Affinage

EXOSC2

Exosome complex component RRP4 · UniProt Q13868

Round 2 corrected
Length
293 aa
Mass
32.8 kDa
Annotated
2026-04-28
130 papers in source corpus 10 papers cited in narrative 10 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EXOSC2 (RRP4) is an essential cap subunit of the RNA exosome, a conserved multisubunit 3'→5' exoribonuclease complex that mediates processing and degradation of diverse RNA substrates. EXOSC2 sits atop the hexameric catalytic ring and confers substrate specificity, preferentially directing the complex toward polyadenylated RNA targets, while also enabling efficient substrate access to the catalytic core for phosphorolytic degradation (PMID:9390555, PMID:17174896, PMID:20488184). The exosome containing EXOSC2 is recruited to AU-rich element (ARE)-containing mRNAs by RNA-binding proteins such as TTP and KSRP, coupling it to rapid cytoplasmic mRNA turnover, and it functions in nucleolar 5.8S rRNA 3'-end processing (PMID:11719186, PMID:15687258, PMID:15635413). Biallelic missense mutations in EXOSC2 cause SHRF syndrome (retinitis pigmentosa, hearing loss, premature ageing, short stature, brachydactyly, and mild intellectual disability); the pathogenic G198D variant disrupts exosome subunit binding, destabilizes the complex, and deregulates autophagy, with autophagy stimulation rescuing loss-of-function phenotypes in Drosophila (PMID:26843489, PMID:31628467).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 1997 High

    The discovery that Rrp4p is an essential 3'→5' exoribonuclease subunit of the yeast exosome complex — and that human EXOSC2 complements the yeast mutation — established the conserved role of this gene in RNA processing and defined the exosome as a multisubunit degradation machine.

    Evidence Biochemical purification, in vitro exoribonuclease assay, and cross-species genetic complementation in yeast

    PMID:9390555

    Open questions at the time
    • Whether EXOSC2 itself contributes catalytic activity or solely serves a structural/substrate-channeling role in the human complex was unresolved
    • Identity of in vivo RNA substrates beyond 5.8S rRNA unknown
  2. 1999 High

    Demonstration that the human exosome exists in distinct nuclear and cytoplasmic pools, with EXOSC2 present in both, revealed compartment-specific functions and linked the complex to the PM-Scl autoantigen.

    Evidence Biochemical fractionation and indirect immunofluorescence in human cells

    PMID:10465791

    Open questions at the time
    • Whether EXOSC2 has compartment-specific roles beyond shared core membership was not addressed
    • Mechanism of nuclear versus cytoplasmic sorting of exosome subcomplexes undefined
  3. 2001 High

    The finding that the human exosome is required for ARE-mediated mRNA decay — recruited by ARE-binding proteins rather than recognizing substrates autonomously — placed EXOSC2-containing complexes at the center of regulated mRNA turnover.

    Evidence Affinity-purified human exosome tested in cell-free ARE-RNA decay assay with immunodepletion controls

    PMID:11719186

    Open questions at the time
    • Direct contact between EXOSC2 and ARE-binding adaptors was not mapped
    • Relative contributions of individual cap subunits to adaptor recruitment unknown
  4. 2005 High

    Identification of TTP and BRF-1 activation domains as direct exosome-recruiting interfaces provided a molecular mechanism for how ARE-containing mRNAs are coupled to 3'→5' exonucleolytic decay via the EXOSC2-containing complex.

    Evidence Co-immunoprecipitation and tethering assays with heterologous RNA-binding domain fusions, dominant-negative overexpression

    PMID:15687258

    Open questions at the time
    • Whether EXOSC2 is the direct binding partner for TTP/BRF-1 or whether another subunit mediates the interaction was not determined
  5. 2006 High

    The crystal structure of the reconstituted 9-subunit human exosome at 3.35 Å resolution revealed the barrel-like architecture with EXOSC2 as a cap subunit and demonstrated processive phosphorolytic activity of the ring, resolving the structural framework for substrate channeling.

    Evidence Recombinant reconstitution and X-ray crystallography of the human exosome complex

    PMID:17174896

    Open questions at the time
    • Structure did not resolve how RNA threads through the cap into the catalytic channel at high resolution
    • Human-specific regulatory contacts of EXOSC2 not detailed
  6. 2010 High

    Reconstitution of archaeal exosomes containing either Rrp4 or Csl4 cap subunits showed that the Rrp4 cap (EXOSC2 ortholog) confers a strong preference for poly(A) substrates, establishing that individual cap subunits dictate substrate specificity of the catalytic ring.

    Evidence In vitro RNA processing assays with defined archaeal exosome subcomplexes and systematic substrate variation

    PMID:20488184

    Open questions at the time
    • Whether the poly(A) preference of Rrp4/EXOSC2 is conserved in the eukaryotic 9-subunit context was not directly tested
    • Structural basis of poly(A) selectivity at the Rrp4 S1/KH domains unresolved
  7. 2016 Medium

    Whole-exome sequencing linked biallelic EXOSC2 missense mutations to SHRF syndrome, a previously unrecognized Mendelian disorder, demonstrating that partial loss of this exosome cap subunit produces tissue-specific pathology distinct from diseases caused by mutations in other exosome subunits.

    Evidence Whole-exome sequencing in three patients from two unrelated families

    PMID:26843489

    Open questions at the time
    • Molecular mechanism by which the mutations compromise exosome function was not characterized in this study
    • Why EXOSC2 mutations produce a different clinical spectrum than EXOSC3/EXOSC8 mutations remained unexplained
  8. 2020 High

    Functional characterization of the SHRF-associated G198D mutation revealed that it disrupts EXOSC2 binding to other exosome subunits, destabilizes the complex, and deregulates autophagy-related gene expression; pharmacological or genetic restoration of autophagy rescued loss-of-function phenotypes, identifying autophagy as a critical downstream effector of exosome integrity.

    Evidence Patient lymphoblasts, CRISPR mutant keratinocytes, Drosophila cross-species rescue experiments, and rapamycin pharmacological rescue

    PMID:31628467

    Open questions at the time
    • Whether autophagy deregulation is a direct consequence of specific RNA misprocessing or a secondary stress response is unclear
    • The EXOSC2-dependent RNA targets whose misprocessing drives the SHRF phenotype have not been identified transcriptome-wide
    • Whether rapamycin-based autophagy stimulation is a viable therapeutic strategy in SHRF patients is untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the identity of specific RNA substrates whose processing depends on the EXOSC2 cap (versus the EXOSC1/Csl4 cap) in human cells, the structural basis for poly(A) selectivity by the EXOSC2 S1/KH domains in the eukaryotic context, and why EXOSC2 mutations produce a tissue-specific disease spectrum (retina, cochlea, skeleton) despite the exosome's ubiquitous expression.
  • No transcriptome-wide identification of EXOSC2-cap-dependent versus EXOSC1-cap-dependent substrates in human cells
  • No high-resolution structure of EXOSC2 with RNA threaded through the channel in the eukaryotic context
  • Tissue-specific vulnerability mechanism for SHRF syndrome unexplained

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 4 GO:0140098 catalytic activity, acting on RNA 3
Localization
GO:0005634 nucleus 2 GO:0005730 nucleolus 2 GO:0005829 cytosol 1
Pathway
R-HSA-8953854 Metabolism of RNA 5 R-HSA-9612973 Autophagy 1
Partners
BRF1EXOSC4EXOSC7KSRPTTP
Complex memberships
RNA exosome

Evidence

Reading pass · 10 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 EXOSC2 (hRrp4/Rrp4p) was identified as a core component of the eukaryotic RNA exosome, a conserved multisubunit complex. Yeast Rrp4p (the ortholog of human EXOSC2) was shown to be an essential 3'→5' exoribonuclease required for 3' processing of 5.8S rRNA. Recombinant Rrp4p exhibited distributive 3'→5' exoribonuclease activity in vitro, and human hRRP4 was found in a comparably sized complex to the yeast exosome, with expression of hRRP4 complementing the yeast rrp4-1 mutation. Biochemical purification, in vitro exoribonuclease assay, genetic complementation (hRRP4 rescuing yeast rrp4-1) Cell High 9390555
1999 The human homolog of yeast Rrp4p (EXOSC2) was confirmed as a component of the human PM-Scl complex (equivalent to the yeast exosome). The human exosome exists in distinct nuclear and cytoplasmic forms; the nuclear form uniquely contains Rrp6p/PM-Scl100. Human Rrp4p (EXOSC2) was shown to complement the yeast rrp4 mutation, establishing functional conservation. The complex contains multiple predicted 3'→5' exoribonucleases. Biochemical fractionation, indirect immunofluorescence, genetic complementation, sequence homology analysis Genes & development High 10465791
2001 The human RNA exosome (containing EXOSC2/hRrp4 as a core subunit) was purified by mass spectrometry and shown to be required for rapid degradation of ARE-containing mRNAs in a cell-free RNA decay system. The exosome does not recognize ARE-containing RNAs autonomously; ARE-binding proteins (such as KSRP) interact with the exosome and recruit it to unstable target mRNAs. Affinity purification/mass spectrometry of human exosome, cell-free RNA decay assay, immunodepletion Cell High 11719186
2005 The ARE-binding proteins TTP and BRF-1 recruit the RNA exosome (which contains EXOSC2 as a core subunit) to ARE-containing mRNAs via two distinct activation domains. The N-terminal activation domain of TTP functions as a binding platform for mRNA decay enzymes including the exosome, linking ARE-mRNAs to 3'→5' exonucleolytic decay. Co-immunoprecipitation, tethering assays with heterologous RNA-binding domain fusions, dominant-negative overexpression Genes & development High 15687258
2006 The 9-subunit human RNA exosome (including EXOSC2/hRrp4) was reconstituted recombinantly and its X-ray crystal structure was determined at 3.35 Å resolution. Human Rrp41/Rrp45 heterodimer displayed processive phosphorolytic 3'→5' exoribonuclease activity, while the intact 9-subunit human exosome also showed processive phosphorolytic activity on AU-rich, poly(A), and generic RNA substrates. The structure revealed the conserved barrel-like architecture with EXOSC2 (Rrp4) as a cap subunit on the ring. Recombinant protein reconstitution, X-ray crystallography (3.35 Å), in vitro exoribonuclease assay with multiple RNA substrates Cell High 17174896
2005 EXOSC2 (hRrp4) was detected as part of the nucleolar proteome in human cells and was shown to flux out of the nucleolus in response to metabolic inhibitors (actinomycin D, 5-fluorouridine, RNase inhibitor), consistent with a role in nucleolar RNA processing. The exosome components including EXOSC2 exit the nucleolus with similar kinetics, indicating stable complex association. SILAC-based quantitative mass spectrometry of nucleolar proteome, in vivo fluorescent protein imaging, metabolic inhibitor treatment Nature Medium 15635413
2008 The archaeal exosome cap subunit Rrp4 (ortholog of human EXOSC2) from Sulfolobus solfataricus is required for efficient RNA degradation but not for polyadenylation by the hexameric catalytic ring. The Rrp4-containing exosome (versus the hexamer alone) enables efficient phosphorolytic degradation of substrates that the hexamer cannot efficiently process alone, demonstrating that the RNA-binding cap confers substrate accessibility to the catalytic core. In vitro reconstitution of archaeal exosome subcomplexes, RNA degradation and polyadenylation assays with varied substrates and conditions Biochemistry High 19053279
2010 The archaeal Rrp4-containing exosome (ortholog of EXOSC2) confers a strong preference for poly(A) RNA substrates, whereas the Csl4-containing exosome prefers A-poor 3'-ends. This demonstrates that the two cap subunits (Rrp4 and Csl4) impart distinct substrate specificities to the same catalytic ring, establishing that EXOSC2/Rrp4 specifically promotes processing of polyadenylated RNA targets. In vitro RNA processing assays with reconstituted archaeal exosome subcomplexes containing either Rrp4 or Csl4, using poly(A), polyU, and heteropolymeric RNA substrates FEBS letters High 20488184
2016 Biallelic missense mutations in EXOSC2 (encoding the RRP4 cap subunit of the RNA exosome) cause a novel human Mendelian syndrome (SHRF) characterized by retinitis pigmentosa, progressive sensorineural hearing loss, premature ageing, short stature, brachydactyly, and mild intellectual disability. Three patients from two unrelated families carried homozygous or compound heterozygous EXOSC2 missense variants, implicating altered RNA exosome function in the pathogenesis and demonstrating tissue-specific consequences distinct from other exosome subunit diseases (EXOSC3, EXOSC8). Whole exome sequencing, clinical ascertainment of three affected individuals from two unrelated families Journal of medical genetics Medium 26843489
2020 The SHRF-associated pathogenic G198D mutation in EXOSC2 prevents binding to other RNA exosome components, resulting in protein and complex instability. Patient-derived lymphoblasts and CRISPR-generated mutant fetal keratinocytes showed altered expression/activities of critical genes including those in the autophagy pathway. In Drosophila, the fly rrp4 ortholog was shown to be essential; fly rrp4 phenotypes (small eye, adult lethality) could be rescued by wild-type human EXOSC2 but not the G198D pathogenic form. Overexpression of MITF transcription factor, or the autophagy genes ATG1 and ATG17 (regulated by MITF), rescued rrp4 inhibition phenotypes. Pharmacological stimulation of autophagy with rapamycin also rescued lethality caused by rrp4 inactivation. Patient-derived lymphoblast analysis, CRISPR knockout in fetal keratinocytes, Drosophila genetics (PBac transposon, RNAi, CRISPR KO), cross-species rescue experiments, rapamycin pharmacological rescue Human molecular genetics High 31628467

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature 3411 32353859
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
1984 Philadelphia chromosomal breakpoints are clustered within a limited region, bcr, on chromosome 22. Cell 1545 6319012
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2011 Systematic and quantitative assessment of the ubiquitin-modified proteome. Molecular cell 1334 21906983
2004 Large-scale characterization of HeLa cell nuclear phosphoproteins. Proceedings of the National Academy of Sciences of the United States of America 1159 15302935
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2005 Nucleolar proteome dynamics. Nature 934 15635413
1985 Structural organization of the bcr gene and its role in the Ph' translocation. Nature 869 2989703
2020 A reference map of the human binary protein interactome. Nature 849 32296183
1983 Localization of the c-ab1 oncogene adjacent to a translocation break point in chronic myelocytic leukaemia. Nature 835 6316147
1997 The exosome: a conserved eukaryotic RNA processing complex containing multiple 3'-->5' exoribonucleases. Cell 807 9390555
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2001 AU binding proteins recruit the exosome to degrade ARE-containing mRNAs. Cell 736 11719186
1992 Sequence identification of 2,375 human brain genes. Nature 708 1538749
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2018 High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. Molecular cell 580 29395067
2020 Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms. Science (New York, N.Y.) 564 33060197
1986 Alternative splicing of RNAs transcribed from the human abl gene and from the bcr-abl fused gene. Cell 476 3021337
2006 Reconstitution, activities, and structure of the eukaryotic RNA exosome. Cell 449 17174896
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2005 Recruitment and activation of mRNA decay enzymes by two ARE-mediated decay activation domains in the proteins TTP and BRF-1. Genes & development 410 15687258
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
1999 The yeast exosome and human PM-Scl are related complexes of 3' --> 5' exonucleases. Genes & development 390 10465791
2003 The p7 protein of hepatitis C virus forms an ion channel that is blocked by the antiviral drug, Amantadine. FEBS letters 355 12560074
2007 Hepatitis C virus p7 and NS2 proteins are essential for production of infectious virus. Journal of virology 352 17537845
1994 Processing in the hepatitis C virus E2-NS2 region: identification of p7 and two distinct E2-specific products with different C termini. Journal of virology 304 7518529
2003 The hepatitis C virus p7 protein forms an ion channel that is inhibited by long-alkyl-chain iminosugar derivatives. Proceedings of the National Academy of Sciences of the United States of America 279 12719519
2007 Hepatitis C virus p7 protein is crucial for assembly and release of infectious virions. PLoS pathogens 277 17658949
2006 Compensatory mutations in E1, p7, NS2, and NS3 enhance yields of cell culture-infectious intergenotypic chimeric hepatitis C virus. Journal of virology 245 17079282
2013 Unusual architecture of the p7 channel from hepatitis C virus. Nature 222 23739335
2003 The p7 polypeptide of hepatitis C virus is critical for infectivity and contains functionally important genotype-specific sequences. Proceedings of the National Academy of Sciences of the United States of America 178 14504405
1998 Reactivity of the HIV-1 nucleocapsid protein p7 zinc finger domains from the perspective of density-functional theory. Proceedings of the National Academy of Sciences of the United States of America 172 9751708
2002 Subcellular localization and topology of the p7 polypeptide of hepatitis C virus. Journal of virology 161 11907211
2010 Intracellular proton conductance of the hepatitis C virus p7 protein and its contribution to infectious virus production. PLoS pathogens 143 20824094
2004 A conserved basic loop in hepatitis C virus p7 protein is required for amantadine-sensitive ion channel activity in mammalian cells but is dispensable for localization to mitochondria. The Journal of general virology 140 14769903
2000 E2-p7 region of the bovine viral diarrhea virus polyprotein: processing and functional studies. Journal of virology 122 11000219
1996 Processing in the pestivirus E2-NS2 region: identification of proteins p7 and E2p7. Journal of virology 118 8648755
1999 Inflammatory responses in the cerebral cortex after ischemia in the P7 neonatal Rat. Stroke 115 10471445
2006 Evidence for the formation of a heptameric ion channel complex by the hepatitis C virus p7 protein in vitro. The Journal of biological chemistry 113 17032656
2010 NMR structure and ion channel activity of the p7 protein from hepatitis C virus. The Journal of biological chemistry 110 20667830
2000 Polymorphism of HIV type 1 gag p7/p1 and p1/p6 cleavage sites: clinical significance and implications for resistance to protease inhibitors. AIDS research and human retroviruses 100 10957718
2008 Genotype-dependent sensitivity of hepatitis C virus to inhibitors of the p7 ion channel. Hepatology (Baltimore, Md.) 99 18828153
2013 hepatitis c Virus p7 is critical for capsid assembly and envelopment. PLoS pathogens 93 23658526
2006 Protein-protein interactions: modeling the hepatitis C virus ion channel p7. Journal of medicinal chemistry 87 16420050
1991 Structural characterization of a 39-residue synthetic peptide containing the two zinc binding domains from the HIV-1 p7 nucleocapsid protein by CD and NMR spectroscopy. FEBS letters 87 1959614
2010 Genomic analysis of carbon monoxide utilization and butanol production by Clostridium carboxidivorans strain P7. PloS one 83 20885952
1999 Binding properties of the human immunodeficiency virus type 1 nucleocapsid protein p7 to a model RNA: elucidation of the structural determinants for function. Journal of molecular biology 75 10074407
1998 Probing the structure of complex macromolecular interactions by homolog specificity scanning: the P1 and P7 plasmid partition systems. The EMBO journal 75 9774351
2016 Mutations in EXOSC2 are associated with a novel syndrome characterised by retinitis pigmentosa, progressive hearing loss, premature ageing, short stature, mild intellectual disability and distinctive gestalt. Journal of medical genetics 74 26843489
2010 A novel Hepatitis C virus p7 ion channel inhibitor, BIT225, inhibits bovine viral diarrhea virus in vitro and shows synergism with recombinant interferon-alpha-2b and nucleoside analogues. Antiviral research 71 20156486
2011 The P7-1 protein of southern rice black-streaked dwarf virus, a fijivirus, induces the formation of tubular structures in insect cells. Archives of virology 64 21671041
1995 Precursor of C4 antisense RNA of bacteriophages P1 and P7 is a substrate for RNase P of Escherichia coli. Proceedings of the National Academy of Sciences of the United States of America 63 7597035
2009 Characterization of determinants important for hepatitis C virus p7 function in morphogenesis by using trans-complementation. Journal of virology 62 19726506
2005 Signal peptide cleavage and internal targeting signals direct the hepatitis C virus p7 protein to distinct intracellular membranes. Journal of virology 61 16306623
1994 The homologous operons for P1 and P7 plasmid partition are autoregulated from dissimilar operator sites. Molecular microbiology 59 8170387
2009 Structural basis for ADP-mediated transcriptional regulation by P1 and P7 ParA. The EMBO journal 58 19461582
2009 Determinants of hepatitis C virus p7 ion channel function and drug sensitivity identified in vitro. Journal of virology 58 19493992
1989 Plasmid-partition functions of the P7 prophage. Journal of molecular biology 57 2585492
2012 Classical swine fever virus p7 protein is a viroporin involved in virulence in swine. Journal of virology 56 22496228
2006 Compensatory mutations at the HIV cleavage sites p7/p1 and p1/p6-gag in therapy-naive and therapy-experienced patients. Antiviral therapy 56 17302250
2009 Post-ischemic hypothermia for 24h in P7 rats rescues hippocampal neuron: association with decreased astrocyte activation and inflammatory cytokine expression. Brain research bulletin 55 19406216
2004 Regulation of hepatitis C virus polyprotein processing by signal peptidase involves structural determinants at the p7 sequence junctions. The Journal of biological chemistry 54 15247249
2012 The p7 protein of hepatitis C virus forms structurally plastic, minimalist ion channels. PLoS computational biology 52 23028296
2010 Secondary structure, dynamics, and architecture of the p7 membrane protein from hepatitis C virus by NMR spectroscopy. Biochimica et biophysica acta 49 20727850
2009 NMR studies of p7 protein from hepatitis C virus. European biophysics journal : EBJ 49 19727701
2013 Three-dimensional structure and interaction studies of hepatitis C virus p7 in 1,2-dihexanoyl-sn-glycero-3-phosphocholine by solution nuclear magnetic resonance. Biochemistry 48 23841474
1995 The tripartite immunity system of phages P1 and P7. FEMS microbiology reviews 48 7669337
2023 Biodegradation of polyester polyurethane by Cladosporium sp. P7: Evaluating its degradation capacity and metabolic pathways. Journal of hazardous materials 44 36706489
1990 The c4 repressors of bacteriophages P1 and P7 are antisense RNAs. Cell 43 1696181
2015 Structural and Functional Properties of the Hepatitis C Virus p7 Viroporin. Viruses 38 26258788
1993 The gag precursor contains a specific HIV-1 protease cleavage site between the NC (P7) and P1 proteins. FEBS letters 38 8224164
2017 Rice black streaked dwarf virus P7-2 forms a SCF complex through binding to Oryza sativa SKP1-like proteins, and interacts with GID2 involved in the gibberellin pathway. PloS one 37 28494021
2010 The subcellular localization of the hepatitis C virus non-structural protein NS2 is regulated by an ion channel-independent function of the p7 protein. The Journal of general virology 37 21177929
2010 Hepatitis C virus p7-a viroporin crucial for virus assembly and an emerging target for antiviral therapy. Viruses 37 21994720
2009 Determination of pore-lining residues in the hepatitis C virus p7 protein. Biophysical journal 37 19167280
2007 Hepatitis C virus p7 protein is localized in the endoplasmic reticulum when it is encoded by a replication-competent genome. The Journal of general virology 35 17170445
2014 The elusive function of the hepatitis C virus p7 protein. Virology 33 25001174
1995 Specific disulfide formation in the oxidation of HIV-1 zinc finger protein nucleocapsid p7. Chemical research in toxicology 33 7548739
1993 Specificity determinants of the P1 and P7 plasmid centromere analogs. Proceedings of the National Academy of Sciences of the United States of America 32 8415682
2014 Proteomic analysis of interaction between P7-1 of Southern rice black-streaked dwarf virus and the insect vector reveals diverse insect proteins involved in successful transmission. Journal of proteomics 31 24650428
2014 Classical swine fever virus and p7 protein induce secretion of IL-1β in macrophages. The Journal of general virology 30 25146005
2015 Cooperation between the Hepatitis C Virus p7 and NS5B Proteins Enhances Virion Infectivity. Journal of virology 29 26355084
2017 Systematic identification of anti-interferon function on hepatitis C virus genome reveals p7 as an immune evasion protein. Proceedings of the National Academy of Sciences of the United States of America 28 28159892
2013 Nonstructural protein P7-2 encoded by Rice black-streaked dwarf virus interacts with SKP1, a core subunit of SCF ubiquitin ligase. Virology journal 28 24176102
2003 Changes in the human immunodeficiency virus p7-p1-p6 gag gene in drug-naive and pretreated patients. Journal of clinical microbiology 28 12624058
2000 Inactivation of HIV-1 nucleocapsid protein P7 by pyridinioalkanoyl thioesters. Characterization of reaction products and proposed mechanism of action. The Journal of biological chemistry 28 10809733
1999 Peptide specificity determinants at P-7 and P-6 enhance the catalytic efficiency of Ca2+/calmodulin-dependent protein kinase I in the absence of activation loop phosphorylation. The Journal of biological chemistry 28 10400638
2013 Purification, characterisation and expression in Saccharomyces cerevisiae of LipG7 an enantioselective, cold-adapted lipase from the Antarctic filamentous fungus Geomyces sp. P7 with unusual thermostability characteristics. Enzyme and microbial technology 27 23683700
2013 Pore-forming activity of pestivirus p7 in a minimal model system supports genus-specific viroporin function. Antiviral research 27 24189547
2012 Packaging accessory protein P7 and polymerase P2 have mutually occluding binding sites inside the bacteriophage 6 procapsid. Journal of virology 27 22896624
2012 The p7 protein of the hepatitis C virus induces cell death differently from the influenza A virus viroporin M2. Virus research 27 23246447
2012 The secretory pathway and the actomyosin motility system are required for plasmodesmatal localization of the P7-1 of rice black-streaked dwarf virus. Archives of virology 27 23271163
1996 The Vpr protein of human immunodeficiency virus type 1 binds to nucleocapsid protein p7 in vitro. Biochemical and biophysical research communications 27 8573160
2022 DTX-P7, a peptide-drug conjugate, is highly effective for non-small cell lung cancer. Journal of hematology & oncology 26 35659720
2020 Assessment of the Multifunctional Behavior of Lupin Peptide P7 and Its Metabolite Using an Integrated Strategy. Journal of agricultural and food chemistry 26 32223157
2010 Comparative NMR studies demonstrate profound differences between two viroporins: p7 of HCV and Vpu of HIV-1. Biochimica et biophysica acta 26 20727848
1999 DNA damage and DNA damage-inducible protein Gadd45 following ischemia in the P7 neonatal rat. Brain research. Developmental brain research 26 10521557
2008 Rrp4 and Csl4 are needed for efficient degradation but not for polyadenylation of synthetic and natural RNA by the archaeal exosome. Biochemistry 25 19053279
2003 Exploration of the P6/P7 region of the peptide-binding site of the human class II major histocompatability complex protein HLA-DR1. The Journal of biological chemistry 25 12952957
2019 HCV p7 as a novel vaccine-target inducing multifunctional CD4+ and CD8+ T-cells targeting liver cells expressing the viral antigen. Scientific reports 24 31575882
2015 Genotype-specific differences in structural features of hepatitis C virus (HCV) p7 membrane protein. Biochimica et biophysica acta 24 25772504
1992 Transcriptional control via translational repression by c4 antisense RNA of bacteriophages P1 and P7. Genes & development 24 1459462
1986 Sequence relations among the IncY plasmid p15B, P1, and P7 prophages. Plasmid 24 3749335
2024 Identification and characterization of a fungal cutinase-like enzyme CpCut1 from Cladosporium sp. P7 for polyurethane degradation. Applied and environmental microbiology 23 38445906
2020 Genetic and genomic studies of pathogenic EXOSC2 mutations in the newly described disease SHRF implicate the autophagy pathway in disease pathogenesis. Human molecular genetics 23 31628467
2015 Complete genome sequence of Clostridium carboxidivorans P7(T), a syngas-fermenting bacterium capable of producing long-chain alcohols. Journal of biotechnology 23 26193629
2013 Mutations in hepatitis C virus p7 reduce both the egress and infectivity of assembled particles via impaired proton channel function. The Journal of general virology 23 23907396
2006 Functional analyses of GB virus B p13 protein: development of a recombinant GB virus B hepatitis virus with a p7 protein. Proceedings of the National Academy of Sciences of the United States of America 23 16492760
2013 Viroporin activity and membrane topology of classic swine fever virus p7 protein. The international journal of biochemistry & cell biology 22 23583663
2002 A recombinant adenovirus expressing p7(Kip1) induces cell cycle arrest and apoptosis in human 786-0 renal carcinoma cells. The Journal of urology 22 12131366
2018 Peptides P4 and P7 derived from E protein inhibit entry of dengue virus serotype 2 via interacting with β3 integrin. Antiviral research 21 29709564
2014 Docking assay of small molecule antivirals to p7 of HCV. Computational biology and chemistry 21 25462337
2010 The evolutionarily conserved subunits Rrp4 and Csl4 confer different substrate specificities to the archaeal exosome. FEBS letters 21 20488184
2008 Reverse genetic analysis of a putative, influenza virus M2 HXXXW-like motif in the p7 protein of hepatitis C virus. Journal of viral hepatitis 20 19175872
2002 Naturally occurring amino acid polymorphisms in human immunodeficiency virus type 1 (HIV-1) Gag p7(NC) and the C-cleavage site impact Gag-Pol processing by HIV-1 protease. Virology 20 11878916
1993 The antirepressor of phage P1. Isolation and interaction with the C1 repressor of P1 and P7. FEBS letters 20 8224242
1993 Sequence analysis of selected regions of the env (V3 loop and gp41) and gag (p7) reading frames of Ethiopian human immunodeficiency virus type 1 strains. Archives of virology 20 8435043
2016 Analysis of uncommon norovirus recombinants from Manaus, Amazon region, Brazil: GII.P22/GII.5, GII.P7/GII.6 and GII.Pg/GII.1. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 19 26861619
2015 Ion channel activity of the CSFV p7 viroporin in surrogates of the ER lipid bilayer. Biochimica et biophysica acta 19 26464198
2011 The influence of different lipid environments on the structure and function of the hepatitis C virus p7 ion channel protein. Molecular membrane biology 19 21604991
2008 Structure and dynamics of the P7 protein from the bacteriophage phi 12. Journal of molecular biology 19 18647606
2013 Efficiency of E2-p7 processing modulates production of infectious hepatitis C virus. Journal of virology 18 23946462
2004 Characterization of GB virus B polyprotein processing reveals the existence of a novel 13-kDa protein with partial homology to hepatitis C virus p7 protein. The Journal of biological chemistry 18 15060070