Affinage

PSMB7

Proteasome subunit beta type-7 · UniProt Q99436

Length
277 aa
Mass
30.0 kDa
Annotated
2026-06-10
100 papers in source corpus 1 papers cited in narrative 2 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 2/2 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PSMB7 (proteasome subunit beta-7) contributes selectively to the peptidyl-glutamyl peptide-hydrolyzing (caspase-like) catalytic activity of the 20S proteasome, as its knockdown in cardiomyocytes specifically reduces this activity without affecting chymotrypsin-like or trypsin-like activities (PMID:23969338). Loss of PSMB7-dependent proteasomal activity induces ER stress, marked by upregulation of DDIT3/CHOP and HSPA5/GRP78, and triggers autophagy, evidenced by accumulation of LC3-positive and MDC-labeled autophagic vacuoles, with these responses exacerbated by anoxia-reoxygenation (PMID:23969338). Beyond these cardiomyocyte loss-of-function findings, no further mechanistic detail on PSMB7 has been characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 2 steps
  1. 2013 Medium

    It was unknown which catalytic activity of the 20S proteasome PSMB7 supports; selective depletion established that PSMB7 contributes specifically to the caspase-like (peptidyl-glutamyl peptide-hydrolyzing) activity.

    Evidence siRNA knockdown with three proteasome activity assays in isolated neonatal cardiomyocytes

    PMID:23969338

    Open questions at the time
    • Single lab, single study without structural confirmation of the active site contribution
    • No reconstitution demonstrating direct catalytic role
    • Restricted to one cell type (cardiomyocytes)
  2. 2013 Medium

    The cellular consequence of losing PSMB7 activity was undefined; knockdown showed that reduced caspase-like proteasome activity drives ER stress and autophagy, linking PSMB7 to proteostatic stress responses under ischemic conditions.

    Evidence siRNA knockdown with RT-qPCR for ER stress markers, LC3 immunohistochemistry, and MDC staining, with anoxia-reoxygenation in neonatal cardiomyocytes

    PMID:23969338

    Open questions at the time
    • Causal mechanism linking caspase-like activity loss to CHOP/GRP78 induction not defined
    • Whether autophagy induction is protective or detrimental not resolved
    • No in vivo validation beyond isolated cardiomyocytes

Open questions

Synthesis pass · forward-looking unresolved questions
  • Whether PSMB7's role extends beyond cardiomyocyte proteostasis and how it integrates into broader proteasome assembly and substrate selection remains unestablished in the available corpus.
  • No structural or assembly-context data for PSMB7 in the timeline
  • No identified physical partners or substrates
  • No tissue-context beyond cardiomyocytes

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 1 GO:0140096 catalytic activity, acting on a protein 1
Pathway
R-HSA-392499 Metabolism of proteins 1
Complex memberships
20S proteasome

Evidence

Reading pass · 2 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2013 Knockdown of PSMB7 in neonatal cardiomyocytes via siRNA specifically decreased peptidyl-glutamyl peptide-hydrolyzing (caspase-like) proteasome activity without affecting chymotrypsin-like or trypsin-like activities, indicating that PSMB7 contributes selectively to this catalytic activity of the 20S proteasome. siRNA knockdown + proteasome activity assays (chymotrypsin-like, trypsin-like, peptidyl-glutamyl peptide-hydrolyzing) in isolated neonatal cardiomyocytes Pathobiology : journal of immunopathology, molecular and cellular biology Medium 23969338
2013 PSMB7 knockdown in cardiomyocytes induced ER stress, as evidenced by increased mRNA expression of DDIT3/CHOP and HSPA5/GRP78, and triggered autophagy marked by increased LC3-positive vacuoles and monodansylcadaverine (MDC)-labeled autophagic vacuoles; the effect was exacerbated after anoxia-reoxygenation. siRNA knockdown + single-cell RT-qPCR for ER stress markers (DDIT3/CHOP, HSPA5/GRP78) + immunohistochemistry for LC3 + MDC staining for autophagic vacuoles in neonatal cardiomyocytes Pathobiology : journal of immunopathology, molecular and cellular biology Medium 23969338

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 Influenza Virus Z-RNAs Induce ZBP1-Mediated Necroptosis. Cell 473 32200799
2008 Histone H2A.Z and DNA methylation are mutually antagonistic chromatin marks. Nature 438 18815594
2001 Structure of the DLM-1-Z-DNA complex reveals a conserved family of Z-DNA-binding proteins. Nature structural biology 265 11524677
2009 The A-Z of bacterial translation inhibitors. Critical reviews in biochemistry and molecular biology 253 19929179
2019 The histone variant H2A.Z in gene regulation. Epigenetics & chromatin 252 31200754
2012 Bacterial cytokinesis: From Z ring to divisome. Cytoskeleton (Hoboken, N.J.) 215 22888013
2008 H2A.Z: view from the top. Structure (London, England : 1993) 215 18275809
2006 DNA architecture: from G to Z. Current opinion in structural biology 215 16714104
2019 Z-DNA and Z-RNA in human disease. Communications biology 176 30729177
2012 Foxa2 and H2A.Z mediate nucleosome depletion during embryonic stem cell differentiation. Cell 169 23260146
2019 H2A.Z facilitates licensing and activation of early replication origins. Nature 146 31875854
2021 Regulatory B cells, A to Z. Allergy 145 33544905
1984 Human Protein Z. The Journal of clinical investigation 119 6707212
2009 The making of tRNAs and more - RNase P and tRNase Z. Progress in molecular biology and translational science 117 19215776
2009 The beauty of being a variant: H2A.Z and the SWR1 complex in plants. Molecular plant 112 19825639
2010 Changes in H2A.Z occupancy and DNA methylation during B-cell lymphomagenesis. Genome research 104 20709945
2011 The sarcomeric Z-disc and Z-discopathies. Journal of biomedicine & biotechnology 97 22028589
2007 Z-DNA, an active element in the genome. Frontiers in bioscience : a journal and virtual library 96 17485386
2009 Characterization of the histone H2A.Z-1 and H2A.Z-2 isoforms in vertebrates. BMC biology 91 20003410
2010 Reconciling the positive and negative roles of histone H2A.Z in gene transcription. Epigenetics 90 20364108
2013 Precise deposition of histone H2A.Z in chromatin for genome expression and maintenance. Biochimica et biophysica acta 88 24459731
2021 Deficient H2A.Z deposition is associated with genesis of uterine leiomyoma. Nature 86 34349258
2007 Arenavirus Z-glycoprotein association requires Z myristoylation but not functional RING or late domains. Journal of virology 84 17581989
2016 Structural basis of H2A.Z recognition by SRCAP chromatin-remodeling subunit YL1. Nature structural & molecular biology 82 26974124
2011 Intrinsic Z-DNA is stabilized by the conformational selection mechanism of Z-DNA-binding proteins. Journal of the American Chemical Society 82 21171590
2009 Acetylation of vertebrate H2A.Z and its effect on the structure of the nucleosome. Biochemistry 81 19385636
2015 H2A.Z: a molecular rheostat for transcriptional control. F1000prime reports 79 25705384
2021 Viral Z-RNA triggers ZBP1-dependent cell death. Current opinion in virology 72 34688984
2016 H2A.Z controls the stability and mobility of nucleosomes to regulate expression of the LH genes. Nature communications 70 27653784
2001 Protein Z in ischaemic stroke. British journal of haematology 69 11472363
2023 Histone variant H2A.Z modulates nucleosome dynamics to promote DNA accessibility. Nature communications 67 36765119
2021 The H2A.Z-nuclesome code in mammals: emerging functions. Trends in genetics : TIG 64 34702577
2009 Human genomic Z-DNA segments probed by the Z alpha domain of ADAR1. Nucleic acids research 60 19276205
2013 Structural polymorphism in the L1 loop regions of human H2A.Z.1 and H2A.Z.2. Acta crystallographica. Section D, Biological crystallography 58 24311584
1990 The human histone H2A.Z gene. Sequence and regulation. The Journal of biological chemistry 56 1697587
2016 H2A.Z.1 Monoubiquitylation Antagonizes BRD2 to Maintain Poised Chromatin in ESCs. Cell reports 55 26804911
2021 Histone variant H2A.Z regulates zygotic genome activation. Nature communications 52 34853314
2015 The DREAM complex promotes gene body H2A.Z for target repression. Genes & development 52 25737279
2009 Histone variant H2A.Z regulates centromere silencing and chromosome segregation in fission yeast. The Journal of biological chemistry 50 19910462
2021 Structural basis of chromatin regulation by histone variant H2A.Z. Nucleic acids research 49 34643712
2016 SMYD3-Mediated H2A.Z.1 Methylation Promotes Cell Cycle and Cancer Proliferation. Cancer research 49 27569210
2019 Znhit1 controls intestinal stem cell maintenance by regulating H2A.Z incorporation. Nature communications 48 30842416
2009 Transcriptional and epigenetic functions of histone variant H2A.Z. Biochemistry and cell biology = Biochimie et biologie cellulaire 48 19234520
2005 Protein Z gene polymorphisms, protein Z concentrations, and ischemic stroke. Stroke 47 15879328
2018 The A-Z of Zika drug discovery. Drug discovery today 46 29935345
2016 Studying Z-DNA and B- to Z-DNA transitions using a cytosine analogue FRET-pair. Nucleic acids research 45 26896804
2023 Structure and Formation of Z-DNA and Z-RNA. Molecules (Basel, Switzerland) 42 36677900
2020 Histone variant H2A.Z regulates nucleosome unwrapping and CTCF binding in mouse ES cells. Nucleic acids research 42 32392318
2021 Multiple roles of H2A.Z in regulating promoter chromatin architecture in human cells. Nature communications 41 33953180
2012 H2A.Z-dependent crosstalk between enhancer and promoter regulates cyclin D1 expression. Oncogene 41 23108396
2021 Non-redundant functions of H2A.Z.1 and H2A.Z.2 in chromosome segregation and cell cycle progression. EMBO reports 40 34423893
2018 Unveiling the pathway to Z-DNA in the protein-induced B-Z transition. Nucleic acids research 40 29584891
2012 DNA methylation, H2A.Z, and the regulation of constitutive expression. Cold Spring Harbor symposia on quantitative biology 40 23250988
2020 Distinct roles for H4 and H2A.Z acetylation in RNA transcription in African trypanosomes. Nature communications 39 32198348
2021 To "Z" or not to "Z": Z-RNA, self-recognition, and the MDA5 helicase. PLoS genetics 38 33983939
2021 H2A.Z overexpression suppresses senescence and chemosensitivity in pancreatic ductal adenocarcinoma. Oncogene 37 33627784
2015 Overexpression, Purification and Characterisation of the Plasmodium falciparum Hsp70-z (PfHsp70-z) Protein. PloS one 37 26083397
2023 Coordinated histone variant H2A.Z eviction and H3.3 deposition control plant thermomorphogenesis. The New phytologist 35 36647799
1997 Z-DNA crystallography . Biopolymers 34 19174848
2007 tRNase Z: the end is not in sight. Cellular and molecular life sciences : CMLS 33 17599240
2022 Tip60-mediated H2A.Z acetylation promotes neuronal fate specification and bivalent gene activation. Molecular cell 31 36417913
2008 Protein Z, a protein seeking a pathology. Thrombosis and haemostasis 31 18841275
1994 Radiolytic signature of Z-DNA. Nucleic acids research 31 7838708
1987 Cytoplasmic Z-RNA. Proceedings of the National Academy of Sciences of the United States of America 31 2442753
1985 Locations of Z-DNA in polytene chromosomes. The Journal of cell biology 30 3988806
2022 Coordinated DNA and histone dynamics drive accurate histone H2A.Z exchange. Science advances 28 35263135
2014 Dynamics of histone variant H3.3 and its coregulation with H2A.Z at enhancers and promoters. Nucleus (Austin, Tex.) 28 24637397
2001 Protein Z. Seminars in thrombosis and hemostasis 28 11668427
1984 Zinc Z-DNA. Nucleic acids research 28 6728681
2020 Variation on a theme: Evolutionary strategies for H2A.Z exchange by SWR1-type remodelers. Current opinion in cell biology 27 33217681
2019 The H2A.Z histone variant integrates Wnt signaling in intestinal epithelial homeostasis. Nature communications 27 31015444
2014 Histone H2A.Z deregulation in prostate cancer. Cause or effect? Cancer metastasis reviews 27 24398858
2015 Expression of Non-acetylatable H2A.Z in Myoblast Cells Blocks Myoblast Differentiation through Disruption of MyoD Expression. The Journal of biological chemistry 26 25839232
2021 INO80 promotes H2A.Z occupancy to regulate cell fate transition in pluripotent stem cells. Nucleic acids research 25 34139016
2019 DNA repair complex licenses acetylation of H2A.Z.1 by KAT2A during transcription. Nature chemical biology 25 31527837
2019 Interbase FRET in RNA: from A to Z. Nucleic acids research 25 31544922
2018 H2A.Z regulates tumorigenesis, metastasis and sensitivity to cisplatin in intrahepatic cholangiocarcinoma. International journal of oncology 25 29532867
2012 Retrogenes moved out of the z chromosome in the silkworm. Journal of molecular evolution 25 22535494
2022 Searching for New Z-DNA/Z-RNA Binding Proteins Based on Structural Similarity to Experimentally Validated Zα Domain. International journal of molecular sciences 24 35054954
2022 H2A.Z's 'social' network: functional partners of an enigmatic histone variant. Trends in biochemical sciences 24 35606214
2007 tRNase Z. Protein and peptide letters 23 17305600
2021 Sequence-dependent cost for Z-form shapes the torsion-driven B-Z transition via close interplay of Z-DNA and DNA bubble. Nucleic acids research 22 33744929
2024 The ancient Z-DNA and Z-RNA specific Zα fold has evolved modern roles in immunity and transcription through the natural selection of flipons. Royal Society open science 21 39092141
2020 VPS72/YL1-Mediated H2A.Z Deposition Is Required for Nuclear Reassembly after Mitosis. Cells 21 32708675
2018 Thermodynamic Model for B-Z Transition of DNA Induced by Z-DNA Binding Proteins. Molecules (Basel, Switzerland) 21 30355979
2023 The TORC1 activates Rpd3L complex to deacetylate Ino80 and H2A.Z and repress autophagy. Science advances 20 36888706
2021 ZSP-1 is a Z granule surface protein required for Z granule fluidity and germline immortality in Caenorhabditis elegans. The EMBO journal 20 33438773
2023 Z-flipon variants reveal the many roles of Z-DNA and Z-RNA in health and disease. Life science alliance 19 37164635
2022 Sex-specific splicing of Z- and W-borne nr5a1 alleles suggests sex determination is controlled by chromosome conformation. Proceedings of the National Academy of Sciences of the United States of America 19 35074916
2008 The Z-disk diseases. Advances in experimental medicine and biology 19 19181098
2020 Vital and Distinct Roles of H2A.Z Isoforms in Hepatocellular Carcinoma. OncoTargets and therapy 18 32547065
2020 Dual conformational recognition by Z-DNA binding protein is important for the B-Z transition process. Nucleic acids research 18 33245772
2024 Role of Z-DNA Binding Protein 1 Sensing Mitochondrial Z-DNA and Triggering Necroptosis in Oxalate-Induced Acute Kidney Injury. Journal of the American Society of Nephrology : JASN 17 39374087
2023 Structural insight into H4K20 methylation on H2A.Z-nucleosome by SUV420H1. Molecular cell 17 37536340
2022 GAS41 mediates proliferation and GEM chemoresistance via H2A.Z.2 and Notch1 in pancreatic cancer. Cellular oncology (Dordrecht, Netherlands) 17 35503594
2013 Knockdown of PSMB7 induces autophagy in cardiomyocyte cultures: possible role in endoplasmic reticulum stress. Pathobiology : journal of immunopathology, molecular and cellular biology 17 23969338
2023 The H2A.Z and NuRD associated protein HMG20A controls early head and heart developmental transcription programs. Nature communications 16 36709316
2022 H2A.Z deposition by SWR1C involves multiple ATP-dependent steps. Nature communications 16 36396651
2021 ylm Has More than a (Z Anchor) Ring to It! Journal of bacteriology 16 32900832
2017 Redundant Functions for Nap1 and Chz1 in H2A.Z Deposition. Scientific reports 16 28883625

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