ATRX is a nuclear SNF2-family ATP-dependent chromatin remodeler. Its full-length protein combines an N-terminal ADD histone-recognition domain with a C-terminal ATPase motor. The ADD domain recognizes H3K9 trimethylation in the context of an unmethylated H3K4, and interactions with HP1 and other chromatin proteins aid targeting. Together with DAXX, ATRX organizes H3.3-containing chromatin at repetitive genomic regions, including pericentric and telomeric sites. The ADD domain also binds the histone-fold region of macroH2A, and ATRX limits macroH2A chromatin accumulation at selected loci. ATRX also protects susceptible genomic regions during replication. The PIP motif contributes to protection against genome-wide replication stress, whereas ATPase activity suppresses telomeric single-stranded DNA in tested human-cell contexts. Dependence on DAXX varies with the chromatin context and endpoint. These activities support chromatin organization and genome stability. Pathogenic germline variants cause ATR-X syndrome, while somatic ATRX loss is associated with alternative telomere maintenance in some tumors.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000228 nuclear chromosome | IEA GO_REF:0000107 | ACCEPT | Summary: ATRX associates with nuclear chromosomes. Reason: The mouse-ortholog transfer agrees with human ATRX immunolocalization at heterochromatic chromosome regions in PMID:10570185. The broad compartment is valid; the more informative pericentric and telomeric locations are represented separately. |
| GO:0000779 condensed chromosome, centromeric region | IEA GO_REF:0000107 | ACCEPT | Summary: ATRX occupies the centromeric region of condensed chromosomes. Reason: Human immunolocalization in PMID:10570185 places ATRX at pericentromeric heterochromatin through mitosis, supporting this regional chromosome annotation. This is not an assertion that ATRX is a kinetochore component. |
| GO:0000781 chromosome, telomeric region | IEA GO_REF:0000120 | ACCEPT | Summary: ATRX is associated with telomeric chromatin. Reason: The combined electronic sources agree with chromatin localization and telomeric H3.3 deposition experiments in PMID:20211137 and PMID:20651253. Occupancy depends on cell context; the distinct subtelomeric localization in human glioma cells is also retained. |
| GO:0000781 chromosome, telomeric region | ISS GO_REF:0000024 | ACCEPT | Summary: Telomere colocalization is consistent with ATRX chromatin targeting. Reason: Keep the source colocalizes_with qualifier and mouse donor unchanged. Telomeric imaging and chromatin studies support the association, but this row is not upgraded to a direct human localization experiment. |
| GO:0000781 chromosome, telomeric region | ISS GO_REF:0000024 | ACCEPT | Summary: Telomeric localization is a conserved ATRX property. Reason: The curated mouse-to-human transfer is consistent with the ATRX–DAXX telomere pathway and the experimental literature. Preserve this located_in assertion separately from the colocalizes_with source row and preserve both original raw GOA records. |
| GO:0000792 heterochromatin | IEA GO_REF:0000120 | ACCEPT | Summary: ATRX is enriched at heterochromatin. Reason: The electronic assignment agrees with the N-terminal chromatin-targeting region, methylated-H3 recognition and direct human heterochromatin localization. It does not imply uniform occupancy of all heterochromatin. |
| GO:0000792 heterochromatin | TAS PMID:10570185 Localization of a putative transcriptional regulator (ATRX) ... | ACCEPT | Summary: Human ATRX localizes at pericentromeric heterochromatin. Reason: PMID:10570185 reports indirect immunofluorescence and confocal microscopy during interphase and mitosis. Retain the supplied TAS evidence code; the broad heterochromatin compartment accurately includes these sites. |
| GO:0003682 chromatin binding | IDA PMID:27029610 ATRX binds to atypical chromatin domains at the 3' exons of ... | ACCEPT | Summary: ATRX binds chromatin at a subset of zinc-finger genes. Reason: PMID:27029610 maps ATRX occupancy at ZNF 3-prime exons in human cell lines by ChIP-seq and related assays. This is core chromatin association, without assigning ATRX the methyltransferase activity of SETDB1. |
| GO:0003682 chromatin binding | IEA GO_REF:0000120 | ACCEPT | Summary: Chromatin binding is integral to ATRX function. Reason: The combined ARBA and orthology assignment agrees with human chromatin occupancy and the ADD histone-recognition domain. Binding does not establish that every occupied locus is remodeled in the same way. |
| GO:0005515 protein binding | IPI PMID:10699177 Cell cycle-dependent phosphorylation of the ATRX protein cor... | KEEP AS NON CORE | Summary: Retain the reported ATRX–HP1alpha association. Reason: PMID:10699177 reports cell-cycle-associated interaction with HP1alpha, but its available abstract does not map the chromoshadow-domain interface. The separately supported chromoshadow-domain-binding annotation already captures that specificity. Retain the supported interaction without transferring a different paper’s interface experiment into this source assertion. Supporting Evidence: PMID:10699177 association with heterochromatin protein 1alpha (HP1alpha) |
| GO:0005515 protein binding | IPI PMID:12953102 The ATRX syndrome protein forms a chromatin-remodeling compl... | KEEP AS NON CORE | Summary: ATRX associates with DAXX in a chromatin-remodeling complex. Reason: Reciprocal HeLa co-IP and complex separation support the pair. Generic binding describes a verified association but does not identify ATRX catalytic activity or make ATRX the autonomous DAXX histone chaperone. |
| GO:0005515 protein binding | IPI PMID:17296936 Interaction between chromatin proteins MECP2 and ATRX is dis... | KEEP AS NON CORE | Summary: ATRX interacts with MeCP2 in the tested mixed-species constructs. Reason: The rat Q00566 supporting entity is compatible with the actual rat MeCP2-e2 bait and human ATRX prey. GST/deletion assays support physical interaction; mouse brain and mouse-cell experiments are separate contexts. No wrong-species or paralog error is established. |
| GO:0005515 protein binding | IPI PMID:22102817 EBV tegument protein BNRF1 disrupts DAXX-ATRX to activate vi... | KEEP AS NON CORE | Summary: The ATRX-DAXX association is disrupted by viral BNRF1. Reason: The actual Results test DAXX-ATRX co-IP and its disruption by WT versus mutant BNRF1. A viral title does not invalidate the ATRX pair. Do not claim purified direct contact from these cellular IPs. |
| GO:0005515 protein binding | IPI PMID:22391447 ATRX-mediated chromatin association of histone variant macro... | KEEP AS NON CORE | Summary: Retain the reported macroH2A interaction alongside the specific histone-binding annotation. Reason: The PMID:22391447 abstract explicitly identifies ATRX as a macroH2A-interacting protein. A histone-binding annotation from this same paper already represents the specific activity, so another replacement is unnecessary. This interaction and negative regulation of macroH2A chromatin association do not establish macroH2A deposition activity. Supporting Evidence: PMID:22391447 as a novel macroH2A-interacting protein |
| GO:0005515 protein binding | IPI PMID:24651726 ATRX dysfunction induces replication defects in primary mous... | KEEP AS NON CORE | Summary: ATRX associates with the MRN complex including RAD50. Reason: HeLa nuclear-extract mass spectrometry, reciprocal RAD50 IP and immunoblot validation establish association. Ethidium-bromide resistance argues against simple DNA bridging but does not isolate a purified binary ATRX-RAD50 interface. |
| GO:0005515 protein binding | IPI PMID:24651726 ATRX dysfunction induces replication defects in primary mous... | KEEP AS NON CORE | Summary: DAXX accompanies ATRX in HeLa nuclear complexes. Reason: The actual ATRX immunoisolation identifies DAXX and MRN components. PMID:12953102 independently corroborates ATRX-DAXX; generic binding need not be removed or transformed into MRN catalysis. |
| GO:0005515 protein binding | IPI PMID:24981860 Human-chromatin-related protein interactions identify a deme... | KEEP AS NON CORE | Summary: The ATRX-DAXX association has independent targeted support. Reason: Targeted experiments in PMID:12953102 independently support the ATRX–DAXX association. Retain this generic interaction as non-core with curator deference; the specific chromatin-remodeling and histone-handling activities are represented separately. |
| GO:0005515 protein binding | IPI PMID:25417162 ATRX directs binding of PRC2 to Xist RNA and Polycomb target... | KEEP AS NON CORE | Summary: ATRX associates with PRC2 containing EZH2. Reason: Selected Results demonstrate contact between purified ATRX and PRC2 and tandem ATRX/EZH2 RNA IP. This supports the curated association at complex level. It does not isolate EZH2 as the direct binding subunit, establish a human-only purified assay, or make ATRX a PRC2 methyltransferase. Preserve experimental-curator judgment while stating those limits. The cited earlier yeast-two-hybrid experiment and purified-reagent species were not independently verified; two linked erratum bodies remain unread. No contradiction or retraction was established. |
| GO:0005515 protein binding | IPI PMID:26373281 Loss of ATRX Suppresses Resolution of Telomere Cohesion to C... | MODIFY | Summary: ATRX associates with macroH2A1.1 through its N-terminal region. Reason: PMID:26373281 Results describe competition for macroH2A1.1 and functional reintroduction of the ATRX macroH2A-binding region. Histone binding is an appropriate refinement of this partner-specific assertion. It is not evidence for autonomous H3.3 chaperone activity or for interpreting every macroH2A-associated phenotype as a new core. Additional purified-fragment work in PMID:40443347 maps macroH2A-H2B recognition to the ATRX ADD domain; this does not establish macroH2A deposition activity. Proposed replacements: histone binding |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | KEEP AS NON CORE | Summary: The ATRX-DAXX association has independent targeted support. Reason: Targeted experiments in PMID:12953102 independently support the ATRX–DAXX association. Retain this generic interaction as non-core with curator deference; the specific chromatin-remodeling and histone-handling activities are represented separately. |
| GO:0005515 protein binding | IPI PMID:27029610 ATRX binds to atypical chromatin domains at the 3' exons of ... | KEEP AS NON CORE | Summary: ATRX associates with TRIM28 in K562 chromatin. Reason: Actual Results and Methods show TRIM28 recovered with ATRX from MNase-solubilized chromatin, with control IP. Retain the physical association without claiming a purified binary interface or rejecting a chromatin complex as a bystander artifact. |
| GO:0005515 protein binding | IPI PMID:27029610 ATRX binds to atypical chromatin domains at the 3' exons of ... | KEEP AS NON CORE | Summary: ATRX associates with SETDB1 in K562 chromatin. Reason: Actual Results and Methods show SETDB1 recovered with ATRX from MNase-solubilized chromatin, with control IP. Retain the physical association without claiming a purified binary interface or rejecting a chromatin complex as a bystander artifact. |
| GO:0005515 protein binding | IPI PMID:27029610 ATRX binds to atypical chromatin domains at the 3' exons of ... | KEEP AS NON CORE | Summary: ATRX associates with ZNF274 in K562 chromatin. Reason: Actual Results and Methods show ZNF274 recovered with ATRX from MNase-solubilized chromatin, with control IP. Retain the physical association without claiming a purified binary interface or rejecting a chromatin complex as a bystander artifact. |
| GO:0005515 protein binding | IPI PMID:27029610 ATRX binds to atypical chromatin domains at the 3' exons of ... | KEEP AS NON CORE | Summary: DAXX is an ATRX co-IP control in K562 chromatin. Reason: DAXX is explicitly recovered as the positive interaction control in the same experiment; independent PMID:12953102 supports the established pair. This source does more than infer interaction from colocalization. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: The ATRX-DAXX association has independent targeted support. Reason: Targeted experiments in PMID:12953102 independently support the ATRX–DAXX association. Retain this generic interaction as non-core with curator deference; the specific chromatin-remodeling and histone-handling activities are represented separately. |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: The ATRX SNF2-like motor binds ATP. Reason: The InterPro-based assignment is supported by the ATP-dependent translocation and chromatin-remodeling assays in PMID:12953102. It is a substrate-binding property of the intact motor, not proof of motor activity in every splice product. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Nuclear localization is conserved in the ATRX lineage. Reason: The PAINT inference is consistent with direct human localization. Human ATRX in WITH/FROM is legitimate target experimental evidence used to place the ancestral assertion, not circular support; no conflicting lineage-specific loss is established. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: ATRX acts in the nucleus. Reason: The electronic subcellular-location and mouse-ortholog evidence agrees with human chromatin and PML-body localization. The broad nuclear annotation is sound. |
| GO:0005634 nucleus | TAS PMID:7874112 Cloning and characterization of a new human Xq13 gene, encod... | ACCEPT | Summary: The original human gene study identifies a nuclear protein. Reason: PMID:7874112 describes the cloned XH2/ATRX product as a putative NTP-binding nuclear protein. Later direct localization supports the compartment; this early paper is not treated as a biochemical demonstration of DNA unwinding. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9007926 | ACCEPT | Summary: ATRX and DAXX assemble in the nucleoplasm. Reason: Reactome R-HSA-9007926 describes formation of the ATRX–DAXX remodeling complex and cites the human biochemical study of Xue and colleagues. Nucleoplasm is consistent with this nuclear assembly event; complex assembly does not alone define a new molecular function. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9670101 | ACCEPT | Summary: The subtelomeric ATRX–DAXX event occurs in the nuclear compartment. Reason: Reactome R-HSA-9670101 concerns subtelomeric chromatin association, cohesin recruitment and TERRA regulation. The underlying human glioma study distinguishes subtelomeric occupancy from chromosome termini. Nucleoplasm is a broad compatible location. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9670114 | ACCEPT | Summary: The telomeric H3.3-deposition machinery acts in the nucleus. Reason: Reactome R-HSA-9670114 describes HIRA-independent H3.3 deposition involving ATRX and DAXX. The event supports the nuclear compartment; direct H3.3 chaperoning by DAXX is not reassigned as an intrinsic ATRX activity. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9670619 | ACCEPT | Summary: Nucleoplasm is a core location of normal ATRX, although this Reactome event describes defective ATRX variants. Reason: The nucleoplasm assertion is compatible with normal ATRX chromatin remodeling and is retained as a core location, consistent with the other source-specific nucleoplasm annotations. Reactome R-HSA-9670619 describes ATRX truncations that fail to bind DAXX and may be undetectable in the nucleus; that mutant behavior is not used to infer localization of every mutant. Independent wild-type evidence includes the human HeLa ATRX–DAXX complex and nuclear-body colocalization in PMID:12953102, together with the normal complex-assembly event R-HSA-9007926. This accepts the normal gene-level compartment without treating the failed-mutant event as an independent wild-type localization assay. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9670620 | ACCEPT | Summary: The normal ATRX compartment remains nucleoplasmic despite the defective-DAXX context of this source event. Reason: Nucleoplasm is part of ATRX's established normal nuclear chromatin-remodeling context. Reactome R-HSA-9670620 specifically describes defective DAXX variants, altered nuclear detection and impaired ATRX binding; it does not demonstrate loss of normal ATRX localization. The normal ATRX–DAXX assembly event R-HSA-9007926 and human biochemical/nuclear-body evidence in PMID:12953102 provide independent support. The broad compartment is accepted consistently with the other nucleoplasm annotations while the mutant-specific limits of this TAS route remain explicit. |
| GO:0005721 pericentric heterochromatin | IBA GO_REF:0000033 | ACCEPT | Summary: Pericentric heterochromatin targeting is a conserved ATRX function. Reason: The PAINT inference is corroborated by human localization in PMID:10570185 and histone-reader evidence in PMID:21421568. The listed fly and mouse descendants support an ancestral judgment; donor count is not used to assess its strength. |
| GO:0005721 pericentric heterochromatin | IEA GO_REF:0000107 | ACCEPT | Summary: ATRX localizes to pericentric heterochromatin. Reason: The mouse-ortholog electronic transfer agrees with direct human localization and ADD-domain targeting. No human-specific loss of this localization is indicated. |
| GO:0005721 pericentric heterochromatin | ISS GO_REF:0000024 | ACCEPT | Summary: Curated orthology supports pericentric localization. Reason: Keep the manual mouse-to-human transfer: pericentric heterochromatin is a major, experimentally supported ATRX compartment. The transferred evidence remains ISS, not a newly asserted human IDA. |
| GO:0006325 chromatin organization | IMP PMID:22391447 ATRX-mediated chromatin association of histone variant macro... | ACCEPT | Summary: ATRX controls histone-variant organization in chromatin. Reason: PMID:22391447 links ATRX loss to increased macroH2A association and accumulation at the human alpha-globin locus. This supports chromatin organization while distinguishing restriction of macroH2A incorporation from the ATRX–DAXX H3.3 deposition pathway. |
| GO:0006338 chromatin remodeling | IBA GO_REF:0000033 | ACCEPT | Summary: Chromatin remodeling is the conserved ATRX catalytic role. Reason: The ancestral PAINT assignment agrees with direct human ATRX-complex remodeling assays. Target ATRX appearing among descendant evidence is expected and does not make the IBA circular. |
| GO:0006338 chromatin remodeling | IMP PMID:10742099 Mutations in ATRX, encoding a SWI/SNF-like protein, cause di... | ACCEPT | Summary: Human ATRX mutations disturb chromatin-associated epigenetic states. Reason: PMID:10742099 reports altered methylation of repeated DNA in ATRX-mutant patients. That phenotype supports the curated chromatin-remodeling interpretation when considered with direct remodeling biochemistry; it does not make ATRX a DNA methyltransferase or turn the phenotype into a purified-motor assay. |
| GO:0006338 chromatin remodeling | IMP PMID:27029610 ATRX binds to atypical chromatin domains at the 3' exons of ... | ACCEPT | Summary: ATRX maintains chromatin organization at atypical ZNF exons. Reason: PMID:27029610 combines human chromatin occupancy with ATRX knockout and loss of H3K9me3 enrichment at selected ZNF regions. Retain the IMP assignment within the established remodeling role; SETDB1, rather than ATRX, supplies the histone methyltransferase activity. |
| GO:0006338 chromatin remodeling | NAS PMID:26340527 The Daxx/Atrx Complex Protects Tandem Repetitive Elements du... | ACCEPT | Summary: ATRX–DAXX supports repeat chromatin under DNA hypomethylation. Reason: PMID:26340527 examines mouse ESCs and finds ATRX–DAXX-dependent repeat repression and H3K9 trimethylation involving Suv39h recruitment. This agrees with ATRX chromatin remodeling, but neither the NAS source nor this biological context establishes intrinsic ATRX histone methylation. |
| GO:0006355 regulation of DNA-templated transcription | TAS PMID:7697714 Mutations in a putative global transcriptional regulator cau... | KEEP AS NON CORE | Summary: Transcriptional regulation is an outcome of ATRX chromatin functions. Reason: The early disease-gene study PMID:7697714 inferred a broad transcriptional role from alpha-globin and other phenotypes. Preserve the contextual annotation without presenting ATRX as a sequence-specific transcription factor or treating all regulated transcripts as direct targets. |
| GO:0010564 regulation of cell cycle process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Cell-cycle progression is affected by ATRX-dependent genome maintenance. Reason: The ARBA term is broad. Replication and chromosome phenotypes support cell-cycle consequences, but the core description is chromatin remodeling and genome maintenance rather than a general cell-cycle regulatory activity. |
| GO:0010571 positive regulation of nuclear cell cycle DNA replication | IEA GO_REF:0000107 | ACCEPT | Summary: ATRX supports fork maintenance and replication recovery under stress. Reason: The mouse ortholog transfer is consistent with delayed S phase after aphidicolin release and increased fork stalling in PMID:24651726. Human ATRX-deficient cells in PMID:23329831 show a reduced origin-firing readout after hydroxyurea treatment. The authors caution that inefficient CldU incorporation during recovery may contribute to that readout, so it does not independently establish direct initiation control. The authors explicitly conclude that ATRX does not regulate replication rate from unchanged fiber lengths after hydroxyurea release. Retention rests on the combined replication-recovery and mouse fork-maintenance evidence within the frequency-or-extent scope of the term, with these assay limits, and does not assert faster elongation or DNA-polymerase activity. Supporting Evidence: PMID:23329831 a reduction in new origin firing in ATRX-deficient cells |
| GO:0010571 positive regulation of nuclear cell cycle DNA replication | ISS GO_REF:0000024 | ACCEPT | Summary: The mouse ortholog inference agrees with replication recovery and fork-maintenance evidence. Reason: PMID:24651726 supports a mouse replication-stress phenotype. The independent human PMID:23329831 study reports reduced origin firing after ATRX loss while explicitly concluding that ATRX does not regulate replication rate. The authors also caution that inefficient CldU incorporation after hydroxyurea release may contribute to the observed origin-firing readout. GO:0010571 includes frequency or extent; the combined recovery and mouse fork-maintenance evidence supports retention without asserting direct initiation control or treating the negative rate result as affirmative evidence. This contribution is contextual to chromatin maintenance and the tested replication conditions. |
| GO:0016604 nuclear body | IDA GO_REF:0000052 | ACCEPT | Summary: ATRX exhibits nuclear-body localization. Reason: The immunofluorescence-curation source is consistent with independent human ATRX nuclear-body observations. The original image set was not reexamined, so this broad IDA location is retained without relabeling every observed punctum as a particular body. |
| GO:0016604 nuclear body | IEA GO_REF:0000117 | ACCEPT | Summary: Nuclear bodies are an established ATRX compartment. Reason: The ARBA assignment is corroborated by human ATRX and DAXX localization in nuclear bodies. The broad label does not claim that ATRX is present in every type of nuclear body. |
| GO:0016604 nuclear body | IPI PMID:12953102 The ATRX syndrome protein forms a chromatin-remodeling compl... | MODIFY | Summary: The cited ATRX–DAXX study identifies PML nuclear bodies. Reason: PMID:12953102 explicitly describes colocalization of a fraction of ATRX and DAXX at promyelocytic leukemia nuclear bodies. PML body is a more informative cellular-component label for this specific source, while the original IPI code and source assertion remain unchanged. Proposed replacements: PML body Supporting Evidence: PMID:12953102 a proportion of ATRX and Daxx colocalize in promyelocytic leukemia nuclear bodies |
| GO:0016605 PML body | IEA GO_REF:0000120 | ACCEPT | Summary: ATRX can localize to PML nuclear bodies. Reason: The electronic subcellular-location and orthology evidence agrees with direct human observations in PMID:12953102. This compartment is compatible with assembly or regulation of ATRX–DAXX and does not imply that every ATRX splice product has identical localization. |
| GO:0016605 PML body | ISS GO_REF:0000024 | ACCEPT | Summary: PML-body localization is supported across mammalian ATRX proteins. Reason: The mouse-to-human ISS transfer is corroborated by the human ATRX–DAXX localization study. Retain the compartment without interpreting colocalization as a defined stoichiometric PML complex. |
| GO:0016887 ATP hydrolysis activity | IEA GO_REF:0000116 | ACCEPT | Summary: ATP hydrolysis powers ATRX remodeling. Reason: The Rhea-based annotation agrees with the ATP-dependent activities of the ATRX motor established biochemically in PMID:12953102. The more informative ATP-dependent chromatin-remodeler function is already present and is used in the core synthesis. |
| GO:0030330 DNA damage response, signal transduction by p53 class mediator | IEA GO_REF:0000107 | UNDECIDED | Summary: The p53-signaling transfer needs its specific donor experiment resolved. Reason: The official MGI comparative GO table (generated 10 March 2023) links a mouse GO:0030330 IMP assertion to PMID:24651726. The inspected Results and fiber/survival Methods establish ATRX-dependent DNA-damage and replication phenotypes, but the specific p53-signaling assay and exact current transfer mapping remain unresolved. Preserve the electronic mouse transfer as UNDECIDED; DNA damage or 53BP1 foci alone are not equated with a p53-mediated signaling step. |
| GO:0030330 DNA damage response, signal transduction by p53 class mediator | ISS GO_REF:0000024 | UNDECIDED | Summary: The manually transferred p53-response annotation remains unresolved. Reason: Preserve the curated ISS assertion and mouse donor. An official historical MGI table identifies PMID:24651726 for a mouse GO:0030330 IMP annotation, while the inspected article sections do not resolve its p53-specific experimental basis. The exact current donor-to-transfer mapping was not reconstructed. Retain UNDECIDED without alleging wrong-gene attribution or curator error. |
| GO:0031297 replication fork processing | IBA GO_REF:0000033 | ACCEPT | Summary: ATRX supports recovery of stalled replication. Reason: The PAINT inference agrees with experimental replication-stress and fork-recovery findings in mammalian ATRX. The curated ancestral placement is retained; the single listed mouse descendant is not considered weak support, and no target-specific loss is established. |
| GO:0031297 replication fork processing | IEA GO_REF:0000107 | ACCEPT | Summary: The conserved ATRX machinery supports replication-fork recovery. Reason: The mouse electronic transfer is consistent with ATRX-associated replication maintenance and human replication-restart experiments described in the manual research notes. This process assignment does not imply that ATRX is a nuclease or that every fork phenotype requires its ATPase in every context. |
| GO:0031297 replication fork processing | ISS GO_REF:0000024 | ACCEPT | Summary: Curated orthology supports ATRX replication-fork processing. Reason: The manual transfer agrees with ATRX-dependent resistance to replication stress and recovery of replication. Preserve the ISS provenance and avoid recasting all ATRX genome-protection mechanisms as a single DAXX-dependent deposition step. |
| GO:0031490 chromatin DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: ATRX engages chromatin DNA as a remodeling substrate. Reason: The PAINT annotation is consistent with direct ATRX-complex DNA-translocation and nucleosome-remodeling assays. It is an ancestral functional inference from the family tree, not a pairwise donor-count claim; no contradictory human-specific loss is known. |
| GO:0031509 subtelomeric heterochromatin formation | IDA PMID:20651253 Daxx is an H3.3-specific histone chaperone and cooperates wi... | ACCEPT | Summary: ATRX–DAXX supports H3.3-containing telomeric heterochromatin. Reason: PMID:20651253 combines complex biochemistry with telomeric recruitment and H3.3 deposition in mouse ESCs. Retain the curated heterochromatin-formation interpretation. ATRX supplies remodeling and targeting within the complex; the directly demonstrated isolated H3.3 chaperone is DAXX. |
| GO:0031509 subtelomeric heterochromatin formation | IEA GO_REF:0000120 | ACCEPT | Summary: ATRX contributes to organization of subtelomeric heterochromatin. Reason: The combined ARBA and orthology inference agrees with ATRX–DAXX-dependent histone-variant chromatin and human subtelomeric occupancy. This is not a claim that ATRX itself writes the H3K9 methyl mark. |
| GO:0031509 subtelomeric heterochromatin formation | IMP PMID:26055325 Genetic Inactivation of ATRX Leads to a Decrease in the Amou... | ACCEPT | Summary: Human ATRX maintains subtelomeric chromatin organization. Reason: PMID:26055325 reports subtelomeric ATRX occupancy and reduced cohesin, TERRA and local RNA polymerase II after ATRX depletion in telomerase-positive human glioma cells. Retain the curator interpretation in the established chromatin role; this experiment is not recast as direct measurement of de novo heterochromatin assembly. |
| GO:0031509 subtelomeric heterochromatin formation | ISS GO_REF:0000024 | ACCEPT | Summary: Subtelomeric heterochromatin organization is consistent with conserved ATRX function. Reason: The curated mouse-to-human transfer agrees with mammalian ATRX–DAXX chromatin studies and human subtelomeric evidence. Cell-specific transcriptional outcomes do not negate the conserved organization role. |
| GO:0032206 positive regulation of telomere maintenance | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: ATRX supports telomere integrity through chromatin maintenance. Reason: The electronic positive-regulation term is interpreted as supporting telomere maintenance, not stimulating ALT or lengthening all telomeres. PMID:24651726 finds that ATRX loss alone does not induce ALT or alter telomere length in its mouse ESC setting; PMID:26055325 similarly does not establish ALT induction in human glioma cells. |
| GO:0032206 positive regulation of telomere maintenance | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The telomere-maintenance transfer is retained with contextual limits. Reason: Conserved ATRX-dependent telomeric chromatin can support telomere integrity. Keep this broad positive-regulatory annotation outside the defining catalytic core; it does not imply telomerase activity, generalized telomere elongation or promotion of ALT. |
| GO:0033044 regulation of chromosome organization | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Chromosome-organization regulation is a broad ATRX consequence. Reason: The ARBA assignment is compatible with effects on histone-variant distribution, heterochromatin and telomeric cohesion. The established direct chromatin functions are more informative for the core synthesis. |
| GO:0042393 histone binding | IDA PMID:20211137 Distinct factors control histone variant H3.3 localization a... | ACCEPT | Summary: ATRX associates with H3.3-containing oligonucleosomes in human cells. Reason: The original selected Results explicitly compare FLAG-HA H3.3 and H3.1 affinity preparations from HeLa and identify ATRX/DAXX with H3.3. Histone association is a central chromatin-recognition facet. Preserve IDA without upgrading the assay to purified direct ATRX-H3.3 binding or an autonomous ATRX histone-chaperone activity. Additional purified-fragment work in PMID:40443347 maps macroH2A-H2B recognition to the ATRX ADD domain; this does not establish macroH2A deposition activity. |
| GO:0042393 histone binding | IDA PMID:22391447 ATRX-mediated chromatin association of histone variant macro... | ACCEPT | Summary: Histone binding includes the experimentally supported macroH2A association. Reason: The original complete abstract directly supports ATRX-macroH2A association and its chromatin-regulatory context. Broad histone binding appropriately covers this recognition facet without assigning histone deposition chemistry to ATRX. Additional purified-fragment work in PMID:40443347 maps macroH2A-H2B recognition to the ATRX ADD domain; this does not establish macroH2A deposition activity. |
| GO:0042393 histone binding | IEA GO_REF:0000120 | ACCEPT | Summary: Histone binding is independently established for ATRX. Reason: Human experimental assertions in PMID:20211137 and PMID:22391447 establish the function independently of the electronic mapping. Preserve the complete original ARBA/mouse/Ensembl supporting-entity tuple. This assessment does not claim to reconstruct the rule or a PAINT tree and does not treat donor count as evidential strength. Additional purified-fragment work in PMID:40443347 maps macroH2A-H2B recognition to the ATRX ADD domain; this does not establish macroH2A deposition activity. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ATRX can promote RNA polymerase II transcription in specific chromatin contexts. Reason: The electronic term is supported by the alpha-globin example but should not be read as a universal activating effect. ATRX also helps repress repeated sequences, so the direction depends on locus and chromatin context. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:22391447 ATRX-mediated chromatin association of histone variant macro... | KEEP AS NON CORE | Summary: ATRX supports alpha-globin transcription by limiting repressive macroH2A association. Reason: PMID:22391447 reports macroH2A accumulation at the human HBA cluster and loss of alpha-globin expression in ATRX-deficient erythroleukemic cells. Retain this locus-specific transcriptional effect outside the core catalytic definition; it is not evidence for sequence-specific DNA-binding transcription-factor activity. |
| GO:0062072 histone H3K9me2/3 reader activity | IDA PMID:21421568 The ATRX-ADD domain binds to H3 tail peptides and reads the ... | ACCEPT | Summary: The ADD domain reads H3K9 methylation in combination with the H3K4 state. Reason: PMID:21421568 directly tests histone-tail recognition and disease-mutant effects. H3K9me3 recognition is inhibited by H3K4 di- or trimethylation, linking the ADD domain to chromatin targeting. The reader term does not imply histone methyltransferase activity. |
| GO:0070087 chromo shadow domain binding | IPI PMID:15882967 The mammalian heterochromatin protein 1 binds diverse nuclea... | ACCEPT | Summary: ATRX binds the HP1 chromoshadow domain through a variant interaction motif. Reason: PMID:15882967 explicitly identifies ATRX among variant PxVxL motif-containing chromoshadow-domain partners and reports binding assays. This specific domain interaction supports heterochromatin targeting and is more informative than generic protein binding. |
| GO:0070198 protein localization to chromosome, telomeric region | IEA GO_REF:0000107 | ACCEPT | Summary: ATRX promotes localization of chromatin components to telomeres. Reason: The mouse electronic transfer agrees with ATRX-dependent DAXX and H3.3 recruitment described in PMID:20211137 and PMID:20651253. This is a targeting role for the complex, not evidence that ATRX alone acts as the H3.3 chaperone. |
| GO:0070198 protein localization to chromosome, telomeric region | ISS GO_REF:0000024 | ACCEPT | Summary: Telomeric protein targeting is a conserved ATRX-associated process. Reason: Retain the curated mouse-to-human transfer for ATRX-dependent localization of the histone-deposition machinery. The process is tied to specific chromatin substrates and should not be generalized to all nuclear protein transport. |
| GO:0072711 cellular response to hydroxyurea | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: ATRX contributes to resistance to hydroxyurea-induced replication stress. Reason: The mouse electronic transfer is consistent with the hydroxyurea sensitivity and fork-stalling analyses in PMID:24651726. This is a treatment-response manifestation of genome-maintenance function, not hydroxyurea binding or metabolism. |
| GO:0072711 cellular response to hydroxyurea | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Hydroxyurea response reflects ATRX-dependent replication maintenance. Reason: The manually transferred mouse annotation agrees with experimental replication-stress phenotypes. Keep the response term as contextual biology, separate from the motor and chromatin-reader activities that define ATRX. |
| GO:0099115 chromosome, subtelomeric region | IDA PMID:26055325 Genetic Inactivation of ATRX Leads to a Decrease in the Amou... | ACCEPT | Summary: ATRX directly occupies subtelomeric regions in human glioma cells. Reason: PMID:26055325 distinguishes ATRX localization near chromosome ends from the telomere termini and confirms subtelomeric occupancy by ChIP. Retain this precise compartment without making it exclusive of other ATRX locations in other cell types. Supporting Evidence: PMID:26055325 Chromatin immunoprecipitation (ChIP) experiments confirmed a subtelomeric localization for ATRX |
| GO:0140658 ATP-dependent chromatin remodeler activity | IDA PMID:12953102 The ATRX syndrome protein forms a chromatin-remodeling compl... | ACCEPT | Summary: ATRX is the ATP-dependent motor of a chromatin-remodeling complex. Reason: PMID:12953102 reports ATP-dependent DNA translocation and alteration of nucleosomal DNA accessibility by human ATRX complexes. The activity is consistent with ATP-driven modulation of histone–DNA contacts. Conventional duplex-unwinding activity was not detected in that study; its historical helicase-family terminology is not used as a new helicase assertion. |
| GO:1904908 negative regulation of maintenance of mitotic sister chromatid cohesion, telomeric | IMP PMID:26373281 Loss of ATRX Suppresses Resolution of Telomere Cohesion to C... | KEEP AS NON CORE | Summary: ATRX promotes resolution of sister-telomere cohesion in the tested tumor-cell contexts. Reason: PMID:26373281 connects ATRX–macroH2A1.1 interactions to tankyrase availability and cohesion resolution. This is a supported specific regulatory outcome, distinct from the cohesin-occupancy and TERRA measurements in human glioma cells in PMID:26055325. Preserve the IMP source without treating all telomere cohesin measurements as the same assay. |
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Download this section (compressed HTML)Q: Which p53-specific experiment underlies the historical mouse GO:0030330 annotation to PMID:24651726, and how does it map to the current human transfers? Does it establish ATRX participation in that cascade rather than a secondary response to replication damage?
Q: Which sequence-verified human ATRX splice products retain functional ADD recognition and ATPase remodeling? Can the strongly truncated P46100-6 product be mapped to the experimentally described ATRXt transcript before transferring isoform-specific results?
Q: How do cell type, telomerase status and local chromatin account for the different ATRX-dependent TERRA and telomeric-cohesion outcomes?
Q: Do the original high-throughput interaction matrices and the corrected PRC2 study resolve the remaining partner-specific assay details without conflating complex association with a purified binary interface?
Experiment: Compare sequence-verified ATRX splice products in matched cells using expression-normalized localization, ADD histone-tail binding and ATP-dependent nucleosome-remodeling assays; include full-length ATRX and domain-disrupting controls.
Experiment: In matched telomerase-positive and ALT cell backgrounds, separate ATRX motor, DAXX-binding and macroH2A-binding perturbations while measuring H3.3 deposition, TERRA, telomeric cohesin occupancy and sister-telomere cohesion as distinct readouts.
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