Affinage

ATXN7

Ataxin-7 · UniProt O15265

Length
892 aa
Mass
95.5 kDa
Annotated
2026-06-09
93 papers in source corpus 25 papers cited in narrative 25 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

ATXN7 is a subunit of the SAGA/STAGA transcriptional coactivator complex that anchors the histone H2B deubiquitination module (DUBm), and through this role governs chromatin organization and photoreceptor/neuronal gene programs (PMID:19226466, PMID:25306109). Its yeast ortholog Sgf73 is required to recruit the DUBm into the SAGA and SLIK HAT complexes, and an N-terminal zinc-finger domain maintains the active, ubiquitin-binding conformation of the catalytic deubiquitinase Ubp8 (PMID:19226466, PMID:25526805, PMID:20510875). ATXN7 binds the cone-rod homeobox factor CRX and is required for normal photoreceptor gene expression, and its loss in vertebrates causes eye morphogenesis defects through elevated Hedgehog signaling and altered crx expression (PMID:11580893, PMID:30445451). Distinct domains of Sgf73 mediate SAGA-independent functions including heterochromatin boundary activity and assembly of the RNAi/RITS silencing complex (PMID:23819448, PMID:26443059). ATXN7 abundance is itself controlled by ubiquitin-proteasome degradation, which feeds back on transcription, and by a STAGA-dependent miR-124/lnc-SCA7 regulatory loop (PMID:30559154, PMID:37075097, PMID:25306109). Polyglutamine expansion in ATXN7 produces both loss of these coactivator functions—reduced promoter occupancy with increased local H2B ubiquitination—and a gain of toxic function: caspase-7 cleavage at D266 is a critical in vivo driver of neurotoxicity, while SUMO2/3-RNF4-mediated clearance, autophagy impairment via a p53-FIP200-ULK1 axis, and NADPH oxidase-dependent oxidative and bioenergetic stress collectively produce selective degeneration of cerebellar Purkinje cells and retinal photoreceptors (PMID:25859008, PMID:30559154, PMID:23236151, PMID:23592174, PMID:22827889, PMID:25647692). Mutations in ATXN7 cause spinocerebellar ataxia type 7 (SCA7) (PMID:25859008).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 2001 High

    Established a direct molecular link between ataxin-7 and the photoreceptor transcription factor CRX, explaining why polyQ expansion selectively perturbs retinal gene expression.

    Evidence Yeast two-hybrid, co-IP, EMSA, and SCA7 transgenic mice

    PMID:11580893

    Open questions at the time
    • Did not place ataxin-7 within the SAGA complex
    • Mechanism of CRX transactivation suppression beyond reduced DNA binding unresolved
  2. 2001 Medium

    Showed that mutant ataxin-7 mislocalizes to neuronal nuclei as N-terminal fragments, sequesters the TFIID subunit TAFII30, and is selectively stabilized, framing SCA7 as a problem of toxic nuclear accumulation.

    Evidence Transgenic mouse immunohistochemistry, confocal microscopy, mRNA vs protein comparison

    PMID:11487572

    Open questions at the time
    • Functional consequence of TAFII30 sequestration not measured
    • Identity of the protease generating N-terminal fragments unknown at this point
  3. 2009 High

    Defined the conserved core function of the ATXN7 ortholog Sgf73 as the anchor recruiting the H2B deubiquitination module into SAGA/SLIK complexes.

    Evidence Yeast genetic deletion, complex fractionation, histone modification assays

    PMID:19226466

    Open questions at the time
    • Whether human ATXN7 anchors the DUBm identically not directly shown here
    • Specific genes whose H2B-ub state is controlled in mammals not defined
  4. 2010 Medium

    Determined that an N-terminal zinc-finger of Sgf73 requires a zinc ion for stable folding, identifying the structural basis of the anchoring domain.

    Evidence Solution NMR, circular dichroism, EDTA zinc chelation

    PMID:20510875

    Open questions at the time
    • Single in vitro study
    • Did not test the domain's anchoring function directly
  5. 2010 Low

    Reported a physical interaction between ataxin-7 and APLP2 whose cleavage fragments contribute cumulative cytotoxicity in SCA7.

    Evidence Yeast two-hybrid, SCA7 brain immunohistochemistry, cell co-expression toxicity assays

    PMID:20732423

    Open questions at the time
    • Interaction identified by yeast two-hybrid with limited orthogonal validation
    • Physiological relevance to neurodegeneration unestablished
  6. 2011 Medium

    Linked SAGA HAT activity to disease by showing Gcn5 reduction accelerates SCA7 degeneration, while implicating non-transcriptional SAGA functions.

    Evidence Genetic epistasis in SCA7 mice, behavior, neuropathology, expression analysis

    PMID:22002997

    Open questions at the time
    • Nature of the non-transcriptional SAGA functions undefined
    • Mechanism connecting Gcn5 loss to faster degeneration unknown
  7. 2011 Medium

    Documented altered linker histone H1c and heterochromatin ultrastructure in SCA7 photoreceptors, tying ATXN7 dysfunction to chromatin architecture.

    Evidence Immunogold, electron tomography, stereology, nuclear extract western blots from SCA7 retinas

    PMID:21970987

    Open questions at the time
    • Causal mechanism linking ATXN7 to H1c loss not established
    • Functional readout for the decondensation phenotype absent
  8. 2012 Medium

    Connected loss of ATXN7 promoter occupancy to increased local H2B monoubiquitination and reduced target (reelin) transcription in human SCA7 cells, providing direct evidence of impaired DUBm function in disease.

    Evidence Human astrocyte ChIP, histone modification analysis, TSA rescue

    PMID:23236151

    Open questions at the time
    • Single target locus examined
    • Whether DUBm catalytic disruption is general across SCA7 genes unknown
  9. 2012 Medium

    Showed polyQ-ATXN7 drives NADPH oxidase-dependent ROS and lowers catalase, implicating oxidative stress as a toxicity pathway amenable to pharmacological reversal.

    Evidence Inducible SCA7 cell model, ROS assays, NOX inhibitor and antioxidant treatment

    PMID:22827889

    Open questions at the time
    • Mechanism linking ATXN7 to NOX activation unknown
    • In vivo validation absent
  10. 2012 Medium

    Established that full-length ATXN7 is cleared by the proteasome while cleaved fragments use both proteasome and autophagy, and that autophagy activation reduces toxicity.

    Evidence Inducible PC12/HEK293T models, proteasome and autophagy inhibition/activation

    PMID:22367614

    Open questions at the time
    • E3 ligases not identified in this study
    • In vivo degradation routes not tested
  11. 2013 Medium

    Identified a JNK/c-Jun stress pathway repressing Nrl as a driver of SCA7 retinopathy, since blocking c-Jun activation rescues rod gene expression.

    Evidence JunAA knock-in × SCA7 mice genetic epistasis, expression analysis, reporter assays

    PMID:17189700

    Open questions at the time
    • How polyQ-ATXN7 activates JNK/c-Jun unresolved
    • Relevance to cerebellar degeneration untested
  12. 2013 Medium

    Defined a p53-dependent autophagy block in which p53 and FIP200 co-aggregate with ATXN7, destabilizing ULK1 and impairing autophagy induction.

    Evidence Co-IP, co-aggregation, autophagy flux assays, p53 inhibitor and aggregation-blocker rescue

    PMID:23592174

    Open questions at the time
    • In vivo confirmation lacking
    • Stoichiometry of FIP200 sequestration not quantified
  13. 2013 Medium

    Showed IFN-β-induced PML nuclear bodies clear mutant ataxin-7 inclusions and improve motor function and Purkinje survival, suggesting a clearance-based therapeutic route.

    Evidence SCA7 knock-in mice, IFN-β treatment, immunohistochemistry, behavior, primary culture

    PMID:23518714

    Open questions at the time
    • Molecular mechanism of PML-mediated clearance not dissected
    • Long-term efficacy unknown
  14. 2013 Medium

    Revealed a STAGA-dependent miR-124/lnc-SCA7 feedback loop controlling ATXN7 mRNA whose disruption by polyQ expansion causes tissue-specific ATXN7 accumulation.

    Evidence STAGA ChIP, miRNA/lncRNA functional assays, SCA7 patient and mouse tissue

    PMID:25306109

    Open questions at the time
    • Quantitative contribution of the feedback loop to disease selectivity unclear
    • Conservation across cell types not fully mapped
  15. 2014 High

    Provided the structural mechanism by which Sgf73 maintains the ubiquitin-binding conformation and folding of the catalytic subunit Ubp8 within the DUBm.

    Evidence X-ray crystallography, mutagenesis, deubiquitinating activity assays

    PMID:25526805

    Open questions at the time
    • Human ATXN7-USP22 module not crystallized here
    • Effect of polyQ tract on DUBm structure not addressed
  16. 2015 High

    Demonstrated that caspase-7 cleavage of ataxin-7 at D266 is a critical in vivo neurotoxicity event, since a cleavage-resistant mutant improves motor function and lifespan.

    Evidence D266N knock-in SCA7 mice, behavior, neuropathology

    PMID:25859008

    Open questions at the time
    • What activates caspase-7 in SCA7 neurons unknown
    • Toxic species generated by the fragment not fully characterized
  17. 2015 Medium

    Extended SAGA-independent roles of Sgf73 to the RNAi machinery, showing it associates with Ago1/Chp1 and is required for RITS assembly and heterochromatin silencing.

    Evidence Fission yeast co-IP, genetic deletion, ChIP, siRNA quantification

    PMID:26443059

    Open questions at the time
    • Whether human ATXN7 has an analogous RNAi role untested
    • Independence from SAGA shown in one organism only
  18. 2015 Medium

    Tied p53 sequestration and NOX1 upregulation to bioenergetic failure in SCA7 cells, linking transcriptional and metabolic dysfunction.

    Evidence Inducible SCA7 PC12 cells, co-aggregation, p53 reporter, metabolic flux, pharmacological rescue

    PMID:25647692

    Open questions at the time
    • In vivo metabolic phenotype not confirmed
    • Causal order of p53 and NOX1 effects unclear
  19. 2019 High

    Identified SUMO2/3-RNF4 as a SUMO-targeted ubiquitin ligase pathway that ubiquitinates and degrades polyQ-ATXN7, defining a clearance route for the toxic protein.

    Evidence Co-IP, PLA, immunofluorescence, proteasome inhibition, overexpression, SCA7 knock-in mouse, patient tissue

    PMID:30559154

    Open questions at the time
    • Therapeutic exploitation of RNF4 not tested in vivo
    • Why endogenous clearance is insufficient unresolved
  20. 2019 Medium

    Defined an essential developmental role for ATXN7 in vertebrate eye morphogenesis and photoreceptor differentiation via restraint of Hedgehog signaling and control of crx.

    Evidence Zebrafish loss-of-function, in situ hybridization, Hedgehog and photoreceptor analysis

    PMID:30445451

    Open questions at the time
    • Direct molecular link between ATXN7 and Hedgehog pathway components unknown
    • Relevance of loss-of-function to polyQ disease unclear
  21. 2022 Low

    Reported sequestration of RNA-binding proteins TDP-43 and TIA1 and altered stress-granule morphology by polyQ-ATXN7, suggesting interplay with RNA metabolism.

    Evidence Immunofluorescence, filter trap, arsenite stress-granule assay, SCA7 cells

    PMID:35689166

    Open questions at the time
    • Co-localization only, no functional consequence established
    • Stress granule dynamics not significantly impaired, weakening mechanistic relevance
  22. 2023 Medium

    Showed that ubiquitin-proteasome-controlled abundance of Sgf73/ATXN7 tunes PIC formation and transcription elongation, integrating protein turnover with coactivator output.

    Evidence Ubiquitylation assays, proteasome inhibition, ChIP, transcription assays in yeast and mammalian cells

    PMID:37075097

    Open questions at the time
    • E3 ligase for normal ATXN7 turnover not pinned down
    • Single lab; physiological context of elongation effect in neurons untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How polyQ expansion mechanistically converts coactivator loss-of-function into the specific combination of caspase cleavage, impaired clearance, and oxidative/metabolic stress that selectively kills Purkinje cells and photoreceptors remains unresolved.
  • No unified model linking transcriptional dysfunction to the multiple toxic pathways
  • Basis of cell-type selectivity not fully explained
  • Human DUBm structure with polyQ tract uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 4 GO:0003677 DNA binding 1 GO:0060089 molecular transducer activity 1
Localization
GO:0005634 nucleus 2 GO:0000228 nuclear chromosome 1 GO:0005829 cytosol 1
Pathway
R-HSA-1643685 Disease 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-4839726 Chromatin organization 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-9612973 Autophagy 2
Partners
APLP2CRXFIP200GCN5RNF4SUMO2TP53USP22/UBP8
Complex memberships
RITS complexSAGA/STAGASLIK/SALSA HAT complexhistone deubiquitination module (DUBm)

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 Ataxin-7 physically interacts with the cone-rod homeobox protein CRX, as demonstrated by yeast two-hybrid assay and co-immunoprecipitation; polyglutamine-expanded ataxin-7 colocalizes with CRX and dramatically suppresses CRX transactivation activity, leading to reduced CRX DNA-binding activity and decreased expression of CRX-regulated photoreceptor genes in SCA7 transgenic mice. Yeast two-hybrid, co-immunoprecipitation, electrophoretic mobility shift assay, RT-PCR, transgenic mouse model Neuron High 11580893
2009 Yeast Sgf73 (ortholog of human ATXN7) is required to recruit the histone deubiquitination module (DUBm) into both the SAGA and Slik(SALSA) HAT complexes, and loss of Sgf73 impairs histone H2B deubiquitination and regulation of transcription at multiple genes. Genetic deletion, complex fractionation, histone modification assays, biochemical reconstitution studies in yeast Epigenetics & chromatin High 19226466
2014 Sgf73 point mutations (yeast ATXN7 ortholog) that disrupt DUBm deubiquitinating activity do so by impairing the ubiquitin-binding fingers region of Ubp8 and destabilizing overall DUBm folding, demonstrating that Sgf73 maintains the organization and ubiquitin-binding conformation of the catalytic subunit Ubp8. X-ray crystallography, solution studies, site-directed mutagenesis, deubiquitinating activity assays Journal of molecular biology High 25526805
2010 The N-terminal zinc finger motif of yeast Sgf73 (residues 1-104) requires a zinc ion to maintain stable folding and conformation, as demonstrated by NMR backbone assignment, secondary structure analysis, and circular dichroism after zinc chelation with EDTA. Solution NMR, circular dichroism, zinc chelation with EDTA Biochemical and biophysical research communications Medium 20510875
2013 C-terminus of yeast Sgf73 (residues 373-402) is essential for heterochromatin boundary function, and this boundary function depends on the HAT module components Ada2, Ada3, and Gcn5 of the SAGA/SLIK complex, but is independent of the deubiquitinase-anchoring domain of Sgf73. Domain deletion analysis, boundary function assays, genetic deletion of SAGA subunits in yeast Genes to cells Medium 23819448
2015 In fission yeast, Sgf73 (ATXN7 ortholog) is physically associated with Ago1 and Chp1 subunits of the RITS complex and is required for RITS complex assembly, pericentromeric heterochromatin silencing, and siRNA generation; this function is independent of SAGA enzymatic activities or structural integrity. Co-immunoprecipitation, genetic deletion, chromatin immunoprecipitation, siRNA quantification in fission yeast Scientific reports Medium 26443059
2015 Proteolytic cleavage of ataxin-7 by caspase-7 at residue D266 is a critical mediator of SCA7 neurotoxicity in vivo; transgenic mice expressing caspase-7-resistant ataxin-7 (D266N mutation) show improved motor performance, reduced neurodegeneration, and substantial lifespan extension compared to SCA7 mice without the D266N mutation. Transgenic mouse model with site-directed caspase cleavage-site mutation (D266N), behavioral testing, neuropathology Human molecular genetics High 25859008
2019 Endogenous ATXN7 and polyQ-expanded ATXN7 are modified by SUMO2/3; RNF4 (a SUMO-targeted ubiquitin ligase) is recruited by SUMO2/3-modified polyQ-ATXN7, leading to its polyubiquitination and proteasomal degradation. Overexpression of RNF4 and/or SUMO2 significantly decreased levels of polyQ-ATXN7, and SUMO2/3 co-localizes with polyQ-ATXN7 inclusions in SCA7 knock-in mouse cerebellum and retina. Co-immunoprecipitation, immunofluorescence, proximity ligation assay, proteasome inhibition, overexpression studies, SCA7 knock-in mouse model, immunohistochemistry Disease models & mechanisms High 30559154
2023 Yeast Sgf73 (ATXN7 ortholog) undergoes ubiquitylation and proteasomal degradation; impaired Sgf73 degradation increases its abundance, enhances TBP recruitment to promoters but impairs transcription elongation, while decreased Sgf73 reduces PIC formation. Similarly, human ataxin-7 undergoes ubiquitylation and proteasomal degradation, alteration of which changes ataxin-7 abundance and is associated with altered transcription. Ubiquitylation assays, proteasome inhibition, chromatin immunoprecipitation, transcription assays in yeast and mammalian cells Genetics Medium 37075097
2012 Polyglutamine-expanded ATXN7 (mutant) decreases ATXN7 occupancy at the reelin promoter, which correlates with increased histone H2B monoubiquitination at that locus, reducing reelin transcription in human SCA7 astrocytes. TSA treatment partially restores reelin transcription. Human astrocyte cell culture model, chromatin immunoprecipitation, histone modification analysis, pharmacological treatment Proceedings of the National Academy of Sciences of the United States of America Medium 23236151
2011 Reducing Gcn5 expression (the HAT catalytic subunit of SAGA) accelerates both cerebellar and retinal degeneration in SCA7 mice, demonstrating that Gcn5 HAT activity within the SAGA complex in which ATXN7 resides contributes to SCA7 disease onset and severity; however, Gcn5 depletion does not further alter known ATXN7 transcriptional targets, suggesting non-transcriptional SAGA functions are involved. Genetic epistasis in transgenic/conditional knockout mouse, behavioral testing, neuropathological analysis, gene expression analysis Human molecular genetics Medium 22002997
2013 STAGA complex (containing ATXN7) is required for transcription initiation of miR-124, which post-transcriptionally regulates ATXN7 mRNA via cross-talk with lnc-SCA7; polyQ expansion in ATXN7 disrupts this regulatory feedback, resulting in neuron-specific increases in ATXN7 expression most prominent in disease-relevant tissues (retina and cerebellum). STAGA ChIP, miRNA expression analysis, lncRNA functional experiments, SCA7 patient and mouse tissue analysis Nature structural & molecular biology Medium 25306109
2001 Mutant ataxin-7 undergoes cytoplasm-to-nucleus translocation and accumulates as N-terminal fragments in neuronal nuclei in SCA7 transgenic mice; mouse TAFII30 (a subunit of TFIID) is markedly sequestered into nuclear inclusions; mutant ataxin-7 is selectively stabilized at the protein level relative to wild-type, as evidenced by discrepancy between mRNA and protein levels in transgenic mice expressing mutant but not wild-type ataxin-7. Transgenic mouse models, immunohistochemistry, confocal microscopy, western blotting, comparative analysis of mRNA vs. protein levels Human molecular genetics Medium 11487572
2006 Polyglutamine-expanded ataxin-7 in rod photoreceptors activates the JNK/c-Jun stress pathway; genetic prevention of c-Jun activation (JunAA knock-in) improves SCA7 retinopathy and partially restores expression of rod-specific genes including the transcription factor Nrl and its downstream phototransduction targets. c-Jun directly represses Nrl transcription. Genetic epistasis (JunAA knock-in × SCA7 transgenic mice), gene expression analysis, transcriptional reporter assays Neurobiology of disease Medium 17189700
2013 Interferon-beta induces PML protein expression and PML nuclear body formation, which mediates clearance of mutant ataxin-7 from neuronal intranuclear inclusions in SCA7 knock-in mice; this is accompanied by improved motor function on behavioral tests and improved Purkinje cell survival in cell culture. SCA7 knock-in mouse model, IFN-β treatment, immunohistochemistry, behavioral testing (Locotronic, Beam Walking), primary cell culture Brain : a journal of neurology Medium 23518714
2013 Mutant ATXN7 inhibits autophagy via a p53-mediated mechanism: increased p53-FIP200 interaction and co-aggregation of p53 and FIP200 into ATXN7 aggregates decreases soluble FIP200, destabilizing ULK1 and reducing capacity for autophagy induction through the ULK1-FIP200-Atg13-Atg101 complex. p53 inhibitor treatment or blocking ATXN7 aggregation restores FIP200/ULK1 levels and increases autophagic activity. Co-immunoprecipitation, co-aggregation assays, western blotting, pharmacological rescue (p53 inhibitor, aggregation blocker), autophagy flux assays in stable inducible SCA7 cell model Journal of molecular neuroscience : MN Medium 23592174
2012 Polyglutamine-expanded ATXN7 induces reactive oxygen species (ROS) production from NADPH oxidase (NOX) complexes; NOX inhibition completely prevents the ROS increase, and both antioxidant treatment and NOX inhibition reduce ATXN7 aggregation and toxicity. Mutant ATXN7 also decreases catalase levels, contributing to oxidative stress. Stable inducible SCA7 cell model, ROS measurement, NOX inhibitor treatment, antioxidant treatment, aggregation assays, cell viability assays BMC neuroscience Medium 22827889
2015 Mutant ATXN7 causes bioenergetic defects through disruption of p53 and NOX1 activity: p53 co-aggregates with mutant ATXN7 reducing its transcriptional activity (50% decrease in AIF and TIGAR), while NOX1 expression increases ~2-fold, collectively resulting in decreased respiratory capacity, increased glycolytic reliance, and 20% reduction in ATP. Restoring p53 function or suppressing NOX1 activity reverses metabolic dysfunction. Stable inducible SCA7 PC12 cell model, co-aggregation assays, p53 transcriptional reporter assays, metabolic flux analysis, pharmacological rescue Biochimica et biophysica acta Medium 25647692
2010 Ataxin-7 physically interacts with APLP2 (amyloid precursor-like protein 2); caspase-3-mediated cleavage of APLP2 generates intracellular C-terminal domains that translocate to the nucleus, and abnormal nuclear relocation of APLP2 N-terminal fragments is detected in SCA7 neuronal intranuclear inclusions. Co-expression of APLP2 ICDs with mutant ataxin-7 causes cumulative cytotoxicity. Yeast two-hybrid (interaction identification), immunohistochemistry in SCA7 brain tissue, co-expression toxicity assays in cells Neurobiology of disease Low 20732423
2011 In SCA7 rod photoreceptor nuclei, the amount of linker histone H1c is strongly reduced and its distribution in facultative heterochromatin is altered, accompanied by fragmentation and decondensation of the most external heterochromatin ring. Acetylated histones H3 and H4 are unchanged in nuclear extracts. Immunogold labeling, stereology, electron tomography, western blotting of nuclear extracts from SCA7 mouse retinas Nucleus (Austin, Tex.) Medium 21970987
2019 Loss-of-function of ATXN7 in zebrafish causes ocular coloboma by elevating Hedgehog signaling in the forebrain, altering proximo-distal patterning of the optic vesicle; at later stages, photoreceptor outer segment formation is incomplete, correlating with altered expression of crx. This demonstrates ATXN7 plays an essential role in vertebrate eye morphogenesis and photoreceptor differentiation. Zebrafish ATXN7 knockdown/knockout, in situ hybridization, Hedgehog pathway analysis, photoreceptor morphology analysis, crx expression analysis Human molecular genetics Medium 30445451
2012 In a stable inducible SCA7 cell model, the ubiquitin-proteasome system (UPS) is essential for degradation of full-length ATXN7 (both normal and expanded), whereas cleaved ATXN7 fragments are degraded by both UPS and autophagy. Inhibition of either pathway worsens mutant ATXN7 toxicity; pharmacological autophagy activation ameliorates toxicity. Stable inducible PC12 and HEK293T cell models, proteasome inhibition, autophagy inhibition/activation, western blotting, cell viability assays Journal of molecular neuroscience : MN Medium 22367614
2002 Ataxin-7 expression is primarily nuclear in most brain regions studied; in cerebellar Purkinje cells, differences in subcellular distribution were observed between SCA7 patients and controls of different ages, suggesting disease-related redistribution. Immunohistochemistry of CNS and non-CNS tissue from SCA7 patients and controls, subcellular localization analysis Acta neuropathologica Low 12070661
2005 An alternative ataxin-7 isoform (ataxin-7b), generated by inclusion of exon 12b causing a frameshift and novel 58-amino acid C-terminus, localizes to a more cytoplasmic location compared to the canonical nuclear ataxin-7a isoform. Northern blot, quantitative RT-PCR, subcellular localization analysis in transfected cells Biochimica et biophysica acta Low 16297465
2022 TDP-43 and TIA1 are sequestered into aggregates formed by polyQ-expanded ATXN7 in SCA7 cells; mutant ATXN7 also localizes to stress granules induced by arsenite and alters their shape; mutant ATXN7 expression increases speckling of stress granule-nucleating protein G3BP1. The dynamics of stress granule assembly and disassembly are not significantly impaired in SCA7 cells. Immunofluorescence, filter trap assay, arsenite-induced stress granule assay, stable SCA7 cell model Molecular neurobiology Low 35689166

Source papers

Stage 0 corpus · 93 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Cloning of the SCA7 gene reveals a highly unstable CAG repeat expansion. Nature genetics 636 9288099
1998 Spinocerebellar ataxia type 7 (SCA7): a neurodegenerative disorder with neuronal intranuclear inclusions. Human molecular genetics 274 9536097
1998 Molecular and clinical correlations in autosomal dominant cerebellar ataxia with progressive macular dystrophy (SCA7). Human molecular genetics 225 9425222
2001 Polyglutamine-expanded ataxin-7 antagonizes CRX function and induces cone-rod dystrophy in a mouse model of SCA7. Neuron 194 11580893
2000 Frequency of SCA1, SCA2, SCA3/MJD, SCA6, SCA7, and DRPLA CAG trinucleotide repeat expansion in patients with hereditary spinocerebellar ataxia from Chinese kindreds. Archives of neurology 141 10768629
1998 Molecular and clinical studies in SCA-7 define a broad clinical spectrum and the infantile phenotype. Neurology 129 9781533
1998 Expanded CAG repeats in Swedish spinocerebellar ataxia type 7 (SCA7) patients: effect of CAG repeat length on the clinical manifestation. Human molecular genetics 127 9425223
2011 Zinc uptake by Streptococcus pneumoniae depends on both AdcA and AdcAII and is essential for normal bacterial morphology and virulence. Molecular microbiology 114 22023106
2014 AdcA and AdcAII employ distinct zinc acquisition mechanisms and contribute additively to zinc homeostasis in Streptococcus pneumoniae. Molecular microbiology 89 24428621
2008 AdcAII, a new pneumococcal Zn-binding protein homologous with ABC transporters: biochemical and structural analysis. Journal of molecular biology 84 18632116
2002 Spinocerebellar ataxia type 7 (SCA7) shows a cone-rod dystrophy phenotype. Experimental eye research 83 12126946
2001 SCA7 mouse models show selective stabilization of mutant ataxin-7 and similar cellular responses in different neuronal cell types. Human molecular genetics 82 11487572
2001 Similarities between spinocerebellar ataxia type 7 (SCA7) cell models and human brain: proteins recruited in inclusions and activation of caspase-3. Human molecular genetics 78 11709544
1998 Analysis of the dynamic mutation in the SCA7 gene shows marked parental effects on CAG repeat transmission. Human molecular genetics 78 9467013
2014 Cross-talking noncoding RNAs contribute to cell-specific neurodegeneration in SCA7. Nature structural & molecular biology 76 25306109
2009 Yeast Sgf73/Ataxin-7 serves to anchor the deubiquitination module into both SAGA and Slik(SALSA) HAT complexes. Epigenetics & chromatin 76 19226466
2001 A survey of spinocerebellar ataxia in South Brazil - 66 new cases with Machado-Joseph disease, SCA7, SCA8, or unidentified disease-causing mutations. Journal of neurology 71 11697524
2013 Interferon β induces clearance of mutant ataxin 7 and improves locomotion in SCA7 knock-in mice. Brain : a journal of neurology 64 23518714
2003 Genomic context drives SCA7 CAG repeat instability, while expressed SCA7 cDNAs are intergenerationally and somatically stable in transgenic mice. Human molecular genetics 58 12490531
2002 Childhood-onset ataxia: testing for large CAG-repeats in SCA2 and SCA7. American journal of medical genetics 57 12116207
2014 The autophagy/lysosome pathway is impaired in SCA7 patients and SCA7 knock-in mice. Acta neuropathologica 55 24859968
1996 The gene for autosomal dominant cerebellar ataxia type II is located in a 5-cM region in 3p12-p13: genetic and physical mapping of the SCA7 locus. American journal of human genetics 55 8940279
2002 Two populations of neuronal intranuclear inclusions in SCA7 differ in size and promyelocytic leukaemia protein content. Brain : a journal of neurology 54 12077003
1999 Spinocerebellar ataxia type 7 (SCA7) - correlations between phenotype and genotype in one large Belgian family. Journal of the neurological sciences 53 10500272
2009 Design of RNAi hairpins for mutation-specific silencing of ataxin-7 and correction of a SCA7 phenotype. PloS one 51 19789634
2003 Spinocerebellar ataxia 7 (SCA7). Cytogenetic and genome research 49 14526176
2000 Evidence for a common Spinocerebellar ataxia type 7 (SCA7) founder mutation in Scandinavia. European journal of human genetics : EJHG 49 11175279
2014 Nonallele specific silencing of ataxin-7 improves disease phenotypes in a mouse model of SCA7. Molecular therapy : the journal of the American Society of Gene Therapy 46 24930601
2011 Gcn5 loss-of-function accelerates cerebellar and retinal degeneration in a SCA7 mouse model. Human molecular genetics 43 22002997
2004 Ataxin-7 aggregation and ubiquitination in infantile SCA7 with 180 CAG repeats. Annals of neurology 43 15349877
2013 New insights into histidine triad proteins: solution structure of a Streptococcus pneumoniae PhtD domain and zinc transfer to AdcAII. PloS one 41 24312273
2012 Reduction of mutant ataxin-7 expression restores motor function and prevents cerebellar synaptic reorganization in a conditional mouse model of SCA7. Human molecular genetics 36 23197655
2012 Reelin is a target of polyglutamine expanded ataxin-7 in human spinocerebellar ataxia type 7 (SCA7) astrocytes. Proceedings of the National Academy of Sciences of the United States of America 36 23236151
2005 Spinocerebellar ataxia type 7 (SCA7): first report of a systematic neuropathological study of the brain of a patient with a very short expanded CAG-repeat. Brain pathology (Zurich, Switzerland) 35 16389941
2000 Macular degeneration associated with aberrant expansion of trinucleotide repeat of the SCA7 gene in 2 Japanese families. Archives of ophthalmology (Chicago, Ill. : 1960) 31 11030825
2021 SCA7 Mouse Cerebellar Pathology Reveals Preferential Downregulation of Key Purkinje Cell-Identity Genes and Shared Disease Signature with SCA1 and SCA2. The Journal of neuroscience : the official journal of the Society for Neuroscience 29 33888607
2014 Allele-specific silencing of mutant Ataxin-7 in SCA7 patient-derived fibroblasts. European journal of human genetics : EJHG 29 24667781
2012 Expanded ataxin-7 cause toxicity by inducing ROS production from NADPH oxidase complexes in a stable inducible Spinocerebellar ataxia type 7 (SCA7) model. BMC neuroscience 29 22827889
1999 Multiple origins of the spinocerebellar ataxia 7 (SCA7) mutation revealed by linkage disequilibrium studies with closely flanking markers, including an intragenic polymorphism (G3145TG/A3145TG). European journal of human genetics : EJHG 29 10602364
2016 AdcAII of Streptococcus pneumoniae Affects Pneumococcal Invasiveness. PloS one 27 26752283
2013 Inhibition of autophagy via p53-mediated disruption of ULK1 in a SCA7 polyglutamine disease model. Journal of molecular neuroscience : MN 27 23592174
2004 Hsp70 and Hsp40 chaperones do not modulate retinal phenotype in SCA7 mice. The Journal of biological chemistry 27 15494410
2001 Molecular analysis of Spinocerebellar ataxias in Koreans: frequencies and reference ranges of SCA1, SCA2, SCA3, SCA6, and SCA7. Molecules and cells 25 11804332
2020 Circular RNA ATXN7 promotes the development of gastric cancer through sponging miR-4319 and regulating ENTPD4. Cancer cell international 24 31997941
2017 Transposon mutagenesis identifies chromatin modifiers cooperating with Ras in thyroid tumorigenesis and detects ATXN7 as a cancer gene. Proceedings of the National Academy of Sciences of the United States of America 24 28584132
2002 Expression of ataxin-7 in CNS and non-CNS tissue of normal and SCA7 individuals. Acta neuropathologica 23 12070661
2018 The Atxn7-overexpressing mice showed hyperactivity and impulsivity which were ameliorated by atomoxetine treatment: A possible animal model of the hyperactive-impulsive phenotype of ADHD. Progress in neuro-psychopharmacology & biological psychiatry 22 30125623
2019 SUMOylation by SUMO2 is implicated in the degradation of misfolded ataxin-7 via RNF4 in SCA7 models. Disease models & mechanisms 21 30559154
2015 Proteolytic cleavage of ataxin-7 promotes SCA7 retinal degeneration and neurological dysfunction. Human molecular genetics 21 25859008
2005 A SCA7 CAG/CTG repeat expansion is stable in Drosophila melanogaster despite modulation of genomic context and gene dosage. Gene 20 15715978
2022 The AdcACB/AdcAII system is essential for zinc homeostasis and an important contributor of Enterococcus faecalis virulence. Virulence 18 35341449
2017 Large normal-range TBP and ATXN7 CAG repeat lengths are associated with increased lifetime risk of depression. Translational psychiatry 18 28585930
2011 The linker histone H1C contributes to the SCA7 nuclear phenotype. Nucleus (Austin, Tex.) 18 21970987
2002 Cloning and expression analysis of the murine homolog of the spinocerebellar ataxia type 7 (SCA7) gene. Gene 18 12039035
2013 C-terminus of the Sgf73 subunit of SAGA and SLIK is important for retention in the larger complex and for heterochromatin boundary function. Genes to cells : devoted to molecular & cellular mechanisms 17 23819448
2012 Differential degradation of full-length and cleaved ataxin-7 fragments in a novel stable inducible SCA7 model. Journal of molecular neuroscience : MN 17 22367614
2007 Massive SCA7 expansion detected in a 7-month-old male with hypotonia, cardiomegaly, and renal compromise. Developmental medicine and child neurology 16 17254003
2019 Loss of zebrafish Ataxin-7, a SAGA subunit responsible for SCA7 retinopathy, causes ocular coloboma and malformation of photoreceptors. Human molecular genetics 15 30445451
2013 Founder effect and ancestral origin of the spinocerebellar ataxia type 7 (SCA7) mutation in Mexican families. Neurogenetics 15 24374739
2017 Clinical and genetic analysis of spinocerebellar ataxia type 7 (SCA7) in Zambian families. Cerebellum & ataxias 14 29214039
1999 Genomic organisation of the spinocerebellar ataxia type 7 (SCA7) gene responsible for autosomal dominant cerebellar ataxia with retinal degeneration. Human genetics 14 10598805
2019 Circular RNA ATXN7 is upregulated in non-small cell lung cancer and promotes disease progression. Oncology letters 13 31186686
2016 Lentiviral vector-mediated overexpression of mutant ataxin-7 recapitulates SCA7 pathology and promotes accumulation of the FUS/TLS and MBNL1 RNA-binding proteins. Molecular neurodegeneration 13 27465358
2016 Mutant CAG Repeats Effectively Targeted by RNA Interference in SCA7 Cells. Genes 13 27999335
2015 Altered p53 and NOX1 activity cause bioenergetic defects in a SCA7 polyglutamine disease model. Biochimica et biophysica acta 13 25647692
2008 Trinucleotide expansions in the SCA7 gene in a large family with spinocerebellar ataxia and craniocervical dystonia. Neuroscience letters 13 18325672
2016 ATXN7 Gene Variants and Expression Predict Post-Operative Clinical Outcomes in Hepatitis B Virus-Related Hepatocellular Carcinoma. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 12 27855399
2014 Uncovering the role of Sgf73 in maintaining SAGA deubiquitinating module structure and activity. Journal of molecular biology 12 25526805
2006 Preventing polyglutamine-induced activation of c-Jun delays neuronal dysfunction in a mouse model of SCA7 retinopathy. Neurobiology of disease 12 17189700
2020 Deletion of the Zinc Transporter Lipoprotein AdcAII Causes Hyperencapsulation of Streptococcus pneumoniae Associated with Distinct Alleles of the Type I Restriction-Modification System. mBio 11 32234814
2023 A novel ubiquitin-proteasome system regulation of Sgf73/ataxin-7 that maintains the integrity of the coactivator SAGA in orchestrating transcription. Genetics 10 37075097
2015 Spinocerebellar ataxia 7 (SCA7) in Indian population: predilection of ATXN7-CAG expansion mutation in an ethnic population. The Indian journal of medical research 10 25900954
2022 The AdcR-regulated AdcA and AdcAII contribute additively to zinc acquisition and virulence in Streptococcus suis. Veterinary microbiology 9 35430524
2022 Key Modulators of the Stress Granule Response TIA1, TDP-43, and G3BP1 Are Altered by Polyglutamine-Expanded ATXN7. Molecular neurobiology 9 35689166
2015 Sgf73, a subunit of SAGA complex, is required for the assembly of RITS complex in fission yeast. Scientific reports 8 26443059
2015 Somatic instability of expanded CAG repeats of ATXN7 in Japanese patients with spinocerebellar ataxia type 7. Documenta ophthalmologica. Advances in ophthalmology 7 25643591
2023 Purkinje-Enriched snRNA-seq in SCA7 Cerebellum Reveals Zebrin Identity Loss as a Central Feature of Polyglutamine Ataxias. bioRxiv : the preprint server for biology 6 37214832
2016 Voice Alterations in Patients With Spinocerebellar Ataxia Type 7 (SCA7): Clinical-Genetic Correlations. Journal of voice : official journal of the Voice Foundation 6 26992556
2013 Genetic variation in ataxia gene ATXN7 influences cerebellar grey matter volume in healthy adults. Cerebellum (London, England) 6 23100044
2010 Solution NMR characterization of Sgf73(1-104) indicates that Zn ion is required to stabilize zinc finger motif. Biochemical and biophysical research communications 5 20510875
2010 Amyloid precursor-like protein 2 cleavage contributes to neuronal intranuclear inclusions and cytotoxicity in spinocerebellar ataxia-7 (SCA7). Neurobiology of disease 5 20732423
2024 YTHDC1-Mediated lncRNA MSC-AS1 m6A Modification Potentiates Laryngeal Squamous Cell Carcinoma Development via Repressing ATXN7 Transcription. Molecular biotechnology 4 38637450
2021 Clinical characterization and the improved molecular diagnosis of autosomal dominant cone-rod dystrophy in patients with SCA7. Molecular vision 4 34012225
2021 Conformation of the Solute-Binding Protein AdcAII Influences Zinc Uptake in Streptococcus pneumoniae. Frontiers in cellular and infection microbiology 4 34490149
2024 ATXN7-Related Cone-Rod Dystrophy: The Integrated Functional Evaluation of the Cerebellum (CERMOI) Study. JAMA ophthalmology 3 38421662
2019 Loss of function in SAGA deubiquitinating module caused by Sgf73 H93A mutation: A molecular dynamics study. Journal of molecular graphics & modelling 3 31202915
2005 Identification and characterization of Spinocerebellar Ataxia Type 7 (SCA7) isoform SCA7b in mice. Biochimica et biophysica acta 3 16297465
2024 Longitudinal MRI and 1H-MRS study of SCA7 mouse forebrain reveals progressive multiregional atrophy and early brain metabolite changes indicating early neuronal and glial dysfunction. PloS one 2 38227598
2024 The 5HT4R agonist velusetrag efficacy on neuropathic chronic intestinal pseudo-obstruction in PrP-SCA7-92Q transgenic mice. Frontiers in pharmacology 2 39139632
2019 A SCA7 premutation may be a novel Mendelian modifier of MS course: A case report. Multiple sclerosis and related disorders 2 30999137
2014 Large scale screening of genetic interaction with sgf73(+) in fission yeast. Yi chuan = Hereditas 1 25076038
2005 [SCA-7. Cone-rod dystrophy in the context of an hereditary ataxia]. Archivos de la Sociedad Espanola de Oftalmologia 1 16311960
2021 Amyotrophic lateral sclerosis associated with a pathological expansion in the ATXN7 gene. Amyotrophic lateral sclerosis & frontotemporal degeneration 0 34870541

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