Atrophin-1 is a broadly expressed transcriptional coregulator with nuclear and cytoplasmic pools. Its transcriptional corepressor activity is enhanced by ETO/MTG8, and it can associate with nuclear-matrix structures containing corepressor machinery. Context-dependent coactivation is reported for the mouse ortholog. Atrophin proteins also associate with FAT1 and contribute to directional migration in vascular smooth muscle cells. Expansion of the ATN1 polyglutamine tract causes dentatorubral-pallidoluysian atrophy, with altered protein processing, localization and cellular toxicity.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:10973986 Atrophin-1, the dentato-rubral and pallido-luysian atrophy g... | ACCEPT | Summary: Retain supported negative regulation of transcription by RNA polymerase II. Reason: Human full-length 26Q and 65Q ATN1 GAL4 fusions repress the thymidine-kinase reporter in Neuro-2a cells; ETO enhances this repression. This directly supports the existing transcriptional-repression assertion, without implying intrinsic DNA binding or histone deacetylase catalysis. Supporting Evidence: |
| GO:0003713 transcription coactivator activity | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain this contextual annotation outside the core molecular-function summary. Reason: Retain the mouse-orthology coactivator inference as a contextual non-core activity. The externally read PMID:17150957 experiment uses mouse Atn1 in a GAL4/HEK293 reporter setting; human ATN1 represses a different reporter in Neuro-2a cells. Species, promoter, cell line and partner context were not isolated as causes of the different outputs. The activation result does not create human IDA evidence or establish that activation is exclusive to mouse ATN1. Supporting Evidence: |
| GO:0003714 transcription corepressor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Retain supported transcription corepressor activity. Reason: Corepressor activity has direct human evidence in PMID:10973986, supporting the inherited functional assignment. The PAINT node and alignment were not replayed; this is corroboration of the function, not independent validation of PTN001015306 placement. Human P54259 in WITH/FROM is expected descendant evidence, not circularity. Supporting Evidence: |
| GO:0003714 transcription corepressor activity | IDA PMID:10973986 Atrophin-1, the dentato-rubral and pallido-luysian atrophy g... | ACCEPT | Summary: Retain supported transcription corepressor activity. Reason: The human ATN1 GAL4 reporter experiment directly establishes corepressor activity, and ETO enhances the effect. Keep this defining molecular function; recruitment/association with HDAC-containing machinery does not give ATN1 intrinsic deacetylase activity. Supporting Evidence: |
| GO:0003714 transcription corepressor activity | IEA GO_REF:0000107 | ACCEPT | Summary: Retain supported transcription corepressor activity. Reason: The mouse-orthology transfer agrees with the independently supported human corepressor function. Preserve the original IEA provenance rather than relabeling it as experimental human evidence. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:10973986 Atrophin-1, the dentato-rubral and pallido-luysian atrophy g... | KEEP AS NON CORE | Summary: Retain this contextual annotation outside the core molecular-function summary. Reason: The ETO/MTG8 interaction is supported by the human ATN1 bait screen and targeted interaction comparisons. Mouse-brain endogenous co-purification is separate corroboration. Retain generic binding as non-core; the informative molecular function is transcription corepression. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:16713569 A protein-protein interaction network for human inherited at... | UNDECIDED | Summary: The exact source-specific assertion remains unresolved. Reason: The complete PMID:16713569 abstract and the UniProt EFEMP2/O95967 interaction entry were read (NbExp=3 is positive curated evidence). The exact ATN1 pair/construct/table in this original screen was not inspected. Preserve the experimental assertion as undecided without claiming it false or inferring the partner activity for ATN1. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:16713569 A protein-protein interaction network for human inherited at... | UNDECIDED | Summary: The exact source-specific assertion remains unresolved. Reason: The complete PMID:16713569 abstract and the UniProt PSME3/P61289 interaction entry were read (NbExp=3 is positive curated evidence). The exact ATN1 pair/construct/table in this original screen was not inspected. Preserve the experimental assertion as undecided without claiming it false or inferring the partner activity for ATN1. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:16713569 A protein-protein interaction network for human inherited at... | UNDECIDED | Summary: The exact source-specific assertion remains unresolved. Reason: The complete PMID:16713569 abstract and the UniProt WDR5/P61964 interaction entry were read (NbExp=7 is positive curated evidence). The exact ATN1 pair/construct/table in this original screen was not inspected. Preserve the experimental assertion as undecided without claiming it false or inferring the partner activity for ATN1. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:16713569 A protein-protein interaction network for human inherited at... | UNDECIDED | Summary: The exact source-specific assertion remains unresolved. Reason: The complete PMID:16713569 abstract and the UniProt EFEMP1/Q12805 interaction entry were read (NbExp=3 is positive curated evidence). The exact ATN1 pair/construct/table in this original screen was not inspected. Preserve the experimental assertion as undecided without claiming it false or inferring the partner activity for ATN1. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:16713569 A protein-protein interaction network for human inherited at... | UNDECIDED | Summary: The exact source-specific assertion remains unresolved. Reason: The complete PMID:16713569 abstract and the UniProt TRIP6/Q15654 interaction entry were read (NbExp=2 is positive curated evidence). The exact ATN1 pair/construct/table in this original screen was not inspected. Preserve the experimental assertion as undecided without claiming it false or inferring the partner activity for ATN1. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:16713569 A protein-protein interaction network for human inherited at... | UNDECIDED | Summary: The exact source-specific assertion remains unresolved. Reason: The complete PMID:16713569 abstract and the UniProt PLEKHA5/Q9HAU0 interaction entry were read (NbExp=2 is positive curated evidence). The exact ATN1 pair/construct/table in this original screen was not inspected. Preserve the experimental assertion as undecided without claiming it false or inferring the partner activity for ATN1. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:16713569 A protein-protein interaction network for human inherited at... | UNDECIDED | Summary: The exact source-specific assertion remains unresolved. Reason: The complete PMID:16713569 abstract and the UniProt RBFOX1/Q9NWB1 interaction entry were read (NbExp=2 is positive curated evidence). The exact ATN1 pair/construct/table in this original screen was not inspected. Preserve the experimental assertion as undecided without claiming it false or inferring the partner activity for ATN1. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:16713569 A protein-protein interaction network for human inherited at... | UNDECIDED | Summary: The exact source-specific assertion remains unresolved. Reason: The complete PMID:16713569 abstract and the UniProt RERE/Q9P2R6 interaction entry were read (NbExp=3 is positive curated evidence). The exact ATN1 pair/construct/table in this original screen was not inspected. Preserve the experimental assertion as undecided without claiming it false or inferring the partner activity for ATN1. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17577209 The interactome of the histone gene regulatory factor HiNF-P... | UNDECIDED | Summary: The exact source-specific assertion remains unresolved. Reason: The complete HiNF-P interactome abstract was read, but the exact ATN1–HINFP assay and construct evidence were not. Abstract emphasis on other validated partners does not refute the curated pair. Leave this source-specific assertion undecided pending the relevant table or experiment. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19131340 Atrophin proteins interact with the Fat1 cadherin and regula... | KEEP AS NON CORE | Summary: Retain this contextual annotation outside the core molecular-function summary. Reason: Selected original Methods and Fig. 3C/Results explicitly identify full-length human Atr1 and human FAT1-derived constructs in 293T co-immunoprecipitation. Thus this pair is supported despite rodent VSMC functional experiments elsewhere. Retain non-core association; do not claim purified direct binding or human VSMC perturbation from this assay. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:20696395 Conserved beta-hairpin recognition by the GYF domains of Smy... | KEEP AS NON CORE | Summary: Retain this contextual annotation outside the core molecular-function summary. Reason: The complete primary abstract explicitly identifies ATN1 among human GIGYF2 associations in the SILAC/MS study. This supports the broad interaction as non-core. It does not transfer GIGYF2 mRNA-surveillance, stress-granule or vesicular-transport functions to ATN1. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:24981860 Human-chromatin-related protein interactions identify a deme... | UNDECIDED | Summary: The exact source-specific assertion remains unresolved. Reason: The complete PMID:24981860 abstract was read, but the exact ATN1–WDR5 pair and its assay/construct details were not. UniProt records positive WDR5 interaction evidence (NbExp=7); the uncertainty is source-specific verification, not absence of reported binding. Leave undecided and do not transfer a study-highlighted complex function to ATN1. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:27705803 A High-Density Map for Navigating the Human Polycomb Complex... | UNDECIDED | Summary: The exact source-specific assertion remains unresolved. Reason: The complete PMID:27705803 abstract was read, but the exact ATN1–WDR5 pair and its assay/construct details were not. UniProt records positive WDR5 interaction evidence (NbExp=7); the uncertainty is source-specific verification, not absence of reported binding. Leave undecided and do not transfer a study-highlighted complex function to ATN1. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | UNDECIDED | Summary: The exact source-specific assertion remains unresolved. Reason: Article body text is present; the exact target interaction data were not verified. The complete abstract was read, but the specific ATN1–WDR5 pair, construct and assay record were not established. The uncertainty concerns source-specific verification, not a claim that the paper or interaction is absent. Repeated curated WDR5 associations provide corroboration, summarized in the notes, without proving that every study used independent experiments or that ATN1 has WDR5's activity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | UNDECIDED | Summary: The exact source-specific assertion remains unresolved. Reason: Article body text is present; the exact target interaction data were not verified. The complete abstract was read, but the specific ATN1–WDR5 pair, construct and assay record were not established. The uncertainty concerns source-specific verification, not a claim that the paper or interaction is absent. Repeated curated WDR5 associations provide corroboration, summarized in the notes, without proving that every study used independent experiments or that ATN1 has WDR5's activity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | UNDECIDED | Summary: The exact source-specific assertion remains unresolved. Reason: Article body text is present; the exact target interaction data were not verified. The complete abstract was read, but the specific ATN1–WDR5 pair, construct and assay record were not established. The uncertainty concerns source-specific verification, not a claim that the paper or interaction is absent. Repeated curated WDR5 associations provide corroboration, summarized in the notes, without proving that every study used independent experiments or that ATN1 has WDR5's activity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:9647693 Atrophin-1, the DRPLA gene product, interacts with two famil... | KEEP AS NON CORE | Summary: Retain this contextual annotation outside the core molecular-function summary. Reason: The complete PMID:9647693 abstract names AIP2, resolved to WWP2/O00308, among five yeast-two-hybrid ATN1 interactors. Retain the supported association as non-core. The abstract says these proteins contain WW domains, but does not establish which domain mediates this particular interaction. Original domain constructs and pair-specific in-vitro results were not accessible in this audit; the four in-vitro confirmations are not assigned to individual pairs. Do not infer a WW-domain interface or the partner's enzymatic activity from domain composition alone. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:9647693 Atrophin-1, the DRPLA gene product, interacts with two famil... | KEEP AS NON CORE | Summary: Retain this contextual annotation outside the core molecular-function summary. Reason: The complete PMID:9647693 abstract names AIP1, resolved to MAGI2/Q86UL8, among five yeast-two-hybrid ATN1 interactors. Retain the supported association as non-core. The abstract says these proteins contain WW domains, but does not establish which domain mediates this particular interaction. Original domain constructs and pair-specific in-vitro results were not accessible in this audit; the four in-vitro confirmations are not assigned to individual pairs. Do not infer a WW-domain interface or the partner's enzymatic activity from domain composition alone. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:9647693 Atrophin-1, the DRPLA gene product, interacts with two famil... | KEEP AS NON CORE | Summary: Retain this contextual annotation outside the core molecular-function summary. Reason: The complete PMID:9647693 abstract names AIP4, resolved to ITCH/Q96J02, among five yeast-two-hybrid ATN1 interactors. Retain the supported association as non-core. The abstract says these proteins contain WW domains, but does not establish which domain mediates this particular interaction. Original domain constructs and pair-specific in-vitro results were not accessible in this audit; the four in-vitro confirmations are not assigned to individual pairs. Do not infer a WW-domain interface or the partner's enzymatic activity from domain composition alone. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:9647693 Atrophin-1, the DRPLA gene product, interacts with two famil... | MODIFY | Summary: Use the supported WW-domain-binding term for the MAGI1 interaction. Reason: The original abstract identifies AIP3/WWP3, now MAGI1/Q96QZ7, as an ATN1 interactor. The reviewed human MAGI1 UniProt record explicitly attributes the interaction to its WW domains and cites PMID:9647693. This specific curated domain attribution supports GO:0050699; the replacement is not inferred merely from MAGI1 containing WW domains. The original domain constructs and pair-specific in-vitro experiment were not independently read, and no particular WW repeat, minimal ATN1 interface or new core function is assigned. Proposed replacements: WW domain binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:9647693 Atrophin-1, the DRPLA gene product, interacts with two famil... | KEEP AS NON CORE | Summary: Retain this contextual annotation outside the core molecular-function summary. Reason: The complete PMID:9647693 abstract names AIP5, resolved to WWP1/Q9H0M0, among five yeast-two-hybrid ATN1 interactors. Retain the supported association as non-core. The abstract says these proteins contain WW domains, but does not establish which domain mediates this particular interaction. Original domain constructs and pair-specific in-vitro results were not accessible in this audit; the four in-vitro confirmations are not assigned to individual pairs. Do not infer a WW-domain interface or the partner's enzymatic activity from domain composition alone. Supporting Evidence: |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Retain supported nucleus. Reason: Nuclear activity is consistent with directly demonstrated human transcriptional corepression and nuclear localization. The PAINT placement itself was not replayed. Preserve the is_active_in qualifier, all descendant sources, and the legitimate self-source P54259. |
| GO:0005634 nucleus | IDA PMID:10085113 Cleavage of atrophin-1 at caspase site aspartic acid 109 mod... | ACCEPT | Summary: Retain supported nucleus. Reason: Selected original human ATN1 expression/immunofluorescence experiments and independent normal-protein studies support nuclear localization. The disease/caspase focus of PMID:10085113 does not invalidate this location, nor does it establish a normal apoptosis-execution activity. Supporting Evidence: |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Retain supported nucleus. Reason: The electronic nuclear assignment agrees with direct human corepressor and localization data. Preserve the ARBA, orthology and UniProt-location source objects without claiming to have rerun their individual inference algorithms. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Retain supported nucleoplasm. Reason: The current Human Protein Atlas subcellular record reports enhanced nucleoplasm localization with two antibodies across its listed human cell-line assays. The record and reliability fields were read; microscopy images were not independently interpreted. |
| GO:0005737 cytoplasm | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain this contextual annotation outside the core molecular-function summary. Reason: Cytoplasmic localization is a valid contextual orthology assignment, corroborated by the normal human brain localization study. Retain outside the defining nuclear corepressor description; nuclear and cytoplasmic pools are not mutually exclusive. |
| GO:0005737 cytoplasm | TAS PMID:7647802 Abnormal gene product identified in hereditary dentatorubral... | KEEP AS NON CORE | Summary: Retain this contextual annotation outside the core molecular-function summary. Reason: The complete PMID:7647802 abstract explicitly reports ATN1 predominantly in neuronal cytoplasm in human brain immunohistochemistry. Retain this location as non-core; do not convert the disease discussion into a developmental or enzymatic activity. Supporting Evidence: |
| GO:0007417 central nervous system development | TAS PMID:7647802 Abnormal gene product identified in hereditary dentatorubral... | UNDECIDED | Summary: The exact source-specific assertion remains unresolved. Reason: The accessible original abstract establishes protein expression/localization in normal and DRPLA human brain, but not the exact central-nervous-system-development assertion. The relevant full-text evidence remains unverified; preserve this TAS assertion as undecided rather than remove it from an incomplete read. Supporting Evidence: |
| GO:0016363 nuclear matrix | IDA PMID:10973986 Atrophin-1, the dentato-rubral and pallido-luysian atrophy g... | ACCEPT | Summary: Retain supported nuclear matrix. Reason: The original human transfection/fractionation experiments support nuclear-matrix association, enhanced by ETO. Both unexpanded and expanded ATN1 remain SDS-soluble in that setting, so this is not solely a pathological insoluble-aggregate observation. Accept the mechanistically relevant location with that experimental context. Supporting Evidence: |
| GO:0016477 cell migration | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain this contextual annotation outside the core molecular-function summary. Reason: Retain the rodent-orthology cell-migration process as non-core. Original VSMC perturbation experiments support a contextual atrophin contribution to migration/orientation; this is not direct human IDA or the defining molecular activity. Supporting Evidence: |
| GO:0019904 protein domain specific binding | IPI PMID:11984006 The Chediak-Higashi protein interacts with SNARE complex and... | KEEP AS NON CORE | Summary: Retain this contextual annotation outside the core molecular-function summary. Reason: Original PMID:11984006 Tables 1 and 3 identify ATN1/U23851 prey with a LYST/U67615 BEACH-domain-containing bait, cDNA nucleotides 9502–10590, in a controlled human-library yeast two-hybrid screen. The bound partner domain is mapped; unresolved ATN1-side residues do not invalidate that mapping. Retain domain-specific binding as non-core. The bait is not asserted to be a minimal interface, and purified ATN1–LYST binding or a human-cell functional validation is not claimed. Supporting Evidence: |
| GO:0030011 maintenance of cell polarity | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain this contextual annotation outside the core molecular-function summary. Reason: Retain the mouse-orthology polarity-maintenance assignment as a contextual non-core role, consistent with the rodent VSMC orientation experiments. Do not rewrite its source as human IDA or infer an additional core molecular function from perturbation alone. Supporting Evidence: |
| GO:0045893 positive regulation of DNA-templated transcription | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: Retain this contextual annotation outside the core molecular-function summary. Reason: This logical IEA follows the retained coactivator assignment and its positive-transcription process relationship. Keep it non-core with the source-specific mouse reporter evidence. The activation and human repression studies differ in several experimental variables; neither a universal activating role nor a species-specific switch is established. Supporting Evidence: |
| GO:0048471 perinuclear region of cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Retain this contextual annotation outside the core molecular-function summary. Reason: Retain the curated UniProt perinuclear-location mapping as contextual non-core localization. It is compatible with cytoplasmic pools and does not displace the better-supported nuclear core function; no new imaging claim is made. |
| GO:0051402 neuron apoptotic process | IDA PMID:10085113 Cleavage of atrophin-1 at caspase site aspartic acid 109 mod... | MARK AS OVER ANNOTATED | Summary: The neuronal specificity exceeds the cited assay scope. Reason: The neuron-specific GO process exceeds the assay scope of this source. Original Methods, Results and captions establish human ATN1 constructs in non-neuronal 293T apoptosis experiments; both 26Q and 65Q enhance the challenged-cell response. Retain the experimental finding, but do not represent it as direct neuronal-process evidence. This is not a claim that pathological participation is impossible or that ATN1 merely being a caspase substrate rules out a functional toxic fragment. Supporting Evidence: |
| GO:0070161 anchoring junction | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Retain this contextual annotation outside the core molecular-function summary. Reason: Retain the UniProt anchoring-junction mapping as a contextual non-core location, consistent with the atrophin/FAT1 junctional literature. This source remains an electronic vocabulary mapping, not newly generated human imaging evidence. |
| GO:0070161 anchoring junction | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain this contextual annotation outside the core molecular-function summary. Reason: Retain the curator-approved rat-to-human location transfer as non-core. Rodent junctional localization is biologically coherent with the FAT1 association; preserve the P54258 donor and ISS provenance rather than calling this a direct human assay. |
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Download this section (compressed HTML)Q: Which promoter, cell-type and protein-partner contexts determine ATN1 repression versus activation?
Q: Which original pair tables and constructs support the unresolved screen-derived ATN1 interactions?
Q: What evidence supports the original central-nervous-system-development assertion beyond expression in brain?
Q: Can the neuron-specific apoptosis annotation be reconciled with the cited non-neuronal cell assay?
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