ASXL2 is a nuclear chromatin regulator with HARE-HTH, DEUBAD and atypical PHD regions. It forms a regulatory subunit of BAP1-containing PR-DUB complexes and stimulates BAP1-mediated removal of ubiquitin from histone H2A. ASXL2 also supports transcriptional coactivation through nuclear-receptor and chromatin-associated interactions, including experimentally established PPAR signaling. These activities influence developmental gene expression and cell differentiation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003677 DNA binding | IEA GO_REF:0000002 | UNDECIDED | Summary: The PHD-derived DNA-binding assertion remains unresolved. Reason: The exact IEA support is IPR026905, the atypical ASX-like PHD domain; IPR007759 is the separate HARE-HTH domain. Chromatin association does not establish direct DNA binding. The current evidence does not resolve the asserted DNA interaction, and the PHD histone-peptide results do not test DNA binding. Preserve the mapping and request its evidence basis; no loss-of-function or wrong-domain removal is established. Propagation Review Root cause: UNRESOLVED Sources checked: InterPro:IPR026905 UNRESOLVED The ASX-like PHD domain is the actual electronic source. Protein-partner binding and the tested histone-tail results do not resolve direct DNA recognition by this domain. This is not a PAINT inference. Supporting Evidence: |
| GO:0003682 chromatin binding | IBA GO_REF:0000033 | ACCEPT | Summary: Chromatin association supports the core regulatory role. Reason: Chromatin association fits the core regulatory role. PMID:21047783 Figure 5 tests FLAG-tagged human ASXL2 in mouse 3T3-L1 cells; the separate Figure 6 differentiation time course uses endogenous ASXL antibodies. These contexts are distinct from human-cell chromatin measurements. The existing PAINT judgment is consistent with chromatin-regulatory biochemical evidence, without establishing sequence-specific DNA recognition or a particular histone-reader activity. The PTN000339786 placement and alignment were not reconstructed. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000339786 UNRESOLVED The ancestral placement was not reconstructed. The target annotation is retained based on independent chromatin-regulatory evidence; this status concerns the unexamined node placement, not a negative target-function claim. |
| GO:0005515 protein binding | IPI PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei... | UNDECIDED | Summary: The source-specific ASXL2–SPOP experiment remains unresolved. Reason: UniProt positively records ASXL2-SPOP (O43791), but the exact pair data, wild-type/mutant configuration and controls in PMID:35512704 remain uninspected. The article studies mutation-directed neo-interactions and names SPOP F133L, yet the accessible body does not identify the ASXL2 pair; the named mutant cannot be assigned to this annotation without its Data S1 evidence. Retain UNDECIDED for the unadjudicated experimental support, without asserting noninteraction or a demonstrated wrong wild-type mapping. Supporting Evidence: |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: Nuclear localization fits ASXL2 function. Reason: Nuclear localization is appropriate for the core chromatin regulator and is independently supported by the current HPA nucleoplasmic assessment. Preserve the original UniProt subcellular-vocabulary mapping. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0191 SUPPORTS TRANSFER SL-0191 is Nucleus and is explicitly mapped to GO:0005634 by the UniProtKB SubcellularLocation2GO mapping. ASXL2 nuclear localization is independently corroborated. No PAINT inference is involved. Supporting Evidence: |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Human immunofluorescence supports nucleoplasmic localization. Reason: The actual HPA page reports enhanced-reliability nucleoplasm localization with both HPA034646 and HPA058040 in A-431, U-251MG and U2OS. The textual assay table was read; image pixels and every antibody validation experiment were not independently assessed. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5689630 | ACCEPT | Summary: The modeled BAP1 assembly includes nucleoplasmic ASXL2. Reason: The live reaction 5689630 and its 5689653/5689678 complexes include the 5689640 ASXL1/ASXL2 set, whose human ASXL2 member 5689629 maps to Q76L83 in nucleoplasm. This validates the modeled compartment and is consistent with HPA. The cached reaction summary foregrounds other partners and is not an ASXL2-specific binding assay. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5690790 | ACCEPT | Summary: The modeled PR-DUB reaction includes nucleoplasmic ASXL2. Reason: The live 5690790 event places the catalytic PR-DUB complex 5690807 and core 5690793 in nucleoplasm, with ASXL2 via set5689640/member5689629. BAP1 is catalytic; ASXL2 is the regulatory subunit. The original source experiments beneath every Reactome citation were not all re-read. |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000002 | ACCEPT | Summary: Transcriptional regulation is a central ASXL2 function. Reason: Transcriptional regulation is a core role independently corroborated by ASXL2 reporter and endogenous-target assays. The broad term remains true alongside the positive PolII child. IPR007759 is the HARE-HTH source signature; the target evidence supports transcriptional regulation without attributing a specific DNA-recognition mechanism to that domain. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR007759 UNRESOLVED The ASXL HARE-HTH signature is present, but its isolated mechanistic contribution and the mapping basis were not separately tested here. Target transcriptional regulation is independently established; this is an InterPro2GO mapping, not PAINT. |
| GO:0009887 animal organ morphogenesis | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Organ morphogenesis is a developmental context. Reason: Retain the broad developmental PAINT assertion as contextual biology rather than the defining molecular mechanism. Existing developmental evidence and the conserved transcriptional-regulatory role are compatible; no target-specific loss is established. The actual ancestral-node placement and all donor experiments remain unverified, so no claim that this phylogenetic transfer was reconstructed is made. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000339786 UNRESOLVED The original developmental ancestral assertion is retained as contextual biology. Its node placement and underlying donor experiments have not been independently reconstructed. |
| GO:0035360 positive regulation of peroxisome proliferator activated receptor signaling pathway | IDA PMID:21047783 Additional sex comb-like (ASXL) proteins 1 and 2 play opposi... | KEEP AS NON CORE | Summary: PPAR signaling enhancement is a receptor-specific output. Reason: The reported PPAR pathway enhancement is supported in the experimental system. It is a context-specific output of the broader transcriptional coactivator role, rather than a separate universal core process. Preserve the original IDA source and distinguish human-protein assays from mouse physiology. Supporting Evidence: |
| GO:0035517 PR-DUB complex | IBA GO_REF:0000033 | ACCEPT | Summary: ASXL2 is a regulatory component of PR-DUB. Reason: PR-DUB membership is core and independently corroborated by ASXL2-specific human biochemical evidence and the live complex hierarchy. The fly/ASXL1 PAINT sources are not rejected for donor count or paralog identity; PTN placement remains unexamined. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000339786 UNRESOLVED The inherited PR-DUB membership assertion is compatible with target biochemistry; the exact IBD placement remains unexamined. UniProtKB:Q8IXJ9 SUPPORTS TRANSFER Human ASXL1 is an experimentally supported BAP1/PR-DUB regulatory partner in PMID:26416890 and PMID:26739236. The same papers directly support ASXL2 complex membership; no reconstruction of the ancestral node is claimed. |
| GO:0042975 peroxisome proliferator activated receptor binding | IBA GO_REF:0000033 | ACCEPT | Summary: PPAR binding is an experimentally grounded coactivator interaction. Reason: PPAR association is an experimentally grounded component of the coactivator mechanism. Human ASXL2 is itself among the descendant evidence; self-WITH/FROM is expected and not circular. Preserve the IBA source objects while marking the unreplayed PTN000339788 placement separately. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000339788 UNRESOLVED The particular IBD placement and alignment were not reconstructed; the matching target experimental annotation independently grounds the function. UniProtKB:Q76L83 SUPPORTS TRANSFER This is the target ASXL2 itself. The matching IDA annotation from PMID:21047783 supplies experimental descendant evidence; self-WITH/FROM is expected and does not imply circular propagation. Supporting Evidence: |
| GO:0042975 peroxisome proliferator activated receptor binding | IDA PMID:21047783 Additional sex comb-like (ASXL) proteins 1 and 2 play opposi... | ACCEPT | Summary: Human ASXL2 binds PPAR in the cited experiment. Reason: Human ASXL2 receptor-interaction experiments support the specific PPAR-binding assertion. This interaction is part of the experimentally grounded coactivator mechanism. The assays do not resolve the two ASXL2 protein products separately. Supporting Evidence: |
| GO:0045600 positive regulation of fat cell differentiation | IDA PMID:21047783 Additional sex comb-like (ASXL) proteins 1 and 2 play opposi... | KEEP AS NON CORE | Summary: Adipogenesis is a contextual output of coactivation. Reason: The adipocyte differentiation outcome is a valid contextual consequence in mouse 3T3-L1 cells expressing human ASXL2. It does not establish experiments in human adipocytes or a universal developmental program, and belongs outside the compact molecular core. Supporting Evidence: |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: Positive PolII regulation is a core transcriptional role. Reason: Positive PolII transcription regulation is core and independently supported for the target. Preserve the PAINT annotation, including target Q76L83 in WITH/FROM; that is not circular evidence. The particular ancestral placement remains unexamined. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000339786 UNRESOLVED The particular IBD placement and alignment were not reconstructed; the matching target experimental annotation independently grounds the function. UniProtKB:Q76L83 SUPPORTS TRANSFER This is the target ASXL2 itself. The matching IDA annotation from PMID:21047783 supplies experimental descendant evidence; self-WITH/FROM is expected and does not imply circular propagation. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:21047783 Additional sex comb-like (ASXL) proteins 1 and 2 play opposi... | ACCEPT | Summary: The target-specific study supports transcriptional activation. Reason: Retain the target-specific positive transcription assertion from the primary study. It supplies the process context for transcriptional coactivation without assigning ASXL2 the catalytic activity of associated histone-modifying enzymes. Supporting Evidence: |
| GO:0035800 deubiquitinase activator activity | IDA PMID:26739236 BAP1/ASXL1 recruitment and activation for H2A deubiquitinati... | NEW | Summary: ASXL2 activates BAP1-dependent histone H2A deubiquitination. Reason: Purified human ASXL2 DEUBAD residues 261-380 stimulate BAP1-dependent H2A-K119 deubiquitination in PMID:26739236 Figure 1e. The Methods identify Q76L83 cDNA and bacterial ASXL2 fragment expression; BAP1 is produced separately. PMID:26416890 independently establishes ASXL2 regulatory-domain association with BAP1 and stimulation of its activity. This is direct activator work, not intrinsic ASXL2 hydrolase activity. The fragment assay does not resolve functions of the two full-length isoforms. |
| GO:0003713 transcription coactivator activity | IDA PMID:21047783 Additional sex comb-like (ASXL) proteins 1 and 2 play opposi... | NEW | Summary: ASXL2 provides transcriptional coactivator activity. Reason: Human ASXL2 receptor association and transcriptional activation assays support this function. It is not an is_a ancestor or descendant of the seeded receptor-binding or chromatin-binding functions. Adipogenic phenotypes remain contextual and are not new process proposals. PMID:30664650 provides corroborating complex-level transcriptional evidence; the direct receptor-coactivation IDA remains grounded in PMID:21047783. |
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Download this section (compressed HTML)Q: What evidence supports direct DNA recognition by the ASXL2 PHD-based electronic mapping, separately from chromatin association and HARE-HTH predictions?
Q: How do the two ASXL2 protein products differ in BAP1 activation, receptor coactivation and MBD5/6-dependent assembly?
Q: Which original ASXL2-SPOP assays and construct controls support the curated interaction?
Experiment: Compare purified full-length ASXL2 products and matched DEUBAD/PHD variants for BAP1 activation on nucleosomal H2A-K119ub and MBD6-dependent complex stability.
Hypothesis: The isoforms preserve separable regulatory interfaces but differ in their assembly or transcriptional effects.
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