ALKBH3 (AlkB homolog 3, also ABH3 or DEPC1) is an Fe(II)- and 2-oxoglutarate-dependent dioxygenase of the AlkB family that directly reverses alkylation damage to nucleic acids. It oxidizes the methyl groups of 1-methyladenine and 3-methylcytosine, releasing them as formaldehyde and regenerating the normal base, and it prefers single-stranded DNA and RNA. In the nucleus it works with the ASCC complex, whose ASCC3 helicase unwinds DNA to expose lesions for ALKBH3, and some tumor cell lines depend on this pathway for resistance to alkylating agents. Unlike ALKBH2, ALKBH3 also repairs methylated RNA and removes N1-methyladenosine from mRNA and tRNA, making it one of the erasers of this modification. It is found in both nucleus and cytoplasm and is overexpressed in several cancers.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005515 protein binding | IPI PMID:22055184 DNA unwinding by ASCC3 helicase is coupled to ALKBH3-depende... | MODIFY | Summary: Binding to ASCC3, the helicase subunit of the ASCC complex with which ALKBH3 co-purifies. Modified to protein-containing complex binding. Reason: The paper purifies ALKBH3 with the whole ASCC complex [PMID:22055184 "We report the purification of the ALKBH3 complex and demonstrate its association with the activating signal cointegrator complex (ASCC)."] and shows the two act together: the ASCC3 helicase generates the single-stranded DNA that ALKBH3 repairs [PMID:22055184 "ASCC3, the largest subunit of ASCC, encodes a 3'-5' DNA helicase, whose activity is crucial for the generation of single-stranded DNA upon which ALKBH3 preferentially functions for dealkylation."]. The informative statement is association with the ASCC complex, GO:0044877 protein-containing complex binding. Per the project's GO:0005515 policy the generic term is replaced by an informative one where the evidence supports it, and removed otherwise; removal is not a claim that the interaction is false. Proposed replacements: protein-containing complex binding Supporting Evidence: PMID:22055184 We report the purification of the ALKBH3 complex and demonstrate its association with the activating signal cointegrator complex (ASCC). PMID:22055184 ASCC3, the largest subunit of ASCC, encodes a 3'-5' DNA helicase, whose activity is crucial for the generation of single-stranded DNA upon which ALKBH3 preferentially functions for dealkylation. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Generic protein binding with GLRX3, from HI-II-14, a proteome-scale yeast two-hybrid map. Uninformative as a function statement; removed. Reason: A screen [PMID:25416956 "A proteome-scale map of the human interactome network."] rather than a study of ALKBH3, and nothing in it supports a more specific molecular function. Per the project's GO:0005515 policy the generic term is replaced by an informative one where the evidence supports it, and removed otherwise; removal is not a claim that the interaction is false. Supporting Evidence: PMID:25416956 A proteome-scale map of the human interactome network. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Generic protein binding with GOLGA2, from HI-II-14, a proteome-scale yeast two-hybrid map. Uninformative as a function statement; removed. Reason: A screen [PMID:25416956 "A proteome-scale map of the human interactome network."] rather than a study of ALKBH3, and nothing in it supports a more specific molecular function. Per the project's GO:0005515 policy the generic term is replaced by an informative one where the evidence supports it, and removed otherwise; removal is not a claim that the interaction is false. Supporting Evidence: PMID:25416956 A proteome-scale map of the human interactome network. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Generic protein binding with IKZF1, from HI-II-14, a proteome-scale yeast two-hybrid map. Uninformative as a function statement; removed. Reason: A screen [PMID:25416956 "A proteome-scale map of the human interactome network."] rather than a study of ALKBH3, and nothing in it supports a more specific molecular function. Per the project's GO:0005515 policy the generic term is replaced by an informative one where the evidence supports it, and removed otherwise; removal is not a claim that the interaction is false. Supporting Evidence: PMID:25416956 A proteome-scale map of the human interactome network. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Generic protein binding with LNX1, from HI-II-14, a proteome-scale yeast two-hybrid map. Uninformative as a function statement; removed. Reason: A screen [PMID:25416956 "A proteome-scale map of the human interactome network."] rather than a study of ALKBH3, and nothing in it supports a more specific molecular function. Per the project's GO:0005515 policy the generic term is replaced by an informative one where the evidence supports it, and removed otherwise; removal is not a claim that the interaction is false. Supporting Evidence: PMID:25416956 A proteome-scale map of the human interactome network. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Generic protein binding with AK8, from HI-II-14, a proteome-scale yeast two-hybrid map. Uninformative as a function statement; removed. Reason: A screen [PMID:25416956 "A proteome-scale map of the human interactome network."] rather than a study of ALKBH3, and nothing in it supports a more specific molecular function. Per the project's GO:0005515 policy the generic term is replaced by an informative one where the evidence supports it, and removed otherwise; removal is not a claim that the interaction is false. Supporting Evidence: PMID:25416956 A proteome-scale map of the human interactome network. |
| GO:0005515 protein binding | IPI PMID:29892012 An interactome perturbation framework prioritizes damaging m... | REMOVE | Summary: Generic protein binding with GOLGA2, from a yeast two-hybrid missense-variant screen. Uninformative as a function statement; removed. Reason: A screen [PMID:29892012 "An interactome perturbation framework prioritizes damaging missense mutations"] rather than a study of ALKBH3, and nothing in it supports a more specific molecular function. Per the project's GO:0005515 policy the generic term is replaced by an informative one where the evidence supports it, and removed otherwise; removal is not a claim that the interaction is false. Supporting Evidence: PMID:29892012 An interactome perturbation framework prioritizes damaging missense mutations |
| GO:0005515 protein binding | IPI PMID:29892012 An interactome perturbation framework prioritizes damaging m... | REMOVE | Summary: Generic protein binding with IKZF1, from a yeast two-hybrid missense-variant screen. Uninformative as a function statement; removed. Reason: A screen [PMID:29892012 "An interactome perturbation framework prioritizes damaging missense mutations"] rather than a study of ALKBH3, and nothing in it supports a more specific molecular function. Per the project's GO:0005515 policy the generic term is replaced by an informative one where the evidence supports it, and removed otherwise; removal is not a claim that the interaction is false. Supporting Evidence: PMID:29892012 An interactome perturbation framework prioritizes damaging missense mutations |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | REMOVE | Summary: Generic protein binding with GOLGA2, from a yeast two-hybrid variant-perturbation screen. Uninformative as a function statement; removed. Reason: A screen [PMID:31515488 "Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations."] rather than a study of ALKBH3, and nothing in it supports a more specific molecular function. Per the project's GO:0005515 policy the generic term is replaced by an informative one where the evidence supports it, and removed otherwise; removal is not a claim that the interaction is false. Supporting Evidence: PMID:31515488 Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | REMOVE | Summary: Generic protein binding with IKZF1, from a yeast two-hybrid variant-perturbation screen. Uninformative as a function statement; removed. Reason: A screen [PMID:31515488 "Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations."] rather than a study of ALKBH3, and nothing in it supports a more specific molecular function. Per the project's GO:0005515 policy the generic term is replaced by an informative one where the evidence supports it, and removed otherwise; removal is not a claim that the interaction is false. Supporting Evidence: PMID:31515488 Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations. |
| GO:0005634 nucleus | EXP PMID:12486230 Reversal of DNA alkylation damage by two human dioxygenases. | ACCEPT | Summary: Nucleus/nucleoplasm, where ALKBH3 repairs alkylated DNA with the ASCC complex. Accepted. Reason: Tagged ALKBH3 is in both nucleus and cytoplasm [PMID:17979886 "EmGFP-hABH1, 3, 4, 6 and 7 were localized in both the cytoplasm and nuclei."]; its DNA-repair work is nuclear, alongside the ASCC helicase [PMID:29144457 "Previous studies established that the dealkylating enzyme, ALKBH3, functions in concert with the ASCC helicase complex"]. Supporting Evidence: PMID:17979886 EmGFP-hABH1, 3, 4, 6 and 7 were localized in both the cytoplasm and nuclei. PMID:29144457 Previous studies established that the dealkylating enzyme, ALKBH3, functions in concert with the ASCC helicase complex |
| GO:0005634 nucleus | EXP PMID:12594517 Human and bacterial oxidative demethylases repair alkylation... | ACCEPT | Summary: Nucleus/nucleoplasm, where ALKBH3 repairs alkylated DNA with the ASCC complex. Accepted. Reason: Tagged ALKBH3 is in both nucleus and cytoplasm [PMID:17979886 "EmGFP-hABH1, 3, 4, 6 and 7 were localized in both the cytoplasm and nuclei."]; its DNA-repair work is nuclear, alongside the ASCC helicase [PMID:29144457 "Previous studies established that the dealkylating enzyme, ALKBH3, functions in concert with the ASCC helicase complex"]. Supporting Evidence: PMID:17979886 EmGFP-hABH1, 3, 4, 6 and 7 were localized in both the cytoplasm and nuclei. PMID:29144457 Previous studies established that the dealkylating enzyme, ALKBH3, functions in concert with the ASCC helicase complex |
| GO:0005634 nucleus | EXP PMID:17979886 Expression and sub-cellular localization of human ABH family... | ACCEPT | Summary: Nucleus/nucleoplasm, where ALKBH3 repairs alkylated DNA with the ASCC complex. Accepted. Reason: Tagged ALKBH3 is in both nucleus and cytoplasm [PMID:17979886 "EmGFP-hABH1, 3, 4, 6 and 7 were localized in both the cytoplasm and nuclei."]; its DNA-repair work is nuclear, alongside the ASCC helicase [PMID:29144457 "Previous studies established that the dealkylating enzyme, ALKBH3, functions in concert with the ASCC helicase complex"]. Supporting Evidence: PMID:17979886 EmGFP-hABH1, 3, 4, 6 and 7 were localized in both the cytoplasm and nuclei. PMID:29144457 Previous studies established that the dealkylating enzyme, ALKBH3, functions in concert with the ASCC helicase complex |
| GO:0005634 nucleus | EXP PMID:29144457 A ubiquitin-dependent signalling axis specific for ALKBH-med... | ACCEPT | Summary: Nucleus/nucleoplasm, where ALKBH3 repairs alkylated DNA with the ASCC complex. Accepted. Reason: Tagged ALKBH3 is in both nucleus and cytoplasm [PMID:17979886 "EmGFP-hABH1, 3, 4, 6 and 7 were localized in both the cytoplasm and nuclei."]; its DNA-repair work is nuclear, alongside the ASCC helicase [PMID:29144457 "Previous studies established that the dealkylating enzyme, ALKBH3, functions in concert with the ASCC helicase complex"]. Supporting Evidence: PMID:17979886 EmGFP-hABH1, 3, 4, 6 and 7 were localized in both the cytoplasm and nuclei. PMID:29144457 Previous studies established that the dealkylating enzyme, ALKBH3, functions in concert with the ASCC helicase complex |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: Nucleus/nucleoplasm, where ALKBH3 repairs alkylated DNA with the ASCC complex. Accepted. Reason: Tagged ALKBH3 is in both nucleus and cytoplasm [PMID:17979886 "EmGFP-hABH1, 3, 4, 6 and 7 were localized in both the cytoplasm and nuclei."]; its DNA-repair work is nuclear, alongside the ASCC helicase [PMID:29144457 "Previous studies established that the dealkylating enzyme, ALKBH3, functions in concert with the ASCC helicase complex"]. Supporting Evidence: PMID:17979886 EmGFP-hABH1, 3, 4, 6 and 7 were localized in both the cytoplasm and nuclei. PMID:29144457 Previous studies established that the dealkylating enzyme, ALKBH3, functions in concert with the ASCC helicase complex |
| GO:0005654 nucleoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Nucleus/nucleoplasm, where ALKBH3 repairs alkylated DNA with the ASCC complex. Accepted. Reason: Tagged ALKBH3 is in both nucleus and cytoplasm [PMID:17979886 "EmGFP-hABH1, 3, 4, 6 and 7 were localized in both the cytoplasm and nuclei."]; its DNA-repair work is nuclear, alongside the ASCC helicase [PMID:29144457 "Previous studies established that the dealkylating enzyme, ALKBH3, functions in concert with the ASCC helicase complex"]. Supporting Evidence: PMID:17979886 EmGFP-hABH1, 3, 4, 6 and 7 were localized in both the cytoplasm and nuclei. PMID:29144457 Previous studies established that the dealkylating enzyme, ALKBH3, functions in concert with the ASCC helicase complex |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Nucleus/nucleoplasm, where ALKBH3 repairs alkylated DNA with the ASCC complex. Accepted. Reason: Tagged ALKBH3 is in both nucleus and cytoplasm [PMID:17979886 "EmGFP-hABH1, 3, 4, 6 and 7 were localized in both the cytoplasm and nuclei."]; its DNA-repair work is nuclear, alongside the ASCC helicase [PMID:29144457 "Previous studies established that the dealkylating enzyme, ALKBH3, functions in concert with the ASCC helicase complex"]. Supporting Evidence: PMID:17979886 EmGFP-hABH1, 3, 4, 6 and 7 were localized in both the cytoplasm and nuclei. PMID:29144457 Previous studies established that the dealkylating enzyme, ALKBH3, functions in concert with the ASCC helicase complex |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-112123 | ACCEPT | Summary: Nucleus/nucleoplasm, where ALKBH3 repairs alkylated DNA with the ASCC complex. Accepted. Reason: Tagged ALKBH3 is in both nucleus and cytoplasm [PMID:17979886 "EmGFP-hABH1, 3, 4, 6 and 7 were localized in both the cytoplasm and nuclei."]; its DNA-repair work is nuclear, alongside the ASCC helicase [PMID:29144457 "Previous studies established that the dealkylating enzyme, ALKBH3, functions in concert with the ASCC helicase complex"]. Supporting Evidence: PMID:17979886 EmGFP-hABH1, 3, 4, 6 and 7 were localized in both the cytoplasm and nuclei. PMID:29144457 Previous studies established that the dealkylating enzyme, ALKBH3, functions in concert with the ASCC helicase complex |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-112124 | ACCEPT | Summary: Nucleus/nucleoplasm, where ALKBH3 repairs alkylated DNA with the ASCC complex. Accepted. Reason: Tagged ALKBH3 is in both nucleus and cytoplasm [PMID:17979886 "EmGFP-hABH1, 3, 4, 6 and 7 were localized in both the cytoplasm and nuclei."]; its DNA-repair work is nuclear, alongside the ASCC helicase [PMID:29144457 "Previous studies established that the dealkylating enzyme, ALKBH3, functions in concert with the ASCC helicase complex"]. Supporting Evidence: PMID:17979886 EmGFP-hABH1, 3, 4, 6 and 7 were localized in both the cytoplasm and nuclei. PMID:29144457 Previous studies established that the dealkylating enzyme, ALKBH3, functions in concert with the ASCC helicase complex |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-112125 | ACCEPT | Summary: Nucleus/nucleoplasm, where ALKBH3 repairs alkylated DNA with the ASCC complex. Accepted. Reason: Tagged ALKBH3 is in both nucleus and cytoplasm [PMID:17979886 "EmGFP-hABH1, 3, 4, 6 and 7 were localized in both the cytoplasm and nuclei."]; its DNA-repair work is nuclear, alongside the ASCC helicase [PMID:29144457 "Previous studies established that the dealkylating enzyme, ALKBH3, functions in concert with the ASCC helicase complex"]. Supporting Evidence: PMID:17979886 EmGFP-hABH1, 3, 4, 6 and 7 were localized in both the cytoplasm and nuclei. PMID:29144457 Previous studies established that the dealkylating enzyme, ALKBH3, functions in concert with the ASCC helicase complex |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5657617 | ACCEPT | Summary: Nucleus/nucleoplasm, where ALKBH3 repairs alkylated DNA with the ASCC complex. Accepted. Reason: Tagged ALKBH3 is in both nucleus and cytoplasm [PMID:17979886 "EmGFP-hABH1, 3, 4, 6 and 7 were localized in both the cytoplasm and nuclei."]; its DNA-repair work is nuclear, alongside the ASCC helicase [PMID:29144457 "Previous studies established that the dealkylating enzyme, ALKBH3, functions in concert with the ASCC helicase complex"]. Supporting Evidence: PMID:17979886 EmGFP-hABH1, 3, 4, 6 and 7 were localized in both the cytoplasm and nuclei. PMID:29144457 Previous studies established that the dealkylating enzyme, ALKBH3, functions in concert with the ASCC helicase complex |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5657637 | ACCEPT | Summary: Nucleus/nucleoplasm, where ALKBH3 repairs alkylated DNA with the ASCC complex. Accepted. Reason: Tagged ALKBH3 is in both nucleus and cytoplasm [PMID:17979886 "EmGFP-hABH1, 3, 4, 6 and 7 were localized in both the cytoplasm and nuclei."]; its DNA-repair work is nuclear, alongside the ASCC helicase [PMID:29144457 "Previous studies established that the dealkylating enzyme, ALKBH3, functions in concert with the ASCC helicase complex"]. Supporting Evidence: PMID:17979886 EmGFP-hABH1, 3, 4, 6 and 7 were localized in both the cytoplasm and nuclei. PMID:29144457 Previous studies established that the dealkylating enzyme, ALKBH3, functions in concert with the ASCC helicase complex |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5657642 | ACCEPT | Summary: Nucleus/nucleoplasm, where ALKBH3 repairs alkylated DNA with the ASCC complex. Accepted. Reason: Tagged ALKBH3 is in both nucleus and cytoplasm [PMID:17979886 "EmGFP-hABH1, 3, 4, 6 and 7 were localized in both the cytoplasm and nuclei."]; its DNA-repair work is nuclear, alongside the ASCC helicase [PMID:29144457 "Previous studies established that the dealkylating enzyme, ALKBH3, functions in concert with the ASCC helicase complex"]. Supporting Evidence: PMID:17979886 EmGFP-hABH1, 3, 4, 6 and 7 were localized in both the cytoplasm and nuclei. PMID:29144457 Previous studies established that the dealkylating enzyme, ALKBH3, functions in concert with the ASCC helicase complex |
| GO:0005737 cytoplasm | EXP PMID:12486230 Reversal of DNA alkylation damage by two human dioxygenases. | ACCEPT | Summary: Cytoplasm. ALKBH3 is nucleocytoplasmic, and its RNA substrates include cytoplasmic mRNA; accepted. Reason: Tagged ALKBH3 is in both nucleus and cytoplasm [PMID:17979886 "EmGFP-hABH1, 3, 4, 6 and 7 were localized in both the cytoplasm and nuclei."], consistent with its activity on mRNA [PMID:26863196 "overexpression of wild-type ALKBH3, but not of an inactive mutant, reduced m1A levels in mRNA"]. Supporting Evidence: PMID:17979886 EmGFP-hABH1, 3, 4, 6 and 7 were localized in both the cytoplasm and nuclei. PMID:26863196 overexpression of wild-type ALKBH3, but not of an inactive mutant, reduced m1A levels in mRNA |
| GO:0005737 cytoplasm | EXP PMID:12594517 Human and bacterial oxidative demethylases repair alkylation... | ACCEPT | Summary: Cytoplasm. ALKBH3 is nucleocytoplasmic, and its RNA substrates include cytoplasmic mRNA; accepted. Reason: Tagged ALKBH3 is in both nucleus and cytoplasm [PMID:17979886 "EmGFP-hABH1, 3, 4, 6 and 7 were localized in both the cytoplasm and nuclei."], consistent with its activity on mRNA [PMID:26863196 "overexpression of wild-type ALKBH3, but not of an inactive mutant, reduced m1A levels in mRNA"]. Supporting Evidence: PMID:17979886 EmGFP-hABH1, 3, 4, 6 and 7 were localized in both the cytoplasm and nuclei. PMID:26863196 overexpression of wild-type ALKBH3, but not of an inactive mutant, reduced m1A levels in mRNA |
| GO:0005737 cytoplasm | EXP PMID:17979886 Expression and sub-cellular localization of human ABH family... | ACCEPT | Summary: Cytoplasm. ALKBH3 is nucleocytoplasmic, and its RNA substrates include cytoplasmic mRNA; accepted. Reason: Tagged ALKBH3 is in both nucleus and cytoplasm [PMID:17979886 "EmGFP-hABH1, 3, 4, 6 and 7 were localized in both the cytoplasm and nuclei."], consistent with its activity on mRNA [PMID:26863196 "overexpression of wild-type ALKBH3, but not of an inactive mutant, reduced m1A levels in mRNA"]. Supporting Evidence: PMID:17979886 EmGFP-hABH1, 3, 4, 6 and 7 were localized in both the cytoplasm and nuclei. PMID:26863196 overexpression of wild-type ALKBH3, but not of an inactive mutant, reduced m1A levels in mRNA |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoplasm. ALKBH3 is nucleocytoplasmic, and its RNA substrates include cytoplasmic mRNA; accepted. Reason: Tagged ALKBH3 is in both nucleus and cytoplasm [PMID:17979886 "EmGFP-hABH1, 3, 4, 6 and 7 were localized in both the cytoplasm and nuclei."], consistent with its activity on mRNA [PMID:26863196 "overexpression of wild-type ALKBH3, but not of an inactive mutant, reduced m1A levels in mRNA"]. Supporting Evidence: PMID:17979886 EmGFP-hABH1, 3, 4, 6 and 7 were localized in both the cytoplasm and nuclei. PMID:26863196 overexpression of wild-type ALKBH3, but not of an inactive mutant, reduced m1A levels in mRNA |
| GO:0006281 DNA repair | IBA GO_REF:0000033 | ACCEPT | Summary: DNA repair, the correct parent of the DNA alkylation repair rows (GO:0006307) the gene also carries. Accepted. Reason: ALKBH3 directly reverses m1A and m3C in DNA [PMID:12486230 "Both enzymes remove 1-methyladenine and 3-methylcytosine from methylated polynucleotides in an alpha-ketoglutarate-dependent reaction, and act by direct damage reversal with the regeneration of the unsubstituted bases."], preferring single-stranded substrates [PMID:12594517 "Whereas AlkB and hABH3 prefer single-stranded nucleic acids, hABH2 acts more efficiently on double-stranded DNA."], with the iron centre of a 2OG-dependent dioxygenase [PMID:16858410 "The hABH3 structure reveals the beta-strand jelly-roll fold that coordinates a catalytically active iron centre by a conserved His1-X-Asp/Glu-X(n)-His2 motif."]. In cells it works with the ASCC complex, whose ASCC3 helicase exposes single-stranded DNA for it [PMID:22055184 "ASCC3, the largest subunit of ASCC, encodes a 3'-5' DNA helicase, whose activity is crucial for the generation of single-stranded DNA upon which ALKBH3 preferentially functions for dealkylation."]. Supporting Evidence: PMID:12486230 Both enzymes remove 1-methyladenine and 3-methylcytosine from methylated polynucleotides in an alpha-ketoglutarate-dependent reaction, and act by direct damage reversal with the regeneration of the unsubstituted bases. PMID:12594517 Whereas AlkB and hABH3 prefer single-stranded nucleic acids, hABH2 acts more efficiently on double-stranded DNA. PMID:16858410 The hABH3 structure reveals the beta-strand jelly-roll fold that coordinates a catalytically active iron centre by a conserved His1-X-Asp/Glu-X(n)-His2 motif. file:genes/human/ALKBH3/ALKBH3-deep-research-affinage.md ALKBH3 is a single-stranded nucleic acid demethylase that reverses N1-methyladenine/N1-methyladenosine (m1A) and N3-methylcytosine/N3-methylcytidine (m3C) lesions in both DNA and RNA PMID:22055184 ASCC3, the largest subunit of ASCC, encodes a 3'-5' DNA helicase, whose activity is crucial for the generation of single-stranded DNA upon which ALKBH3 preferentially functions for dealkylation. |
| GO:0006281 DNA repair | IEA GO_REF:0000002 | ACCEPT | Summary: DNA repair, the correct parent of the DNA alkylation repair rows (GO:0006307) the gene also carries. Accepted. Reason: ALKBH3 directly reverses m1A and m3C in DNA [PMID:12486230 "Both enzymes remove 1-methyladenine and 3-methylcytosine from methylated polynucleotides in an alpha-ketoglutarate-dependent reaction, and act by direct damage reversal with the regeneration of the unsubstituted bases."], preferring single-stranded substrates [PMID:12594517 "Whereas AlkB and hABH3 prefer single-stranded nucleic acids, hABH2 acts more efficiently on double-stranded DNA."], with the iron centre of a 2OG-dependent dioxygenase [PMID:16858410 "The hABH3 structure reveals the beta-strand jelly-roll fold that coordinates a catalytically active iron centre by a conserved His1-X-Asp/Glu-X(n)-His2 motif."]. In cells it works with the ASCC complex, whose ASCC3 helicase exposes single-stranded DNA for it [PMID:22055184 "ASCC3, the largest subunit of ASCC, encodes a 3'-5' DNA helicase, whose activity is crucial for the generation of single-stranded DNA upon which ALKBH3 preferentially functions for dealkylation."]. Supporting Evidence: PMID:12486230 Both enzymes remove 1-methyladenine and 3-methylcytosine from methylated polynucleotides in an alpha-ketoglutarate-dependent reaction, and act by direct damage reversal with the regeneration of the unsubstituted bases. PMID:12594517 Whereas AlkB and hABH3 prefer single-stranded nucleic acids, hABH2 acts more efficiently on double-stranded DNA. PMID:16858410 The hABH3 structure reveals the beta-strand jelly-roll fold that coordinates a catalytically active iron centre by a conserved His1-X-Asp/Glu-X(n)-His2 motif. file:genes/human/ALKBH3/ALKBH3-deep-research-affinage.md ALKBH3 is a single-stranded nucleic acid demethylase that reverses N1-methyladenine/N1-methyladenosine (m1A) and N3-methylcytosine/N3-methylcytidine (m3C) lesions in both DNA and RNA PMID:22055184 ASCC3, the largest subunit of ASCC, encodes a 3'-5' DNA helicase, whose activity is crucial for the generation of single-stranded DNA upon which ALKBH3 preferentially functions for dealkylation. |
| GO:0006307 DNA alkylation repair | IDA PMID:20714506 Mechanistic insight into the recognition of single-stranded ... | ACCEPT | Summary: DNA alkylation repair by direct reversal of methylated bases. Core process; accepted. Reason: ALKBH3 directly reverses m1A and m3C in DNA [PMID:12486230 "Both enzymes remove 1-methyladenine and 3-methylcytosine from methylated polynucleotides in an alpha-ketoglutarate-dependent reaction, and act by direct damage reversal with the regeneration of the unsubstituted bases."], preferring single-stranded substrates [PMID:12594517 "Whereas AlkB and hABH3 prefer single-stranded nucleic acids, hABH2 acts more efficiently on double-stranded DNA."], with the iron centre of a 2OG-dependent dioxygenase [PMID:16858410 "The hABH3 structure reveals the beta-strand jelly-roll fold that coordinates a catalytically active iron centre by a conserved His1-X-Asp/Glu-X(n)-His2 motif."]. In cells it works with the ASCC complex, whose ASCC3 helicase exposes single-stranded DNA for it [PMID:22055184 "ASCC3, the largest subunit of ASCC, encodes a 3'-5' DNA helicase, whose activity is crucial for the generation of single-stranded DNA upon which ALKBH3 preferentially functions for dealkylation."]. Supporting Evidence: PMID:12486230 Both enzymes remove 1-methyladenine and 3-methylcytosine from methylated polynucleotides in an alpha-ketoglutarate-dependent reaction, and act by direct damage reversal with the regeneration of the unsubstituted bases. PMID:12594517 Whereas AlkB and hABH3 prefer single-stranded nucleic acids, hABH2 acts more efficiently on double-stranded DNA. PMID:16858410 The hABH3 structure reveals the beta-strand jelly-roll fold that coordinates a catalytically active iron centre by a conserved His1-X-Asp/Glu-X(n)-His2 motif. file:genes/human/ALKBH3/ALKBH3-deep-research-affinage.md ALKBH3 is a single-stranded nucleic acid demethylase that reverses N1-methyladenine/N1-methyladenosine (m1A) and N3-methylcytosine/N3-methylcytidine (m3C) lesions in both DNA and RNA PMID:22055184 ASCC3, the largest subunit of ASCC, encodes a 3'-5' DNA helicase, whose activity is crucial for the generation of single-stranded DNA upon which ALKBH3 preferentially functions for dealkylation. |
| GO:0006307 DNA alkylation repair | IDA PMID:22055184 DNA unwinding by ASCC3 helicase is coupled to ALKBH3-depende... | ACCEPT | Summary: DNA alkylation repair by direct reversal of methylated bases. Core process; accepted. Reason: ALKBH3 directly reverses m1A and m3C in DNA [PMID:12486230 "Both enzymes remove 1-methyladenine and 3-methylcytosine from methylated polynucleotides in an alpha-ketoglutarate-dependent reaction, and act by direct damage reversal with the regeneration of the unsubstituted bases."], preferring single-stranded substrates [PMID:12594517 "Whereas AlkB and hABH3 prefer single-stranded nucleic acids, hABH2 acts more efficiently on double-stranded DNA."], with the iron centre of a 2OG-dependent dioxygenase [PMID:16858410 "The hABH3 structure reveals the beta-strand jelly-roll fold that coordinates a catalytically active iron centre by a conserved His1-X-Asp/Glu-X(n)-His2 motif."]. In cells it works with the ASCC complex, whose ASCC3 helicase exposes single-stranded DNA for it [PMID:22055184 "ASCC3, the largest subunit of ASCC, encodes a 3'-5' DNA helicase, whose activity is crucial for the generation of single-stranded DNA upon which ALKBH3 preferentially functions for dealkylation."]. Supporting Evidence: PMID:12486230 Both enzymes remove 1-methyladenine and 3-methylcytosine from methylated polynucleotides in an alpha-ketoglutarate-dependent reaction, and act by direct damage reversal with the regeneration of the unsubstituted bases. PMID:12594517 Whereas AlkB and hABH3 prefer single-stranded nucleic acids, hABH2 acts more efficiently on double-stranded DNA. PMID:16858410 The hABH3 structure reveals the beta-strand jelly-roll fold that coordinates a catalytically active iron centre by a conserved His1-X-Asp/Glu-X(n)-His2 motif. file:genes/human/ALKBH3/ALKBH3-deep-research-affinage.md ALKBH3 is a single-stranded nucleic acid demethylase that reverses N1-methyladenine/N1-methyladenosine (m1A) and N3-methylcytosine/N3-methylcytidine (m3C) lesions in both DNA and RNA PMID:22055184 ASCC3, the largest subunit of ASCC, encodes a 3'-5' DNA helicase, whose activity is crucial for the generation of single-stranded DNA upon which ALKBH3 preferentially functions for dealkylation. |
| GO:0006307 DNA alkylation repair | IEA GO_REF:0000002 | ACCEPT | Summary: DNA alkylation repair by direct reversal of methylated bases. Core process; accepted. Reason: ALKBH3 directly reverses m1A and m3C in DNA [PMID:12486230 "Both enzymes remove 1-methyladenine and 3-methylcytosine from methylated polynucleotides in an alpha-ketoglutarate-dependent reaction, and act by direct damage reversal with the regeneration of the unsubstituted bases."], preferring single-stranded substrates [PMID:12594517 "Whereas AlkB and hABH3 prefer single-stranded nucleic acids, hABH2 acts more efficiently on double-stranded DNA."], with the iron centre of a 2OG-dependent dioxygenase [PMID:16858410 "The hABH3 structure reveals the beta-strand jelly-roll fold that coordinates a catalytically active iron centre by a conserved His1-X-Asp/Glu-X(n)-His2 motif."]. In cells it works with the ASCC complex, whose ASCC3 helicase exposes single-stranded DNA for it [PMID:22055184 "ASCC3, the largest subunit of ASCC, encodes a 3'-5' DNA helicase, whose activity is crucial for the generation of single-stranded DNA upon which ALKBH3 preferentially functions for dealkylation."]. Supporting Evidence: PMID:12486230 Both enzymes remove 1-methyladenine and 3-methylcytosine from methylated polynucleotides in an alpha-ketoglutarate-dependent reaction, and act by direct damage reversal with the regeneration of the unsubstituted bases. PMID:12594517 Whereas AlkB and hABH3 prefer single-stranded nucleic acids, hABH2 acts more efficiently on double-stranded DNA. PMID:16858410 The hABH3 structure reveals the beta-strand jelly-roll fold that coordinates a catalytically active iron centre by a conserved His1-X-Asp/Glu-X(n)-His2 motif. file:genes/human/ALKBH3/ALKBH3-deep-research-affinage.md ALKBH3 is a single-stranded nucleic acid demethylase that reverses N1-methyladenine/N1-methyladenosine (m1A) and N3-methylcytosine/N3-methylcytidine (m3C) lesions in both DNA and RNA PMID:22055184 ASCC3, the largest subunit of ASCC, encodes a 3'-5' DNA helicase, whose activity is crucial for the generation of single-stranded DNA upon which ALKBH3 preferentially functions for dealkylation. |
| GO:0008198 ferrous iron binding | IDA PMID:16858410 Human ABH3 structure and key residues for oxidative demethyl... | ACCEPT | Summary: Ferrous iron binding: the crystal structure shows the catalytic Fe(II) centre. Accepted as the cofactor-binding activity of the dioxygenase. Reason: [PMID:16858410 "The hABH3 structure reveals the beta-strand jelly-roll fold that coordinates a catalytically active iron centre by a conserved His1-X-Asp/Glu-X(n)-His2 motif."] Supporting Evidence: PMID:16858410 The hABH3 structure reveals the beta-strand jelly-roll fold that coordinates a catalytically active iron centre by a conserved His1-X-Asp/Glu-X(n)-His2 motif. |
| GO:0008283 cell population proliferation | IMP PMID:22055184 DNA unwinding by ASCC3 helicase is coupled to ALKBH3-depende... | KEEP AS NON CORE | Summary: Cell population proliferation: losing ALKBH3 reduces proliferation of tumor lines that depend on it. A consequence of unrepaired alkylation damage; kept as non-core. Reason: [PMID:22055184 "loss of ALKBH3 or ASCC3 leads to increased 3-methylcytosine and reduced cell proliferation"] The proliferation defect is cell-type specific and follows from accumulated 3-methylcytosine, so it is retained as a consequence, not a core process. Supporting Evidence: PMID:22055184 loss of ALKBH3 or ASCC3 leads to increased 3-methylcytosine and reduced cell proliferation |
| GO:0035515 oxidative RNA demethylase activity | IDA PMID:16174769 Repair of methylation damage in DNA and RNA by mammalian Alk... | ACCEPT | Summary: Oxidative RNA demethylase activity. ALKBH3 repairs methylated RNA as well as DNA; accepted. Reason: ALKBH3, unlike ALKBH2, also demethylates RNA [PMID:12594517 "AlkB and hABH3, but not hABH2, also repair RNA"], including m1A in mRNA [PMID:26863410 "Moreover, m(1)A in mRNA is reversible by ALKBH3, a known DNA/RNA demethylase."], [PMID:26863196 "overexpression of wild-type ALKBH3, but not of an inactive mutant, reduced m1A levels in mRNA"]. Supporting Evidence: PMID:12594517 AlkB and hABH3, but not hABH2, also repair RNA PMID:26863410 Moreover, m(1)A in mRNA is reversible by ALKBH3, a known DNA/RNA demethylase. PMID:26863196 overexpression of wild-type ALKBH3, but not of an inactive mutant, reduced m1A levels in mRNA PMID:16174769 The mAbh2 and mAbh3 release modified bases from both DNA and RNA. |
| GO:0035515 oxidative RNA demethylase activity | IEA GO_REF:0000117 | ACCEPT | Summary: Oxidative RNA demethylase activity. ALKBH3 repairs methylated RNA as well as DNA; accepted. Reason: ALKBH3, unlike ALKBH2, also demethylates RNA [PMID:12594517 "AlkB and hABH3, but not hABH2, also repair RNA"], including m1A in mRNA [PMID:26863410 "Moreover, m(1)A in mRNA is reversible by ALKBH3, a known DNA/RNA demethylase."], [PMID:26863196 "overexpression of wild-type ALKBH3, but not of an inactive mutant, reduced m1A levels in mRNA"]. Supporting Evidence: PMID:12594517 AlkB and hABH3, but not hABH2, also repair RNA PMID:26863410 Moreover, m(1)A in mRNA is reversible by ALKBH3, a known DNA/RNA demethylase. PMID:26863196 overexpression of wild-type ALKBH3, but not of an inactive mutant, reduced m1A levels in mRNA PMID:16174769 The mAbh2 and mAbh3 release modified bases from both DNA and RNA. |
| GO:0035516 broad specificity oxidative DNA demethylase activity | IDA PMID:12486230 Reversal of DNA alkylation damage by two human dioxygenases. | ACCEPT | Summary: Broad specificity oxidative DNA demethylase activity: ALKBH3 removes m1A and m3C from DNA. Core activity; accepted. Reason: ALKBH3 directly reverses m1A and m3C in DNA [PMID:12486230 "Both enzymes remove 1-methyladenine and 3-methylcytosine from methylated polynucleotides in an alpha-ketoglutarate-dependent reaction, and act by direct damage reversal with the regeneration of the unsubstituted bases."], preferring single-stranded substrates [PMID:12594517 "Whereas AlkB and hABH3 prefer single-stranded nucleic acids, hABH2 acts more efficiently on double-stranded DNA."], with the iron centre of a 2OG-dependent dioxygenase [PMID:16858410 "The hABH3 structure reveals the beta-strand jelly-roll fold that coordinates a catalytically active iron centre by a conserved His1-X-Asp/Glu-X(n)-His2 motif."]. Supporting Evidence: PMID:12486230 Both enzymes remove 1-methyladenine and 3-methylcytosine from methylated polynucleotides in an alpha-ketoglutarate-dependent reaction, and act by direct damage reversal with the regeneration of the unsubstituted bases. PMID:12594517 Whereas AlkB and hABH3 prefer single-stranded nucleic acids, hABH2 acts more efficiently on double-stranded DNA. PMID:16858410 The hABH3 structure reveals the beta-strand jelly-roll fold that coordinates a catalytically active iron centre by a conserved His1-X-Asp/Glu-X(n)-His2 motif. file:genes/human/ALKBH3/ALKBH3-deep-research-affinage.md ALKBH3 is a single-stranded nucleic acid demethylase that reverses N1-methyladenine/N1-methyladenosine (m1A) and N3-methylcytosine/N3-methylcytidine (m3C) lesions in both DNA and RNA |
| GO:0035516 broad specificity oxidative DNA demethylase activity | IDA PMID:16174769 Repair of methylation damage in DNA and RNA by mammalian Alk... | ACCEPT | Summary: Broad specificity oxidative DNA demethylase activity: ALKBH3 removes m1A and m3C from DNA. Core activity; accepted. Reason: ALKBH3 directly reverses m1A and m3C in DNA [PMID:12486230 "Both enzymes remove 1-methyladenine and 3-methylcytosine from methylated polynucleotides in an alpha-ketoglutarate-dependent reaction, and act by direct damage reversal with the regeneration of the unsubstituted bases."], preferring single-stranded substrates [PMID:12594517 "Whereas AlkB and hABH3 prefer single-stranded nucleic acids, hABH2 acts more efficiently on double-stranded DNA."], with the iron centre of a 2OG-dependent dioxygenase [PMID:16858410 "The hABH3 structure reveals the beta-strand jelly-roll fold that coordinates a catalytically active iron centre by a conserved His1-X-Asp/Glu-X(n)-His2 motif."]. Supporting Evidence: PMID:12486230 Both enzymes remove 1-methyladenine and 3-methylcytosine from methylated polynucleotides in an alpha-ketoglutarate-dependent reaction, and act by direct damage reversal with the regeneration of the unsubstituted bases. PMID:12594517 Whereas AlkB and hABH3 prefer single-stranded nucleic acids, hABH2 acts more efficiently on double-stranded DNA. PMID:16858410 The hABH3 structure reveals the beta-strand jelly-roll fold that coordinates a catalytically active iron centre by a conserved His1-X-Asp/Glu-X(n)-His2 motif. file:genes/human/ALKBH3/ALKBH3-deep-research-affinage.md ALKBH3 is a single-stranded nucleic acid demethylase that reverses N1-methyladenine/N1-methyladenosine (m1A) and N3-methylcytosine/N3-methylcytidine (m3C) lesions in both DNA and RNA |
| GO:0035516 broad specificity oxidative DNA demethylase activity | IDA PMID:16858410 Human ABH3 structure and key residues for oxidative demethyl... | ACCEPT | Summary: Broad specificity oxidative DNA demethylase activity: ALKBH3 removes m1A and m3C from DNA. Core activity; accepted. Reason: ALKBH3 directly reverses m1A and m3C in DNA [PMID:12486230 "Both enzymes remove 1-methyladenine and 3-methylcytosine from methylated polynucleotides in an alpha-ketoglutarate-dependent reaction, and act by direct damage reversal with the regeneration of the unsubstituted bases."], preferring single-stranded substrates [PMID:12594517 "Whereas AlkB and hABH3 prefer single-stranded nucleic acids, hABH2 acts more efficiently on double-stranded DNA."], with the iron centre of a 2OG-dependent dioxygenase [PMID:16858410 "The hABH3 structure reveals the beta-strand jelly-roll fold that coordinates a catalytically active iron centre by a conserved His1-X-Asp/Glu-X(n)-His2 motif."]. Supporting Evidence: PMID:12486230 Both enzymes remove 1-methyladenine and 3-methylcytosine from methylated polynucleotides in an alpha-ketoglutarate-dependent reaction, and act by direct damage reversal with the regeneration of the unsubstituted bases. PMID:12594517 Whereas AlkB and hABH3 prefer single-stranded nucleic acids, hABH2 acts more efficiently on double-stranded DNA. PMID:16858410 The hABH3 structure reveals the beta-strand jelly-roll fold that coordinates a catalytically active iron centre by a conserved His1-X-Asp/Glu-X(n)-His2 motif. file:genes/human/ALKBH3/ALKBH3-deep-research-affinage.md ALKBH3 is a single-stranded nucleic acid demethylase that reverses N1-methyladenine/N1-methyladenosine (m1A) and N3-methylcytosine/N3-methylcytidine (m3C) lesions in both DNA and RNA |
| GO:0035516 broad specificity oxidative DNA demethylase activity | IDA PMID:20714506 Mechanistic insight into the recognition of single-stranded ... | ACCEPT | Summary: Broad specificity oxidative DNA demethylase activity: ALKBH3 removes m1A and m3C from DNA. Core activity; accepted. Reason: ALKBH3 directly reverses m1A and m3C in DNA [PMID:12486230 "Both enzymes remove 1-methyladenine and 3-methylcytosine from methylated polynucleotides in an alpha-ketoglutarate-dependent reaction, and act by direct damage reversal with the regeneration of the unsubstituted bases."], preferring single-stranded substrates [PMID:12594517 "Whereas AlkB and hABH3 prefer single-stranded nucleic acids, hABH2 acts more efficiently on double-stranded DNA."], with the iron centre of a 2OG-dependent dioxygenase [PMID:16858410 "The hABH3 structure reveals the beta-strand jelly-roll fold that coordinates a catalytically active iron centre by a conserved His1-X-Asp/Glu-X(n)-His2 motif."]. Supporting Evidence: PMID:12486230 Both enzymes remove 1-methyladenine and 3-methylcytosine from methylated polynucleotides in an alpha-ketoglutarate-dependent reaction, and act by direct damage reversal with the regeneration of the unsubstituted bases. PMID:12594517 Whereas AlkB and hABH3 prefer single-stranded nucleic acids, hABH2 acts more efficiently on double-stranded DNA. PMID:16858410 The hABH3 structure reveals the beta-strand jelly-roll fold that coordinates a catalytically active iron centre by a conserved His1-X-Asp/Glu-X(n)-His2 motif. file:genes/human/ALKBH3/ALKBH3-deep-research-affinage.md ALKBH3 is a single-stranded nucleic acid demethylase that reverses N1-methyladenine/N1-methyladenosine (m1A) and N3-methylcytosine/N3-methylcytidine (m3C) lesions in both DNA and RNA |
| GO:0035516 broad specificity oxidative DNA demethylase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Broad specificity oxidative DNA demethylase activity: ALKBH3 removes m1A and m3C from DNA. Core activity; accepted. Reason: ALKBH3 directly reverses m1A and m3C in DNA [PMID:12486230 "Both enzymes remove 1-methyladenine and 3-methylcytosine from methylated polynucleotides in an alpha-ketoglutarate-dependent reaction, and act by direct damage reversal with the regeneration of the unsubstituted bases."], preferring single-stranded substrates [PMID:12594517 "Whereas AlkB and hABH3 prefer single-stranded nucleic acids, hABH2 acts more efficiently on double-stranded DNA."], with the iron centre of a 2OG-dependent dioxygenase [PMID:16858410 "The hABH3 structure reveals the beta-strand jelly-roll fold that coordinates a catalytically active iron centre by a conserved His1-X-Asp/Glu-X(n)-His2 motif."]. Supporting Evidence: PMID:12486230 Both enzymes remove 1-methyladenine and 3-methylcytosine from methylated polynucleotides in an alpha-ketoglutarate-dependent reaction, and act by direct damage reversal with the regeneration of the unsubstituted bases. PMID:12594517 Whereas AlkB and hABH3 prefer single-stranded nucleic acids, hABH2 acts more efficiently on double-stranded DNA. PMID:16858410 The hABH3 structure reveals the beta-strand jelly-roll fold that coordinates a catalytically active iron centre by a conserved His1-X-Asp/Glu-X(n)-His2 motif. file:genes/human/ALKBH3/ALKBH3-deep-research-affinage.md ALKBH3 is a single-stranded nucleic acid demethylase that reverses N1-methyladenine/N1-methyladenosine (m1A) and N3-methylcytosine/N3-methylcytidine (m3C) lesions in both DNA and RNA |
| GO:0035516 broad specificity oxidative DNA demethylase activity | IMP PMID:22055184 DNA unwinding by ASCC3 helicase is coupled to ALKBH3-depende... | ACCEPT | Summary: Broad specificity oxidative DNA demethylase activity: ALKBH3 removes m1A and m3C from DNA. Core activity; accepted. Reason: ALKBH3 directly reverses m1A and m3C in DNA [PMID:12486230 "Both enzymes remove 1-methyladenine and 3-methylcytosine from methylated polynucleotides in an alpha-ketoglutarate-dependent reaction, and act by direct damage reversal with the regeneration of the unsubstituted bases."], preferring single-stranded substrates [PMID:12594517 "Whereas AlkB and hABH3 prefer single-stranded nucleic acids, hABH2 acts more efficiently on double-stranded DNA."], with the iron centre of a 2OG-dependent dioxygenase [PMID:16858410 "The hABH3 structure reveals the beta-strand jelly-roll fold that coordinates a catalytically active iron centre by a conserved His1-X-Asp/Glu-X(n)-His2 motif."]. Supporting Evidence: PMID:12486230 Both enzymes remove 1-methyladenine and 3-methylcytosine from methylated polynucleotides in an alpha-ketoglutarate-dependent reaction, and act by direct damage reversal with the regeneration of the unsubstituted bases. PMID:12594517 Whereas AlkB and hABH3 prefer single-stranded nucleic acids, hABH2 acts more efficiently on double-stranded DNA. PMID:16858410 The hABH3 structure reveals the beta-strand jelly-roll fold that coordinates a catalytically active iron centre by a conserved His1-X-Asp/Glu-X(n)-His2 motif. file:genes/human/ALKBH3/ALKBH3-deep-research-affinage.md ALKBH3 is a single-stranded nucleic acid demethylase that reverses N1-methyladenine/N1-methyladenosine (m1A) and N3-methylcytosine/N3-methylcytidine (m3C) lesions in both DNA and RNA |
| GO:0051213 dioxygenase activity | IEA GO_REF:0000002 | ACCEPT | Summary: Dioxygenase activity, from the InterPro AlkB family signature. Correct parent of the specific demethylase activities; accepted. Reason: ALKBH3 directly reverses m1A and m3C in DNA [PMID:12486230 "Both enzymes remove 1-methyladenine and 3-methylcytosine from methylated polynucleotides in an alpha-ketoglutarate-dependent reaction, and act by direct damage reversal with the regeneration of the unsubstituted bases."], preferring single-stranded substrates [PMID:12594517 "Whereas AlkB and hABH3 prefer single-stranded nucleic acids, hABH2 acts more efficiently on double-stranded DNA."], with the iron centre of a 2OG-dependent dioxygenase [PMID:16858410 "The hABH3 structure reveals the beta-strand jelly-roll fold that coordinates a catalytically active iron centre by a conserved His1-X-Asp/Glu-X(n)-His2 motif."]. Supporting Evidence: PMID:12486230 Both enzymes remove 1-methyladenine and 3-methylcytosine from methylated polynucleotides in an alpha-ketoglutarate-dependent reaction, and act by direct damage reversal with the regeneration of the unsubstituted bases. PMID:12594517 Whereas AlkB and hABH3 prefer single-stranded nucleic acids, hABH2 acts more efficiently on double-stranded DNA. PMID:16858410 The hABH3 structure reveals the beta-strand jelly-roll fold that coordinates a catalytically active iron centre by a conserved His1-X-Asp/Glu-X(n)-His2 motif. file:genes/human/ALKBH3/ALKBH3-deep-research-affinage.md ALKBH3 is a single-stranded nucleic acid demethylase that reverses N1-methyladenine/N1-methyladenosine (m1A) and N3-methylcytosine/N3-methylcytidine (m3C) lesions in both DNA and RNA |
| GO:1990930 mRNA N1-methyladenosine dioxygenase activity | IDA PMID:26863196 The dynamic N(1)-methyladenosine methylome in eukaryotic mes... | ACCEPT | Summary: mRNA N1-methyladenosine dioxygenase activity: ALKBH3 removes m1A from mRNA. Accepted. Reason: ALKBH3, unlike ALKBH2, also demethylates RNA [PMID:12594517 "AlkB and hABH3, but not hABH2, also repair RNA"], including m1A in mRNA [PMID:26863410 "Moreover, m(1)A in mRNA is reversible by ALKBH3, a known DNA/RNA demethylase."], [PMID:26863196 "overexpression of wild-type ALKBH3, but not of an inactive mutant, reduced m1A levels in mRNA"]. Supporting Evidence: PMID:12594517 AlkB and hABH3, but not hABH2, also repair RNA PMID:26863410 Moreover, m(1)A in mRNA is reversible by ALKBH3, a known DNA/RNA demethylase. PMID:26863196 overexpression of wild-type ALKBH3, but not of an inactive mutant, reduced m1A levels in mRNA |
| GO:1990930 mRNA N1-methyladenosine dioxygenase activity | IDA PMID:26863410 Transcriptome-wide mapping reveals reversible and dynamic N(... | ACCEPT | Summary: mRNA N1-methyladenosine dioxygenase activity: ALKBH3 removes m1A from mRNA. Accepted. Reason: ALKBH3, unlike ALKBH2, also demethylates RNA [PMID:12594517 "AlkB and hABH3, but not hABH2, also repair RNA"], including m1A in mRNA [PMID:26863410 "Moreover, m(1)A in mRNA is reversible by ALKBH3, a known DNA/RNA demethylase."], [PMID:26863196 "overexpression of wild-type ALKBH3, but not of an inactive mutant, reduced m1A levels in mRNA"]. Supporting Evidence: PMID:12594517 AlkB and hABH3, but not hABH2, also repair RNA PMID:26863410 Moreover, m(1)A in mRNA is reversible by ALKBH3, a known DNA/RNA demethylase. PMID:26863196 overexpression of wild-type ALKBH3, but not of an inactive mutant, reduced m1A levels in mRNA |
| GO:1990930 mRNA N1-methyladenosine dioxygenase activity | IEA GO_REF:0000120 | ACCEPT | Summary: mRNA N1-methyladenosine dioxygenase activity: ALKBH3 removes m1A from mRNA. Accepted. Reason: ALKBH3, unlike ALKBH2, also demethylates RNA [PMID:12594517 "AlkB and hABH3, but not hABH2, also repair RNA"], including m1A in mRNA [PMID:26863410 "Moreover, m(1)A in mRNA is reversible by ALKBH3, a known DNA/RNA demethylase."], [PMID:26863196 "overexpression of wild-type ALKBH3, but not of an inactive mutant, reduced m1A levels in mRNA"]. Supporting Evidence: PMID:12594517 AlkB and hABH3, but not hABH2, also repair RNA PMID:26863410 Moreover, m(1)A in mRNA is reversible by ALKBH3, a known DNA/RNA demethylase. PMID:26863196 overexpression of wild-type ALKBH3, but not of an inactive mutant, reduced m1A levels in mRNA |
| GO:2000766 negative regulation of cytoplasmic translation | IDA PMID:26863196 The dynamic N(1)-methyladenosine methylome in eukaryotic mes... | MARK AS OVER ANNOTATED | Summary: Negative regulation of cytoplasmic translation, from the m1A methylome study: m1A correlates with higher translation and ALKBH3 removes it, but ALKBH3 was never perturbed with translation as the readout. Marked as over-annotated. Reason: The study links m1A to translation [PMID:26863196 "strongly indicating a functional role for m(1)A in promoting translation of methylated mRNA."] and shows ALKBH3 lowers mRNA m1A [PMID:26863196 "overexpression of wild-type ALKBH3, but not of an inactive mutant, reduced m1A levels in mRNA"]. The effect on translation is inferred from a correlation in re-analysed ribosome-profiling data together with ALKBH3's activity on the mark; the paper itself calls ALKBH3 only a likely candidate eraser. A translation effect of ALKBH3 has not been measured, so the process claim over-reaches the evidence. Supporting Evidence: PMID:26863196 strongly indicating a functional role for m(1)A in promoting translation of methylated mRNA. PMID:26863196 overexpression of wild-type ALKBH3, but not of an inactive mutant, reduced m1A levels in mRNA |
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Experiment: Catalytic-dead ALKBH3 knock-in with ribosome profiling to test whether its m1A removal changes translation directly.
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