Affinage

RUVBL2

RuvB-like 2 · UniProt Q9Y230

Length
463 aa
Mass
51.2 kDa
Annotated
2026-04-28
73 papers in source corpus 36 papers cited in narrative 38 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RUVBL2 is an AAA+ ATPase that forms alternating heterohexameric rings with RUVBL1 and functions as a versatile co-chaperone platform for the assembly and maturation of diverse macromolecular complexes. The RUVBL1–RUVBL2 complex possesses ATPase and DNA helicase activities regulated by its insertion domain (DII), which undergoes conformational transitions that couple nucleotide hydrolysis to client protein interactions; binding partners such as PIH1D1 (R2TP), INO80, DHX34, and CCDC103 allosterically modulate ATPase output through DII and N-terminal gatekeeper elements (PMID:31049401, PMID:33205750, PMID:28591576, PMID:17157868). Through these chaperone activities, RUVBL2 drives assembly of PIKK signaling complexes, the Fanconi anemia core complex, γ-tubulin ring complexes, U5 snRNPs, snoRNPs, and axonemal dynein arms, while also promoting protein disaggregation and aggresome formation (PMID:20371770, PMID:25428364, PMID:33355144, PMID:28561026, PMID:23858445, PMID:26303906). RUVBL2 additionally functions at chromatin as a transcriptional co-regulator—mediating H2A.Z exchange, RNA polymerase II cluster formation, and regulation of beta-catenin/TCF, GATA3, and BMAL1 targets—and its unusually slow intrinsic ATPase activity (~13 ATP/day) serves as a conserved biochemical timer that sets circadian period across eukaryotes (PMID:19696079, PMID:36171202, PMID:11080158, PMID:24167278, PMID:40140583).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1999 High

    Establishing the enzymatic identity: RUVBL2 was shown to be a single-stranded DNA-stimulated ATPase and 5′-to-3′ DNA helicase that forms a large complex with RUVBL1, defining it as an active nucleotide-hydrolyzing enzyme rather than a passive scaffold.

    Evidence In vitro ATPase and helicase assays with purified recombinant proteins, Co-IP and gel filtration

    PMID:10428817

    Open questions at the time
    • Physiological substrates for helicase activity undefined
    • Oligomeric state of the active species unresolved
  2. 2000 High

    Linking RUVBL2 to transcriptional regulation: identification as a beta-catenin/TBP-binding protein that antagonizes RUVBL1 in Wnt/beta-catenin signaling established a direct role in transcription factor modulation.

    Evidence Reciprocal Co-IP, reporter gene assays, and Drosophila Wingless genetic epistasis

    PMID:11080158

    Open questions at the time
    • Mechanism of antagonism between RUVBL1 and RUVBL2 on TCF targets unknown
    • Whether ATPase activity is required for transcriptional regulation untested
  3. 2006 High

    Defining the oligomeric architecture: the human RUVBL1–RUVBL2 complex was shown to form a dodecamer of two stacked heterohexameric rings with synergistic ATPase activity requiring both subunits, resolving contradictions about helicase activity (absent for the human complex).

    Evidence Crystal structure (DII truncation), negative-stain EM, Walker B mutagenesis, SAXS

    PMID:17157868 PMID:21933716

    Open questions at the time
    • Full-length DII structure unresolved at high resolution
    • Whether dodecamer vs. hexamer is the physiologically relevant state unclear
  4. 2009 High

    Revealing a chromatin remodeling function: RUVBL2 was shown to catalyze H2A.Z exchange via TIP60-dependent H2A acetylation, connecting its ATPase activity to histone variant dynamics.

    Evidence Purification of H2A.Z-interacting complexes, in vitro nucleosome exchange assay with ATPase mutants

    PMID:19696079

    Open questions at the time
    • Genome-wide loci requiring RUVBL2-dependent H2A.Z exchange not mapped
    • Whether RUVBL2 directly contacts nucleosomes unknown
  5. 2010 High

    Establishing RUVBL2 as a pan-PIKK chaperone: RUVBL1/2 were found to associate with all six PIKK family kinases and regulate their mRNA and protein abundance, linking the complex to DNA damage, NMD, and mTOR signaling.

    Evidence Co-IP with each PIKK, siRNA knockdown reducing PIKK levels and signaling

    PMID:20371770

    Open questions at the time
    • Whether regulation of PIKK mRNA is direct or indirect unresolved
    • Mechanism of PIKK protein stabilization not defined
  6. 2012 High

    Resolving DII conformational dynamics: cryo-EM revealed two coexisting conformations (compact and stretched) driven by DII movements, establishing that DII acts as a regulatory gate for DNA binding and client access.

    Evidence Cryo-EM image classification and 3D reconstruction at ~15 Å

    PMID:23002137

    Open questions at the time
    • Which conformation is favored during specific client interactions unknown
    • Resolution insufficient for atomic-level DII mechanism
  7. 2013 High

    Connecting RUVBL2 to cilia motility: Reptin was shown to directly interact with Lrrc6 and be required for cytoplasmic dynein arm assembly, explaining ciliopathy phenotypes.

    Evidence Co-IP, zebrafish reptin mutant with reduced dynein arm density by TEM

    PMID:23858445

    Open questions at the time
    • Whether RUVBL2 acts as a chaperone for specific dynein subunits not determined
    • Role of RUVBL1 in this complex untested
  8. 2014 High

    Identifying RUVBL2 as essential for Fanconi anemia core complex stability: native purification showed RUVBL1–RUVBL2 co-purify with the FA core, and their depletion caused FA complex degradation, ICL sensitivity, and aplastic anemia in conditional KO mice.

    Evidence Native AP-MS, siRNA knockdown, FANCD2 monoubiquitination assay, conditional mouse KO

    PMID:25428364

    Open questions at the time
    • Direct binding interface between RUVBL and FA subunits not mapped
    • Whether RUVBL acts during FA complex assembly or maintenance unclear
  9. 2015 High

    Discovering a protein disaggregase activity: RUVBL1/2 were shown to disassemble amyloid fibrils and protein aggregates in vitro and promote aggresome formation in cells, with unfolded polypeptides stimulating their ATPase.

    Evidence siRNA screen, in vitro disaggregation assay, ATPase stimulation by aggregates, synphilin-1 binding mapped to barrel opening

    PMID:26303906

    Open questions at the time
    • Substrate selectivity of disaggregase activity unknown
    • Relationship to other disaggregases (e.g. p97/VCP) not defined
  10. 2017 High

    Revealing how client proteins regulate RUVBL ATPase cycling: Ino80INS was shown to stimulate RUVBL ATPase 16-fold and promote dodecamerization, with ATP driving collapse to hexamers, establishing an assembly–disassembly chaperone cycle. Separately, ZNHIT2 was identified as bridging RUVBL2 to U5 snRNP assembly.

    Evidence Reconstitution, cryo-EM, XLMS for Ino80; AP-MS and siRNA for ZNHIT2/U5

    PMID:28561026 PMID:28591576

    Open questions at the time
    • Whether hexamer–dodecamer cycling occurs for all client interactions unresolved
    • Structural basis of ZNHIT2–RUVBL2 interface at atomic resolution not available
  11. 2019 High

    Structural elucidation of the R2TP co-chaperone mechanism: cryo-EM showed that PIH1D1 binding to RUVBL2 DII destabilizes an N-terminal gatekeeper segment, coupling client recruitment to nucleotide exchange regulation.

    Evidence Cryo-EM of R2TP complex, comparison of nucleotide-bound states

    PMID:31049401

    Open questions at the time
    • How gatekeeper destabilization propagates to downstream client release unknown
    • Whether all R2TP clients use the same allosteric mechanism untested
  12. 2020 High

    Demonstrating subunit-specific allosteric regulation: DHX34 was shown to act exclusively on RUVBL2 subunits, inducing N-terminal conformational changes that prevent nucleotide binding, providing a client-specific ATPase shutoff mechanism for NMD complex regulation.

    Evidence Cryo-EM, subunit-specific ATPase-dead mutant analysis, in vitro binding

    PMID:33205750

    Open questions at the time
    • Functional consequence of DHX34-induced ATPase inhibition on NMD efficiency not directly tested
    • Whether other clients also target RUVBL2 selectively unknown
  13. 2020 High

    Expanding chaperone clients to the cytoskeleton: RUVBL1–RUVBL2 was shown to assemble γTuRC from subcomplexes without itself becoming part of the final product, establishing it as a transient assembly factor for microtubule nucleation.

    Evidence siRNA depletion with γTuRC composition analysis, heterologous reconstitution, cryo-EM of product

    PMID:33355144

    Open questions at the time
    • Which γTuRC subcomplexes directly bind RUVBL unknown
    • Whether R2TP or a distinct adaptor mediates γTuRC assembly not established
  14. 2022 High

    Linking RUVBL2 to RNA Pol II cluster formation and transcription initiation: rapid depletion showed RUVBL2 co-occupies promoters with unphosphorylated Pol II and is required for Pol II clustering and nascent RNA synthesis.

    Evidence ChIP-seq, auxin-inducible degron, live-cell Pol II imaging, tethering assay

    PMID:36171202

    Open questions at the time
    • Whether RUVBL2 promotes Pol II clustering via phase separation or structural scaffolding unknown
    • Direct physical contact with Pol II not demonstrated
  15. 2025 High

    Identifying RUVBL2 as a conserved circadian timer: the extremely slow intrinsic ATPase rate (~13 ATP/day) was shown to set circadian period across eukaryotes, with specific variants producing arrhythmic, short-, or long-period phenotypes in the mouse SCN.

    Evidence Enzymatic ATPase assay, AAV-mediated SCN delivery of RUVBL2 variants, cross-species Co-IP with clock proteins

    PMID:40140583

    Open questions at the time
    • How slow ATPase kinetics mechanistically translate to ~24-hour timing unknown
    • Whether RUVBL1 ATPase contributes independently to period-setting untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major open question: how a single RUVBL1–RUVBL2 hexameric ring integrates signals from dozens of client-specific adaptors (PIH1D1, ZNHIT2, Ino80INS, CCDC103, DHX34) to coordinate assembly of structurally unrelated complexes, and whether the slow ATPase cycle that times the circadian clock is the same catalytic cycle that drives rapid chaperone-assisted assembly.
  • No unified structural model of client prioritization or queuing at the RUVBL ring
  • In vivo ATPase rates during specific assembly reactions unmeasured
  • Whether circadian and chaperone functions are genetically separable untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140657 ATP-dependent activity 7 GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 4 GO:0044183 protein folding chaperone 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 3 GO:0005694 chromosome 2 GO:0005829 cytosol 2
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-4839726 Chromatin organization 2 R-HSA-73894 DNA Repair 2 R-HSA-9909396 Circadian clock 2 R-HSA-8953854 Metabolism of RNA 1
Partners
BMAL1CCDC103DHX34LRRC6PIH1D1RPAP3RUVBL1ZNHIT2
Complex memberships
INO80 chromatin remodeling complexR2TP (RUVBL1-RUVBL2-RPAP3-PIH1D1)TIP60/NuA4 complex

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Reptin52 (RUVBL2) was identified as an interacting partner of Pontin52 (RUVBL1); both proteins bind beta-catenin and TBP, and they antagonistically regulate beta-catenin/TCF-mediated transcriptional activation. Drosophila orthologs dpontin and dreptin act antagonistically in Wingless signaling in vivo. Co-immunoprecipitation, reporter gene assays, Drosophila genetic epistasis The EMBO journal High 11080158
1999 TIP49b (RUVBL2) is a single-stranded DNA-stimulated ATPase and ATP-dependent DNA helicase with 5'-to-3' polarity (opposite to TIP49a/RUVBL1). TIP49b and TIP49a bind each other and form a ~700 kDa complex in cells. Enzyme ATPase and helicase assays in vitro, co-immunoprecipitation, gel filtration The Journal of biological chemistry High 10428817
2006 Recombinant human TIP48 (RUVBL2) and TIP49 (RUVBL1) form a stable equimolar complex with synergistic ATPase activity; both subunits are required for ATP hydrolysis (catalytic mutants in either abolish activity). The complex forms a dodecamer of two stacked hexameric rings with C6 symmetry by EM. No DNA helicase or branch migration activity was detected for the human complex. In vitro ATPase assay, Walker B mutagenesis, negative-stain electron microscopy, 3D reconstruction Journal of molecular biology High 17157868
2008 Yeast Rvb1/Rvb2 (RUVBL1/RUVBL2 orthologs) form a heterohexameric ring; the complex has ATPase activity stimulated by double-stranded DNA with overhangs and exhibits 5'-to-3' DNA helicase activity. Individual Rvb proteins also have helicase activity, but weaker than the complex. In vitro ATPase assay, DNA helicase assay, electron microscopy, size exclusion chromatography Journal of molecular biology High 18234224
2010 RUVBL1 and RUVBL2 associate with each PIKK family member (ATM, ATR, mTOR, DNA-PK, SMG-1, TRRAP) and regulate PIKK abundance at the mRNA level. Knockdown of RUVBL1/2 decreases PIKK levels and impairs PIKK-mediated signaling. RUVBL1/2 associate with SMG-1 and mRNPs in the cytoplasm and promote formation of NMD surveillance complexes. Co-immunoprecipitation, siRNA knockdown, immunoblot, mRNA quantification Science signaling High 20371770
2011 Crystal structure of human RuvBL1-RuvBL2 complex (domain II truncation) reveals a dodecamer of two heterohexameric rings with alternating RUVBL1/RUVBL2 monomers bound to ADP/ATP. Domain II auto-inhibits helicase/ATPase activity; truncation of DII leads to increased ATP consumption. DII interacts with the retained part of DII across rings. X-ray crystallography, small-angle X-ray scattering, in vitro ATPase assay Journal of structural biology High 21933716
2012 Cryo-EM structures of human RuvBL1-RuvBL2 reveal two coexisting conformations (compact and stretched) driven by movements in domain II (DII). DII domains connect to the AAA+ core and bind nucleic acids; conformational transitions regulate exposure of DNA-binding regions. Cryo-electron microscopy, image classification, 3D reconstruction at ~15 Å Nucleic acids research High 23002137
2001 TIP49b (RUVBL2) was identified as an ATF2-interacting protein by yeast two-hybrid; the interaction is phosphorylation-dependent and requires ATF2 residues 150-248. Forced expression of TIP49b attenuates ATF2 transcriptional activity under normal conditions and after UV/IR/p38 activation; a competing ATF2 peptide relieved suppression. Yeast two-hybrid, co-immunoprecipitation, reporter gene assay, forced expression/competition Molecular and cellular biology Medium 11713276
2009 TIP48 (RUVBL2) and TIP49 (RUVBL1) play a major role in catalyzing TIP60-mediated H2A acetylation-induced H2A.Z exchange via their ATPase activities. Two distinct H2A.Z-interacting complexes (small and big) were purified from human cells; the small complex containing TIP48/49 enhances H2A.Z-H2B dimer incorporation specifically after H2A acetylation. Biochemical purification, in vitro nucleosome exchange assay, ATPase mutant analysis Nucleic acids research High 19696079
2010 TIP49b (RUVBL2) monomers cooperatively bind single-stranded DNA, stimulating a slow ATPase; monomers support 3'-to-5' DNA unwinding requiring a 3'-protruding tail ≥30 nucleotides. In contrast, TIP49b hexamers are inactive for ATP hydrolysis and DNA unwinding. In vitro DNA binding, ATPase assay, DNA helicase assay with defined substrates The FEBS journal Medium 20553504
2013 Reptin/RUVBL2 directly interacts with the PCD protein Lrrc6/Seahorse in zebrafish; this interaction is critical for Lrrc6 function in vivo. In reptin mutants, axonemal dynein arm density is reduced despite unchanged/elevated dynein mRNA. Reptin is enriched in the cytosol and colocalizes with Lrrc6, suggesting the complex functions in cytoplasmic dynein arm assembly. Co-immunoprecipitation, immunofluorescence colocalization, zebrafish genetics (reptin mutant), transmission EM of axonemes Proceedings of the National Academy of Sciences of the United States of America High 23858445
2013 GATA3 associates with RUVBL2 and together they repress Cdkn2c transcription to facilitate Th2 cell proliferation. GATA3 binds the Cdkn2c locus in an RUVBL2-dependent manner; RUVBL2 knockdown decreased antigen-induced Th2 expansion and reduced airway inflammation in vivo. Co-immunoprecipitation, ChIP, siRNA knockdown, in vivo mouse model Proceedings of the National Academy of Sciences of the United States of America High 24167278
2013 TIP48/Reptin (RUVBL2) is required for chromatin remodeling at the CCND1 locus in estrogen-stimulated cells: TIP48 promotes H2A.Z acetylation and exchange, which triggers dissociation of a repressive intragenic loop and enables estrogen receptor binding to the CCND1 promoter. ChIP, RNAi knockdown, chromatin conformation capture, co-immunoprecipitation PLoS genetics Medium 23637611
2014 RuvBL1-RuvBL2 co-purify with the Fanconi anemia core complex under stringent native conditions. Depletion of RUVBL1-RUVBL2 in human cells leads to co-depletion of the FA core complex, DNA crosslinker sensitivity, chromosomal instability, and defective FANCD2 monoubiquitination. Conditional RuvBL1 KO in mouse hematopoietic stem cells causes aplastic anemia. Native affinity purification-MS, siRNA knockdown, conditional mouse KO, ICL sensitivity assay Nucleic acids research High 25428364
2014 YY1 oligomers interact with RuvBL1-RuvBL2 complexes; YY1 interacts preferentially with RuvBL1 in vitro. DNA binding by YY1 oligomers is enhanced in the presence of RuvBL1-RuvBL2. YY1 and the ATPase activity of RuvBL2 are required for RAD51 foci formation during homologous recombination. In vitro binding, electron microscopy, bimolecular fluorescence complementation, ATPase mutant, RAD51 foci assay The Journal of biological chemistry Medium 24990942
2015 RUVBL1 and RUVBL2 function as disaggregases/chaperones for aggresome formation: their depletion suppresses aggresome formation and causes buildup of cytoplasmic aggregates. The aggresome substrate synphilin-1 interacts directly with the RuvbL1 barrel-like structure near the central channel opening. Unfolded polypeptides and amyloid fibrils stimulate RuvbL ATPase activity; RuvbL promotes disassembly of protein aggregates. siRNA screen, co-immunoprecipitation, in vitro ATPase stimulation assay, amyloid disaggregation assay, yeast genetic experiments The EMBO journal High 26303906
2017 RUVBL1/RUVBL2 (R2TP/PFDL complex) interact with the U5 snRNP primarily through ZNHIT2; ZNHIT2 directly binds RUVBL2 via its zinc-finger HIT domain. Disruption of ZNHIT2 or RUVBL2 impairs U5 snRNP protein composition, indicating a function in U5 snRNP assembly. Multiple-target affinity purification-MS, co-immunoprecipitation, siRNA knockdown, snRNP complex analysis Nature communications High 28561026
2017 An Ino80 ATPase domain (Ino80INS) stimulates Rvb1/Rvb2 ATPase activity 16-fold and promotes dodecamerization; cryo-EM and cross-linking MS show Ino80INS binds asymmetrically along the dodecamerization interface. ATP addition collapses the stimulated dodecamer into hexamers, suggesting ATP-driven hexamer/dodecamer cycling as a chaperone mechanism for complex assembly. In vitro ATPase assay, cryo-EM, cross-linking mass spectrometry, integrative modeling Cell reports High 28591576
2005 TIP48 (RUVBL2) relocalizes during mitosis: in interphase it is nuclear with a nuclear periphery pattern; upon mitotic entry it is excluded from condensing chromosomes and associates with the mitotic apparatus; during anaphase some localizes to centrosomes and the midzone/midbody. This relocalization is independent of microtubule assembly. Immunofluorescence microscopy during cell cycle, biochemical fractionation, microtubule depolymerization Experimental cell research Medium 16157330
2019 Cryo-EM structures of the R2TP complex (RUVBL1-RUVBL2-RPAP3-PIH1D1) show that PIH1D1 binding to the DII domain of RUVBL2 induces conformational rearrangements that destabilize an N-terminal segment of RUVBL2 acting as a gatekeeper to nucleotide exchange, thereby regulating RUVBL2 ATPase activity. Cryo-electron microscopy, structural comparison of nucleotide-bound states Science advances High 31049401
2019 RUVBL1/2 ATPase activity is required for PAQosome maturation/dissociation and for DNA replication. Pharmacological inhibition of RUVBL1/2 ATPase activity causes S-phase arrest and replication catastrophe in NSCLC cells. ATPase inhibitor treatment, PAQosome complex analysis, cell cycle assay, replication fork assay Cell chemical biology Medium 31883965
2020 Cryo-EM reveals that DHX34 (NMD RNA helicase) directly interacts with RUVBL1-RUVBL2 in vitro and in cells, inducing extensive changes in the N-termini of every RUVBL2 subunit, stabilizing a conformation that does not bind nucleotide and thereby downregulating ATP hydrolysis. DHX34 acts exclusively on RUVBL2 subunits (shown by ATPase-deficient mutants of RUVBL1 vs. RUVBL2). Cryo-electron microscopy, in vitro binding assay, Co-immunoprecipitation, ATPase-deficient mutant analysis eLife High 33205750
2020 RUVBL2 interacts with core clock proteins (including BMAL1) on chromatin at E-box loci to regulate the circadian phase. Cordycepin (a RUVBL2 ATPase inhibitor) causes disassembly of the RUVBL2-BMAL1 interaction and disruption of the circadian super-complex, leading to a 12-hour phase shift. Crystal structure of RUVBL2 complexed with a cordycepin metabolite was solved. Crystal structure, Co-immunoprecipitation, spike-in ChIP-seq, pharmacological perturbation, in vivo mouse jet-lag model Science translational medicine High 32376767
2020 RUVBL1-RUVBL2 controls assembly and composition of the γ-tubulin ring complex (γTuRC) in human cells. RUVBL interacts with γTuRC subcomplexes but is not part of fully assembled γTuRC. In a heterologous coexpression system, RUVBL assembles γTuRC from core subunits; reconstituted γTuRC has nucleation activity confirmed by cryo-EM. siRNA depletion with γTuRC composition analysis, heterologous coexpression reconstitution, Co-immunoprecipitation, cryo-EM at ~4 Å Science advances High 33355144
2017 Liver-specific knockout of Reptin/RUVBL2 decreases mTOR protein abundance; primary hepatocyte experiments demonstrate RUVBL2 maintains mTOR protein levels through its ATPase activity. Loss of RUVBL2 causes opposing effects on mTORC1 (inhibition) and mTORC2 (enhancement), affecting lipogenesis/cholesterol and gluconeogenesis programs respectively. Inducible liver-specific KO mouse, primary hepatocyte ATPase inhibition, signaling pathway analysis by immunoblot Gut High 29074727
2009 RUVBL2 was identified as an AS160-binding protein by tandem affinity purification/mass spectrometry. In adipocytes, RUVBL2 is mainly cytosolic. RUVBL2 depletion inhibits insulin-stimulated GLUT4 translocation and glucose uptake by reducing AS160 phosphorylation; reintroduction of RUVBL2 rescues this defect. Tandem affinity purification-MS, Co-immunoprecipitation, siRNA knockdown, GLUT4 translocation assay Cell research Medium 19532121
2011 RuvBl2 cooperates with Ets2 to regulate hTERT transcription in colon cancer. SILAC proteomic and molecular studies identified RuvBl2 as a co-regulator of Ets2-driven hTERT promoter activity. SILAC proteomics, co-immunoprecipitation, reporter assay, ChIP FEBS letters Medium 21763315
2022 RUVBL2 co-occupies promoters with unphosphorylated RNA Pol II and promotes RPB1 CTD clustering and transcription initiation. Rapid depletion of RUVBL2 decreases the number of Pol II clusters and inhibits nascent RNA synthesis. Tethering RUVBL2 to an active promoter enhances Pol II clustering. ChIP-seq, rapid nuclear depletion (degron), live-cell imaging of Pol II clusters, RNA synthesis assay (EU labeling), tethering assay Nature communications High 36171202
2012 RUVBL2 is a transcriptional repressor of ARF: ectopic RUVBL2 decreases ARF levels and RUVBL2 knockdown increases ARF. RUVBL2 binds the distal region of the ARF promoter (ChIP) and represses ARF transcription, downregulating p53 in an ARF-dependent manner. ChIP, ectopic expression and siRNA knockdown, luciferase reporter assay FEBS letters Medium 22285491
2022 RUVBL2 functions as an indispensable chaperone for nuclear export of NFAT5 under hypotonicity, a process driven by exportin-T (XPOT). RUVBL2 was identified by siRNA screening and proteomics; its role in NFAT5 nuclear export is tonicity-regulated. siRNA screening, proteomics, Co-immunoprecipitation, nuclear export assay Journal of cell science Medium 35635291
2025 RUVBL2 (and orthologs) is a conserved eukaryotic clock component whose ATPase activity (hydrolyzing only ~13 ATP/day, extremely slow) regulates circadian period. RUVBL2 variants identified as arrhythmic, short-period, or long-period when delivered by AAV to the mouse SCN. RUVBL2 orthologs physically interact with core clock proteins in humans, Drosophila, and Neurospora. ATPase enzymatic assay, AAV-mediated SCN delivery, circadian locomotor assay, Co-immunoprecipitation across species, RUVBL2 variant mutagenesis Nature High 40140583
2022 Ruvbl2 functions as a suppressor of cardiomyocyte proliferation in zebrafish: loss-of-function (deletion allele) causes ventricular hyperplasia via hyperproliferation; constitutive myocardial overexpression suppresses cardiomyocyte proliferation and rescues hyperproliferation. Heat-shock-inducible Ruvbl2 overexpression during regeneration suppresses cardiomyocyte proliferation and leads to scarring. Zebrafish deletion allele, transgenic overexpression (constitutive and inducible), BrdU/EdU proliferation assay, heart regeneration model Frontiers in cell and developmental biology High 35178388
2016 Ruvbl2 was detected in mitochondria-enriched fractions in leukemic cells via BioID proximity labeling of POLG. Transgenic overexpression from an alternative translation initiation site resulted in mitochondrial co-localization of Ruvbl2. BioID proximity labeling, subcellular fractionation, transgenic overexpression with fluorescence colocalization Mitochondrion Low 27845271
2025 Cryo-EM structure of the human RUVBL1-RUVBL2-CCDC103 complex (R2C) at 3.2 Å resolution shows a hetero-hexameric RUVBL1-RUVBL2 ring bound to three CCDC103 molecules via their RUVBL2-binding domains (RBDs). Unlike RPAP3 in R2TP, CCDC103 lacks PIH1D1-binding and TPR domains; its flexible N-terminal region regulates RUVBL1-RUVBL2 oligomerization. PCD patient mutations in CCDC103 impair dynein assembly via this complex. Cryo-electron microscopy at 3.2 Å, biochemical reconstitution, disease mutation analysis bioRxivpreprint High
2024 Rvb1 and Rvb2 have distinct active sites: replacing the arginine finger of Rvb1 vs. Rvb2 has different effects on catalytic activity of the complex and on interaction with binding partners. Long-range conformational changes from the active site propagate to the insertion domain (DII), providing a mechanism for relaying ATPase activity to cofactor-binding domains. Arginine finger variants affect snoRNP biogenesis. In vitro ATPase assay, mutagenesis of arginine fingers, molecular dynamics simulation, genetic screen, Co-immunoprecipitation bioRxivpreprint Medium
2022 Rvb1 and Rvb2 couple transcription and translation during glucose starvation: they are enriched at promoters and mRNAs of alternative glucose metabolism genes. Engineered Rvb1/2 binding to mRNAs sequesters them into mRNP granules, represses translation, and drives further transcriptional upregulation. Depletion of Rvb2 decreases gene mRNA induction but upregulates protein synthesis during starvation. ChIP-seq, RNA-seq, mRNA tethering assay, stress granule imaging, polysome profiling, yeast genetics eLife Medium 36107469
2021 Reptin52/RUVBL2 interacts with HIF-2α both in nuclear and cytoplasmic fractions. This interaction reduces HIF-2 transcriptional activity and EPO secretion under hypoxia by impairing HIF-2α stability via a non-canonical PHD-VHL-proteasome-independent mechanism; ERK1/2 pathway inactivation favors the cytoplasmic RUVBL2-HIF-2α interaction. Co-immunoprecipitation (nuclear/cytoplasmic fractions), reporter assay, EPO secretion assay, pathway inhibitor experiments Biochemical and biophysical research communications Medium 33865222
2022 DPCD directly interacts with RUVBL1 and RUVBL2 in vitro and in cells. DPCD binds primarily via the DII domains of RUVBL1/RUVBL2 and disrupts the dodecameric state of the R1R2 complex upon binding, converting it to smaller species. Co-immunoprecipitation, in vitro binding, SAXS, cross-linking MS, electron microscopy Journal of molecular biology Medium 35901867

Source papers

Stage 0 corpus · 73 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Pontin52 and reptin52 function as antagonistic regulators of beta-catenin signalling activity. The EMBO journal 238 11080158
2009 RVB1/RVB2: running rings around molecular biology. Molecular cell 192 19524533
2010 AAA+ proteins RUVBL1 and RUVBL2 coordinate PIKK activity and function in nonsense-mediated mRNA decay. Science signaling 130 20371770
1999 TIP49b, a new RuvB-like DNA helicase, is included in a complex together with another RuvB-like DNA helicase, TIP49a. The Journal of biological chemistry 122 10428817
2011 Structural and functional insights into a dodecameric molecular machine - the RuvBL1/RuvBL2 complex. Journal of structural biology 104 21933716
2017 R2TP/Prefoldin-like component RUVBL1/RUVBL2 directly interacts with ZNHIT2 to regulate assembly of U5 small nuclear ribonucleoprotein. Nature communications 94 28561026
2005 Myc interacts genetically with Tip48/Reptin and Tip49/Pontin to control growth and proliferation during Drosophila development. Proceedings of the National Academy of Sciences of the United States of America 86 16087886
2006 Dodecameric structure and ATPase activity of the human TIP48/TIP49 complex. Journal of molecular biology 85 17157868
2014 Autoantibodies to RuvBL1 and RuvBL2: a novel systemic sclerosis-related antibody associated with diffuse cutaneous and skeletal muscle involvement. Arthritis care & research 84 24023044
2013 Chaperone-like activity of the AAA+ proteins Rvb1 and Rvb2 in the assembly of various complexes. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 82 23530256
2012 A forward genetic screen reveals roles for Nfkbid, Zeb1, and Ruvbl2 in humoral immunity. Proceedings of the National Academy of Sciences of the United States of America 81 22761313
2008 Yeast Rvb1 and Rvb2 are ATP-dependent DNA helicases that form a heterohexameric complex. Journal of molecular biology 76 18234224
2001 TIP49b, a regulator of activating transcription factor 2 response to stress and DNA damage. Molecular and cellular biology 66 11713276
2020 RUVBL1-RUVBL2 AAA-ATPase: a versatile scaffold for multiple complexes and functions. Current opinion in structural biology 60 33129013
2010 Rvb1-Rvb2: essential ATP-dependent helicases for critical complexes. Biochemistry and cell biology = Biochimie et biologie cellulaire 60 20130677
2019 RUVBL1/RUVBL2 ATPase Activity Drives PAQosome Maturation, DNA Replication and Radioresistance in Lung Cancer. Cell chemical biology 56 31883965
2009 Cooperative action of TIP48 and TIP49 in H2A.Z exchange catalyzed by acetylation of nucleosomal H2A. Nucleic acids research 54 19696079
2011 Clustering of GLUT4, TUG, and RUVBL2 protein levels correlate with myosin heavy chain isoform pattern in skeletal muscles, but AS160 and TBC1D1 levels do not. Journal of applied physiology (Bethesda, Md. : 1985) 52 21799128
2013 Reptin/Ruvbl2 is a Lrrc6/Seahorse interactor essential for cilia motility. Proceedings of the National Academy of Sciences of the United States of America 51 23858445
2012 Conformational transitions regulate the exposure of a DNA-binding domain in the RuvBL1-RuvBL2 complex. Nucleic acids research 51 23002137
2015 RuvbL1 and RuvbL2 enhance aggresome formation and disaggregate amyloid fibrils. The EMBO journal 47 26303906
2020 Assembly of the asymmetric human γ-tubulin ring complex by RUVBL1-RUVBL2 AAA ATPase. Science advances 46 33355144
2005 Relocalization of human chromatin remodeling cofactor TIP48 in mitosis. Experimental cell research 45 16157330
2017 Regulation of Rvb1/Rvb2 by a Domain within the INO80 Chromatin Remodeling Complex Implicates the Yeast Rvbs as Protein Assembly Chaperones. Cell reports 43 28591576
2014 Structure of Yin Yang 1 oligomers that cooperate with RuvBL1-RuvBL2 ATPases. The Journal of biological chemistry 43 24990942
2019 Structural mechanism for regulation of the AAA-ATPases RUVBL1-RUVBL2 in the R2TP co-chaperone revealed by cryo-EM. Science advances 39 31049401
2010 Oligomeric assembly and interactions within the human RuvB-like RuvBL1 and RuvBL2 complexes. The Biochemical journal 39 20412048
2010 Comparison of the multiple oligomeric structures observed for the Rvb1 and Rvb2 proteins. Biochemistry and cell biology = Biochimie et biologie cellulaire 38 20130681
2022 The transcriptional coactivator RUVBL2 regulates Pol II clustering with diverse transcription factors. Nature communications 36 36171202
2020 Chemical perturbations reveal that RUVBL2 regulates the circadian phase in mammals. Science translational medicine 36 32376767
2014 Abundance of the Fanconi anaemia core complex is regulated by the RuvBL1 and RuvBL2 AAA+ ATPases. Nucleic acids research 35 25428364
2012 Integrated regulation of PIKK-mediated stress responses by AAA+ proteins RUVBL1 and RUVBL2. Nucleus (Austin, Tex.) 35 22540023
2013 TIP48/Reptin and H2A.Z requirement for initiating chromatin remodeling in estrogen-activated transcription. PLoS genetics 33 23637611
2013 The AAA+ ATPase RUVBL2 is a critical mediator of MLL-AF9 oncogenesis. Leukemia 32 23403462
2013 Gata3/Ruvbl2 complex regulates T helper 2 cell proliferation via repression of Cdkn2c expression. Proceedings of the National Academy of Sciences of the United States of America 28 24167278
2011 RuvBl2 cooperates with Ets2 to transcriptionally regulate hTERT in colon cancer. FEBS letters 25 21763315
1999 Isolation, molecular characterization, and tissue-specific expression of ECP-51 and ECP-54 (TIP49), two homologous, interacting erythroid cytosolic proteins. Biochimica et biophysica acta 25 10524211
2017 Liver Reptin/RUVBL2 controls glucose and lipid metabolism with opposite actions on mTORC1 and mTORC2 signalling. Gut 23 29074727
2019 Identification of RUVBL1 and RUVBL2 as Novel Cellular Interactors of the Ebola Virus Nucleoprotein. Viruses 22 31018511
2009 RUVBL2, a novel AS160-binding protein, regulates insulin-stimulated GLUT4 translocation. Cell research 21 19532121
2020 Sorafenib as an Inhibitor of RUVBL2. Biomolecules 19 32295120
2019 The AAA+ATPase RUVBL2 is essential for the oncogenic function of c-MYB in acute myeloid leukemia. Leukemia 19 31138842
2015 Yeast rvb1 and rvb2 proteins oligomerize as a conformationally variable dodecamer with low frequency. Journal of molecular biology 18 25636407
2025 The P-loop NTPase RUVBL2 is a conserved clock component across eukaryotes. Nature 16 40140583
2020 Regulation of RUVBL1-RUVBL2 AAA-ATPases by the nonsense-mediated mRNA decay factor DHX34, as evidenced by Cryo-EM. eLife 14 33205750
2000 Human TIP49b/RUVBL2 gene: genomic structure, expression pattern, physical link to the human CGB/LHB gene cluster on chromosome 19q13.3. Annales de genetique 14 10998447
2016 Characterizing the mitochondrial DNA polymerase gamma interactome by BioID identifies Ruvbl2 localizes to the mitochondria. Mitochondrion 12 27845271
2016 Proteomic and Genomic Analyses of the Rvb1 and Rvb2 Interaction Network upon Deletion of R2TP Complex Components. Molecular & cellular proteomics : MCP 11 26831523
2012 RUVBL2 is a novel repressor of ARF transcription. FEBS letters 11 22285491
2013 RuvBL2 is involved in histone deacetylase inhibitor PCI-24781-induced cell death in SK-N-DZ neuroblastoma cells. PloS one 10 23977108
2010 3'- to 5' DNA unwinding by TIP49b proteins. The FEBS journal 10 20553504
2020 PPARγ enhanced Adiponectin polymerization and trafficking by promoting RUVBL2 expression during adipogenic differentiation. Gene 9 32877748
2021 Novel HIF-2α interaction with Reptin52 impairs HIF-2 transcriptional activity and EPO secretion. Biochemical and biophysical research communications 8 33865222
2022 Deciphering cellular and molecular determinants of human DPCD protein in complex with RUVBL1/RUVBL2 AAA-ATPases. Journal of molecular biology 7 35901867
2008 Cloning, expression, purification, crystallization and preliminary X-ray analysis of the human RuvBL1-RuvBL2 complex. Acta crystallographica. Section F, Structural biology and crystallization communications 7 18765919
2007 Functional and comparative characterization of Saccharomyces cerevisiae RVB1 and RVB2 genes with bacterial Ruv homologues. FEMS yeast research 7 17302941
2024 Knockdown of RUVBL2 improves hnRNPA2/B1-stress granules dynamics to inhibit perioperative neurocognitive disorders in aged mild cognitive impairment rats. Aging cell 6 39610020
2022 Unconventional tonicity-regulated nuclear trafficking of NFAT5 mediated by KPNB1, XPOT and RUVBL2. Journal of cell science 6 35635291
2022 Rvb1/Rvb2 proteins couple transcription and translation during glucose starvation. eLife 6 36107469
2009 Reptin52 expression during in vitro neural differentiation of human embryonic stem cells. Neuroscience letters 6 19444951
2016 RuvB-Like Protein 2 (Ruvbl2) Has a Role in Directing the Neuroectodermal Differentiation of Mouse Embryonic Stem Cells. Stem cells and development 5 27469992
2021 Leishmania major RUVBL1 has a hexameric conformation in solution and, in the presence of RUVBL2, forms a heterodimer with ATPase activity. Archives of biochemistry and biophysics 4 33775623
2021 Reptin/RUVBL2 is required for hepatocyte proliferation in vivo, liver regeneration and homeostasis. Liver international : official journal of the International Association for the Study of the Liver 3 33792165
2020 Modeling of a 14 kDa RUVBL2-Binding Domain with Medium Resolution Cryo-EM Density. Journal of chemical information and modeling 3 32175735
2024 A novel LINC02321 promotes cell proliferation and decreases cisplatin sensitivity in bladder cancer by regulating RUVBL2. Translational oncology 2 38677015
2022 Ruvbl2 Suppresses Cardiomyocyte Proliferation During Zebrafish Heart Development and Regeneration. Frontiers in cell and developmental biology 2 35178388
2023 Genetic and chemical targeting of the ATPase complex TIP48 and 49 impairs acute myeloid leukemia. Leukemia 1 37491463
2018 NMR assignment and solution structure of the external DII domain of the yeast Rvb2 protein. Biomolecular NMR assignments 1 29569106
2026 RUVBL2 Regulates Microglia Metabolic Reprogramming to Mediate Stress Granules Aggregation Exacerbating Postoperative Delirium in Aged Mild Cognitive Impairment Rats. Aging cell 0 41931282
2026 RUVBL1 and RUVBL2 are druggable MYC effector regulators in neuroblastoma cells. iScience 0 41940329
2025 Profiling of RUVBL2-Induced Transcriptome Alterations Highlights a Critical Role for Chromatin Remodeling in Ovarian Cancer. BioFactors (Oxford, England) 0 40757751
2025 ASPH interacts with RUVBL2 to promote tumor metastasis in lung adenocarcinoma via MAPK and Notch signaling pathways. Frontiers of medicine 0 41454078
2024 Differential roles of putative arginine fingers of AAA+ ATPases Rvb1 and Rvb2. bioRxiv : the preprint server for biology 0 38798342