Activation-induced cytidine deaminase (AID), encoded by AICDA, is a zinc-dependent deaminase that converts cytosine to uracil in exposed single-stranded DNA. In activated B lymphocytes it initiates immunoglobulin somatic hypermutation and class-switch recombination; downstream DNA repair converts these lesions into sequence changes or recombination intermediates. Nuclear import, export and cytoplasmic retention constrain access to the genome. RNA interactions and transcription-associated partners help regulate substrate access, while mistargeted deamination can damage non-immunoglobulin genes. Human AICDA deficiency disrupts antibody diversification and causes a form of hyper-IgM immunodeficiency.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000932 P-body | IBA GO_REF:0000033 | UNDECIDED | Summary: Ancestral P-body localization remains unresolved for human AID. Reason: The PTN001419581 assertion is a PAINT ancestral inference, not a count of APOBEC donor matches. Human AID shuttles between nucleus and cytoplasm (PMID:14769937; PMID:32484799), but those observations do not identify a P-body pool. The underlying IBD experiment and target-specific P-body evidence were not recovered. Preserve curator uncertainty without inferring loss of localization from diffuse cytoplasmic observations. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN001419581 UNRESOLVED Actual ancestral node from the seeded IBA. The IBD experiment/tree placement was not independently recovered; target evidence and the resulting judgment are described in the rationale. No donor-count or circularity argument is made. Supporting Evidence: PMID:14769937 hAID-GFP was localized primarily in the cytoplasm |
| GO:0003723 RNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: RNA binding is experimentally supported and regulates AID substrate access. Reason: Human AID cloned from Ramos cells and expressed in Sf9 copurifies with inhibitory RNA; RNase treatment exposes its DNA-deamination activity (PMID:12651944). Mouse switch-RNA experiments further show sequence/structure-dependent RNA association and targeting (PMID:25957684). These independent observations support the inherited RNA-binding function without equating binding with RNA editing. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000355219 UNRESOLVED Actual ancestral node from the seeded IBA. The IBD experiment/tree placement was not independently recovered; target evidence and the resulting judgment are described in the rationale. No donor-count or circularity argument is made. Supporting Evidence: PMID:12651944 Remarkably, it has no measurable deaminase activity on single-stranded DNA unless pretreated with RNase to remove inhibitory RNA bound to AID. |
| GO:0004126 cytidine deaminase activity | IBA GO_REF:0000033 | ACCEPT | Summary: The inherited cytidine-deaminase capacity has direct human biochemical support. Reason: GO:0004126 formally describes free cytidine/deoxycytidine deamination. Human Ramos-derived GST-AID directly converts both free nucleosides in PMID:12651944 Figure 4b, as well as deaminating ssDNA. Retain this genuine catalytic capacity while distinguishing it from the DNA-polymer substrate underlying antibody diversification. The DNA-specific core is expressed with the verified broader deaminase term because no matching specific MF was recovered. PTN000355219 is the ancestral source; the target appearing among descendant evidence is legitimate, not circular. The public original Results (https://pmc.ncbi.nlm.nih.gov/articles/PMC153055/, Figure 4b) state: "AID is most active when deaminating the free deoxynucleoside, CdR β deoxyuridine"; that externally inspected assay establishes capacity beyond the cached abstract's background statement. The local record is abstract-only. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000355219 UNRESOLVED Actual ancestral node from the seeded IBA. The IBD experiment/tree placement was not independently recovered; target evidence and the resulting judgment are described in the rationale. No donor-count or circularity argument is made. Supporting Evidence: PMID:18722174 Activation-induced deaminase (AID) deaminates deoxycytidine residues in immunoglobulin genes, triggering antibody diversification. PMID:12651944 exhibits deaminase activity on free deoxycytidine in solution |
| GO:0004126 cytidine deaminase activity | IDA PMID:18722174 Interaction between antibody-diversification enzyme AID and ... | ACCEPT | Summary: AID catalytic deamination is established; the source convention is retained. Reason: PMID:18722174 describes AID deamination of immunoglobulin DNA and maps CTNNBL1 interaction. Its full assay details were not recovered. GO:0004126 formally describes free cytidine/deoxycytidine deamination. Human Ramos-derived GST-AID directly converts both free nucleosides in PMID:12651944 Figure 4b, as well as deaminating ssDNA. Retain this genuine catalytic capacity while distinguishing it from the DNA-polymer substrate underlying antibody diversification. The DNA-specific core is expressed with the verified broader deaminase term because no matching specific MF was recovered. The public original Results (https://pmc.ncbi.nlm.nih.gov/articles/PMC153055/, Figure 4b) state: "AID is most active when deaminating the free deoxynucleoside, CdR β deoxyuridine"; that externally inspected assay establishes capacity beyond the cached abstract's background statement. The local record is abstract-only. Supporting Evidence: PMID:18722174 Activation-induced deaminase (AID) deaminates deoxycytidine residues in immunoglobulin genes, triggering antibody diversification. PMID:12651944 exhibits deaminase activity on free deoxycytidine in solution |
| GO:0004126 cytidine deaminase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined electronic deaminase inference agrees with measured human activity. Reason: GO:0004126 formally describes free cytidine/deoxycytidine deamination. Human Ramos-derived GST-AID directly converts both free nucleosides in PMID:12651944 Figure 4b, as well as deaminating ssDNA. Retain this genuine catalytic capacity while distinguishing it from the DNA-polymer substrate underlying antibody diversification. The DNA-specific core is expressed with the verified broader deaminase term because no matching specific MF was recovered. The mouse Aicda donor supports conserved chemistry; the individual ARBA predicates and Ensembl donor record were not independently reconstructed. The public original Results (https://pmc.ncbi.nlm.nih.gov/articles/PMC153055/, Figure 4b) state: "AID is most active when deaminating the free deoxynucleoside, CdR β deoxyuridine"; that externally inspected assay establishes capacity beyond the cached abstract's background statement. The local record is abstract-only. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00043384 UNRESOLVED Rule identifier retained. Its predicates were not inspected; independent target biology supports the annotation judgment without certifying the rule internals. UniProtKB:Q9WVE0 SUPPORTS TRANSFER Mouse Aicda donor. PMID:10373455 reports purified mouse GST-AID free-cytidine activity, and PMID:12651944 independently measures the same capacity in a human preparation. ensembl:ENSMUSP00000040524 UNRESOLVED Seeded Ensembl donor retained; its current record and term-specific evidence chain were not independently retrieved. Human biochemical evidence independently corroborates the activity. Supporting Evidence: PMID:12651944 exhibits deaminase activity on free deoxycytidine in solution |
| GO:0004126 cytidine deaminase activity | NAS PMID:10950930 Isolation, tissue distribution, and chromosomal localization... | ACCEPT | Summary: The historical human cloning annotation is corroborated by later human enzymology. Reason: PMID:10950930 establishes the human AICDA orthologue and conserved deaminase motif rather than a new kinetic assay. GO:0004126 formally describes free cytidine/deoxycytidine deamination. Human Ramos-derived GST-AID directly converts both free nucleosides in PMID:12651944 Figure 4b, as well as deaminating ssDNA. Retain this genuine catalytic capacity while distinguishing it from the DNA-polymer substrate underlying antibody diversification. The DNA-specific core is expressed with the verified broader deaminase term because no matching specific MF was recovered. The public original Results (https://pmc.ncbi.nlm.nih.gov/articles/PMC153055/, Figure 4b) state: "AID is most active when deaminating the free deoxynucleoside, CdR β deoxyuridine"; that externally inspected assay establishes capacity beyond the cached abstract's background statement. The local record is abstract-only. Supporting Evidence: PMID:10950930 We have isolated the human orthologue of mouse AID cDNA, which has an open reading frame of 198 residues containing a conserved cytidine deaminase motif. PMID:12651944 exhibits deaminase activity on free deoxycytidine in solution |
| GO:0005515 protein binding | IPI PMID:16387847 PKA-mediated phosphorylation regulates the function of activ... | REMOVE | Summary: Generic binding to PRKAR1A does not identify a distinct AID molecular function. Reason: PMID:16387847 co-immunoprecipitates AID with the PKA holoenzyme. AID is a regulated phosphorylation substrate; the experiment does not establish that it independently scaffolds or activates the regulatory subunit. Remove the uninformative GO:0005515 assertion without denying the reported interaction or its curator provenance. |
| GO:0005515 protein binding | IPI PMID:16387847 PKA-mediated phosphorylation regulates the function of activ... | REMOVE | Summary: Generic binding to PRKACA does not identify a distinct AID molecular function. Reason: PMID:16387847 shows PKA-dependent phosphorylation of AID and association with PKA subunits. The authors leave binary versus holoenzyme-mediated association unresolved. AID is the substrate, not the kinase. Remove the uninformative GO:0005515 assertion without denying the reported interaction or its curator provenance. |
| GO:0005515 protein binding | IPI PMID:18722174 Interaction between antibody-diversification enzyme AID and ... | REMOVE | Summary: Generic binding to CTNNBL1 does not identify a distinct AID molecular function. Reason: PMID:18722174 identifies CTNNBL1 by two-hybrid and co-immunoprecipitation and links interaction mutants to antibody diversification. This supports an interaction but does not assign a distinct adaptor activity to AID. Remove the uninformative GO:0005515 assertion without denying the reported interaction or its curator provenance. Supporting Evidence: PMID:18722174 Here, by use of two-hybrid and coimmunoprecipitation assays, we identify CTNNBL1 (also known as NAP) as an AID-specific interactor. |
| GO:0005515 protein binding | IPI PMID:19412186 Active nuclear import and cytoplasmic retention of activatio... | REMOVE | Summary: Generic binding to KPNA3 does not identify a distinct AID molecular function. Reason: PMID:19412186 studies active import and cytoplasmic retention; the specific KPNA3 pair is preserved as the curator assertion. Available evidence supports AID as transport cargo, not as the import receptor. Remove the uninformative GO:0005515 assertion without denying the reported interaction or its curator provenance. Supporting Evidence: PMID:19412186 AID is unable to passively diffuse into the nucleus, despite its small size, and its nuclear entry requires active import mediated by a conformational nuclear localization signal. |
| GO:0005515 protein binding | IPI PMID:19412186 Active nuclear import and cytoplasmic retention of activatio... | REMOVE | Summary: Generic binding to KPNA5 does not identify a distinct AID molecular function. Reason: PMID:19412186 studies AID nuclear transport; the exact KPNA5 experiment is not in the accessible abstract. The reported association is retained as provenance, without inventing a transport-adaptor function for its cargo. Remove the uninformative GO:0005515 assertion without denying the reported interaction or its curator provenance. Supporting Evidence: PMID:19412186 AID is unable to passively diffuse into the nucleus, despite its small size, and its nuclear entry requires active import mediated by a conformational nuclear localization signal. |
| GO:0005515 protein binding | IPI PMID:19412186 Active nuclear import and cytoplasmic retention of activatio... | REMOVE | Summary: Generic binding to KPNA1 does not identify a distinct AID molecular function. Reason: PMID:19412186 supports conformational-NLS-dependent import; PMID:21385873 independently tests karyopherin binding. AID is the transported substrate, not the transport machinery. Remove the uninformative GO:0005515 assertion without denying the reported interaction or its curator provenance. Supporting Evidence: PMID:19412186 AID is unable to passively diffuse into the nucleus, despite its small size, and its nuclear entry requires active import mediated by a conformational nuclear localization signal. |
| GO:0005515 protein binding | IPI PMID:21385873 CTNNBL1 is a novel nuclear localization sequence-binding pro... | REMOVE | Summary: Generic binding to KPNA1 does not identify a distinct AID molecular function. Reason: PMID:21385873 tests karyopherin association with AID NLS variants. This is cargo recognition; it does not make AID a nuclear transport receptor. Remove the uninformative GO:0005515 assertion without denying the reported interaction or its curator provenance. Supporting Evidence: PMID:21385873 Binding of GST-AID mutants to FLAG-CTNNBL1 and HA-tagged karyopherin Ξ±1 was assessed as in B, except using ant-HA antibody to detect bound HA-karyopherin Ξ±1. |
| GO:0005515 protein binding | IPI PMID:21518874 Histone chaperone Spt6 is required for class switch recombin... | REMOVE | Summary: Generic binding to SUPT6H does not identify a distinct AID molecular function. Reason: PMID:21518874 identifies Spt6 by two-hybrid and proteomics and separates its effect on switching from hypermutation. AID is the DNA deaminase; association does not assign histone-chaperone activity to AID. Remove the uninformative GO:0005515 assertion without denying the reported interaction or its curator provenance. Supporting Evidence: PMID:21518874 Here we identified Spt6 as an AID-interacting protein by yeast two-hybrid screening and immunoprecipitation followed by mass spectrometry. |
| GO:0005515 protein binding | IPI PMID:21722948 Thymine DNA glycosylase is essential for active DNA demethyl... | REMOVE | Summary: Generic binding to GADD45A does not identify a distinct AID molecular function. Reason: PMID:21722948 reports AID, TDG and GADD45A association; recovered Figure 6 includes tagged human-cell co-immunoprecipitations and endogenous mouse P19 complexes. This does not by itself establish that AID is an adaptor or DNA glycosylase. Remove the uninformative GO:0005515 assertion without denying the reported interaction or its curator provenance. Supporting Evidence: PMID:21722948 TDG interacts with the deaminase AID and the damage response protein GADD45a. |
| GO:0005515 protein binding | IPI PMID:21722948 Thymine DNA glycosylase is essential for active DNA demethyl... | REMOVE | Summary: Generic binding to TDG does not identify a distinct AID molecular function. Reason: PMID:21722948 supports association in a proposed coupled demethylation pathway. TDG performs glycosylase chemistry; the interaction does not assign that activity to AID. Remove the uninformative GO:0005515 assertion without denying the reported interaction or its curator provenance. Supporting Evidence: PMID:21722948 TDG interacts with the deaminase AID and the damage response protein GADD45a. |
| GO:0005515 protein binding | IPI PMID:22085931 Optimal functional levels of activation-induced deaminase sp... | REMOVE | Summary: Generic binding to DNAJA2 does not identify a distinct AID molecular function. Reason: PMID:22085931 explicitly reports in-vitro binding to both DNAJA1 and DNAJA2, although only DNAJA1 stabilizes functional AID in the tested cellular settings. AID is a chaperone client. Remove the uninformative GO:0005515 assertion without denying the reported interaction or its curator provenance. Supporting Evidence: PMID:22085931 Although both major cytoplasmic type I Hsp40s, DnaJa1 and DnaJa2, are induced upon B-cell activation and interact with AID in vitro, only DnaJa1 overexpression increases AID levels and biological activity in cell lines. |
| GO:0005515 protein binding | IPI PMID:22085931 Optimal functional levels of activation-induced deaminase sp... | REMOVE | Summary: Generic binding to HSPA8 does not identify a distinct AID molecular function. Reason: PMID:22085931 concerns chaperone-dependent AID stability; the HSPA8-specific pair details were not recovered beyond the curator record. Generic association does not establish a chaperone or cochaperone activity of AID. Remove the uninformative GO:0005515 assertion without denying the reported interaction or its curator provenance. Supporting Evidence: PMID:22085931 Although both major cytoplasmic type I Hsp40s, DnaJa1 and DnaJa2, are induced upon B-cell activation and interact with AID in vitro, only DnaJa1 overexpression increases AID levels and biological activity in cell lines. |
| GO:0005515 protein binding | IPI PMID:22085931 Optimal functional levels of activation-induced deaminase sp... | REMOVE | Summary: Generic binding to DNAJA1 does not identify a distinct AID molecular function. Reason: PMID:22085931 directly supports DNAJA1 association and stabilization of AID. This is a client relationship, not evidence that AID folds other proteins. Remove the uninformative GO:0005515 assertion without denying the reported interaction or its curator provenance. Supporting Evidence: PMID:22085931 Although both major cytoplasmic type I Hsp40s, DnaJa1 and DnaJa2, are induced upon B-cell activation and interact with AID in vitro, only DnaJa1 overexpression increases AID levels and biological activity in cell lines. |
| GO:0005515 protein binding | IPI PMID:26867650 TGF-Ξ² triggers HBV cccDNA degradation through AID-dependent ... | REMOVE | Summary: Generic binding to HBV core protein does not identify a distinct AID molecular function. Reason: PMID:26867650 reports HBV-core-promoted recruitment of AID to viral cccDNA. This supports context-dependent recruitment for deamination without establishing a separate generic binding function. Remove the uninformative GO:0005515 assertion without denying the reported interaction or its curator provenance. Supporting Evidence: PMID:26867650 Moreover, the HBV core protein promotes the interaction between AID and viral cccDNA. |
| GO:0005634 nucleus | EXP PMID:21385873 CTNNBL1 is a novel nuclear localization sequence-binding pro... | ACCEPT | Summary: Nuclear entry places AID at its DNA substrates. Reason: PMID:21385873 measures localization of AID NLS/export variants in human cells and CTNNBL1-dependent nuclear accumulation in chicken DT40 cells. The nuclear compartment is independently supported by human patient and Ramos-cell measurements (PMID:32484799). This does not imply constitutively nuclear localization. Supporting Evidence: PMID:21385873 Furthermore, the CTNNBL1/AID interaction depends on amino acids forming the AID conformational NLS with CTNNBL1-deficient cells showing a partial defect in AID nuclear accumulation. PMID:32484799 We found that the M466V mutation interfered with the association of CTNNBL1 with AID, resulting in decreased AID in the nuclei of patient EBV-transformed B cell lines and of CTNNBL1 466V/V Ramos B cells engineered to express only CTNNBL1 M466V using CRISPR/Cas9 technology. |
| GO:0005634 nucleus | EXP PMID:32484799 Disease-associated CTNNBL1 mutation impairs somatic hypermut... | ACCEPT | Summary: Human B-cell experiments establish a nuclear AID pool. Reason: PMID:32484799 measures reduced nuclear AID in patient EBV-transformed B cells and engineered human Ramos cells carrying CTNNBL1 M466V. The experiment supports normal nuclear localization and its regulation, rather than a function unique to the mutant. Supporting Evidence: PMID:32484799 We found that the M466V mutation interfered with the association of CTNNBL1 with AID, resulting in decreased AID in the nuclei of patient EBV-transformed B cell lines and of CTNNBL1 466V/V Ramos B cells engineered to express only CTNNBL1 M466V using CRISPR/Cas9 technology. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Inherited nuclear localization is corroborated directly in human B cells. Reason: PTN000355219 places the localization on an ancestor. Human nuclear AID and altered nuclear accumulation after CTNNBL1 perturbation independently support the target assertion (PMID:32484799); no evolutionary loss is indicated. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000355219 UNRESOLVED Actual ancestral node from the seeded IBA. The IBD experiment/tree placement was not independently recovered; target evidence and the resulting judgment are described in the rationale. No donor-count or circularity argument is made. Supporting Evidence: PMID:32484799 We found that the M466V mutation interfered with the association of CTNNBL1 with AID, resulting in decreased AID in the nuclei of patient EBV-transformed B cell lines and of CTNNBL1 466V/V Ramos B cells engineered to express only CTNNBL1 M466V using CRISPR/Cas9 technology. |
| GO:0005634 nucleus | IDA PMID:14769937 Activation-induced cytidine deaminase shuttles between nucle... | ACCEPT | Summary: Human AID undergoes regulated nuclear import and export. Reason: PMID:14769937 expressed human AID-GFP in mouse NIH3T3 cells; leptomycin B shifted the fusion into the nucleus. The heterologous host and export-inhibited condition are explicit. Independent human B-cell data confirm the compartment (PMID:32484799). Supporting Evidence: PMID:14769937 By this treatment, hAID-GFP changed its subcellular localization from the cytoplasm to the nucleus. PMID:32484799 We found that the M466V mutation interfered with the association of CTNNBL1 with AID, resulting in decreased AID in the nuclei of patient EBV-transformed B cell lines and of CTNNBL1 466V/V Ramos B cells engineered to express only CTNNBL1 M466V using CRISPR/Cas9 technology. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic nuclear localization agrees with measured human AID distribution. Reason: The UniProt nuclear-location mapping and ARBA inference are independently corroborated by human patient/Ramos measurements (PMID:32484799). ARBA rule internals were not inspected; acceptance rests on positive target evidence. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00026330 UNRESOLVED Rule identifier retained. Its predicates were not inspected; independent target biology supports the annotation judgment without certifying the rule internals. UniProtKB-SubCell:SL-0191 SUPPORTS TRANSFER UniProt subcellular-location vocabulary source; retained at its stated compartment resolution and corroborated by AID localization/transport experiments. Supporting Evidence: PMID:32484799 We found that the M466V mutation interfered with the association of CTNNBL1 with AID, resulting in decreased AID in the nuclei of patient EBV-transformed B cell lines and of CTNNBL1 466V/V Ramos B cells engineered to express only CTNNBL1 M466V using CRISPR/Cas9 technology. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: A cytoplasmic AID pool is a conserved regulatory feature. Reason: The PTN000355219 inference agrees with human-AID imaging and nuclear-shuttling studies (PMID:14769937; PMID:19412186). Cytoplasmic retention restricts genome access; it does not contradict the nuclear pool. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000355219 UNRESOLVED Actual ancestral node from the seeded IBA. The IBD experiment/tree placement was not independently recovered; target evidence and the resulting judgment are described in the rationale. No donor-count or circularity argument is made. Supporting Evidence: PMID:14769937 hAID-GFP was localized primarily in the cytoplasm PMID:19412186 AID is unable to passively diffuse into the nucleus, despite its small size, and its nuclear entry requires active import mediated by a conformational nuclear localization signal. |
| GO:0005737 cytoplasm | IDA GO_REF:0000054 | ACCEPT | Summary: The fusion-protein localization is consistent with independent human-AID imaging. Reason: GO_REF:0000054 records curated fusion-protein observations; the individual image was not re-inspected. Human AID-GFP localization in PMID:14769937 and transport work in PMID:19412186 independently support the broad cytoplasmic compartment. The evidence does not warrant choosing a particular cytoplasmic granule. Supporting Evidence: PMID:14769937 hAID-GFP was localized primarily in the cytoplasm PMID:19412186 AID is unable to passively diffuse into the nucleus, despite its small size, and its nuclear entry requires active import mediated by a conformational nuclear localization signal. |
| GO:0005737 cytoplasm | IDA PMID:14769937 Activation-induced cytidine deaminase shuttles between nucle... | ACCEPT | Summary: The cited experiment directly observes cytoplasmic human AID-GFP. Reason: PMID:14769937 uses human AID-GFP in mouse NIH3T3 cells and observes primarily cytoplasmic signal before export inhibition. This is a direct human-protein experiment in a heterologous cell host. Supporting Evidence: PMID:14769937 hAID-GFP was localized primarily in the cytoplasm |
| GO:0005737 cytoplasm | IDA PMID:18722174 Interaction between antibody-diversification enzyme AID and ... | ACCEPT | Summary: Cytoplasmic AID is independently established despite incomplete access to this experiment. Reason: PMID:18722174 is available as an abstract with AID/CTNNBL1 interaction and mutagenesis results; its localization panel was not recovered. Defer to that curator assignment because independent human-AID imaging establishes the same broad location (PMID:14769937). Supporting Evidence: PMID:14769937 hAID-GFP was localized primarily in the cytoplasm |
| GO:0005737 cytoplasm | IEA GO_REF:0000117 | ACCEPT | Summary: The automated cytoplasmic prediction matches experimentally observed distribution. Reason: ARBA00026971 predicates were not independently inspected. The target judgment rests on human-AID imaging and retention/import experiments, not on assumed rule validity (PMID:14769937; PMID:19412186). Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00026971 UNRESOLVED Rule identifier retained. Its predicates were not inspected; independent target biology supports the annotation judgment without certifying the rule internals. Supporting Evidence: PMID:14769937 hAID-GFP was localized primarily in the cytoplasm PMID:19412186 AID is unable to passively diffuse into the nucleus, despite its small size, and its nuclear entry requires active import mediated by a conformational nuclear localization signal. |
| GO:0005829 cytosol | IEA GO_REF:0000044 | ACCEPT | Summary: Cytosolic AID is part of its regulated nucleocytoplasmic distribution. Reason: The UniProt SL-0091 mapping is compatible with the soluble AID pool and its cytoplasmic retention machinery described in PMID:19412186. This more specific database localization does not establish P-body occupancy. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0091 SUPPORTS TRANSFER UniProt subcellular-location vocabulary source; retained at its stated compartment resolution and corroborated by AID localization/transport experiments. Supporting Evidence: PMID:19412186 AID is unable to passively diffuse into the nucleus, despite its small size, and its nuclear entry requires active import mediated by a conformational nuclear localization signal. |
| GO:0008270 zinc ion binding | IEA GO_REF:0000002 | ACCEPT | Summary: Zinc binding supports the catalytic deaminase center. Reason: The InterPro signatures agree with the catalytic zinc-containing AID fold. PMID:10373455 reports inhibition of mouse GST-AID cytidine-deaminase activity by zinc chelation. Independently, PMID:28757211 resolves the zinc-containing active site of engineered human AID constructs. The mouse biochemical result and human structural result support the metal-binding judgment with their distinct experimental scopes. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR013158 SUPPORTS TRANSFER Domain/signature source from the seeded GO mapping. Human AID structural evidence in PMID:28757211 independently establishes the catalytic zinc site; mouse GST-AID chelation in PMID:10373455 is corroborative, not a human biochemical assay. InterPro:IPR016192 SUPPORTS TRANSFER Domain/signature source from the seeded GO mapping. Human AID structural evidence in PMID:28757211 independently establishes the catalytic zinc site; mouse GST-AID chelation in PMID:10373455 is corroborative, not a human biochemical assay. Supporting Evidence: PMID:10373455 In vitro experiments using a glutathione S-transferase AID fusion protein revealed significant cytidine deaminase activity that is blocked by tetrahydrouridine and by zinc chelation. PMID:28757211 The active site is comprised of the catalytic proton-donating residue E58 and the Zn2+ ion coordinated by H56, C87, C90, and usually a fourth ligand, e.g., a water in the dCMP complex or a cacodylic acid from an Apo-AID crystallization condition (Figures 4G and S4G). |
| GO:0016445 somatic diversification of immunoglobulins | IDA PMID:18722174 Interaction between antibody-diversification enzyme AID and ... | ACCEPT | Summary: AID performs the initiating DNA-deamination step of antibody diversification. Reason: PMID:18722174 links AID interaction mutants to reduced hypermutation and class switching; human AICDA deficiency independently removes both processes (PMID:11007475). The product performs the deamination step itself, so this is participation rather than an inference from necessity alone. Supporting Evidence: PMID:18722174 Activation-induced deaminase (AID) deaminates deoxycytidine residues in immunoglobulin genes, triggering antibody diversification. PMID:11007475 Three major abnormalities characterize AID deficiency: (1) the absence of immunoglobulin class switch recombination, (2) the lack of immunoglobulin somatic hypermutations, and (3) lymph node hyperplasia caused by the presence of giant germinal centers. |
| GO:0016445 somatic diversification of immunoglobulins | IEA GO_REF:0000117 | ACCEPT | Summary: The automated immunoglobulin-diversification assignment is biologically correct. Reason: ARBA00088467 internals remain uninspected, but human enzymology and immunodeficiency evidence independently establish the AID-catalyzed initiating step (PMID:12651944; PMID:11007475). Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00088467 UNRESOLVED Rule identifier retained. Its predicates were not inspected; independent target biology supports the annotation judgment without certifying the rule internals. Supporting Evidence: PMID:11007475 Three major abnormalities characterize AID deficiency: (1) the absence of immunoglobulin class switch recombination, (2) the lack of immunoglobulin somatic hypermutations, and (3) lymph node hyperplasia caused by the presence of giant germinal centers. |
| GO:0016446 somatic hypermutation of immunoglobulin genes | IMP PMID:21518874 Histone chaperone Spt6 is required for class switch recombin... | ACCEPT | Summary: AID directly initiates somatic hypermutation. Reason: PMID:21518874 uses AID-dependent mutation assays, including a human BL2 reporter with a C-terminally truncated AID-ER construct; the paper distinguishes Spt6 effects on switching from mutation. Its title is not evidence against AID hypermutation. Human patient/Ramos observations independently establish the native immunoglobulin process (PMID:11007475; PMID:32484799). Supporting Evidence: PMID:21518874 AID knockdown by three different siRNA oligos inhibited loss of GFP fluorescence, as well as the accumulation of point mutations in the GFP gene and cell death PMID:18722174 Activation-induced deaminase (AID) deaminates deoxycytidine residues in immunoglobulin genes, triggering antibody diversification. PMID:11007475 Three major abnormalities characterize AID deficiency: (1) the absence of immunoglobulin class switch recombination, (2) the lack of immunoglobulin somatic hypermutations, and (3) lymph node hyperplasia caused by the presence of giant germinal centers. |
| GO:0016554 cytidine to uridine editing | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: AID can edit encapsidated viral RNA in the reported human-cell model. Reason: PMID:23341589 introduces the unfused expression construct explicitly as human AID and carries that AID/GFP comparison through the nucleocapsid RNA experiments; human and mouse AID-ER are separately identified in a parallel assay. RNA C-to-U changes persist with polymerase/RNase-H controls and are enriched by core immunoprecipitation. This positive target context corroborates the inherited RNA-editing capacity, without establishing an endogenous immunoglobulin RNA substrate or replacing the DNA-deamination mechanism. The complete PAINT IBD chain remains uninspected. The public Results at https://pmc.ncbi.nlm.nih.gov/articles/PMC3568302/ explicitly introduce "a human AID expression vector"; that construct detail was inspected externally and is not present in the local abstract-only record. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000355219 UNRESOLVED Actual PAINT ancestral node. The IBD/tree was not recovered, but independent human-AID HBV RNA-editing experiments in PMID:23341589 corroborate the capacity in a restricted viral context; this does not assert RNA editing as the physiological antibody-diversification mechanism. Supporting Evidence: PMID:23341589 Taken together, the results indicate that AID can deaminate the nucleocapsid RNA of HBV. |
| GO:0016787 hydrolase activity | IEA GO_REF:0000002 | MODIFY | Summary: Direct substrate assays support a more specific cytidine-deaminase term. Reason: Human AID assays in PMID:12651944 measure deamination of free cytidine/deoxycytidine as well as DNA-bound cytosine. Refine this compatible broad InterPro hydrolase assertion to GO:0004126 for the measured free-nucleoside capacity. Live GO places GO:0004126 below both GO:0016814 and GO:0019239; those two parents are siblings, so changing between them would not be a descendant refinement. The DNA-substrate core remains separately represented by generic deaminase MF and the existing DNA-cytosine-deamination process. The public original Results (https://pmc.ncbi.nlm.nih.gov/articles/PMC153055/, Figure 4b) state: "AID is most active when deaminating the free deoxynucleoside, CdR β deoxyuridine"; that externally inspected assay establishes capacity beyond the cached abstract's background statement. The local record is abstract-only. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: InterPro:IPR016192 SUPPORTS TRANSFER Domain/signature source from the seeded GO mapping. Human AID biochemistry independently supports zinc-dependent deamination; signature presence alone is not used to infer an untested substrate. Proposed replacements: cytidine deaminase activity Supporting Evidence: PMID:18722174 Activation-induced deaminase (AID) deaminates deoxycytidine residues in immunoglobulin genes, triggering antibody diversification. PMID:12651944 exhibits deaminase activity on free deoxycytidine in solution |
| GO:0016814 hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amidines | IEA GO_REF:0000002 | MODIFY | Summary: Direct substrate assays support a more specific cytidine-deaminase term. Reason: Human AID assays in PMID:12651944 measure deamination of free cytidine/deoxycytidine as well as DNA-bound cytosine. Refine this compatible broad InterPro hydrolase assertion to GO:0004126 for the measured free-nucleoside capacity. Live GO places GO:0004126 below both GO:0016814 and GO:0019239; those two parents are siblings, so changing between them would not be a descendant refinement. The DNA-substrate core remains separately represented by generic deaminase MF and the existing DNA-cytosine-deamination process. The public original Results (https://pmc.ncbi.nlm.nih.gov/articles/PMC153055/, Figure 4b) state: "AID is most active when deaminating the free deoxynucleoside, CdR β deoxyuridine"; that externally inspected assay establishes capacity beyond the cached abstract's background statement. The local record is abstract-only. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: InterPro:IPR013158 SUPPORTS TRANSFER Domain/signature source from the seeded GO mapping. Human AID biochemistry independently supports zinc-dependent deamination; signature presence alone is not used to infer an untested substrate. Proposed replacements: cytidine deaminase activity Supporting Evidence: PMID:18722174 Activation-induced deaminase (AID) deaminates deoxycytidine residues in immunoglobulin genes, triggering antibody diversification. PMID:12651944 exhibits deaminase activity on free deoxycytidine in solution |
| GO:0030183 B cell differentiation | NAS PMID:11007475 Activation-induced cytidine deaminase (AID) deficiency cause... | KEEP AS NON CORE | Summary: AID-dependent antibody diversification contributes to the terminal B-cell differentiation context. Reason: The human deficiency study reports loss of class switching and somatic hypermutation within B-cell terminal differentiation. AID performs the initiating immunoglobulin-DNA deamination step, so this is positive functional context rather than mere generic metabolic necessity. Retain the broad developmental assertion as non-core; the integrated core already identifies the directly performed antibody-diversification chemistry. Giant germinal centers do not establish that all stages of differentiation are normal, and no such exclusion is inferred. Supporting Evidence: PMID:11007475 Three major abnormalities characterize AID deficiency: (1) the absence of immunoglobulin class switch recombination, (2) the lack of immunoglobulin somatic hypermutations, and (3) lymph node hyperplasia caused by the presence of giant germinal centers. PMID:18722174 Activation-induced deaminase (AID) deaminates deoxycytidine residues in immunoglobulin genes, triggering antibody diversification. |
| GO:0031625 ubiquitin protein ligase binding | IPI PMID:23277564 Solubility-based genetic screen identifies RING finger prote... | KEEP AS NON CORE | Summary: AID binds its regulatory ubiquitin ligase RNF126. Reason: PMID:23277564 identifies and validates RNF126 binding and AID ubiquitylation. This is a specific regulatory enzyme-client interaction; it does not make AID an E3 ligase or a ubiquitination-pathway catalyst. Retain this contextual binding function outside the principal antibody-diversification core. Supporting Evidence: PMID:23277564 We identify a unique cofactor, RING finger protein 126 (RNF126), verify its interaction by traditional techniques, and show that it has functional consequences as RNF126 is able to ubiquitylate AID. |
| GO:0032991 protein-containing complex | IPI PMID:21255825 The RNA exosome targets the AID cytidine deaminase to both s... | KEEP AS NON CORE | Summary: AID associates with transcription-linked RNA-exosome complexes. Reason: PMID:21255825 isolates AID-associated material from human Ramos cells using DNA affinity, size chromatography and affinity purification, with RNA-exosome components detected and functional exosome stimulation of AID deamination. This supports the broad assembly context beyond an isolated co-immunoprecipitation hit. Retain it as non-core without assigning AID a constitutive RNA-exosome core-subunit role. Direct versus indirect contact within this purified functional assembly remains unresolved. Supporting Evidence: PMID:21255825 We used a combination of DNA affinity, size chromatography and affinity purification for isolating AID complexes. PMID:21255825 Together, our findings indicate that AID either directly or indirectly associates with the RNA exosome complex in cells. |
| GO:0033262 regulation of nuclear cell cycle DNA replication | IMP PMID:19734146 Speckled-like pattern in the germinal center (SLIP-GC), a nu... | MARK AS OVER ANNOTATED | Summary: The experiment establishes AID-dependent DNA damage, not a defined replication-control step. Reason: The full PMID:19734146 Results assign replication-factory localization to SLIP-GC and show that AID knockdown suppresses DNA damage and apoptosis caused by SLIP-GC depletion. The authors report no apparent proliferation effect from SLIP-GC reduction. GO:0033262 requires regulation of nuclear cell-cycle DNA replication; the AID-dependent damage phenotype does not identify that regulatory work. Retain the positive toxicity evidence without treating AID as a demonstrated replication regulator. Supporting Evidence: PMID:19734146 Reduction of SLIP-GC levels in the Burkitt lymphoma cell line Raji and in non-Hodgkin lymphoma cell lines resulted in an increase in DNA breaks and apoptosis that was AID-dependent, as simultaneous reduction of AID abrogated the deleterious effects of SLIP-GC reduction. |
| GO:0042802 identical protein binding | IPI PMID:19412186 Active nuclear import and cytoplasmic retention of activatio... | KEEP AS NON CORE | Summary: Human AID self-association is supported, with substrate-dependent assembly scope. Reason: The original PMID:19412186 self-binding panel remains curator-sourced because its full Results were not recovered. Independently read human AID experiments in PMID:28757211 provide positive G4-DNA-dependent oligomerization and interface-mutant evidence. Retain self-association as a contextual supporting property, not a separate core function. The biochemical assays use engineered soluble constructs, while full-length, untagged internal mutants were tested in mouse splenic B-cell class-switching rescue. Neither the existing binding term nor these experiments require a fixed obligatory native homodimer. Supporting Evidence: PMID:28757211 G4 substrates induce cooperative AID oligomerization. |
| GO:0044029 positive regulation of gene expression via chromosomal CpG island demethylation | IDA PMID:21496894 Hydroxylation of 5-methylcytosine by TET1 promotes active DN... | KEEP AS NON CORE | Summary: AID participates in an experimental demethylation pathway under defined expression conditions. Reason: Recovered PMID:21496894 Results show human-ORF AID expression in HEK293 cells enhances demethylation of a hydroxymethylated reporter and reduces TET1-induced 5hmC. Mouse brain AAV expression is distinct from the physiological Tet1/Apobec1 loss-of-function evidence. This supports contextual pathway participation. It does not demonstrate purified AID directly removing the methyl group or establish a general endogenous human CpG-island targeting program; the paper itself leaves the reacting intermediate unresolved. Supporting Evidence: PMID:21496894 demethylation of both exogenously introduced and endogenous 5hmCs is promoted by the AID (activation-induced deaminase)/APOBEC (apolipoprotein B mRNA-editing enzyme complex) family of cytidine deaminases. |
| GO:0045869 negative regulation of single stranded viral RNA replication via double stranded DNA intermediate | IBA GO_REF:0000033 | UNDECIDED | Summary: Retroviral replication restriction is not settled by the recovered AID studies. Reason: The PTN001419581 inference requires the RNA-virus process defined by GO:0045869. Human AID restricts L1 and MusD retrotransposition in PMID:19188259, but mobile-element assays do not automatically establish restriction of infectious RNA-virus replication. The positive HBV studies concern a DNA virus. The ancestral IBD source and appropriate human viral assay remain unresolved; this is not evidence of evolutionary loss. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN001419581 UNRESOLVED Actual ancestral node from the seeded IBA. The IBD experiment/tree placement was not independently recovered; target evidence and the resulting judgment are described in the rationale. No donor-count or circularity argument is made. |
| GO:0051607 defense response to virus | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: AID has experimentally supported antiviral activity in HBV model systems. Reason: PMID:26867650 links AID-dependent deamination to HBV cccDNA degradation. PMID:23341589 independently compares AICDA-proficient and deficient human BL2 cells and shows lower viral nucleocapsid DNA with endogenous AID. These positive target observations support the broad inherited defense process while keeping it contextual and distinct from the unresolved retroviral-specific assertion. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN001419581 UNRESOLVED Actual ancestral node from the seeded IBA. The IBD experiment/tree placement was not independently recovered; target evidence and the resulting judgment are described in the rationale. No donor-count or circularity argument is made. Supporting Evidence: PMID:26867650 This suppression by TGF-Ξ² is abrogated when AID or the activity of uracil-DNA glycosylase (UNG) is absent, which indicates that AID deamination and the UNG-mediated excision of uracil act in concert to degrade viral cccDNA. |
| GO:0070383 DNA cytosine deamination | IBA GO_REF:0000033 | ACCEPT | Summary: DNA cytosine deamination is the central AID reaction. Reason: PTN001419581 inheritance is independently corroborated by purified human AID substrate assays and antibody-diversification studies (PMID:12651944; PMID:18722174). AID creates uracil lesions; downstream repair enzymes perform excision and recombination. The target's own descendant evidence is legitimate grounding for an ancestral assertion. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001419581 UNRESOLVED Actual ancestral node from the seeded IBA. The IBD experiment/tree placement was not independently recovered; target evidence and the resulting judgment are described in the rationale. No donor-count or circularity argument is made. Supporting Evidence: PMID:18722174 Activation-induced deaminase (AID) deaminates deoxycytidine residues in immunoglobulin genes, triggering antibody diversification. |
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Download this section (compressed HTML)Q: Which GO molecular-function term should explicitly represent EC 3.5.4.38 / RHEA:50948 DNA-cytosine deamination? GO:0004126 formally describes free nucleosides, a separately measured AID capacity; GO:0019239 captures the shared deamination chemistry. The existing GO:0070383 DNA cytosine deamination already encodes the DNA specificity on the process side. A specific molecular-function replacement remains unresolved without inventing an ID.
Q: Can the PTN001419581 IBD evidence establish AID P-body localization and infectious retroviral restriction, distinct from cytoplasmic localization, HBV restriction and L1/MusD retrotransposition?
Q: Under which endogenous human conditions does AID edit RNA, beyond the HBV nucleocapsid expression system in PMID:23341589, and what experimental descendants ground the PTN000355219 ancestral RNA-editing assertion?
Q: Which endogenous human contexts reproduce the AID-dependent demethylation phenotype, and which modified base or intermediate is directly deaminated? The positive human-cell reporter result does not settle the reacting intermediate.
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