Affinage

PSMC3IP

Homologous-pairing protein 2 homolog · UniProt Q9P2W1

Length
217 aa
Mass
24.9 kDa
Annotated
2026-06-10
56 papers in source corpus 36 papers cited in narrative 36 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PSMC3IP (HOP2/GT198/TBPIP) is a nuclear protein that functions principally as an essential cofactor for the DMC1 and RAD51 recombinases during homologous recombination, while also serving as a tissue-specific transcriptional regulator. In meiosis it localizes to chromosomes before and during synapsis and is required to repair programmed double-strand breaks and to prevent synaptonemal complex formation between nonhomologous chromosomes (PMID:9708739, PMID:14667414). It acts as a stable heterodimer with MND1, whose chromatin localization depends on HOP2 (PMID:11940665); this heterodimer binds DNA—preferring duplex and three-stranded branch intermediates—and stimulates DMC1- and RAD51-mediated strand invasion and exchange up to 35-fold (PMID:15249670, PMID:15834424, PMID:16407260). Mechanistically, HOP2-MND1 acts through a bipartite scheme: it stabilizes the recombinase-ssDNA presynaptic filament and facilitates capture of duplex DNA to nucleate the synaptic complex (PMID:17639081, PMID:17639080), and it codiffuses with the DMC1-ssDNA complex, clamping ssDNA-dsDNA junctions and maintaining an expanded DNA bubble to enable homology recognition (PMID:41746729). The heterodimer additionally serves as a sequence-fidelity switch that suppresses illegitimate recombination between microhomologous substrates via its recombinase-interaction surface (PMID:39463417). Structurally HOP2-MND1 forms a curved/V-shaped rod with juxtaposed winged-helix DNA-binding domains, leucine-zipper coiled coils, and a C-terminal helical bundle that engages the recombinase nucleofilament (PMID:24150939, PMID:24711446, PMID:25740648). Independent of recombination, PSMC3IP acts as a nuclear-receptor coactivator that binds the DNA-binding domains of ERα/β, AR, GR, PR, and TRβ1 and potentiates their transcription (PMID:11739747), interacts with the proteasomal ATPase PSMC3/TBP-1 to augment AR-driven transcription (PMID:19325002), and modulates osteoblast and adipocyte differentiation through interactions with ATF4 and CEBPα (PMID:31433867, PMID:34600885). A homozygous in-frame deletion (p.Glu201del) in the C-terminal acidic domain causes XX gonadal dysgenesis by abolishing estrogen-driven coactivation and impairing recombinase stimulation (PMID:21963259, PMID:25820426), and the recombination function underlies PARP-inhibitor and irradiation sensitivity in mitotic and cancer cells (PMID:37163373).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 1998 High

    Established that HOP2 is a meiotic chromosome factor required for repair of double-strand breaks and for fidelity of synapsis, distinguishing it from break-formation machinery.

    Evidence Genetic analysis and immunofluorescence of hop2 mutant yeast meiotic chromosome spreads

    PMID:9708739

    Open questions at the time
    • No biochemical activity defined
    • Partner proteins unknown
    • Molecular basis of synapsis defect not resolved
  2. 2002 High

    Identified MND1 as HOP2's obligate partner, defining the functional unit as a heterodimer and showing HOP2 directs MND1 to chromatin.

    Evidence Co-immunoprecipitation, immunofluorescence and genetic epistasis in meiotic cells

    PMID:11940665

    Open questions at the time
    • Biochemical mechanism of the complex unknown
    • Direct DNA/recombinase activities not yet shown
  3. 2002 High

    Revealed a recombination-independent role: PSMC3IP/GT198 is a tissue-specific coactivator binding nuclear-receptor DNA-binding domains and is regulated by phosphorylation.

    Evidence Yeast two-hybrid, in vitro binding, reporter and in vitro kinase assays

    PMID:11739747

    Open questions at the time
    • In vivo relevance of each receptor interaction not established
    • Coactivation mechanism (chromatin/cofactor recruitment) undefined
  4. 2003 High

    Confirmed in mammals that HOP2 is required for homologous chromosome synapsis and meiotic DSB repair without affecting break formation.

    Evidence Hop2 knockout mouse cytological analysis of spermatocytes

    PMID:14667414

    Open questions at the time
    • Direct molecular substrate not defined in vivo
    • Relationship to recombinase activity not yet biochemically shown
  5. 2004 High

    Demonstrated direct biochemical activity: purified HOP2 binds dsDNA and stimulates DMC1-mediated pairing, and the HOP2-MND1 heterodimer stimulates DMC1 strand assimilation, placing HOP2/MND1/DMC1 in one pathway.

    Evidence Reconstituted in vitro pairing/strand assimilation assays, deletion analysis, genetic epistasis

    PMID:15192114 PMID:15249670

    Open questions at the time
    • RAD51 specificity unresolved across species
    • Structural basis of recombinase stimulation unknown
  6. 2005 High

    Showed that MND1 binding switches off HOP2's intrinsic D-loop activity and creates the interface enabling the heterodimer to physically engage and strongly stimulate both RAD51 and DMC1.

    Evidence In vitro D-loop and strand invasion assays, co-immunoprecipitation

    PMID:15834424

    Open questions at the time
    • Conformational change not structurally defined
    • Division of labor between subunits unclear
  7. 2006 High

    Defined the bipartite/conformational logic of the complex—coiled-coil-mediated dimerization, MND1-induced HOP2 conformational change, C-terminal DNA binding, and recombinase stimulation—and extended activity to human proteins.

    Evidence Purified protein biochemistry, mutagenesis, strand exchange assays, sedimentation analysis (human and yeast)

    PMID:16407260 PMID:16581767 PMID:16675459

    Open questions at the time
    • Atomic structure still lacking
    • Quantitative kinetics of stimulation unresolved
  8. 2007 High

    Dissected the dual mechanism: HOP2-MND1 both stabilizes the recombinase-ssDNA presynaptic filament and promotes duplex DNA capture for synaptic complex assembly, with HOP2 as the DNA-binding and MND1 as the RAD51-interacting subunit.

    Evidence Reconstituted filament-stability and duplex-capture assays, interaction mapping, EM (yeast and mouse)

    PMID:17426123 PMID:17639080 PMID:17639081

    Open questions at the time
    • Structural arrangement on the filament not resolved
    • Cross-species recombinase specificity differences unexplained
  9. 2009 High

    Connected the coactivator role to the proteasomal ATPase PSMC3/TBP-1, which binds the HOP2 N-terminal leucine zipper and augments androgen-receptor transcription at target promoters.

    Evidence Yeast two-hybrid, Co-IP in LNCaP cells, reporter assays and ChIP

    PMID:19325002

    Open questions at the time
    • Mechanism linking proteasome ATPase to transcription unclear
    • Generality beyond AR/PSA promoter untested
  10. 2011 Medium

    Provided a human disease link, showing that a C-terminal acidic-domain deletion (p.Glu201del) causes XX gonadal dysgenesis by abolishing estrogen-driven coactivation.

    Evidence Homozygosity mapping, exome sequencing, cell-based reporter assay

    PMID:21963259

    Open questions at the time
    • Single functional readout (reporter only)
    • Effect on recombinase function not tested in this study
    • How a coactivation defect produces dysgenesis unresolved
  11. 2013 High

    Refined subunit autonomy and disease association: HOP2 alone has ATP-independent recombinase activity partly active in vivo, while truncating GT198 mutations and dominant-negative splice variants disrupt RAD51 foci, coactivation, and promote tumor growth.

    Evidence In vitro strand exchange, Mnd1 knockout mouse, germline mutation screening, RAD51 foci assays, xenografts

    PMID:23946868 PMID:23946869 PMID:24304900

    Open questions at the time
    • Cancer-association statistics limited to single-lab cohorts
    • Dominant-negative mechanism not structurally defined
  12. 2014 High

    Established structural and mechanistic detail: HOP2's N-terminal winged-helix DNA-binding fold, and HOP2-MND1-induced conformational changes that reprogram RAD51 nucleotide/DNA-binding behavior during filament formation and homology search.

    Evidence NMR solution structure with mutagenesis; in vitro strand exchange and nucleotide/DNA-binding assays with RAD51 mutants

    PMID:24711446 PMID:24943459

    Open questions at the time
    • Full heterodimer structure not yet solved
    • Conformational change in RAD51 not visualized directly
  13. 2015 High

    Delivered the architecture and disease mechanism: a curved rod with juxtaposed winged-helix domains and a recombinase-engaging helical bundle, and direct evidence that p.Glu201del weakens RAD51/DMC1 association and stimulation.

    Evidence Crystal structure and SAXS/EM, deletion analysis, modeling onto the nucleofilament; mutant protein interaction and strand-invasion assays

    PMID:24150939 PMID:25740648 PMID:25820426

    Open questions at the time
    • Cryo-EM of the complex on a filament not available
    • How disease mutant affects both transcription and recombination jointly unresolved
  14. 2017 Medium

    Extended GT198 to angiogenesis and tumor-cell-of-origin biology by linking its activation to VEGF expression and tube formation.

    Evidence Cell culture activation/overexpression, VEGF reporter and tube-formation assays, xenograft models

    PMID:28881671

    Open questions at the time
    • Molecular pathway to VEGF undefined
    • Single-lab evidence
  15. 2018 High

    Quantified the specificity of recombinase engagement in budding yeast, showing rapid high-affinity binding to DMC1-ssDNA filaments but not RAD51- or RPA-ssDNA.

    Evidence Single-molecule DNA-curtain real-time binding measurements

    PMID:30420424

    Open questions at the time
    • Species divergence in RAD51 vs DMC1 specificity unresolved
    • Structural basis of selective binding unknown
  16. 2019 High

    Defined a coactivator role in bone: HOP2 binds ATF4 via its Zip domain and enhances ATF4-dependent transcription, with KO and compound-heterozygote mice phenocopying osteopenia.

    Evidence Yeast two-hybrid, deletion mapping, reporter assays, knockout mouse skeletal phenotype, genetic epistasis

    PMID:31433867

    Open questions at the time
    • Direct chromatin co-occupancy of HOP2-ATF4 not shown
    • Relationship to recombination function in osteoblasts unclear
  17. 2021 High

    Defined an opposing differentiation role in fat: HOP2 binds CEBPα and suppresses its transactivation to inhibit adipogenesis, with KO mice showing increased adiposity.

    Evidence Pull-down, endogenous Co-IP, reporter assays, stable overexpression, knockout mouse, ChIP

    PMID:34600885

    Open questions at the time
    • How HOP2 suppresses rather than coactivates here is unexplained
    • Tissue-specific switch between coactivation and repression undefined
  18. 2021 Medium

    Linked PSMC3IP-dependent HR to cancer radioresistance and stemness, with Oct4A upstream regulation.

    Evidence Knockdown, clonogenic and self-renewal assays, PARP inhibitor combinations in HNSCC

    PMID:34079088

    Open questions at the time
    • Upstream Oct4A regulation mechanism not rigorously defined
    • Direct HR contribution vs indirect effects not separated
  19. 2023 High

    Established PSMC3IP/MND1 as targetable HR factors in mitotic cells: their loss causes toxic RAD51 foci, HR defects and PARPi/IR sensitivity even in BRCA1/53BP1-deficient cells, with rescue dependent on the intact D-loop function lost in p.Glu201del.

    Evidence Genome-scale CRISPR screens, depletion, RAD51 foci, HR reporter, PARPi assays, WT vs mutant rescue

    PMID:37163373

    Open questions at the time
    • Therapeutic window in patient tumors untested
    • Source of toxic RAD51 foci not fully mechanistically defined
  20. 2023 High

    Resolved the kinetic mechanism of DMC1 filament stimulation: HOP2-MND1 binds DNA first to recruit DMC1 and enhance nucleation rate, distinct from Swi5-Sfr1 which slows dissociation.

    Evidence Single-molecule FRET and TPM with order-of-addition experiments (fission yeast)

    PMID:37395447

    Open questions at the time
    • Conservation of nucleation mechanism in human proteins not shown here
    • Coordination with other mediators in vivo unclear
  21. 2024 High

    Defined a fidelity-switch function: HOP2-MND1 promotes recombination on homologous/mismatched substrates but suppresses illegitimate recombination on microhomology via its recombinase-interaction surface, not DNA binding.

    Evidence In vitro strand exchange with separation-of-function variants and defined mismatch/microhomology substrates

    PMID:39463417

    Open questions at the time
    • In vivo relevance of fidelity switch untested
    • Structural basis of microhomology discrimination unknown
  22. 2025 Medium

    Placed HOP2 downstream of GDF15 in adipogenic control, where it mediates GDF15-induced CEBPα suppression.

    Evidence GDF15 overexpression with HOP2 knockdown and adipogenesis assays

    PMID:39814165

    Open questions at the time
    • Direct GDF15-HOP2 signaling link not defined
    • Single functional epistasis readout
  23. 2026 High

    Captured the homology-search mechanism in human proteins: HOP2-MND1 codiffuses with the DMC1-ssDNA complex, clamps ssDNA-dsDNA junctions and maintains an expanded migrating DNA bubble enabling homology recognition.

    Evidence Single-molecule imaging of reconstituted human DMC1/HOP2-MND1 system

    PMID:41746729

    Open questions at the time
    • Coupling of bubble maintenance to downstream strand exchange not resolved
    • Structure of the migrating complex not solved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PSMC3IP is partitioned between its recombination and transcriptional-coactivator/repressor roles in different tissues, and what regulatory signals (e.g. phosphorylation) toggle these functions, remains unresolved.
  • Tissue-specific control of dual function undefined
  • No structural model unifying coactivation and recombination domains
  • Direct chromatin-targeting mechanism of the coactivator role unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 5 GO:0098772 molecular function regulator activity 4 GO:0140096 catalytic activity, acting on a protein 4 GO:0140110 transcription regulator activity 4 GO:0140097 catalytic activity, acting on DNA 3
Localization
GO:0005634 nucleus 3 GO:0005694 chromosome 3
Pathway
R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1474165 Reproduction 3 R-HSA-1266738 Developmental Biology 2 R-HSA-73894 DNA Repair 2
Partners
ARATF4CEBPADMC1ESR1MND1PSMC3RAD51
Complex memberships
HOP2-MND1 heterodimer

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 Yeast Hop2 (ortholog of PSMC3IP) localizes to meiotic chromosomes prior to and during synapsis, independent of double-strand breaks, and is required to prevent synaptonemal complex formation between nonhomologous chromosomes; hop2 mutants sustain wild-type DSB levels but these breaks remain unrepaired. Genetic analysis of hop2 mutant, immunofluorescence localization, meiotic chromosome spreads Cell High 9708739
2002 Hop2 and Mnd1 co-immunoprecipitate from meiotic cell extracts and form a complex; Mnd1 localization to chromatin requires Hop2; they act together to promote meiotic chromosome pairing and DSB repair. Co-immunoprecipitation, immunofluorescence, genetic epistasis (null mutant analysis) Molecular and cellular biology High 11940665
2003 Mouse Hop2 knockout spermatocytes fail to synapse homologous chromosomes (very limited synapsis) and cannot repair meiotic DSBs, despite normal DSB formation and processing, demonstrating a direct role in promoting homologous chromosome synapsis. Hop2 knockout mouse, immunofluorescence of meiotic chromosome spreads, cytological analysis Developmental cell High 14667414
2004 Purified mouse TBPIP/HOP2 protein stimulates DMC1-mediated homologous pairing in vitro; this stimulation requires HOP2 to first bind double-stranded DNA; the C-terminal basic region is required for DNA binding and pairing stimulation activity; HOP2 did not stimulate RAD51-mediated pairing in this study. In vitro homologous pairing assay with purified proteins, deletion analysis, DNA-binding assays The Journal of biological chemistry High 15192114
2004 Saccharomyces cerevisiae Hop2 and Mnd1 form a stable heterodimer with higher affinity for double-stranded than single-stranded DNA; this heterodimer stimulates the strand assimilation activity of Dmc1 in vitro; genetic double mutant analysis places HOP2, MND1, and DMC1 in the same pathway for homologous chromosome juxtaposition. Protein purification, biochemical strand assimilation assay, double-mutant genetic epistasis, DNA-binding assays Proceedings of the National Academy of Sciences of the United States of America High 15249670
2005 Mouse Hop2 alone can efficiently form D-loops; upon association with Mnd1, this Hop2 D-loop activity is abrogated; the Hop2-Mnd1 heterodimer physically interacts with both Rad51 and Dmc1 recombinases and stimulates their strand invasion activity up to 35-fold. In vitro D-loop assay, co-immunoprecipitation, reconstituted strand invasion assay with purified proteins Nature structural & molecular biology High 15834424
2006 Human TBPIP/Hop2-Mnd1 complex significantly stimulates Dmc1- and Rad51-mediated strand exchange and preferentially binds three-stranded DNA branch intermediates. Purification of human TBPIP/Hop2-Mnd1 complex, in vitro strand exchange assay, DNA-binding assays The Journal of biological chemistry High 16407260
2006 Interaction with Mnd1 provokes conformational changes in Hop2 that abrogate its own recombinase activity and generate a new molecular interface enabling Hop2-Mnd1 heterodimer to physically interact with and stimulate Dmc1; coiled-coil motifs in Hop2 and Mnd1 are essential for their mutual interaction; a C-terminal region is required for DNA binding and single-strand annealing by the heterodimer; a point mutation in Hop2 dissociates strand invasion from DNA binding/annealing. Purified protein biochemistry, mutagenesis, in vitro recombination assays, sedimentation analysis The Journal of biological chemistry High 16675459
2006 Mnd1/Hop2 is required for Dmc1-mediated interhomolog crossover recombination; in mnd1 rad51 and hop2 rad51 double mutants, crossover recombination can still occur, indicating Mnd1/Hop2 functions specifically in the Dmc1-dependent pathway and is required for stable strand invasion between homologous chromosomes. Genetic epistasis (double-mutant analysis), recombination assays in S. cerevisiae Molecular and cellular biology High 16581767
2007 Hop2-Mnd1 stimulates Dmc1-mediated recombination via two distinct mechanisms: (1) stabilizing the Dmc1-ssDNA nucleoprotein filament, and (2) facilitating duplex DNA capture by the Dmc1-ssDNA filament to promote synaptic complex formation on long duplex DNAs. In vitro strand invasion and synaptic complex formation assays, nucleoprotein filament stability assays with purified proteins Genes & development High 17639081
2007 Hop2 is the major DNA-binding subunit of the Hop2-Mnd1 complex while Mnd1 is the prominent Rad51-interaction entity; Hop2-Mnd1 stabilizes the Rad51-ssDNA nucleoprotein filament and enhances duplex DNA capture by the Rad51-ssDNA filament (bipartite mechanism). In vitro protein-DNA binding assays, Rad51-interaction mapping, presynaptic filament stability assays, duplex DNA capture assays with purified proteins Genes & development High 17639080
2007 Fission yeast spHop2-Mnd1 interacts by co-immunoprecipitation; it binds ssDNA ends of 3'-tailed DNA, promotes renaturation of complementary ssDNA, catalyzes strand exchange with short oligonucleotides, and stimulates spDmc1-dependent strand exchange and strand invasion. Mouse Hop2 or Hop2-Mnd1 stimulates both hRad51 and hDmc1, revealing evolutionary divergence in recombinase specificity. Co-immunoprecipitation, electron microscopy, in vitro strand exchange and strand invasion assays with purified proteins from S. pombe and mouse Nucleic acids research High 17426123
2002 GT198/PSMC3IP was identified as a tissue-specific nuclear coactivator that interacts with the DNA-binding domains (DBDs) of nuclear receptors (ERα/β, TRβ1, AR, GR, PR); interaction was shown by in vitro binding and yeast two-hybrid; GT198 potently stimulates transcription mediated by these receptors; PKA, PKC, and MAPK can phosphorylate GT198 in vitro, and cotransfection of these kinases regulates GT198 transcriptional activity. Yeast two-hybrid, in vitro binding assay, transcription reporter assays, in vitro kinase phosphorylation assays Molecular and cellular biology High 11739747
2009 TBP-1 (PSMC3, 19S proteasome ATPase) directly binds TBPIP/PSMC3IP through TBPIP's N-terminal leucine zipper; AR is physically associated with both TBP-1 and TBPIP in vitro and in LNCaP cells; TBP-1 augments AR-mediated transcription additively with TBPIP; TBP-1 is transiently recruited to the PSA gene promoter androgen response element in a ligand-dependent manner. Yeast two-hybrid, in vitro binding, co-immunoprecipitation in LNCaP cells, transcription reporter assays, chromatin immunoprecipitation Endocrinology High 19325002
2010 Hop2-Mnd1 heterodimer efficiently condenses double-stranded DNA via formation of DNA condensates, visualized at single-molecule level; condensation is concentration-dependent, reversible, and specific to the heterodimer (neither Hop2 nor Mnd1 alone can do this); condensation is accelerated by divalent metal ions (Mn2+>Mg2+>Ca2+); Hop2-Mnd1/Dmc1/ssDNA nucleoprotein filaments also condense dsDNA in a heterodimer concentration-dependent manner paralleling strand exchange activity. Single-molecule optical tweezers, video fluorescence microscopy, DNA condensation assays Biophysical journal High 21112301
2011 A homozygous 3-bp deletion in PSMC3IP (p.Glu201del) in the C-terminal acidic domain causes XX female gonadal dysgenesis; the mutation abolishes PSMC3IP coactivation of estrogen-driven transcription in cell lines, while not affecting the meiotic recombination domain (C-terminus absent in yeast). Homozygosity mapping, whole-exome sequencing, transcription reporter assay in cell lines American journal of human genetics Medium 21963259
2013 HOP2 alone (without MND1) can promote strand invasion, co-aggregation of ssDNA with duplex DNA, base unstacking on ssDNA, and formation of three-strand synaptic intermediates; this HOP2-only recombinase activity does not require ATP and is more sensitive to mismatches than DMC1; in Mnd1-/- spermatocytes expressing HOP2 without functional HOP2-MND1 complex, a fraction shows chromosome synapsis and DSB repair. In vitro strand exchange assay, in vitro ssDNA binding, Mnd1 knockout mouse analysis, immunofluorescence of spermatocytes Nucleic acids research High 24304900
2013 Inactivating germline mutations in GT198/PSMC3IP (including nonsense mutation p.Q104X) are found in familial and early-onset breast and ovarian cancer patients; the truncating p.Q104X mutation abolishes DNA damage-induced Rad51 foci formation, demonstrating a functional requirement for PSMC3IP in homologous recombination repair. Germline mutation screening, Sanger sequencing, Rad51 foci immunofluorescence after DNA damage Genes & cancer Medium 23946868
2013 GT198 splice variants lacking the full C-terminal domain act as dominant negatives: they counteract wild-type GT198 transcriptional coactivation activity and abolish Rad51 foci formation during radiation-induced DNA damage; expression of GT198 variant but not wild type induces tumor growth in nude mice. Transcription reporter assays, Rad51 foci immunofluorescence, in vivo xenograft tumor growth assay Genes & cancer Medium 23946869
2013 Small angle X-ray scattering (SAXS) and electron microscopy reveal that the Hop2-Mnd1 heterodimer forms a V-shaped molecule with three distinct DNA binding sites; N-terminal dsDNA-binding functions of Hop2 and Mnd1 cooperate to mediate synaptic complex assembly, while ssDNA binding by the Hop2 C-terminus stabilizes the DMC1-ssDNA filament. SAXS, electron microscopy, deletion mutagenesis, in vitro DNA-binding assays, strand invasion assays Nucleic acids research High 24150939
2014 HOP2-MND1 induces conformational changes in RAD51 that alter its nucleotide cofactor interactions and DNA-binding specificity: it enables RAD51 DNA strand exchange without divalent metal ions required for ATP binding, offsets the K133A ATP-binding mutation, helps load RAD51 on ssDNA restricting dsDNA-binding during presynaptic filament formation, and promotes dsDNA binding during homology search by removing inhibitory effect of ssDNA. In vitro strand exchange assays, nucleotide-binding assays, DNA-binding assays with purified proteins and RAD51 mutants Nature communications High 24943459
2014 The N-terminal domain of mouse HOP2 adopts a winged-helix (WH) DNA-binding fold as determined by NMR solution structure; helix 3 and wing 1 of the WH domain mediate DNA binding; a coiled-coil region mediates HOP2 self-association; mutations in key residues of the WH domain impair DNA binding and strand invasion activity. NMR solution structure determination, mutagenesis, DNA-binding assays, strand invasion assays The Journal of biological chemistry High 24711446
2015 Crystal structure of Hop2-Mnd1 reveals a curved rod-like structure with three leucine zippers and two kinked junctions, juxtaposed winged-helix domains at one end, and a helical bundle-like structure at the other; the helical bundle is sufficient for interacting with the Dmc1-ssDNA nucleofilament; molecular modeling suggests the curved rod fits into the helical groove of the nucleofilament. X-ray crystallography, deletion analysis, molecular modeling Nucleic acids research High 25740648
2015 The HOP2 p.del201Glu mutation (associated with XX ovarian dysgenesis) diminishes association of Hop2-Mnd1 with both RAD51 and DMC1 and reduces functional stimulation of their recombinase activity; both Hop2 and Mnd1 interact with RAD51 via their C-terminal regions; ATP enhances the interaction between Hop2-Mnd1 and RAD51; distinct DNA-binding activities of Hop2-Mnd1 mediate different aspects of RAD51 presynaptic filament stabilization vs. homologous DNA pairing stimulation. In vitro protein interaction assays, mutagenesis of C-terminal domains, strand invasion assays, presynaptic filament stabilization assays Nucleic acids research High 25820426
2015 PSMC3IP and EPSTI1 modulate the extrinsic apoptotic pathway in estrogen receptor-positive and triple-negative breast cancer cell lines, as demonstrated by modulation of apoptotic markers upon gene knockdown/overexpression. Gene knockdown/overexpression in cell lines, apoptosis marker analysis PloS one Low 25590583
2017 GT198/PSMC3IP-expressing pericytes give rise to tumor cells; activation of GT198 induces VEGF expression; GT198 promotes tube formation in cultured U251 cells, supporting a role in angiogenesis. Cell culture overexpression/activation, VEGF reporter assay, tube formation assay, in vivo xenograft and vaccination models Oncotarget Medium 28881671
2018 Yeast Hop2-Mnd1 binds rapidly to Dmc1-ssDNA filaments with high affinity (residence time ~1.3 min) in a highly specific manner; no association of Hop2-Mnd1 with Rad51-ssDNA or RPA-ssDNA was detected, demonstrating Dmc1-specific binding in S. cerevisiae. Single-molecule imaging using DNA curtains, real-time binding measurements The Journal of biological chemistry High 30420424
2019 Hop2 physically interacts with ATF4 transcription factor via its Zip domain (identified by yeast two-hybrid and confirmed by interaction assays); Hop2 enhances ATF4-dependent transcription; Hop2-/- mice exhibit an osteopenic phenotype similar to Atf4-/- mice with decreased Osteocalcin mRNA and reduced type I collagen synthesis; compound heterozygous Atf4+/-:Hop2+/- mice display the same skeletal defects as Hop2-/- mice. Yeast two-hybrid, deletional mapping, transcription reporter assay, Hop2 knockout mouse skeletal phenotype, genetic epistasis (compound heterozygotes) Journal of bone and mineral research High 31433867
2021 Hop2 physically interacts with CEBPα (confirmed by pull-down with recombinant proteins and co-immunoprecipitation of endogenous proteins from preadipocytes and adipocytes); Hop2 suppresses CEBPα-mediated transactivation; Hop2 stable overexpression inhibits adipocyte differentiation; Hop2-/- mice exhibit increased adiposity and adipogenic marker gene expression; ChIP shows higher CEBPα binding to PPARγ promoter in Hop2-/- adipose-derived MSCs. Pull-down, co-immunoprecipitation, transcription reporter assay, stable overexpression, Hop2 knockout mouse, ChIP The Journal of biological chemistry High 34600885
2021 Oct4 A transcriptionally regulates PSMC3IP expression; knockdown of PSMC3IP reduces HNSCC self-renewal capacity and clonogenic cell survival after irradiation, indicating PSMC3IP contributes to homologous recombination-mediated radioresistance and cancer stem cell phenotype. Knockdown of PSMC3IP, clonogenic survival assay, self-renewal assay, PARP inhibitor combination studies Oncogene Medium 34079088
2023 Depletion of PSMC3IP or MND1 in mitotic cells causes sensitivity to PARP inhibitors and ionizing radiation, independently of alternative lengthening of telomeres; depleted cells accumulate toxic RAD51 foci and show impaired homology-directed DNA repair; PARPi sensitivity occurs even in BRCA1/TP53BP1-deficient cells; wild-type PSMC3IP reverses PARPi sensitivity but the p.Glu201del ovarian dysgenesis mutant does not, linking the D-loop formation function to PARPi sensitivity. Genome-scale CRISPR screens, PSMC3IP/MND1 depletion, RAD51 foci immunofluorescence, HR reporter assay, PARP inhibitor sensitivity assays, rescue with wild-type vs mutant PSMC3IP Cell reports High 37163373
2023 Fission yeast Hop2-Mnd1 and Swi5-Sfr1 stimulate Dmc1 filament assembly by distinct mechanisms: Hop2-Mnd1 enhances the binding rate (nucleation) of Dmc1 at ssDNA/dsDNA junctions by binding DNA first to recruit Dmc1, while Swi5-Sfr1 specifically reduces the Dmc1 dissociation rate during nucleation; both proteins together allow further stimulation. Single-molecule FRET (smFRET), tethered particle motion (TPM), order-of-addition experiments with purified proteins Nucleic acids research High 37395447
2024 Hop2-Mnd1 acts as a DNA sequence fidelity switch for Dmc1: it upregulates Dmc1 activity with fully homologous or mismatch-containing substrates, but suppresses illegitimate recombination between substrates with only microhomology; suppression of illegitimate recombination requires the Dmc1 filament interaction attributable to Hop2-Mnd1 but not its DNA binding activity, as demonstrated by separation-of-function variants. In vitro strand exchange assays with Hop2-Mnd1 separation-of-function variants, DNA substrates with defined mismatches/microhomology Nature communications High 39463417
2025 GDF15 overexpression upregulates Hop2/PSMC3IP expression in pre-adipocytes; Hop2 mediates GDF15-induced suppression of C/EBPα expression and inhibition of adipogenesis, as Hop2 knockdown during GDF15 overexpression abolishes the suppression of C/EBPα. GDF15 overexpression, Hop2 knockdown, adipogenesis assay, gene expression analysis Molecular and cellular endocrinology Medium 39814165
2026 Human DMC1-ssDNA presynaptic complex employs diffusion-based homology search generating a migrating DNA bubble; HOP2-MND1 codiffuses with the DMC1-ssDNA presynaptic complex, clamps the ssDNA-dsDNA junctions, and maintains an expanded DNA bubble to enable homology recognition that cannot occur without HOP2-MND1 or free DMC1. Single-molecule imaging of human proteins, reconstituted in vitro system Proceedings of the National Academy of Sciences of the United States of America High 41746729
1997 Mouse TBPIP (ortholog of PSMC3IP) was cloned as a TBP-1-interacting protein; it co-localizes with TBP-1 in vivo and enhances TBP-1's inhibitory action on Tat-mediated transactivation of HIV replication in vitro. Protein-protein interaction cloning, co-localization, transactivation reporter assay Biochemical and biophysical research communications Low 9345291

Source papers

Stage 0 corpus · 56 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 The meiosis-specific Hop2 protein of S. cerevisiae ensures synapsis between homologous chromosomes. Cell 166 9708739
2005 The Hop2 and Mnd1 proteins act in concert with Rad51 and Dmc1 in meiotic recombination. Nature structural & molecular biology 144 15834424
2003 The Hop2 protein has a direct role in promoting interhomolog interactions during mouse meiosis. Developmental cell 142 14667414
2002 The Mnd1 protein forms a complex with hop2 to promote homologous chromosome pairing and meiotic double-strand break repair. Molecular and cellular biology 120 11940665
2007 Hop2/Mnd1 acts on two critical steps in Dmc1-promoted homologous pairing. Genes & development 101 17639081
2007 Bipartite stimulatory action of the Hop2-Mnd1 complex on the Rad51 recombinase. Genes & development 100 17639080
2004 Heterodimeric complexes of Hop2 and Mnd1 function with Dmc1 to promote meiotic homolog juxtaposition and strand assimilation. Proceedings of the National Academy of Sciences of the United States of America 94 15249670
2011 XX ovarian dysgenesis is caused by a PSMC3IP/HOP2 mutation that abolishes coactivation of estrogen-driven transcription. American journal of human genetics 80 21963259
2002 Identification and characterization of a tissue-specific coactivator, GT198, that interacts with the DNA-binding domains of nuclear receptors. Molecular and cellular biology 77 11739747
2006 Molecular activities of meiosis-specific proteins Hop2, Mnd1, and the Hop2-Mnd1 complex. The Journal of biological chemistry 65 16675459
2013 Mechanistic insights into the role of Hop2-Mnd1 in meiotic homologous DNA pairing. Nucleic acids research 51 24150939
2006 Stimulation of DNA strand exchange by the human TBPIP/Hop2-Mnd1 complex. The Journal of biological chemistry 49 16407260
2015 Significance of ligand interactions involving Hop2-Mnd1 and the RAD51 and DMC1 recombinases in homologous DNA repair and XX ovarian dysgenesis. Nucleic acids research 45 25820426
2014 HOP2-MND1 modulates RAD51 binding to nucleotides and DNA. Nature communications 44 24943459
2018 Primary Ovarian Insufficiency and Azoospermia in Carriers of a Homozygous PSMC3IP Stop Gain Mutation. The Journal of clinical endocrinology and metabolism 43 29240891
2015 Crystal structure of Hop2-Mnd1 and mechanistic insights into its role in meiotic recombination. Nucleic acids research 43 25740648
2021 Oct4 confers stemness and radioresistance to head and neck squamous cell carcinoma by regulating the homologous recombination factors PSMC3IP and RAD54L. Oncogene 40 34079088
2013 The dual role of HOP2 in mammalian meiotic homologous recombination. Nucleic acids research 39 24304900
2007 Stimulation of fission yeast and mouse Hop2-Mnd1 of the Dmc1 and Rad51 recombinases. Nucleic acids research 39 17426123
2006 Mnd1/Hop2 facilitates Dmc1-dependent interhomolog crossover formation in meiosis of budding yeast. Molecular and cellular biology 39 16581767
2004 Positive role of the mammalian TBPIP/HOP2 protein in DMC1-mediated homologous pairing. The Journal of biological chemistry 36 15192114
2015 Comprehensive Cross-Linking Mass Spectrometry Reveals Parallel Orientation and Flexible Conformations of Plant HOP2-MND1. Journal of proteome research 35 26535604
2014 The third exon of the budding yeast meiotic recombination gene HOP2 is required for calcium-dependent and recombinase Dmc1-specific stimulation of homologous strand assimilation. The Journal of biological chemistry 32 24798326
2010 Hop2-Mnd1 condenses DNA to stimulate the synapsis phase of DNA strand exchange. Biophysical journal 24 21112301
2017 Malignant pericytes expressing GT198 give rise to tumor cells through angiogenesis. Oncotarget 22 28881671
2009 Tat-binding protein-1 (TBP-1), an ATPase of 19S regulatory particles of the 26S proteasome, enhances androgen receptor function in cooperation with TBP-1-interacting protein/Hop2. Endocrinology 22 19325002
2013 Inactivating Mutations in GT198 in Familial and Early-Onset Breast and Ovarian Cancers. Genes & cancer 20 23946868
2000 Molecular cloning and characterization of a human homologue of TBPIP, a BRCA1 locus-related gene. Gene 20 10806355
1997 Molecular cloning and characterization of a novel TBP-1 interacting protein (TBPIP):enhancement of TBP-1 action on Tat by TBPIP. Biochemical and biophysical research communications 20 9345291
2018 Dynamic interactions of the homologous pairing 2 (Hop2)-meiotic nuclear divisions 1 (Mnd1) protein complex with meiotic presynaptic filaments in budding yeast. The Journal of biological chemistry 19 30420424
2015 Breast cancer genes PSMC3IP and EPSTI1 play a role in apoptosis regulation. PloS one 17 25590583
2013 GT198 Splice Variants Display Dominant-Negative Activities and Are Induced by Inactivating Mutations. Genes & cancer 17 23946869
2019 Hop2 Interacts with ATF4 to Promote Osteoblast Differentiation. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 16 31433867
2022 HOP1 and HOP2 are involved in salt tolerance by facilitating the brassinosteroid-related nucleo-cytoplasmic partitioning of the HSP90-BIN2 complex. Plant, cell & environment 15 36123951
2016 GT198 Expression Defines Mutant Tumor Stroma in Human Breast Cancer. The American journal of pathology 14 27001628
1999 Splicing of the meiosis-specific HOP2 transcript utilizes a unique 5' splice site. Molecular and cellular biology 14 10567519
2014 Solution structure and DNA-binding properties of the winged helix domain of the meiotic recombination HOP2 protein. The Journal of biological chemistry 13 24711446
2016 Hop2 and Sae3 Are Required for Dmc1-Mediated Double-Strand Break Repair via Homolog Bias during Meiosis. Molecules and cells 12 27329041
2013 Human ovarian cancer stroma contains luteinized theca cells harboring tumor suppressor gene GT198 mutations. The Journal of biological chemistry 11 24097974
2018 Knockdown of PSMC3IP suppresses the proliferation and xenografted tumorigenesis of hepatocellular carcinoma cell. Journal of cellular biochemistry 10 30362169
2014 No mutations in the PSMC3IP gene identified in a Swedish cohort of women with primary ovarian insufficiency. Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation 10 24481226
2022 Biallelic mutations in PSMC3IP are associated with secondary amenorrhea: expanding the spectrum of premature ovarian insufficiency. Journal of assisted reproduction and genetics 9 35352317
2015 Entamoeba histolytica Dmc1 Catalyzes Homologous DNA Pairing and Strand Exchange That Is Stimulated by Calcium and Hop2-Mnd1. PloS one 9 26422142
2023 Hop2-Mnd1 and Swi5-Sfr1 stimulate Dmc1 filament assembly using distinct mechanisms. Nucleic acids research 8 37395447
2023 MND1 and PSMC3IP control PARP inhibitor sensitivity in mitotic cells. Cell reports 7 37163373
2021 Hop2 interacts with the transcription factor CEBPα and suppresses adipocyte differentiation. The Journal of biological chemistry 7 34600885
2021 Two novel biallelic mutations in PSMC3IP in a patient affected by premature ovarian insufficiency. Molecular medicine reports 7 34878148
2017 GT198 (PSMC3IP) germline variants in early-onset breast cancer patients from hereditary breast and ovarian cancer families. Genes & cancer 7 28435519
2023 The Hop2-Mnd1 Complex and Its Regulation of Homologous Recombination. Biomolecules 6 37189409
2020 Oncoprotein GT198 vaccination delays tumor growth in MMTV-PyMT mice. Cancer letters 6 32061755
2025 GDF15 inhibits early-stage adipocyte differentiation by enhancing HOP2 expression and suppressing C/EBPα expression. Molecular and cellular endocrinology 4 39814165
2024 Hop2-Mnd1 functions as a DNA sequence fidelity switch in Dmc1-mediated DNA recombination. Nature communications 2 39463417
2021 GT198 Is a Target of Oncology Drugs and Anticancer Herbs. Frontiers in oral health 2 34476412
2017 Wing 1 of protein HOP2 is as important as helix 3 in DNA binding by MD simulation. Journal of biomolecular structure & dynamics 2 28531371
2023 Genomic targets of HOP2 are enriched for features found at recombination hotspots. bioRxiv : the preprint server for biology 1 36747711
2026 HOP2-MND1 chaperones a diffusing DMC1-ssDNA complex to survey dsDNA for homology recognition during meiotic recombination. Proceedings of the National Academy of Sciences of the United States of America 0 41746729

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