AUTS2 is a nonenzymatic regulator of transcription and neuronal cytoskeletal organization. In the nucleus, it participates in noncanonical PRC1 complexes containing PCGF3 or PCGF5 and recruits the histone acetyltransferase EP300/P300 and casein kinase II. P300 recruitment promotes transcriptional activation, while recruited CK2 can inhibit RING1B-dependent histone H2A ubiquitination. The AUTS2 HX-repeat region contributes to P300 association. Mouse studies also support cytoplasmic roles in Rac1/Cdc42 signaling, actin organization, neuronal migration and neurite extension. Its nuclear and cytoplasmic activities depend on cellular context and protein form.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000785 chromatin | NAS PMID:22325352 PCGF homologs, CBX proteins, and RYBP define functionally di... | ACCEPT | Summary: Chromatin association is a core aspect of AUTS2 transcriptional recruitment. Reason: The cited human Polycomb complex study identifies AUTS2 in PCGF3/5 assemblies. Independent AUTS2 chromatin occupancy in PMID:25519132 and the selected PMID:34637754 experiments supports this location without implying sequence-specific DNA recognition. |
| GO:0001764 neuron migration | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain neuronal migration as a donor-supported developmental role. Reason: The mouse migration and rescue experiments support this ISS annotation; it is outside the primary nuclear recruitment core. The supporting mouse cytoplasmic study is PMID:25533347; the original human transfer or electronic source identifier is retained. Supporting Evidence: PMID:25533347 cortical neuronal migration and neuritogenesis |
| GO:0003682 chromatin binding | IDA PMID:25519132 An AUTS2-Polycomb complex activates gene expression in the C... | ACCEPT | Summary: AUTS2 associates with chromatin in transcriptionally active complexes. Reason: PMID:25519132 chromatin occupancy and targeted reporter experiments support chromatin association. GAL4 tethering does not demonstrate autonomous sequence-specific DNA binding, and this broad chromatin-binding term does not require that stronger claim. |
| GO:0005515 protein binding | IPI PMID:25519132 An AUTS2-Polycomb complex activates gene expression in the C... | MODIFY | Summary: Specify binding to the histone acetyltransferase EP300. Reason: The original partner Q09472 is EP300/P300. Human AUTS2 constructs and recombinant interaction/recruitment experiments in PMID:25519132 support histone acetyltransferase binding. P300 supplies catalytic acetyltransferase activity; AUTS2 does not acquire it through recruitment. Proposed replacements: histone acetyltransferase binding Supporting Evidence: PMID:25519132 AUTS2-mediated recruitment of P300 leads to gene activation. |
| GO:0005515 protein binding | IPI PMID:25519132 An AUTS2-Polycomb complex activates gene expression in the C... | KEEP AS NON CORE | Summary: Retain the demonstrated PCGF5 interaction. Reason: PMID:25519132 supports association with the specified PCGF5 partner, including its bridging role in AUTS2-containing complexes. The generic binding statement is correct but does not itself describe the core transcriptional mechanism; no more specific binding term is established here. |
| GO:0005515 protein binding | IPI PMID:25519132 An AUTS2-Polycomb complex activates gene expression in the C... | KEEP AS NON CORE | Summary: Retain RING1B association with its bridging limitation. Reason: The cited experiments support AUTS2 association with Q99496/RNF2 in a complex, with PCGF5 required for the tested association. This is not presented as purified autonomous AUTS2–RING1B binding or AUTS2 ubiquitin-ligase catalysis. |
| GO:0005515 protein binding | IPI PMID:27705803 A High-Density Map for Navigating the Human Polycomb Complex... | UNDECIDED | Summary: The exact PCGF5 interaction record remains unverified. Reason: The complete cached PMID:27705803 abstract describes human affinity-purification mass spectrometry, but the exact AUTS2–PCGF5 record and supporting experiment have not been inspected. Independent complex evidence does not replace assessment of this particular source assertion. |
| GO:0005515 protein binding | IPI PMID:27705803 A High-Density Map for Navigating the Human Polycomb Complex... | UNDECIDED | Summary: The exact RNF2 interaction record remains unverified. Reason: The complete PMID:27705803 abstract establishes study design, not the particular AUTS2–RNF2 pair. The relevant interaction table remains uninspected; neither a wrong-paper claim nor removal is justified. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | UNDECIDED | Summary: The BioPlex 2.0 PCGF5 pair remains source-specific uncertainty. Reason: The complete PMID:28514442 abstract reports human co-complex affinity-purification data. Its exact AUTS2–PCGF5 record, assay configuration and target-table evidence were not independently read, so the source assertion is left unresolved. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | UNDECIDED | Summary: The BioPlex 3.0 PCGF5 pair remains source-specific uncertainty. Reason: PMID:33961781 compares human 293T and HCT116 interaction networks. The exact AUTS2–PCGF5 experiment or table entry remains unread. The cached full-text flag is preserved and is not a claim that the complete relevant data were inspected. |
| GO:0005515 protein binding | IPI PMID:34637754 NRF1 association with AUTS2-Polycomb mediates specific gene ... | MODIFY | Summary: Specify the experimentally resolved P300 interaction. Reason: PMID:34637754 tests human AUTS2 constructs in human cell lines. Reciprocal P300 co-immunoprecipitation and HX-repeat perturbations support the specified Q09472 interaction. The replacement describes binding to the histone acetyltransferase without assigning its catalytic activity to AUTS2. Separate mouse neural-differentiation experiments do not establish a human neuronal assay. Proposed replacements: histone acetyltransferase binding Supporting Evidence: PMID:34637754 HX repeat disrupted P300 interaction |
| GO:0005515 protein binding | IPI PMID:34637754 NRF1 association with AUTS2-Polycomb mediates specific gene ... | KEEP AS NON CORE | Summary: Retain the RING1B association observed with human AUTS2. Reason: In PMID:34637754, the tested human AUTS2 variants retained RING1B association while particular HX-repeat variants lost P300 association. This supports the specific source pair without asserting a direct purified interface or catalytic activity for AUTS2. |
| GO:0005634 nucleus | EXP PMID:25519132 An AUTS2-Polycomb complex activates gene expression in the C... | ACCEPT | Summary: Nuclear localization is integral to AUTS2 chromatin function. Reason: The experimental annotation is consistent with the human nuclear reporter and interaction experiments in PMID:25519132. Retain the curator-supplied location; broader cytoplasmic roles do not contradict nuclear localization. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: Retain the electronic nuclear localization as a core cellular context. Reason: The UniProt subcellular-location mapping is independently consistent with the nuclear and chromatin experiments. Nucleus covers the chromatin-associated pool as well as the nucleoplasmic pool and is not replaced solely to collapse existing location annotations. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Retain the experimentally curated nucleoplasmic location. Reason: The HPA-derived IDA annotation agrees with AUTS2 nuclear activity. The original HPA image was not inspected; retention defers to that curated location rather than claiming to have independently measured its compartment. |
| GO:0005856 cytoskeleton | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Retain the broad cytoskeletal location for the cytoplasmic AUTS2 pool. Reason: The UniProt location mapping and mouse cytoplasmic experiments in PMID:25533347 support cytoskeletal localization. Actin-cytoskeleton colocalization is already represented by a separate annotation. These locations do not imply direct actin binding or a human neuronal experiment. |
| GO:0010592 positive regulation of lamellipodium assembly | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain the donor-supported lamellipodium phenotype. Reason: Mouse perturbation supports lamellipodium regulation as a contextual cytoplasmic role. The supporting mouse cytoplasmic study is PMID:25533347; the original human transfer or electronic source identifier is retained. |
| GO:0015629 actin cytoskeleton | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain actin-cytoskeleton colocalization with its original qualifier. Reason: Mouse localization supports this compartment; colocalizes_with is preserved without claiming direct actin binding. The supporting mouse cytoplasmic study is PMID:25533347; the original human transfer or electronic source identifier is retained. |
| GO:0030036 actin cytoskeleton organization | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain cytoskeletal organization as a contextual role. Reason: Mouse cellular perturbations support this ISS process outside the nuclear core. The supporting mouse cytoplasmic study is PMID:25533347; the original human transfer or electronic source identifier is retained. |
| GO:0030426 growth cone | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Retain growth-cone localization as a neuronal context. Reason: The electronic location is corroborated by mouse neuronal localization. The supporting mouse cytoplasmic study is PMID:25533347; the original human transfer or electronic source identifier is retained. |
| GO:0030426 growth cone | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain the independently sourced growth-cone transfer. Reason: Mouse localization supports this ISS annotation without a human experiment claim. The supporting mouse cytoplasmic study is PMID:25533347; the original human transfer or electronic source identifier is retained. |
| GO:0031507 heterochromatin formation | NAS PMID:22325352 PCGF homologs, CBX proteins, and RYBP define functionally di... | MARK AS OVER ANNOTATED | Summary: General PRC1 compaction should not be assigned uniformly to AUTS2. Reason: The selected PMID:22325352 chromatin-compaction experiments emphasize PRC1.4/PCGF4, whereas AUTS2 is recovered with distinct PCGF3/5 assemblies. PMID:25519132 and PMID:34637754 establish activating AUTS2-containing complexes. The NAS term overgeneralizes a heterogeneous complex family; this does not assert that AUTS2 can never repress transcription in another context. Supporting Evidence: PMID:22325352 We isolated PRC1.4 by FLAG-purification from NFH-PCGF4-containing extracts |
| GO:0035022 positive regulation of Rac protein signal transduction | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain Rac-pathway regulation without assigning GEF catalysis. Reason: Mouse Rac activation experiments support regulation; exchange factors perform catalysis. The supporting mouse cytoplasmic study is PMID:25533347; the original human transfer or electronic source identifier is retained. Supporting Evidence: PMID:25533347 AUTS2 activates Rac1 to induce lamellipodia |
| GO:0035102 PRC1 complex | NAS PMID:22325352 PCGF homologs, CBX proteins, and RYBP define functionally di... | ACCEPT | Summary: AUTS2 is a component of noncanonical PRC1 assemblies. Reason: The human complex purification in PMID:22325352 supports AUTS2 membership in PCGF3/5-associated PRC1. Later functional evidence resolves an activating role for particular AUTS2 complexes; membership does not require every PRC1 member to compact chromatin or repress transcription. Supporting Evidence: PMID:22325352 PCGF3 and PCGF5 recovered AUTS2, FBRS and FBRSL1 |
| GO:0045893 positive regulation of DNA-templated transcription | NAS PMID:22325352 PCGF homologs, CBX proteins, and RYBP define functionally di... | ACCEPT | Summary: Retain positive regulation of transcription as a core biological role. Reason: The broad transcriptional-activation term is consistent with AUTS2 recruitment of P300 and the human reporter experiments in PMID:25519132. The existing RNA polymerase II-specific annotation supplies the narrower coverage. The original PMID:22325352 complex-purification citation is preserved and is not represented as the direct activation experiment. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:25519132 An AUTS2-Polycomb complex activates gene expression in the C... | ACCEPT | Summary: Retain the experimentally supported transcriptional activation process. Reason: Human AUTS2 reporter/recruitment experiments in PMID:25519132 support activation of RNA polymerase II transcription. Preserve acts_upstream_of_or_within exactly; the activity is mediated through recruited factors rather than intrinsic P300 or CK2 catalysis. Supporting Evidence: PMID:25519132 AUTS2-mediated recruitment of P300 leads to gene activation. |
| GO:0048675 axon extension | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain donor-supported axon extension. Reason: Mouse neurite assays and in-vivo axon measurements support the transfer. The supporting mouse cytoplasmic study is PMID:25533347; the original human transfer or electronic source identifier is retained. |
| GO:0097484 dendrite extension | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain donor-supported dendrite extension. Reason: Mouse neuronal measurements distinguish dendrites from axons and support this transfer. The supporting mouse cytoplasmic study is PMID:25533347; the original human transfer or electronic source identifier is retained. |
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Download this section (compressed HTML)Q: How do the sequence-verified natural human AUTS2 products differ in P300 recruitment, PRC1 composition and cytoplasmic function, given that long/short labels and engineered fragments do not uniquely map to the four UniProt products?
Q: Which AUTS2-PCGF5 and AUTS2-RNF2 experiment records in the Polycomb and BioPlex interaction datasets support the four unresolved source-specific annotations?
Q: How does AUTS2 regulate Rac1/Cdc42 signaling in human neurons, and which interacting exchange factors or other proteins perform the nucleotide-exchange step?
Q: Which DNA-binding partners recruit AUTS2-containing PRC1 in human neuronal cell types with low NRF1 expression?
Experiment: Compare sequence-verified natural human products at matched expression in neuronal cells using endogenous P300 and PRC1 co-immunoprecipitation, chromatin occupancy and nascent transcription. Measure recruited enzyme activity separately from AUTS2 interaction and recruitment.
Experiment: Use endogenous depletion and rescue with interaction-selective AUTS2 variants to separate P300-dependent nuclear transcription from Rac1/Cdc42-dependent cytoplasmic morphology, with matched localization and protein-abundance controls.
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