔEx9) interacts with a different deubiquitinase partner (BAP1 instead of UCH37) via its altered C-terminus, redirecting proteasome specificity. The novel exon 8-10 fusion creates a de novo binding site for tumor suppressor FBXW7, resulting in its selective proteasome-mediated degradation. Proteome Profiler Human Ubiquitin Array, co-immunoprecipitation, patient-derived organoids, xenograft models, murine hydrodynamic transfection Journal of hepatology Medium 39788431
2023 ADRM1/Rpn13 functions in DNA end resection as part of a proteasome variant (CDW19S) that assembles at broken chromatin. ADRM1Rpn13 inhibits DNA resection and is removed by CRL4WDR70-catalyzed ubiquitination upon commitment to extensive resection. HBx protein (from HBV) interferes with ADRM1Rpn13 degradation, leading to a resection barrier and homologous recombination deficiency. Co-immunoprecipitation, DNA damage repair assays, ubiquitination assay, HBx expression, HR assay The Journal of clinical investigation Medium 37815873
2016 Rpn13 and Rpn10 are the main proteasomal receptors for ubiquitin-like (UBL) domain-containing shuttle proteins (mHR23B and ubiquilins/Plic-1 and -4) that deliver ubiquitinated cargo to the proteasome. In double Rpn10/Rpn13 knockout hepatocytes, these shuttle proteins fail to associate with the proteasome. Conditional double-knockout mouse, co-immunoprecipitation, genetic rescue by re-expression PLoS genetics High 26222436
2016 MHC class I processing of the NY-ESO-1 antigen is governed by both Rpn10 and Rpn13 ubiquitin receptors as well as by immunoproteasomes, and is regulated by non-canonical ubiquitination on non-lysine sites rather than canonical K48-linked chains at K124. siRNA knockdown of Rpn13 and Rpn10, antigen presentation assay, ubiquitination site mutagenesis The Journal of biological chemistry Medium 26903513
2025 Conditional deletion of Rpn13 in primordial germ cells (PGCs) in mice causes infertility in both sexes with dramatic reduction in germ cells in testes and ovaries. Mechanistically, Rpn13 deletion disrupts 26S proteasome assembly in germ cells, reduces PGC numbers, and blocks meiosis of spermatocytes at the zygotene stage during prophase I. Conditional knockout mouse (PGC-specific), proteasome assembly assay, histological and meiosis staging analysis Cells Medium 40422199
2025 A Protea-Tac degrader incorporating ADRM1/Rpn13 as the ubiquitin receptor component integrates into 26S proteasomes without altering their structural or functional integrity. Proximity of target proteins (c-Fos, BRD4, Flag-TDP43, HA-tau, GFP-ODC) to the proteasome via Rpn13-antibody chimera results in their ubiquitin-independent degradation. Chimeric protein reconstitution, proteasome integrity assays, targeted degradation assays for multiple substrates, in vivo xenograft mouse model bioRxivpreprint Medium bio_10.1101_2025.08.18.670774
2025 PhIX-MS and cryo-EM placed the thioredoxin domain of redox sensor TXNL1 near RPN2/PSMD1 and RPN13/ADRM1 at the proteasome regulatory particle, positioning it to reduce substrates prior to proteolysis. PhIX-MS (photo-induced in situ crosslinking-mass spectrometry), cryo-electron microscopy, AlphaFold modeling bioRxivpreprint Low bio_10.1101_2025.07.31.667872
2020 RA190 has no measurable effect on any of the known interactions of Rpn13 in vitro, and no physical engagement of Rpn13 by RA190 was detected in cellulo on C88 or any other residue. Chemical proteomics in two cell lines showed that dozens of other proteins are heavily engaged by RA190. Increasing or reducing Rpn13 levels had no effect on RA190 sensitivity of HeLa or melanoma cells, indicating Rpn13 is NOT the physiologically relevant target of RA190. In vitro protein interaction assays, chemical proteomics (activity-based protein profiling), cell viability assays with Rpn13 modulation Cell chemical biology Medium 32857985

Source papers

Stage 0 corpus · 73 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 Proteasome subunit Rpn13 is a novel ubiquitin receptor. Nature 546 18497817
2006 Proteasome recruitment and activation of the Uch37 deubiquitinating enzyme by Adrm1. Nature cell biology 293 16906146
2006 hRpn13/ADRM1/GP110 is a novel proteasome subunit that binds the deubiquitinating enzyme, UCH37. The EMBO journal 207 17139257
2013 A bis-benzylidine piperidone targeting proteasome ubiquitin receptor RPN13/ADRM1 as a therapy for cancer. Cancer cell 143 24332045
2014 Autoubiquitination of the 26S proteasome on Rpn13 regulates breakdown of ubiquitin conjugates. The EMBO journal 139 24811749
2015 Mechanism of UCH-L5 activation and inhibition by DEUBAD domains in RPN13 and INO80G. Molecular cell 106 25702870
2010 Regulators of the proteasome pathway, Uch37 and Rpn13, play distinct roles in mouse development. PloS one 81 21048919
1994 Merosin promotes neurite growth and Schwann cell migration in vitro and nerve regeneration in vivo: evidence using an antibody to merosin, ARM-1. Developmental biology 80 8026618
2017 Structure of the Rpn13-Rpn2 complex provides insights for Rpn13 and Uch37 as anticancer targets. Nature communications 73 28598414
2015 Redundant Roles of Rpn10 and Rpn13 in Recognition of Ubiquitinated Proteins and Cellular Homeostasis. PLoS genetics 72 26222436
2015 A reversible and highly selective inhibitor of the proteasomal ubiquitin receptor rpn13 is toxic to multiple myeloma cells. Journal of the American Chemical Society 70 25914958
2016 Targeting proteasome ubiquitin receptor Rpn13 in multiple myeloma. Leukemia 69 27118409
2010 Regulation of NF-kappaB activity and inducible nitric oxide synthase by regulatory particle non-ATPase subunit 13 (Rpn13). Proceedings of the National Academy of Sciences of the United States of America 60 20634424
2020 The CCDC43-ADRM1 axis regulated by YY1, promotes proliferation and metastasis of gastric cancer. Cancer letters 56 32278016
2006 Adrm1, a putative cell adhesion regulating protein, is a novel proteasome-associated factor. Journal of molecular biology 56 16815440
2017 Structure and energetics of pairwise interactions between proteasome subunits RPN2, RPN13, and ubiquitin clarify a substrate recruitment mechanism. The Journal of biological chemistry 47 28442575
2013 Amplification Target ADRM1: Role as an Oncogene and Therapeutic Target for Ovarian Cancer. International journal of molecular sciences 43 23377018
2009 Knockdown of the novel proteasome subunit Adrm1 located on the 20q13 amplicon inhibits colorectal cancer cell migration, survival and tumorigenicity. Oncology reports 42 19148532
2008 Comprehensive analysis of 20q13 genes in ovarian cancer identifies ADRM1 as amplification target. Genes, chromosomes & cancer 41 18615678
2019 Development and preclinical validation of a novel covalent ubiquitin receptor Rpn13 degrader in multiple myeloma. Leukemia 40 30962579
2015 The E3 ubiquitin ligase parkin is recruited to the 26 S proteasome via the proteasomal ubiquitin receptor Rpn13. The Journal of biological chemistry 37 25666615
2001 Distinctly different gene structure of KLK4/KLK-L1/prostase/ARM1 compared with other members of the kallikrein family: intracellular localization, alternative cDNA forms, and Regulation by multiple hormones. DNA and cell biology 35 11506707
1999 Functional cloning of ARM-1, an adhesion-regulating molecule upregulated in metastatic tumor cells. Clinical & experimental metastasis 34 10919708
2019 HDAC8 affects MGMT levels in glioblastoma cell lines via interaction with the proteasome receptor ADRM1. Genes & cancer 33 31798765
2014 ADRM1 gene amplification is a candidate driver for metastatic gastric cancers. Clinical & experimental metastasis 33 24968865
2019 Structural basis for the recognition of K48-linked Ub chain by proteasomal receptor Rpn13. Cell discovery 30 30962947
2014 Mechanism of the Rpn13-induced activation of Uch37. Protein & cell 30 24752541
2010 Phospho-ΔNp63α/Rpn13-dependent regulation of LKB1 degradation modulates autophagy in cancer cells. Aging 29 21191146
2020 An Extended Conformation for K48 Ubiquitin Chains Revealed by the hRpn2:Rpn13:K48-Diubiquitin Structure. Structure (London, England : 1993) 28 32160516
2018 Covalent Rpn13-Binding Inhibitors for the Treatment of Ovarian Cancer. ACS omega 28 30288466
2018 RA190, a Proteasome Subunit ADRM1 Inhibitor, Suppresses Intrahepatic Cholangiocarcinoma by Inducing NF-KB-Mediated Cell Apoptosis. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 27 29913454
2015 A High Affinity hRpn2-Derived Peptide That Displaces Human Rpn13 from Proteasome in 293T Cells. PloS one 26 26466095
2015 Structural plasticity allows UCH37 to be primed by RPN13 or locked down by INO80G. Molecular cell 25 25747657
2016 RPN13/ADRM1 inhibitor reverses immunosuppression by myeloid-derived suppressor cells. Oncotarget 24 27655678
2015 ADRM1-amplified metastasis gene in gastric cancer. Genes, chromosomes & cancer 23 26052681
2020 Physical and Functional Analysis of the Putative Rpn13 Inhibitor RA190. Cell chemical biology 22 32857985
2015 Binding of SGTA to Rpn13 selectively modulates protein quality control. Journal of cell science 22 26169395
2020 Proteomic analysis identifies mechanism(s) of overcoming bortezomib resistance via targeting ubiquitin receptor Rpn13. Leukemia 20 32424294
2016 Major Histocompatibility Complex (MHC) Class I Processing of the NY-ESO-1 Antigen Is Regulated by Rpn10 and Rpn13 Proteins and Immunoproteasomes following Non-lysine Ubiquitination. The Journal of biological chemistry 19 26903513
2014 Inherent asymmetry in the 26S proteasome is defined by the ubiquitin receptor RPN13. The Journal of biological chemistry 19 24429290
2009 Adrm1 interacts with Atp6v0d2 and regulates osteoclast differentiation. Biochemical and biophysical research communications 19 19818731
2006 A Phg2-Adrm1 pathway participates in the nutrient-controlled developmental response in Dictyostelium. Molecular biology of the cell 19 16987957
2014 SUMOylation of Psmd1 controls Adrm1 interaction with the proteasome. Cell reports 17 24910440
2011 Knockdown of ovarian cancer amplification target ADRM1 leads to downregulation of GIPC1 and upregulation of RECK. Genes, chromosomes & cancer 17 21432940
2020 Bis-benzylidine Piperidone RA190 treatment of hepatocellular carcinoma via binding RPN13 and inhibiting NF-κB signaling. BMC cancer 15 32375699
2016 The Ubiquitin Receptor ADRM1 Modulates HAP40-Induced Proteasome Activity. Molecular neurobiology 15 27815841
2023 Adhesion-regulating molecule 1 (ADRM1) can be a potential biomarker and target for bladder cancer. Scientific reports 14 37684377
2017 Early and consistent overexpression of ADRM1 in ovarian high-grade serous carcinoma. Journal of ovarian research 14 28784174
2022 Exosomal circ-ADRM1 promotes lung adenocarcinoma progression and induces macrophage M2 polarization through regulating MMP14 mRNA and protein. Anti-cancer drugs 13 36454975
2018 Shigella effector IpaH4.5 targets 19S regulatory particle subunit RPN13 in the 26S proteasome to dampen cytotoxic T lymphocyte activation. Cellular microbiology 13 30414351
2016 SGTA interacts with the proteasomal ubiquitin receptor Rpn13 via a carboxylate clamp mechanism. Scientific reports 13 27827410
2019 Phosphorylation of Tyr-950 in the proteasome scaffolding protein RPN2 modulates its interaction with the ubiquitin receptor RPN13. The Journal of biological chemistry 12 31064842
2022 GMEB2 Promotes the Growth of Colorectal Cancer by Activating ADRM1 Transcription and NF-κB Signalling and Is Positively Regulated by the m6A Reader YTHDF1. Cancers 11 36551532
2020 Structure-function analyses of candidate small molecule RPN13 inhibitors with antitumor properties. PloS one 11 31940398
2020 ADRM1 as a therapeutic target in hepatocellular carcinoma. The Kaohsiung journal of medical sciences 11 32916039
2020 Mechanistic Studies of the Multiple Myeloma and Melanoma Cell-Selective Toxicity of the Rpn13-Binding Peptoid KDT-11. Cell chemical biology 10 32857986
2010 Phosphorylated TP63 induces transcription of RPN13, leading to NOS2 protein degradation. The Journal of biological chemistry 9 20959455
2009 [Silencing of Adrm1 by RNA interference suppresses proliferation of colorectal cancer cells]. Zhonghua zhong liu za zhi [Chinese journal of oncology] 9 20137344
2021 [Changes in the mitochondrial subproteome of mouse brain Rpn13-binding proteins induced by the neurotoxin MPTP and the neuroprotector isatin]. Biomeditsinskaia khimiia 8 33645522
2021 Chirality and asymmetry increase the potency of candidate ADRM1/RPN13 inhibitors. PloS one 8 34506530
2023 Discovery of a non-covalent ligand for Rpn-13, a therapeutic target for hematological cancers. Bioorganic & medicinal chemistry letters 7 37714498
2023 Hepatitis B virus infection disrupts homologous recombination in hepatocellular carcinoma by stabilizing resection inhibitor ADRM1. The Journal of clinical investigation 6 37815873
2025 Spliced exon9 ADRM1 promotes liver oncogenicity via selective degradation of tumor suppressor FBXW7. Journal of hepatology 5 39788431
2023 ADRM1/RPN13 attenuates cartilage extracellular matrix degradation via enhancing UCH37-mediated ALK5 deubiquitination. International journal of biological macromolecules 5 37406898
2018 Ubiquitin Receptor RPN13 Mediates the Inhibitory Interaction of Diphenyldihaloketones CLEFMA and EF24 With the 26S Proteasome. Frontiers in chemistry 4 30280096
2023 Development and anticancer properties of Up284, a spirocyclic candidate ADRM1/RPN13 inhibitor. PloS one 3 37315065
2025 Effects of ADRM1 on osteoblast differentiation and mineralization in osteoporosis. American journal of translational research 1 39959199
2025 Ubiquitin Receptor RPN13-Mediated "Candidatus Liberibacter asiaticus" Virulence Effector Degradation to Positively Regulate Immunity. Journal of agricultural and food chemistry 1 40192613
2024 Preclinical studies of RA475, a guanidine-substituted spirocyclic candidate RPN13/ADRM1 inhibitor for treatment of ovarian cancer. PloS one 1 38990850
2026 Ubiquitin-mediated downregulation of the proteasome subunit ADRM1 mediates in vitro capacitation of bovine spermatozoa. Animal reproduction science 0 42140061
2025 Non-Redundant Essential Roles of Proteasomal Ubiquitin Receptors Rpn10 and Rpn13 in Germ Cell Formation and Fertility. Cells 0 40422199
2025 IGF2BP1-Mediates m6A Modification of KLF4 and Upregulates ADRM1 to Affect EndMT in Diabetic Atherosclerosis. Acta Cardiologica Sinica 0 41018284
2025 Comprehensive analysis and experimental confirmation identify ADRM1 plays an oncogenic and immunosuppression role in KIRC. Biochemical and biophysical research communications 0 41406707

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