ADNP is a zinc-finger and homeobox-containing chromatin regulator that recognizes DNA sequences and assembles the ChAHP complex with CHD4 and HP1 proteins. Its sequence-specific targeting recruits chromatin-remodeling activity to control transcription and local genome organization. ADNP also binds HP1 chromoshadow domains, supporting a complementary mode of recruitment to H3K9me3-marked heterochromatin. In mouse embryonic cells, ADNP controls lineage-gene expression and SINE repression and competes with CTCF at shared binding motifs. ADNP additionally has context-dependent cytoplasmic functions involving beta-catenin, microtubule end-binding proteins and neuronal morphogenesis. Heterozygous pathogenic variants cause Helsmoortel-van der Aa syndrome. The NAPVSIPQ sequence within ADNP is pharmacologically active as an isolated peptide.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Nuclear localization is conserved and agrees with ADNP chromatin activity. Reason: The PAINT assertion is inherited from PANTHER:PTN000405125. The target protein in the descendant evidence list is a legitimate source of experimental grounding, not circularity. The ChAHP literature independently supports nuclear function; no ADNP-specific loss of nuclear activity is evident. The node placement is retained without treating the descendant list as pairwise transfers. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000405125 SUPPORTS TRANSFER PAINT ancestor supplying the inherited nuclear/gene-regulatory assertion. Descendant experimental evidence is compatible with the target; no clade-specific loss was established. Node placement is retained, not reconstructed as pairwise donor similarity. Supporting Evidence: PMID:29795351 ADNP interacts with the chromatin remodeller CHD4 and the chromatin architectural protein HP1 to form a stable complex, which we refer to as ChAHP. |
| GO:0010468 regulation of gene expression | IBA GO_REF:0000033 | ACCEPT | Summary: Regulation of gene expression is a central inherited function. Reason: PANTHER:PTN000405125 supplies a phylogenetic assertion consistent with ADNP-mediated transcriptional control. Mouse knockout/promoter-association experiments and the independently characterized ChAHP mechanism support the broad process. Broadness alone does not make this core function peripheral. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000405125 SUPPORTS TRANSFER PAINT ancestor supplying the inherited nuclear/gene-regulatory assertion. Descendant experimental evidence is compatible with the target; no clade-specific loss was established. Node placement is retained, not reconstructed as pairwise donor similarity. Supporting Evidence: PMID:29795351 Besides mediating complex assembly, ADNP recognizes DNA motifs that specify binding of ChAHP to euchromatin. PMID:29795351 ChAHP-mediated repression, however, acts in a locally restricted manner by establishing inaccessible chromatin around its DNA-binding sites and does not depend on H3K9me3-modified nucleosomes. |
| GO:0003677 DNA binding | IEA GO_REF:0000002 | ACCEPT | Summary: The homeodomain-associated DNA-binding annotation captures a core activity. Reason: InterPro:IPR001356 supports a broad DNA-binding inference. Independent ADNP-specific DNA-motif recognition in PMID:29795351 corroborates DNA binding without requiring the domain mapping itself to specify a polymerase, motif or regulatory sign. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR001356 SUPPORTS TRANSFER Homeodomain InterPro mapping; broad DNA-binding inference agrees with independent ADNP motif-recognition evidence. Detailed mapping-rule predicates were not re-derived. Supporting Evidence: PMID:29795351 Besides mediating complex assembly, ADNP recognizes DNA motifs that specify binding of ChAHP to euchromatin. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: The UniProt nucleus mapping agrees with nuclear ADNP function. Reason: UniProtKB-SubCell:SL-0191 maps the nuclear location recorded in the cached UniProt entry. Chromatin-association experiments and the ChAHP complex independently support this compartment; the mapping need not resolve a narrower nuclear subcompartment. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0191 SUPPORTS TRANSFER UniProt nucleus vocabulary mapping; cached UniProt location and independent nuclear chromatin studies support the result. Supporting Evidence: PMID:31491387 we demonstrate that the ChAHP complex (CHD4, ADNP, HP1) competes with CTCF for a common set of binding motifs |
| GO:0005694 chromosome | IEA GO_REF:0000044 | ACCEPT | Summary: Chromosome association is a broad description of ADNP chromatin localization. Reason: UniProtKB-SubCell:SL-0468 is consistent with ADNP association with chromosomal DNA and chromatin. The source supports a broad cellular component; the separately available chromatin term does not make chromosome association biologically non-core. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0468 SUPPORTS TRANSFER UniProt chromosome vocabulary mapping; broad location agrees with chromatin association and is not treated as a separate mechanistic experiment. Supporting Evidence: PMID:31491387 ChAHP-bound loci are mainly situated within less diverged SINE B2 transposable elements. |
| GO:0005515 protein binding | IPI PMID:20562864 Human POGZ modulates dissociation of HP1alpha from mitotic c... | MODIFY | Summary: The CBX5/HP1alpha association is better represented by chromo shadow domain binding. Reason: The original POGZ-centered proteomics study supplies the curated ADNP interaction; its abstract does not describe an ADNP domain-mapping experiment. The curated interaction is retained. The more informative replacement uses independent mechanistic evidence: ADNP PxVxL-mutant experiments in PMID:38960717 test HP1-dependent chromatin recruitment, together with the domain-mapping study assessed in PMID:21267468. The interaction screen itself is not treated as having mapped the domain, and binding of different HP1 paralogs does not imply simultaneous occupancy by all three. Proposed replacements: chromo shadow domain binding Supporting Evidence: PMID:38960717 To do this, we generated ADNPPxVxL motif point mutants (Supplemental Fig. S6B) and performed ChIP-seq. PMID:38960717 Abrogating the HP1 interaction in this way resulted in a loss of ADNP signal specifically at H3K9 trimethylated transposons, including LTR and LINE1 families, which are bound by ADNP2 PMID:21267468 Yet, recruitment of ADNP to H3K9me3 was severely impaired in presence of the mutant HP1Ξ² W170A protein compared to the wild type HP1Ξ² protein. |
| GO:0005515 protein binding | IPI PMID:21888893 Analysis of the human HP1 interactome reveals novel binding ... | MODIFY | Summary: The CBX5/HP1alpha association is better represented by chromo shadow domain binding. Reason: The original study uses tandem-affinity purification and mass spectrometry of HP1 isotypes. The accessible abstract describes the screen, not the ADNP interface. The curated interaction is retained. The more informative replacement uses independent mechanistic evidence: ADNP PxVxL-mutant experiments in PMID:38960717 test HP1-dependent chromatin recruitment, together with the domain-mapping study assessed in PMID:21267468. The interaction screen itself is not treated as having mapped the domain, and binding of different HP1 paralogs does not imply simultaneous occupancy by all three. Proposed replacements: chromo shadow domain binding Supporting Evidence: PMID:38960717 To do this, we generated ADNPPxVxL motif point mutants (Supplemental Fig. S6B) and performed ChIP-seq. PMID:38960717 Abrogating the HP1 interaction in this way resulted in a loss of ADNP signal specifically at H3K9 trimethylated transposons, including LTR and LINE1 families, which are bound by ADNP2 PMID:21267468 Yet, recruitment of ADNP to H3K9me3 was severely impaired in presence of the mutant HP1Ξ² W170A protein compared to the wild type HP1Ξ² protein. |
| GO:0005515 protein binding | IPI PMID:21888893 Analysis of the human HP1 interactome reveals novel binding ... | MODIFY | Summary: The CBX1/HP1beta association is better represented by chromo shadow domain binding. Reason: The original study uses tandem-affinity purification and mass spectrometry of HP1 isotypes. The accessible abstract describes the screen, not the ADNP interface. The curated interaction is retained. The more informative replacement uses independent mechanistic evidence: ADNP PxVxL-mutant experiments in PMID:38960717 test HP1-dependent chromatin recruitment, together with the domain-mapping study assessed in PMID:21267468. The interaction screen itself is not treated as having mapped the domain, and binding of different HP1 paralogs does not imply simultaneous occupancy by all three. Proposed replacements: chromo shadow domain binding Supporting Evidence: PMID:38960717 To do this, we generated ADNPPxVxL motif point mutants (Supplemental Fig. S6B) and performed ChIP-seq. PMID:38960717 Abrogating the HP1 interaction in this way resulted in a loss of ADNP signal specifically at H3K9 trimethylated transposons, including LTR and LINE1 families, which are bound by ADNP2 PMID:21267468 Yet, recruitment of ADNP to H3K9me3 was severely impaired in presence of the mutant HP1Ξ² W170A protein compared to the wild type HP1Ξ² protein. |
| GO:0005515 protein binding | IPI PMID:21888893 Analysis of the human HP1 interactome reveals novel binding ... | MODIFY | Summary: The CBX3/HP1gamma association is better represented by chromo shadow domain binding. Reason: The original study uses tandem-affinity purification and mass spectrometry of HP1 isotypes. The accessible abstract describes the screen, not the ADNP interface. The curated interaction is retained. The more informative replacement uses independent mechanistic evidence: ADNP PxVxL-mutant experiments in PMID:38960717 test HP1-dependent chromatin recruitment, together with the domain-mapping study assessed in PMID:21267468. The interaction screen itself is not treated as having mapped the domain, and binding of different HP1 paralogs does not imply simultaneous occupancy by all three. Proposed replacements: chromo shadow domain binding Supporting Evidence: PMID:38960717 To do this, we generated ADNPPxVxL motif point mutants (Supplemental Fig. S6B) and performed ChIP-seq. PMID:38960717 Abrogating the HP1 interaction in this way resulted in a loss of ADNP signal specifically at H3K9 trimethylated transposons, including LTR and LINE1 families, which are bound by ADNP2 PMID:21267468 Yet, recruitment of ADNP to H3K9me3 was severely impaired in presence of the mutant HP1Ξ² W170A protein compared to the wild type HP1Ξ² protein. |
| GO:0005515 protein binding | IPI PMID:24981860 Human-chromatin-related protein interactions identify a deme... | MODIFY | Summary: The CBX1/HP1beta association is better represented by chromo shadow domain binding. Reason: The original human chromatin-interaction map supplies association evidence. Its accessible abstract does not map an ADNP binding surface. The curated interaction is retained. The more informative replacement uses independent mechanistic evidence: ADNP PxVxL-mutant experiments in PMID:38960717 test HP1-dependent chromatin recruitment, together with the domain-mapping study assessed in PMID:21267468. The interaction screen itself is not treated as having mapped the domain, and binding of different HP1 paralogs does not imply simultaneous occupancy by all three. Proposed replacements: chromo shadow domain binding Supporting Evidence: PMID:38960717 To do this, we generated ADNPPxVxL motif point mutants (Supplemental Fig. S6B) and performed ChIP-seq. PMID:38960717 Abrogating the HP1 interaction in this way resulted in a loss of ADNP signal specifically at H3K9 trimethylated transposons, including LTR and LINE1 families, which are bound by ADNP2 PMID:21267468 Yet, recruitment of ADNP to H3K9me3 was severely impaired in presence of the mutant HP1Ξ² W170A protein compared to the wild type HP1Ξ² protein. |
| GO:0005515 protein binding | IPI PMID:24981860 Human-chromatin-related protein interactions identify a deme... | MODIFY | Summary: The CBX3/HP1gamma association is better represented by chromo shadow domain binding. Reason: The original human chromatin-interaction map supplies association evidence. Its accessible abstract does not map an ADNP binding surface. The curated interaction is retained. The more informative replacement uses independent mechanistic evidence: ADNP PxVxL-mutant experiments in PMID:38960717 test HP1-dependent chromatin recruitment, together with the domain-mapping study assessed in PMID:21267468. The interaction screen itself is not treated as having mapped the domain, and binding of different HP1 paralogs does not imply simultaneous occupancy by all three. Proposed replacements: chromo shadow domain binding Supporting Evidence: PMID:38960717 To do this, we generated ADNPPxVxL motif point mutants (Supplemental Fig. S6B) and performed ChIP-seq. PMID:38960717 Abrogating the HP1 interaction in this way resulted in a loss of ADNP signal specifically at H3K9 trimethylated transposons, including LTR and LINE1 families, which are bound by ADNP2 PMID:21267468 Yet, recruitment of ADNP to H3K9me3 was severely impaired in presence of the mutant HP1Ξ² W170A protein compared to the wild type HP1Ξ² protein. |
| GO:0005515 protein binding | IPI PMID:27705803 A High-Density Map for Navigating the Human Polycomb Complex... | MODIFY | Summary: The CBX5/HP1alpha association is better represented by chromo shadow domain binding. Reason: The original human Polycomb interactome supplies association evidence. Its accessible abstract does not establish the ADNP contact surface. The curated interaction is retained. The more informative replacement uses independent mechanistic evidence: ADNP PxVxL-mutant experiments in PMID:38960717 test HP1-dependent chromatin recruitment, together with the domain-mapping study assessed in PMID:21267468. The interaction screen itself is not treated as having mapped the domain, and binding of different HP1 paralogs does not imply simultaneous occupancy by all three. Proposed replacements: chromo shadow domain binding Supporting Evidence: PMID:38960717 To do this, we generated ADNPPxVxL motif point mutants (Supplemental Fig. S6B) and performed ChIP-seq. PMID:38960717 Abrogating the HP1 interaction in this way resulted in a loss of ADNP signal specifically at H3K9 trimethylated transposons, including LTR and LINE1 families, which are bound by ADNP2 PMID:21267468 Yet, recruitment of ADNP to H3K9me3 was severely impaired in presence of the mutant HP1Ξ² W170A protein compared to the wild type HP1Ξ² protein. |
| GO:0005515 protein binding | IPI PMID:27705803 A High-Density Map for Navigating the Human Polycomb Complex... | MODIFY | Summary: The CBX1/HP1beta association is better represented by chromo shadow domain binding. Reason: The original human Polycomb interactome supplies association evidence. Its accessible abstract does not establish the ADNP contact surface. The curated interaction is retained. The more informative replacement uses independent mechanistic evidence: ADNP PxVxL-mutant experiments in PMID:38960717 test HP1-dependent chromatin recruitment, together with the domain-mapping study assessed in PMID:21267468. The interaction screen itself is not treated as having mapped the domain, and binding of different HP1 paralogs does not imply simultaneous occupancy by all three. Proposed replacements: chromo shadow domain binding Supporting Evidence: PMID:38960717 To do this, we generated ADNPPxVxL motif point mutants (Supplemental Fig. S6B) and performed ChIP-seq. PMID:38960717 Abrogating the HP1 interaction in this way resulted in a loss of ADNP signal specifically at H3K9 trimethylated transposons, including LTR and LINE1 families, which are bound by ADNP2 PMID:21267468 Yet, recruitment of ADNP to H3K9me3 was severely impaired in presence of the mutant HP1Ξ² W170A protein compared to the wild type HP1Ξ² protein. |
| GO:0005515 protein binding | IPI PMID:27705803 A High-Density Map for Navigating the Human Polycomb Complex... | MODIFY | Summary: The CBX3/HP1gamma association is better represented by chromo shadow domain binding. Reason: The original human Polycomb interactome supplies association evidence. Its accessible abstract does not establish the ADNP contact surface. The curated interaction is retained. The more informative replacement uses independent mechanistic evidence: ADNP PxVxL-mutant experiments in PMID:38960717 test HP1-dependent chromatin recruitment, together with the domain-mapping study assessed in PMID:21267468. The interaction screen itself is not treated as having mapped the domain, and binding of different HP1 paralogs does not imply simultaneous occupancy by all three. Proposed replacements: chromo shadow domain binding Supporting Evidence: PMID:38960717 To do this, we generated ADNPPxVxL motif point mutants (Supplemental Fig. S6B) and performed ChIP-seq. PMID:38960717 Abrogating the HP1 interaction in this way resulted in a loss of ADNP signal specifically at H3K9 trimethylated transposons, including LTR and LINE1 families, which are bound by ADNP2 PMID:21267468 Yet, recruitment of ADNP to H3K9me3 was severely impaired in presence of the mutant HP1Ξ² W170A protein compared to the wild type HP1Ξ² protein. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: The CBX3/HP1gamma association is better represented by chromo shadow domain binding. Reason: The original BioPlex study supplies a curated interaction. The local full-text extraction is partial and does not expose the pair-level data table. The curated interaction is retained. The more informative replacement uses independent mechanistic evidence: ADNP PxVxL-mutant experiments in PMID:38960717 test HP1-dependent chromatin recruitment, together with the domain-mapping study assessed in PMID:21267468. The interaction screen itself is not treated as having mapped the domain, and binding of different HP1 paralogs does not imply simultaneous occupancy by all three. Proposed replacements: chromo shadow domain binding Supporting Evidence: PMID:38960717 To do this, we generated ADNPPxVxL motif point mutants (Supplemental Fig. S6B) and performed ChIP-seq. PMID:38960717 Abrogating the HP1 interaction in this way resulted in a loss of ADNP signal specifically at H3K9 trimethylated transposons, including LTR and LINE1 families, which are bound by ADNP2 PMID:21267468 Yet, recruitment of ADNP to H3K9me3 was severely impaired in presence of the mutant HP1Ξ² W170A protein compared to the wild type HP1Ξ² protein. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MODIFY | Summary: The CBX1/HP1beta association is better represented by chromo shadow domain binding. Reason: The original OpenCell study uses endogenous tagging. The local extraction does not expose this pair record, so no ADNP-specific affinity or stoichiometry is inferred from the platform description. The curated interaction is retained. The more informative replacement uses independent mechanistic evidence: ADNP PxVxL-mutant experiments in PMID:38960717 test HP1-dependent chromatin recruitment, together with the domain-mapping study assessed in PMID:21267468. The interaction screen itself is not treated as having mapped the domain, and binding of different HP1 paralogs does not imply simultaneous occupancy by all three. Proposed replacements: chromo shadow domain binding Supporting Evidence: PMID:38960717 To do this, we generated ADNPPxVxL motif point mutants (Supplemental Fig. S6B) and performed ChIP-seq. PMID:38960717 Abrogating the HP1 interaction in this way resulted in a loss of ADNP signal specifically at H3K9 trimethylated transposons, including LTR and LINE1 families, which are bound by ADNP2 PMID:21267468 Yet, recruitment of ADNP to H3K9me3 was severely impaired in presence of the mutant HP1Ξ² W170A protein compared to the wild type HP1Ξ² protein. |
| GO:0005515 protein binding | IPI PMID:36950384 Protein interaction studies in human induced neurons indicat... | MODIFY | Summary: The CBX3/HP1gamma association is better represented by chromo shadow domain binding. Reason: The original study profiles endogenous interactions in human induced neurons. The cached body describes the IP-MS workflow, but the pair-level supplementary table was not independently recovered. The curated interaction is retained. The more informative replacement uses independent mechanistic evidence: ADNP PxVxL-mutant experiments in PMID:38960717 test HP1-dependent chromatin recruitment, together with the domain-mapping study assessed in PMID:21267468. The interaction screen itself is not treated as having mapped the domain, and binding of different HP1 paralogs does not imply simultaneous occupancy by all three. Proposed replacements: chromo shadow domain binding Supporting Evidence: PMID:38960717 To do this, we generated ADNPPxVxL motif point mutants (Supplemental Fig. S6B) and performed ChIP-seq. PMID:38960717 Abrogating the HP1 interaction in this way resulted in a loss of ADNP signal specifically at H3K9 trimethylated transposons, including LTR and LINE1 families, which are bound by ADNP2 PMID:21267468 Yet, recruitment of ADNP to H3K9me3 was severely impaired in presence of the mutant HP1Ξ² W170A protein compared to the wild type HP1Ξ² protein. |
| GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding | IEA GO_REF:0000107 | ACCEPT | Summary: ADNP recognizes regulatory DNA sequences and targets ChAHP to chromatin. Reason: The mouse Adnp donor traces to PMID:17222401, which reports promoter association by ChIP alongside altered gene expression. ChIP alone does not prove direct sequence discrimination. Independent DNA-motif recognition in PMID:29795351 and motif competition with CTCF in PMID:31491387 provide that stronger evidence. The conserved ADNP function supports the transfer without assigning sequence specificity from the homeobox alone. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q9Z103 SUPPORTS TRANSFER The mouse Adnp donor traces to PMID:17222401, which reports promoter association by ChIP alongside altered gene expression. ChIP alone does not prove direct sequence discrimination. Independent DNA-motif recognition in PMID:29795351 and motif competition with CTCF in PMID:31491387 provide that stronger evidence. The conserved ADNP function supports the transfer without assigning sequence specificity from the homeobox alone. ensembl:ENSMUSP00000085316 SUPPORTS TRANSFER Compara protein identifier supplied alongside the UniProt donor in the unchanged source object. The stored donor audit resolves the paired ortholog; this identifier is not counted as independent experimental evidence. Supporting Evidence: PMID:17222401 The pluripotent P19 cells were used for ADNP-chromatin-immunoprecipitation, showing direct interactions with multiple relevant gene promoters including members of the up-regulated as well as the down-regulated gene clusters. PMID:29795351 Besides mediating complex assembly, ADNP recognizes DNA motifs that specify binding of ChAHP to euchromatin. PMID:42413491 the transcription factor ADNP forms the ChAHP complex with the chromatin remodeler CHD4 and HP1 proteins, acting as a site-specific regulator of transcription and an antagonist of CTCF binding PMID:31491387 we demonstrate that the ChAHP complex (CHD4, ADNP, HP1) competes with CTCF for a common set of binding motifs |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IEA GO_REF:0000107 | ACCEPT | Summary: ADNP is a DNA-binding transcription factor regulating Pol II gene expression. Reason: The mouse Adnp donor annotation is grounded in promoter-association and expression experiments in PMID:17222401. ADNP recognizes DNA motifs and targets ChAHP to lineage-regulatory genes (PMID:29795351). Repression is a well-supported output, but the broader source term also accommodates context-dependent regulation; it need not be replaced by a directional child. No redundant NEW repressor annotation is retained. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q9Z103 SUPPORTS TRANSFER The mouse Adnp donor annotation is grounded in promoter-association and expression experiments in PMID:17222401. ADNP recognizes DNA motifs and targets ChAHP to lineage-regulatory genes (PMID:29795351). Repression is a well-supported output, but the broader source term also accommodates context-dependent regulation; it need not be replaced by a directional child. No redundant NEW repressor annotation is retained. ensembl:ENSMUSP00000085316 SUPPORTS TRANSFER Compara protein identifier supplied alongside the UniProt donor in the unchanged source object. The stored donor audit resolves the paired ortholog; this identifier is not counted as independent experimental evidence. Supporting Evidence: PMID:17222401 The pluripotent P19 cells were used for ADNP-chromatin-immunoprecipitation, showing direct interactions with multiple relevant gene promoters including members of the up-regulated as well as the down-regulated gene clusters. PMID:29795351 Besides mediating complex assembly, ADNP recognizes DNA motifs that specify binding of ChAHP to euchromatin. PMID:42413491 the transcription factor ADNP forms the ChAHP complex with the chromatin remodeler CHD4 and HP1 proteins, acting as a site-specific regulator of transcription and an antagonist of CTCF binding PMID:29795351 Genetic ablation of ChAHP components in mouse embryonic stem cells results in spontaneous differentiation concomitant with premature activation of lineage-specific genes |
| GO:0005507 copper ion binding | IEA GO_REF:0000107 | UNDECIDED | Summary: Copper binding by native ADNP remains unresolved. Reason: The rat Adnp donor IDA cites PMID:14706557. Its accessible abstract establishes NAP effects on amyloid-beta aggregation and biotin-NAP binding to amyloid-beta. Copper metabolism is indexed in the primary PubMed record, so omission of copper from the abstract cannot refute the curator's assay. The full binding experiment and its molecular species were not recovered. Neither zinc-finger architecture nor absence of a UniProt copper keyword excludes copper binding. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q9JKL8 UNRESOLVED The rat Adnp donor IDA cites PMID:14706557. Its accessible abstract establishes NAP effects on amyloid-beta aggregation and biotin-NAP binding to amyloid-beta. Copper metabolism is indexed in the primary PubMed record, so omission of copper from the abstract cannot refute the curator's assay. The full binding experiment and its molecular species were not recovered. Neither zinc-finger architecture nor absence of a UniProt copper keyword excludes copper binding. ensembl:ENSRNOP00000014595 UNRESOLVED Compara protein identifier supplied alongside the UniProt donor in the unchanged source object. The stored donor audit resolves the paired ortholog; this identifier is not counted as independent experimental evidence. Supporting Evidence: PMID:14706557 Further assays showed biotin-NAP binding to Abeta. PMID:14706557 Here, NAP was shown to inhibit Abeta aggregation using: (1) fluorimetry; (2) electron microscopy; (3) high-throughput screening of Abeta deposition onto a synthetic template (synthaloid); and (4) Congo Red staining of neurons. |
| GO:0005576 extracellular region | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Astrocyte-derived extracellular ADNP immunoreactivity supports a non-core localization. Reason: PMID:16845437 reports ADNP-like immunoreactivity in rat astrocyte-conditioned medium and an increase after VIP exposure. The accessible primary Methods/Results describe size-resolved ADNP immunodetection and recombinant-protein competition controls for the antibody. This is positive localization evidence, and neither the modest fold change nor absence of a signal peptide disproves extracellular localization. Retain the ortholog projection with astrocyte and molecular-species scope; the route of release and exact extracellular forms remain less resolved than nuclear ADNP function. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q9JKL8 SUPPORTS TRANSFER PMID:16845437 reports ADNP-like immunoreactivity in rat astrocyte-conditioned medium and an increase after VIP exposure. The accessible primary Methods/Results describe size-resolved ADNP immunodetection and recombinant-protein competition controls for the antibody. This is positive localization evidence, and neither the modest fold change nor absence of a signal peptide disproves extracellular localization. Retain the ortholog projection with astrocyte and molecular-species scope; the route of release and exact extracellular forms remain less resolved than nuclear ADNP function. ensembl:ENSRNOP00000014595 SUPPORTS TRANSFER Compara protein identifier supplied alongside the UniProt donor in the unchanged source object. The stored donor audit resolves the paired ortholog; this identifier is not counted as independent experimental evidence. Supporting Evidence: PMID:16845437 In addition, ADNP-like immunoreactivity in the extracellular milieu of astrocytes increased by approximately 1.4 fold after incubation of the astrocytes with VIP. PMID:16845437 Here, we investigate the subcellular localization of ADNP through cell fractionation, gel electrophoresis, immunoblotting and immunocytochemistry using alpha-CNAP, an antibody directed to the neuroprotective NAP fragment that constitutes part of an N-terminal epitope of ADNP. |
| GO:0006357 regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | ACCEPT | Summary: Pol II transcriptional regulation is a core ADNP function. Reason: The mouse donor PMID:17222401 combines altered expression in Adnp-deficient embryos with ADNP promoter association in P19 cells. The ChAHP study independently connects sequence recognition and complex assembly to control of lineage-specific transcription. These data support the broad source term without requiring every affected gene to have the same regulatory sign. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q9Z103 SUPPORTS TRANSFER The mouse donor PMID:17222401 combines altered expression in Adnp-deficient embryos with ADNP promoter association in P19 cells. The ChAHP study independently connects sequence recognition and complex assembly to control of lineage-specific transcription. These data support the broad source term without requiring every affected gene to have the same regulatory sign. ensembl:ENSMUSP00000085316 SUPPORTS TRANSFER Compara protein identifier supplied alongside the UniProt donor in the unchanged source object. The stored donor audit resolves the paired ortholog; this identifier is not counted as independent experimental evidence. Supporting Evidence: PMID:17222401 The pluripotent P19 cells were used for ADNP-chromatin-immunoprecipitation, showing direct interactions with multiple relevant gene promoters including members of the up-regulated as well as the down-regulated gene clusters. PMID:29795351 Besides mediating complex assembly, ADNP recognizes DNA motifs that specify binding of ChAHP to euchromatin. PMID:42413491 the transcription factor ADNP forms the ChAHP complex with the chromatin remodeler CHD4 and HP1 proteins, acting as a site-specific regulator of transcription and an antagonist of CTCF binding |
| GO:0007614 short-term memory | IEA GO_REF:0000107 | UNDECIDED | Summary: The peptide memory experiment does not by itself resolve the native ADNP process annotation. Reason: PMID:12212775 measures Morris-water-maze performance after inhaled NAP in middle-aged rats. This is positive evidence for that treatment and behavioral context. The full paper and the bridge from an isolated peptide to endogenous ADNP participation were not established. A neuronal gene can participate in memory through regulation; the term is not rejected simply because it is organismal. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q9JKL8 UNRESOLVED PMID:12212775 measures Morris-water-maze performance after inhaled NAP in middle-aged rats. This is positive evidence for that treatment and behavioral context. The full paper and the bridge from an isolated peptide to endogenous ADNP participation were not established. A neuronal gene can participate in memory through regulation; the term is not rejected simply because it is organismal. ensembl:ENSRNOP00000014595 UNRESOLVED Compara protein identifier supplied alongside the UniProt donor in the unchanged source object. The stored donor audit resolves the paired ortholog; this identifier is not counted as independent experimental evidence. Supporting Evidence: PMID:12212775 NAP was administered by inhalation. PMID:12212775 Results showed that in the paradigm of the Morris water maze, assessing short-term memory, only the NAP-treated middle-aged rats and not placebo-treated rats showed significant improvements by the end of the testing period. |
| GO:0008013 beta-catenin binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Beta-catenin binding is a supported context-dependent ADNP interaction. Reason: The mouse donor PMID:32533114 includes endogenous co-immunoprecipitation in ESCs and neural progenitors, domain mapping and interaction of in-vitro-translated proteins. ADNP associates with the beta-catenin armadillo region and stabilizes beta-catenin during neural differentiation. This is a specific interaction beyond a broad screen. Its developmental signaling context supports non-core retention; the distinct WNT-repressive colorectal-cancer context in PMID:27903678 does not invalidate the interaction or establish a scientific dispute. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q9Z103 SUPPORTS TRANSFER The mouse donor PMID:32533114 includes endogenous co-immunoprecipitation in ESCs and neural progenitors, domain mapping and interaction of in-vitro-translated proteins. ADNP associates with the beta-catenin armadillo region and stabilizes beta-catenin during neural differentiation. This is a specific interaction beyond a broad screen. Its developmental signaling context supports non-core retention; the distinct WNT-repressive colorectal-cancer context in PMID:27903678 does not invalidate the interaction or establish a scientific dispute. ensembl:ENSMUSP00000085316 SUPPORTS TRANSFER Compara protein identifier supplied alongside the UniProt donor in the unchanged source object. The stored donor audit resolves the paired ortholog; this identifier is not counted as independent experimental evidence. Supporting Evidence: PMID:32533114 Mechanistically, ADNP functions to stabilize Ξ²-Catenin through binding to its armadillo domain which prevents its association with key components of the degradation complex: Axin and APC. |
| GO:0009743 response to carbohydrate | IEA GO_REF:0000107 | UNDECIDED | Summary: The carbohydrate-response transfer cannot be adjudicated from the available source. Reason: The rat IEP traces to PMID:19130308. The accessible abstract describes ADNP expression under nitric-oxide-pathway manipulation and kainate seizure, but does not resolve the carbohydrate stimulus underlying this annotation. Expression evidence is not categorically invalid for a response term. Full source details are required before accepting or rejecting this particular transfer. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q9JKL8 UNRESOLVED The rat IEP traces to PMID:19130308. The accessible abstract describes ADNP expression under nitric-oxide-pathway manipulation and kainate seizure, but does not resolve the carbohydrate stimulus underlying this annotation. Expression evidence is not categorically invalid for a response term. Full source details are required before accepting or rejecting this particular transfer. ensembl:ENSRNOP00000014595 UNRESOLVED Compara protein identifier supplied alongside the UniProt donor in the unchanged source object. The stored donor audit resolves the paired ortholog; this identifier is not counted as independent experimental evidence. Supporting Evidence: PMID:19130308 Treatment with nitric oxide (NO) synthase (NOS) inhibitor N(G)-nitro-L: -arginine methyl ester (L: -NAME) caused a decrease in ADNP expression in granule cells which persisted 3 days post-treatment. |
| GO:0010468 regulation of gene expression | IEA GO_REF:0000107 | ACCEPT | Summary: The mouse transfer agrees with ADNP regulation of gene expression. Reason: PMID:32533114 connects mouse ADNP perturbation and rescue to changes in neural gene expression and beta-catenin signaling. Independently, ADNP DNA recognition and ChAHP assembly directly regulate transcription. The broad term is correct at the resolution of this source and is compatible with the separate PAINT assertion. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q9Z103 SUPPORTS TRANSFER PMID:32533114 connects mouse ADNP perturbation and rescue to changes in neural gene expression and beta-catenin signaling. Independently, ADNP DNA recognition and ChAHP assembly directly regulate transcription. The broad term is correct at the resolution of this source and is compatible with the separate PAINT assertion. ensembl:ENSMUSP00000085316 SUPPORTS TRANSFER Compara protein identifier supplied alongside the UniProt donor in the unchanged source object. The stored donor audit resolves the paired ortholog; this identifier is not counted as independent experimental evidence. Supporting Evidence: PMID:29795351 Besides mediating complex assembly, ADNP recognizes DNA motifs that specify binding of ChAHP to euchromatin. PMID:32533114 Here, we show that ADNP is required for neural induction and differentiation by enhancing Wnt signaling. |
| GO:0010629 negative regulation of gene expression | IEA GO_REF:0000107 | ACCEPT | Summary: Negative regulation of gene expression is independently established for ADNP. Reason: The rat donor PMID:15314252 foregrounds NAP and p53, and its full native-protein evidence remains unresolved. Independent ChAHP studies establish ADNP-dependent repression at sequence-defined chromatin sites. The broad term accommodates both lineage-gene regulation and Pol III SINE repression (PMID:29795351; PMID:42413492), so narrowing this source assertion exclusively to Pol II would lose supported biological scope. This positive independent evidence supports the human term without resolving or validating the original rat peptide-to-native-protein transfer. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q9JKL8 UNRESOLVED The rat donor PMID:15314252 foregrounds NAP and p53, and its full native-protein evidence remains unresolved. Independent ChAHP studies establish ADNP-dependent repression at sequence-defined chromatin sites. The broad term accommodates both lineage-gene regulation and Pol III SINE repression (PMID:29795351; PMID:42413492), so narrowing this source assertion exclusively to Pol II would lose supported biological scope. This positive independent evidence supports the human term without resolving or validating the original rat peptide-to-native-protein transfer. ensembl:ENSRNOP00000014595 SUPPORTS TRANSFER Compara protein identifier supplied alongside the UniProt donor in the unchanged source object. The stored donor audit resolves the paired ortholog; this identifier is not counted as independent experimental evidence. Supporting Evidence: PMID:29795351 ChAHP-mediated repression, however, acts in a locally restricted manner by establishing inaccessible chromatin around its DNA-binding sites and does not depend on H3K9me3-modified nucleosomes. PMID:42413492 ChAHP directly inhibits POL III transcription by blocking TFIIIB recruitment without affecting TFIIIC binding. |
| GO:0010976 positive regulation of neuron projection development | IEA GO_REF:0000107 | UNDECIDED | Summary: The positive neuron-projection transfer requires resolution of peptide and endogenous-protein evidence. Reason: PMID:15800376 reports neurite outgrowth after separate ADNF-9 and NAP treatments in rat cultures, with serum dependence. The NAP result must not be attributed solely to the other peptide or presumed to be a combined treatment. Full experimental coverage was not recovered. Native ADNP influences neuronal morphology, but the context-dependent findings in PMID:36631597 do not establish a universal opposite sign. The precise positive process assignment remains unresolved. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q9JKL8 UNRESOLVED PMID:15800376 reports neurite outgrowth after separate ADNF-9 and NAP treatments in rat cultures, with serum dependence. The NAP result must not be attributed solely to the other peptide or presumed to be a combined treatment. Full experimental coverage was not recovered. Native ADNP influences neuronal morphology, but the context-dependent findings in PMID:36631597 do not establish a universal opposite sign. The precise positive process assignment remains unresolved. ensembl:ENSRNOP00000014595 UNRESOLVED Compara protein identifier supplied alongside the UniProt donor in the unchanged source object. The stored donor audit resolves the paired ortholog; this identifier is not counted as independent experimental evidence. Supporting Evidence: PMID:15800376 Using MAP2-FITC immunofluorescent labeling, we found that ADNF-9 and NAP promoted neurite outgrowth in a concentration-dependent manner, with maximal activity observed at femtomolar concentrations. PMID:15800376 However, the outgrowth-promoting effect was abolished in the absence of serum, suggesting that soluble factors might be necessary for the neurotrophic activity. |
| GO:0030182 neuron differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: ADNP participates in neuronal differentiation through context-dependent regulatory activity. Reason: PMID:32533114 uses mouse ESC neural differentiation with Adnp disruption and rescue, measures neural markers, and identifies beta-catenin stabilization as part of the mechanism. PMID:29795351 also links ChAHP regulation of lineage genes to neuronal differentiation. These results support participation by a regulator, not merely a disease association. Retain this developmental process as non-core relative to the broadly reusable chromatin functions. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q9Z103 SUPPORTS TRANSFER PMID:32533114 uses mouse ESC neural differentiation with Adnp disruption and rescue, measures neural markers, and identifies beta-catenin stabilization as part of the mechanism. PMID:29795351 also links ChAHP regulation of lineage genes to neuronal differentiation. These results support participation by a regulator, not merely a disease association. Retain this developmental process as non-core relative to the broadly reusable chromatin functions. ensembl:ENSMUSP00000085316 SUPPORTS TRANSFER Compara protein identifier supplied alongside the UniProt donor in the unchanged source object. The stored donor audit resolves the paired ortholog; this identifier is not counted as independent experimental evidence. Supporting Evidence: PMID:29795351 Genetic ablation of ChAHP components in mouse embryonic stem cells results in spontaneous differentiation concomitant with premature activation of lineage-specific genes and in a failure to differentiate towards the neuronal lineage. |
| GO:0030424 axon | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Axon localization is retained as a neuronal-context distribution. Reason: The rat Adnp donor traces to native-protein immunodetection in PMID:18072088, rather than a localization experiment on administered NAP. The available source supports neuronal cytoplasmic distribution; detailed compartment interpretation is retained with curator deference where full figures are unavailable. The independent full-protein/14-3-3 study PMID:36631597 supports regulated cytoplasmic localization. This neuronal pool can coexist with nuclear chromatin activity, and is not excluded by nuclear fractionation in a different cell system. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q9JKL8 SUPPORTS TRANSFER The rat Adnp donor traces to native-protein immunodetection in PMID:18072088, rather than a localization experiment on administered NAP. The available source supports neuronal cytoplasmic distribution; detailed compartment interpretation is retained with curator deference where full figures are unavailable. The independent full-protein/14-3-3 study PMID:36631597 supports regulated cytoplasmic localization. This neuronal pool can coexist with nuclear chromatin activity, and is not excluded by nuclear fractionation in a different cell system. ensembl:ENSRNOP00000014595 SUPPORTS TRANSFER Compara protein identifier supplied alongside the UniProt donor in the unchanged source object. The stored donor audit resolves the paired ortholog; this identifier is not counted as independent experimental evidence. Supporting Evidence: PMID:19130308 The dentate gyrus (DG) of the normal rat brain contains activity-dependent neuroprotective protein (ADNP) which is widely distributed in the cytoplasm of neurons and astrocytes. PMID:18072088 We investigated the pattern of ADNP expression by immunohistology in normal rat brain |
| GO:0030425 dendrite | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Dendrite localization is retained as a neuronal-context distribution. Reason: The rat Adnp donor traces to native-protein immunodetection in PMID:19130308, rather than a localization experiment on administered NAP. The available source supports neuronal cytoplasmic distribution; detailed compartment interpretation is retained with curator deference where full figures are unavailable. The independent full-protein/14-3-3 study PMID:36631597 supports regulated cytoplasmic localization. This neuronal pool can coexist with nuclear chromatin activity, and is not excluded by nuclear fractionation in a different cell system. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q9JKL8 SUPPORTS TRANSFER The rat Adnp donor traces to native-protein immunodetection in PMID:19130308, rather than a localization experiment on administered NAP. The available source supports neuronal cytoplasmic distribution; detailed compartment interpretation is retained with curator deference where full figures are unavailable. The independent full-protein/14-3-3 study PMID:36631597 supports regulated cytoplasmic localization. This neuronal pool can coexist with nuclear chromatin activity, and is not excluded by nuclear fractionation in a different cell system. ensembl:ENSRNOP00000014595 SUPPORTS TRANSFER Compara protein identifier supplied alongside the UniProt donor in the unchanged source object. The stored donor audit resolves the paired ortholog; this identifier is not counted as independent experimental evidence. Supporting Evidence: PMID:19130308 The dentate gyrus (DG) of the normal rat brain contains activity-dependent neuroprotective protein (ADNP) which is widely distributed in the cytoplasm of neurons and astrocytes. PMID:18072088 We investigated the pattern of ADNP expression by immunohistology in normal rat brain |
| GO:0033484 intracellular nitric oxide homeostasis | IEA GO_REF:0000107 | UNDECIDED | Summary: The intracellular nitric-oxide homeostasis assignment remains uncertain. Reason: PMID:16938277 compares ADNF-9, NAP, combined peptide and control treatment groups after neonatal rat hypoxia-ischemia. NAP has its own treatment arm; it is incorrect to attribute half of that arm to ADNF-9. The reported NO/nitrite changes do not, from the accessible abstract alone, establish the relevant intracellular pool or native ADNP homeostatic mechanism. Full methods and protein-level linkage remain unresolved. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q9JKL8 UNRESOLVED PMID:16938277 compares ADNF-9, NAP, combined peptide and control treatment groups after neonatal rat hypoxia-ischemia. NAP has its own treatment arm; it is incorrect to attribute half of that arm to ADNF-9. The reported NO/nitrite changes do not, from the accessible abstract alone, establish the relevant intracellular pool or native ADNP homeostatic mechanism. Full methods and protein-level linkage remain unresolved. ensembl:ENSRNOP00000014595 UNRESOLVED Compara protein identifier supplied alongside the UniProt donor in the unchanged source object. The stored donor audit resolves the paired ortholog; this identifier is not counted as independent experimental evidence. Supporting Evidence: PMID:16938277 ADNF-9, NAP, and ADNF-9+NAP were injected (intraperitoneally; i.p.) as a single dose immediately after the hypoxia period. PMID:15800376 The active site for ADNF function is localized to a 9-amino-acid stretch (SALLRSIPA; ADNF-9). |
| GO:0042277 peptide binding | IEA GO_REF:0000107 | UNDECIDED | Summary: The measured NAP-amyloid-beta binding is clear, but its native-protein interpretation is unresolved. Reason: PMID:14706557 explicitly reports biotin-NAP binding to amyloid-beta. This supports peptide binding by the assayed fragment. The accessible source does not resolve whether an endogenous ADNP species or the full protein presents this interaction, and the complete experiment is unavailable. No claim that the curator annotated the wrong protein is made from an abstract-only cache. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q9JKL8 UNRESOLVED PMID:14706557 explicitly reports biotin-NAP binding to amyloid-beta. This supports peptide binding by the assayed fragment. The accessible source does not resolve whether an endogenous ADNP species or the full protein presents this interaction, and the complete experiment is unavailable. No claim that the curator annotated the wrong protein is made from an abstract-only cache. ensembl:ENSRNOP00000014595 UNRESOLVED Compara protein identifier supplied alongside the UniProt donor in the unchanged source object. The stored donor audit resolves the paired ortholog; this identifier is not counted as independent experimental evidence. Supporting Evidence: PMID:14706557 Further assays showed biotin-NAP binding to Abeta. PMID:14706557 These results suggest that part of the neuroprotective mechanism exerted by NAP is through modulation of toxic protein folding in the extracellular milieu. |
| GO:0043025 neuronal cell body | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Neuronal cell body localization is retained as a neuronal-context distribution. Reason: The rat Adnp donor traces to native-protein immunodetection in PMID:19130308, rather than a localization experiment on administered NAP. The available source supports neuronal cytoplasmic distribution; detailed compartment interpretation is retained with curator deference where full figures are unavailable. The independent full-protein/14-3-3 study PMID:36631597 supports regulated cytoplasmic localization. This neuronal pool can coexist with nuclear chromatin activity, and is not excluded by nuclear fractionation in a different cell system. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q9JKL8 SUPPORTS TRANSFER The rat Adnp donor traces to native-protein immunodetection in PMID:19130308, rather than a localization experiment on administered NAP. The available source supports neuronal cytoplasmic distribution; detailed compartment interpretation is retained with curator deference where full figures are unavailable. The independent full-protein/14-3-3 study PMID:36631597 supports regulated cytoplasmic localization. This neuronal pool can coexist with nuclear chromatin activity, and is not excluded by nuclear fractionation in a different cell system. ensembl:ENSRNOP00000014595 SUPPORTS TRANSFER Compara protein identifier supplied alongside the UniProt donor in the unchanged source object. The stored donor audit resolves the paired ortholog; this identifier is not counted as independent experimental evidence. Supporting Evidence: PMID:19130308 The dentate gyrus (DG) of the normal rat brain contains activity-dependent neuroprotective protein (ADNP) which is widely distributed in the cytoplasm of neurons and astrocytes. PMID:18072088 We investigated the pattern of ADNP expression by immunohistology in normal rat brain |
| GO:0043524 negative regulation of neuron apoptotic process | IEA GO_REF:0000107 | UNDECIDED | Summary: The antiapoptotic transfer requires clarification of the endogenous ADNP mechanism. Reason: The rat source PMID:16938277 reports fewer apoptotic cells after NAP treatment in an injury model; the NAP-only group is distinct from ADNF-9 and combined treatment groups. The additional mouse source PMID:10037502 includes ADNP cloning and neuroprotection by NAP in mixed cultures. These accessible results support peptide neuroprotection, while their complete experimental coverage and the exact native ADNP contribution remain unresolved. This does not deny that ADNP can regulate neuronal survival. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q9JKL8 UNRESOLVED The rat source PMID:16938277 reports fewer apoptotic cells after NAP treatment in an injury model; the NAP-only group is distinct from ADNF-9 and combined treatment groups. The additional mouse source PMID:10037502 includes ADNP cloning and neuroprotection by NAP in mixed cultures. These accessible results support peptide neuroprotection, while their complete experimental coverage and the exact native ADNP contribution remain unresolved. This does not deny that ADNP can regulate neuronal survival. ensembl:ENSRNOP00000014595 UNRESOLVED Compara protein identifier supplied alongside the UniProt donor in the unchanged source object. The stored donor audit resolves the paired ortholog; this identifier is not counted as independent experimental evidence. Supporting Evidence: PMID:16938277 Histopathological evaluation demonstrated that ADNF-9 and NAP significantly diminished number of "apoptotic cells" in the hippocampal CA1, CA2, CA3, and gyrus dentatus regions in both hemispheres (ligated and nonligated). PMID:10037502 In mixed neuron-astrocyte cultures, NAPVSIPQ provided neuroprotection at subfemtomolar concentrations against toxicity associated with tetrodotoxin (electrical blockade), the beta-amyloid peptide (the Alzheimer's disease neurotoxin), N-methyl-D-aspartate (excitotoxicity), and the human immunodeficiency virus envelope protein. |
| GO:0044849 estrous cycle | IEA GO_REF:0000107 | REMOVE | Summary: The rat estrous-cycle annotation is biologically inapplicable to human ADNP. Reason: The live GO:0044849 definition specifies an ovulation cycle in which endometrium is resorbed if pregnancy does not occur; humans instead have a menstrual cycle. PMID:16023261 genuinely measures ADNP mRNA across rat estrous phases, so donor identity is not the problem. Orthology does not transfer this species-specific process to humans. The decision does not depend on treating IEP evidence as inherently invalid or on a failed formal taxon constraint. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: LINEAGE OR TAXON MISMATCH Sources checked: UniProtKB:Q9JKL8 SUPPORTS SOURCE BUT NOT TARGET The live GO:0044849 definition specifies an ovulation cycle in which endometrium is resorbed if pregnancy does not occur; humans instead have a menstrual cycle. PMID:16023261 genuinely measures ADNP mRNA across rat estrous phases, so donor identity is not the problem. Orthology does not transfer this species-specific process to humans. The decision does not depend on treating IEP evidence as inherently invalid or on a failed formal taxon constraint. ensembl:ENSRNOP00000014595 SUPPORTS SOURCE BUT NOT TARGET Compara protein identifier supplied alongside the UniProt donor in the unchanged source object. The stored donor audit resolves the paired ortholog; this identifier is not counted as independent experimental evidence. Supporting Evidence: PMID:16023261 Significant increases in the expression of the VIP receptor type 2 (VPAC2) mRNA and parallel increases in a novel VIP responsive gene, activity-dependent neuroprotective protein (ADNP) mRNA were detected in the rat vagina during the estrus phase. |
| GO:0045773 positive regulation of axon extension | IEA GO_REF:0000107 | UNDECIDED | Summary: NAP-dependent axon outgrowth is supported; attribution to endogenous ADNP remains unresolved. Reason: The accessible abstract and Discussion of PMID:19047645 use NAP to model ADNP signaling and report Fyn-dependent axon outgrowth. The siRNA described there targets Fyn. The local full-text extraction lacks complete Results and Methods, so it cannot establish that no additional ADNP experiments exist. Neuronal context and the native-protein mechanism need resolution; context-specific knockdown phenotypes in PMID:36631597 are not treated as universal sign inversion. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q9JKL8 UNRESOLVED The accessible abstract and Discussion of PMID:19047645 use NAP to model ADNP signaling and report Fyn-dependent axon outgrowth. The siRNA described there targets Fyn. The local full-text extraction lacks complete Results and Methods, so it cannot establish that no additional ADNP experiments exist. Neuronal context and the native-protein mechanism need resolution; context-specific knockdown phenotypes in PMID:36631597 are not treated as universal sign inversion. ensembl:ENSRNOP00000014595 UNRESOLVED Compara protein identifier supplied alongside the UniProt donor in the unchanged source object. The stored donor audit resolves the paired ortholog; this identifier is not counted as independent experimental evidence. Supporting Evidence: PMID:19047645 NAPVSIPQ (NAP), a potent active fragment of ADNP, potentiated axon outgrowth in cerebellar granule neurons by activating the sequential tyrosine phosphorylation of Fyn kinase and the scaffold protein Crk-associated substrate (Cas). PMID:19047645 Pharmacological inhibition of Fyn kinase or expression of a Fyn kinase siRNA abolished NAP-mediated axon outgrowth. |
| GO:0046068 cGMP metabolic process | IEA GO_REF:0000107 | UNDECIDED | Summary: The cGMP response to NAP does not yet resolve endogenous ADNP participation. Reason: PMID:11438390 reports a 2.5-4-fold intracellular cGMP increase after exogenous NAP exposure in rat cortical cultures. This is a positive peptide-treatment result, not a demonstrated endogenous human ADNP experiment. The human IEA transfer, rather than the rat donor record, remains unresolved: complete source experiments and the native-product link have not been established. Independent ChAHP repression evidence supports GO:0010629 but neither establishes nor contradicts ADNP participation in cGMP metabolism. Absence of a cyclic-nucleotide catalytic domain does not exclude regulatory participation, so the available evidence supports uncertainty rather than a confident rejection. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q9JKL8 UNRESOLVED PMID:11438390 reports a 2.5-4-fold intracellular cGMP increase after exogenous NAP exposure in rat cortical cultures. This is a positive peptide-treatment result, not a demonstrated endogenous human ADNP experiment. The human IEA transfer, rather than the rat donor record, remains unresolved: complete source experiments and the native-product link have not been established. Independent ChAHP repression evidence supports GO:0010629 but neither establishes nor contradicts ADNP participation in cGMP metabolism. Absence of a cyclic-nucleotide catalytic domain does not exclude regulatory participation, so the available evidence supports uncertainty rather than a confident rejection. ensembl:ENSRNOP00000014595 UNRESOLVED Compara protein identifier supplied alongside the UniProt donor in the unchanged source object. The stored donor audit resolves the paired ortholog; this identifier is not counted as independent experimental evidence. Supporting Evidence: PMID:11438390 In rat cerebral cortical cultures, 10(-16)-10(-7) M NAP increased intracellular cyclic guanosine monophosphate (cGMP) (2.5-4-fold) and 10(-10) M NAP increased extracellular nitric oxide (NO) by 60%. |
| GO:0048487 beta-tubulin binding | IEA GO_REF:0000107 | UNDECIDED | Summary: Direct beta-tubulin binding by native ADNP remains unresolved. Reason: PMID:16893427 identifies betaIII-tubulin using NAP affinity chromatography. Native ADNP microtubule association and EB interactions (PMID:25178163) make cytoskeletal biology plausible, but EB binding does not establish or exclude direct tubulin binding. The complete donor binding experiment and its applicability to native ADNP could not be recovered, so the specific interaction is left undecided. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q9JKL8 UNRESOLVED PMID:16893427 identifies betaIII-tubulin using NAP affinity chromatography. Native ADNP microtubule association and EB interactions (PMID:25178163) make cytoskeletal biology plausible, but EB binding does not establish or exclude direct tubulin binding. The complete donor binding experiment and its applicability to native ADNP could not be recovered, so the specific interaction is left undecided. ensembl:ENSRNOP00000014595 UNRESOLVED Compara protein identifier supplied alongside the UniProt donor in the unchanged source object. The stored donor audit resolves the paired ortholog; this identifier is not counted as independent experimental evidence. Supporting Evidence: PMID:16893427 This study aimed to identify the neuronal target for the potent neuroprotective peptide NAP. PMID:16893427 Affinity chromatography identified the brain-specific betaIII-tubulin as a major NAP binding protein. PMID:25178163 The NAP motif of activity-dependent neuroprotective protein (ADNP) regulates dendritic spines through microtubule end binding proteins |
| GO:0050805 negative regulation of synaptic transmission | IEA GO_REF:0000107 | UNDECIDED | Summary: The D-NAP/ethanol result needs an explicit native-product interpretation before transfer. Reason: PMID:15963648 studies D-NAP in rat hippocampal preparations: it augments ethanol-dependent inhibition of LTP and NMDA responses, whereas D-NAP alone has no reported effect. That positive result is specific to the administered compound and treatment context. The full source and a mechanistic bridge to endogenous ADNP were not recovered. The donor IMP label alone does not prove a gene perturbation, and neither an abstract-only assay nor absent native-product evidence warrants a blanket denial of ADNP synaptic regulation. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q9JKL8 UNRESOLVED PMID:15963648 studies D-NAP in rat hippocampal preparations: it augments ethanol-dependent inhibition of LTP and NMDA responses, whereas D-NAP alone has no reported effect. That positive result is specific to the administered compound and treatment context. The full source and a mechanistic bridge to endogenous ADNP were not recovered. The donor IMP label alone does not prove a gene perturbation, and neither an abstract-only assay nor absent native-product evidence warrants a blanket denial of ADNP synaptic regulation. ensembl:ENSRNOP00000014595 UNRESOLVED Compara protein identifier supplied alongside the UniProt donor in the unchanged source object. The stored donor audit resolves the paired ortholog; this identifier is not counted as independent experimental evidence. Supporting Evidence: PMID:15963648 Application of D-NAP alone had no effect on LTP induction or expression. PMID:15963648 Surprisingly, when D-NAP (10(-7) M) and ethanol were co-applied or applied sequentially, LTP was completely absent. |
| GO:0051965 positive regulation of synapse assembly | IEA GO_REF:0000107 | UNDECIDED | Summary: The synapse-assembly transfer is unresolved at the assay and native-product level. Reason: PMID:15800376 reports increased synaptophysin expression after ADNF-9 and NAP treatments in neuronal cultures. This is a relevant synaptic marker response, but the accessible abstract does not resolve additional structural synapse measurements or how the NAP treatment establishes endogenous ADNP participation. Full source adjudication is needed; the separate treatment arms must not be conflated. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q9JKL8 UNRESOLVED PMID:15800376 reports increased synaptophysin expression after ADNF-9 and NAP treatments in neuronal cultures. This is a relevant synaptic marker response, but the accessible abstract does not resolve additional structural synapse measurements or how the NAP treatment establishes endogenous ADNP participation. Full source adjudication is needed; the separate treatment arms must not be conflated. ensembl:ENSRNOP00000014595 UNRESOLVED Compara protein identifier supplied alongside the UniProt donor in the unchanged source object. The stored donor audit resolves the paired ortholog; this identifier is not counted as independent experimental evidence. Supporting Evidence: PMID:15800376 Finally, we found that ADNF-9 and NAP increased synaptophysin expression in both rat hippocampal and cortical cultures. |
| GO:0080164 regulation of nitric oxide metabolic process | IEA GO_REF:0000107 | UNDECIDED | Summary: Nitric-oxide regulation by native ADNP cannot be concluded from the accessible treatment study. Reason: PMID:11438390 reports increased extracellular nitric oxide after NAP treatment of rat cortical cultures, with NO-affecting concentrations distinct from neuroprotective concentrations. The peptide effect is positive, while its connection to endogenous human ADNP remains unresolved. This is a judgment on the human IEA transfer; it does not invalidate the experimental rat donor record. Complete source experiments and a native-product link have not been established. Independent chromatin-repression evidence supports GO:0010629 but does not contradict possible regulation of NO metabolism, and nuclear localization alone does not exclude such regulation. The human process assertion therefore remains uncertain. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q9JKL8 UNRESOLVED PMID:11438390 reports increased extracellular nitric oxide after NAP treatment of rat cortical cultures, with NO-affecting concentrations distinct from neuroprotective concentrations. The peptide effect is positive, while its connection to endogenous human ADNP remains unresolved. This is a judgment on the human IEA transfer; it does not invalidate the experimental rat donor record. Complete source experiments and a native-product link have not been established. Independent chromatin-repression evidence supports GO:0010629 but does not contradict possible regulation of NO metabolism, and nuclear localization alone does not exclude such regulation. The human process assertion therefore remains uncertain. ensembl:ENSRNOP00000014595 UNRESOLVED Compara protein identifier supplied alongside the UniProt donor in the unchanged source object. The stored donor audit resolves the paired ortholog; this identifier is not counted as independent experimental evidence. Supporting Evidence: PMID:11438390 However, the concentrations of NAP, SNV and VIP affecting NO production did not match the neuro-protective doses. |
| GO:0090263 positive regulation of canonical Wnt signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: ADNP positively regulates Wnt signaling during neural differentiation in the mouse model. Reason: PMID:32533114 connects ADNP-beta-catenin interaction to reduced beta-catenin degradation, Wnt reporter output and neural differentiation. The effect is developmental-stage dependent, and the paper distinguishes neural induction from undifferentiated ESCs. Retain the mouse-to-human functional inference with that scope. WNT repression in human colorectal cancer (PMID:27903678) is a different cellular context, not evidence that the positive neural result is false. Recovered PMID:40498903 further shows that ADNP overexpression reduces Wnt3a responsiveness in human neural progenitor cells without changing baseline reporter output. This human cellular context bounds the mouse-derived positive inference; it does not reverse the original mouse result or establish uniform Wnt activation by ADNP. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q9Z103 SUPPORTS TRANSFER PMID:32533114 connects ADNP-beta-catenin interaction to reduced beta-catenin degradation, Wnt reporter output and neural differentiation. The effect is developmental-stage dependent, and the paper distinguishes neural induction from undifferentiated ESCs. Retain the mouse-to-human functional inference with that scope. WNT repression in human colorectal cancer (PMID:27903678) is a different cellular context, not evidence that the positive neural result is false. Recovered PMID:40498903 further shows that ADNP overexpression reduces Wnt3a responsiveness in human neural progenitor cells without changing baseline reporter output. This human cellular context bounds the mouse-derived positive inference; it does not reverse the original mouse result or establish uniform Wnt activation by ADNP. ensembl:ENSMUSP00000085316 SUPPORTS TRANSFER Compara protein identifier supplied alongside the UniProt donor in the unchanged source object. The stored donor audit resolves the paired ortholog; this identifier is not counted as independent experimental evidence. Supporting Evidence: PMID:32533114 Loss of ADNP promotes the formation of the degradation complex and Ξ²-Catenin degradation via ubiquitin-proteasome pathway, resulting in down-regulation of key neuroectoderm developmental genes. PMID:40498903 ADNP overexpression did not affect baseline Wnt signalling (Fig. 7E) but significantly reduced Wnt3a responsiveness in both genotypes (Fig. 7F). |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9940477 | ACCEPT | Summary: The nucleoplasmic ChAHP assembly supports this localization. Reason: The cached Reactome:R-HSA-9940477 entry identifies ADNP, CHD4 and HP1 components of ChAHP and describes ADNP-dependent chromatin targeting. The source event places this assembly in the nucleoplasm, consistent with the independent primary ChAHP study. Complex-localization support is sufficient for this compartment annotation without extrapolating every pathway function to ADNP. Propagation Review Root cause: NO FAILURE CORE Sources checked: Reactome:R-HSA-9940477 SUPPORTS TRANSFER Cached ChAHP assembly event with ADNP as a component; nucleoplasmic localization agrees with the primary complex study. Supporting Evidence: PMID:29795351 ADNP interacts with the chromatin remodeller CHD4 and the chromatin architectural protein HP1 to form a stable complex, which we refer to as ChAHP. |
| GO:0005694 chromosome | ISS GO_REF:0000024 | ACCEPT | Summary: Chromosome association is supported at the broad level of the mouse transfer. Reason: The stored donor audit finds a mouse chromosome annotation from the UniProt subcellular-location mapping rather than a separately resolved experiment for this exact term. That limits the independence of this particular route; it does not contradict the source term. Independent ChIP and ChAHP evidence support ADNP on chromosomal chromatin, so the broad location is retained as core. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q9Z103 SOURCE WEAK OR INFERRED The stored donor audit finds a mouse chromosome annotation from the UniProt subcellular-location mapping rather than a separately resolved experiment for this exact term. That limits the independence of this particular route; it does not contradict the source term. Independent ChIP and ChAHP evidence support ADNP on chromosomal chromatin, so the broad location is retained as core. Supporting Evidence: PMID:31491387 ChAHP-bound loci are mainly situated within less diverged SINE B2 transposable elements. |
| GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding | ISS GO_REF:0000024 | ACCEPT | Summary: ADNP recognizes regulatory DNA sequences and targets ChAHP to chromatin. Reason: The mouse Adnp donor traces to PMID:17222401, which reports promoter association by ChIP alongside altered gene expression. ChIP alone does not prove direct sequence discrimination. Independent DNA-motif recognition in PMID:29795351 and motif competition with CTCF in PMID:31491387 provide that stronger evidence. The conserved ADNP function supports the transfer without assigning sequence specificity from the homeobox alone. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q9Z103 SUPPORTS TRANSFER The mouse Adnp donor traces to PMID:17222401, which reports promoter association by ChIP alongside altered gene expression. ChIP alone does not prove direct sequence discrimination. Independent DNA-motif recognition in PMID:29795351 and motif competition with CTCF in PMID:31491387 provide that stronger evidence. The conserved ADNP function supports the transfer without assigning sequence specificity from the homeobox alone. Supporting Evidence: PMID:17222401 The pluripotent P19 cells were used for ADNP-chromatin-immunoprecipitation, showing direct interactions with multiple relevant gene promoters including members of the up-regulated as well as the down-regulated gene clusters. PMID:29795351 Besides mediating complex assembly, ADNP recognizes DNA motifs that specify binding of ChAHP to euchromatin. PMID:42413491 the transcription factor ADNP forms the ChAHP complex with the chromatin remodeler CHD4 and HP1 proteins, acting as a site-specific regulator of transcription and an antagonist of CTCF binding PMID:31491387 we demonstrate that the ChAHP complex (CHD4, ADNP, HP1) competes with CTCF for a common set of binding motifs |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | ISS GO_REF:0000024 | ACCEPT | Summary: ADNP is a DNA-binding transcription factor regulating Pol II gene expression. Reason: The mouse Adnp donor annotation is grounded in promoter-association and expression experiments in PMID:17222401. ADNP recognizes DNA motifs and targets ChAHP to lineage-regulatory genes (PMID:29795351). Repression is a well-supported output, but the broader source term also accommodates context-dependent regulation; it need not be replaced by a directional child. No redundant NEW repressor annotation is retained. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q9Z103 SUPPORTS TRANSFER The mouse Adnp donor annotation is grounded in promoter-association and expression experiments in PMID:17222401. ADNP recognizes DNA motifs and targets ChAHP to lineage-regulatory genes (PMID:29795351). Repression is a well-supported output, but the broader source term also accommodates context-dependent regulation; it need not be replaced by a directional child. No redundant NEW repressor annotation is retained. Supporting Evidence: PMID:17222401 The pluripotent P19 cells were used for ADNP-chromatin-immunoprecipitation, showing direct interactions with multiple relevant gene promoters including members of the up-regulated as well as the down-regulated gene clusters. PMID:29795351 Besides mediating complex assembly, ADNP recognizes DNA motifs that specify binding of ChAHP to euchromatin. PMID:42413491 the transcription factor ADNP forms the ChAHP complex with the chromatin remodeler CHD4 and HP1 proteins, acting as a site-specific regulator of transcription and an antagonist of CTCF binding PMID:29795351 Genetic ablation of ChAHP components in mouse embryonic stem cells results in spontaneous differentiation concomitant with premature activation of lineage-specific genes |
| GO:0006357 regulation of transcription by RNA polymerase II | ISS GO_REF:0000024 | ACCEPT | Summary: Pol II transcriptional regulation is a core ADNP function. Reason: The mouse donor PMID:17222401 combines altered expression in Adnp-deficient embryos with ADNP promoter association in P19 cells. The ChAHP study independently connects sequence recognition and complex assembly to control of lineage-specific transcription. These data support the broad source term without requiring every affected gene to have the same regulatory sign. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q9Z103 SUPPORTS TRANSFER The mouse donor PMID:17222401 combines altered expression in Adnp-deficient embryos with ADNP promoter association in P19 cells. The ChAHP study independently connects sequence recognition and complex assembly to control of lineage-specific transcription. These data support the broad source term without requiring every affected gene to have the same regulatory sign. Supporting Evidence: PMID:17222401 The pluripotent P19 cells were used for ADNP-chromatin-immunoprecipitation, showing direct interactions with multiple relevant gene promoters including members of the up-regulated as well as the down-regulated gene clusters. PMID:29795351 Besides mediating complex assembly, ADNP recognizes DNA motifs that specify binding of ChAHP to euchromatin. PMID:42413491 the transcription factor ADNP forms the ChAHP complex with the chromatin remodeler CHD4 and HP1 proteins, acting as a site-specific regulator of transcription and an antagonist of CTCF binding |
| GO:0005515 protein binding | IPI PMID:29795351 Activity-dependent neuroprotective protein recruits HP1 and ... | MODIFY | Summary: The CBX3/HP1gamma association is better represented by chromo shadow domain binding. Reason: The original study defines the stable ADNP-CHD4-HP1 complex and its chromatin-targeting role. The curated interaction is retained. The more informative replacement uses independent mechanistic evidence: ADNP PxVxL-mutant experiments in PMID:38960717 test HP1-dependent chromatin recruitment, together with the domain-mapping study assessed in PMID:21267468. The interaction screen itself is not treated as having mapped the domain, and binding of different HP1 paralogs does not imply simultaneous occupancy by all three. Proposed replacements: chromo shadow domain binding Supporting Evidence: PMID:38960717 To do this, we generated ADNPPxVxL motif point mutants (Supplemental Fig. S6B) and performed ChIP-seq. PMID:38960717 Abrogating the HP1 interaction in this way resulted in a loss of ADNP signal specifically at H3K9 trimethylated transposons, including LTR and LINE1 families, which are bound by ADNP2 PMID:21267468 Yet, recruitment of ADNP to H3K9me3 was severely impaired in presence of the mutant HP1Ξ² W170A protein compared to the wild type HP1Ξ² protein. |
| GO:0005515 protein binding | IPI PMID:29795351 Activity-dependent neuroprotective protein recruits HP1 and ... | MODIFY | Summary: ADNP recruits CHD4-containing chromatin-remodeling activity to selected chromatin sites. Reason: The partner is CHD4 (UniProtKB:Q14839). PMID:29795351 establishes the stable ChAHP complex and ADNP-dependent DNA recognition; PMID:42413491 separates sequence-directed recruitment from CHD4 remodeling activity. This satisfies GO:0140463, which describes bringing a protein together with chromatin to establish or maintain its localization. The replacement uses positive recruitment evidence rather than inferring an adaptor from interaction alone. Proposed replacements: chromatin-protein adaptor activity Supporting Evidence: PMID:29795351 Besides mediating complex assembly, ADNP recognizes DNA motifs that specify binding of ChAHP to euchromatin. PMID:42413491 Our findings support a model in which ADNP recruits chromatin-remodeling activity in a sequence-specific manner, enabling transcriptional control and local modulation of chromatin architecture. PMID:42413491 we demonstrate in mouse embryonic stem cells that the CHD4 subunit is essential for antagonizing CTCF and silencing the transcription of transposons, whereas HP1 proteins are dispensable |
| GO:0090575 RNA polymerase II transcription regulator complex | IDA PMID:29795351 Activity-dependent neuroprotective protein recruits HP1 and ... | ACCEPT | Summary: ADNP is a component of a Pol II transcription-regulatory complex. Reason: PMID:29795351 defines ChAHP as a stable ADNP-CHD4-HP1 complex controlling lineage-specific gene expression. This supports the broad Pol II regulator-complex term carried by the human IDA. Other ChAHP outputs, including Pol III SINE regulation, do not negate that membership. No unsupported assertion that every HP1 paralog simultaneously occupies one complex is needed. Supporting Evidence: PMID:29795351 ADNP interacts with the chromatin remodeller CHD4 and the chromatin architectural protein HP1 to form a stable complex, which we refer to as ChAHP. PMID:38960717 We previously discovered ChAHP, a protein complex with repressive activity against short interspersed element (SINE) retrotransposons that is composed of the transcription factor ADNP, chromatin remodeler CHD4, and HP1 proteins. |
| GO:0000785 chromatin | ISA GO_REF:0000113 | ACCEPT | Summary: ADNP is chromatin-associated through sequence recognition and partner-dependent recruitment. Reason: TFClass:3.1.8 supplies the class-based source assertion. Independent promoter association (PMID:17222401), ChAHP DNA recognition (PMID:29795351) and dual chromatin-targeting modes (PMID:38960717) support the location beyond the classification. These mechanisms include euchromatic sequence-defined sites and HP1-dependent heterochromatin recruitment. Propagation Review Root cause: NO FAILURE CORE Sources checked: tfclass:3.1.8 SUPPORTS TRANSFER TFClass class identifier is preserved from the source assertion; independent ADNP-specific chromatin/transcription experiments substantiate the assigned term. The complete class-alignment derivation was not reconstructed. Supporting Evidence: PMID:29795351 ChAHP-mediated repression, however, acts in a locally restricted manner by establishing inaccessible chromatin around its DNA-binding sites and does not depend on H3K9me3-modified nucleosomes. PMID:17222401 A comparison between non-differentiated and neuro-differentiated P19 cells revealed increased chromatin interaction of ADNP with chromatin from differentiated cells. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | ISA GO_REF:0000113 | ACCEPT | Summary: ADNP is a DNA-binding transcription factor regulating Pol II gene expression. Reason: TFClass:3.1.8 class membership supplies this sequence-based inference. ADNP recognizes DNA motifs and targets ChAHP to lineage-regulatory genes (PMID:29795351). Repression is a well-supported output, but the broader source term also accommodates context-dependent regulation; it need not be replaced by a directional child. No redundant NEW repressor annotation is retained. Propagation Review Root cause: NO FAILURE CORE Sources checked: tfclass:3.1.8 SUPPORTS TRANSFER TFClass class identifier is preserved from the source assertion; independent ADNP-specific chromatin/transcription experiments substantiate the assigned term. The complete class-alignment derivation was not reconstructed. Supporting Evidence: PMID:17222401 The pluripotent P19 cells were used for ADNP-chromatin-immunoprecipitation, showing direct interactions with multiple relevant gene promoters including members of the up-regulated as well as the down-regulated gene clusters. PMID:29795351 Besides mediating complex assembly, ADNP recognizes DNA motifs that specify binding of ChAHP to euchromatin. PMID:42413491 the transcription factor ADNP forms the ChAHP complex with the chromatin remodeler CHD4 and HP1 proteins, acting as a site-specific regulator of transcription and an antagonist of CTCF binding PMID:29795351 Genetic ablation of ChAHP components in mouse embryonic stem cells results in spontaneous differentiation concomitant with premature activation of lineage-specific genes |
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Download this section (compressed HTML)Q: For ADNP annotations derived from NAP treatments, which assays distinguish native full-length protein, an endogenous processed product and an administered synthetic fragment? The stored donor mapping identifies the source papers, but its abstract classifier cannot adjudicate all of their experimental coverage. Can the original donor curators resolve the undecided transfers using the full methods?
Suggested experts: RGD GO curators, GO Central, Ensembl Compara / GOA
Q: Can estrous-cycle orthology projections be restricted so that a rat process defined by endometrial resorption is not transferred to human proteins? The broad Theria constraint does not encode the distinction from menstruation.
Suggested experts: GO ontology editors, Ensembl Compara / GOA
Q: Which current complex representation best distinguishes ChAHP from ChAHP2 and accommodates its Pol II and Pol III regulatory contexts? The existing Pol II regulator-complex annotation is valid for that output, while the named complex also has other transcriptional roles.
Suggested experts: Complex Portal curators, GO ontology editors
Q: Which cell-state features determine whether ADNP stabilizes beta-catenin during mouse neural differentiation or attenuates WNT output in human colorectal cancer and Wnt3a-stimulated human neural progenitors?
Suggested experts: ADNP researchers, Wnt signaling curators
Experiment: Build on existing ADNP/HP1 interface mutagenesis by measuring endogenous human ADNP occupancy, CHD4 recruitment and repeat transcription after targeted interface perturbation in neural progenitors. Compare HP1-dependent heterochromatin sites with sequence-dependent sites, with matched expression and protein stability controls.
Hypothesis: HP1-paralog usage and sequence-specific DNA targeting determine different ADNP chromatin distributions in human cells.
Type: targeted perturbation and chromatin profiling
Experiment: Combine intact-protein analysis and targeted peptidomics of cells and conditioned medium with isotope-labeled NAP standards and appropriate recovery controls. Relate any detected species to loss and rescue of native ADNP. Failure to detect a peptide in one context would bound that context rather than establish universal absence.
Hypothesis: Endogenous ADNP molecular forms explain some, but not necessarily all, biological activities modeled by NAP treatment.
Type: proteomics and functional rescue
Experiment: Test compositionally defined recombinant ADNP preparations with substrate/product measurements, appropriate enzyme-free controls and targeted candidate-site mutants. Separate ADNP catalysis from activity supplied by associated proteins before assigning a methyltransferase molecular function.
Hypothesis: The methyltransferase activity measured in ADNP immunoprecipitates is intrinsic to ADNP.
Type: in vitro enzymology
What is not known β curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: The relationship between NAP treatment effects and the activities of endogenous ADNP molecular species remains incompletely resolved.
OPEN BIOLOGYCURATION RESIDUAL_SUBGAP
What is known: NAP is an active ADNP-derived sequence, and native ADNP has both nuclear and cytoplasmic functions. The accessed donor studies often foreground isolated peptide treatments; incomplete full-source coverage prevents universal claims about endogenous cleavage or its absence.
Significance: This distinction affects interpretation of the undecided ortholog-projected peptide assays.
Provenance (the field's own admissions):
Gap: The cell-state determinants of ADNP effects on Wnt signaling need to be reconciled across developmental and cancer contexts.
OPEN BIOLOGY RESIDUAL_SUBGAP
What is known: Mouse neural differentiation provides beta-catenin binding/stabilization evidence, while colorectal-cancer models show WNT repression. Different contexts do not establish that either observation is erroneous.
Significance: Human transfer should preserve the neural context rather than assert one universal regulatory sign.
Provenance (the field's own admissions):
Gap: Intrinsic methyltransferase catalysis by purified ADNP is not established by the accessible immunoprecipitate evidence.
OPEN BIOLOGY RESIDUAL_SUBGAP
What is known: PMID:41174994 reports activity in fractions containing overexpressed ADNP and effects of nonsense variants. The available abstract does not separate ADNP catalysis from activity of associated proteins.
Significance: No methyltransferase GO function is assigned from the unresolved catalytic attribution.
Provenance (the field's own admissions):
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