Affinage

APOBEC1

C->U-editing enzyme APOBEC-1 · UniProt P41238

Length
236 aa
Mass
28.2 kDa
Annotated
2026-04-28
100 papers in source corpus 40 papers cited in narrative 39 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

APOBEC1 is a zinc-dependent cytidine deaminase that serves as the catalytic subunit of the apolipoprotein B mRNA editing holoenzyme, converting C6666 to U to produce apoB48, and edits dozens of additional mRNA targets predominantly in 3′ UTRs (PMID:8626621, PMID:21258325, PMID:24946870). APOBEC1 requires RNA-binding cofactors—RBM47 as the principal in vivo partner and A1CF contributing in a tissue-specific manner—that recognize the mooring sequence and remodel the RNA stem-loop to expose the target cytidine for deamination (PMID:10669759, PMID:24916387, PMID:30309881, PMID:15659357). Beyond RNA editing, APOBEC1 binds AU-rich elements in 3′ UTRs of mRNAs such as COX-2, c-myc, Cyp7a1, and IL-8, stabilizing them post-transcriptionally through a mechanism dependent on its RNA-binding activity but independent of catalytic editing (PMID:10688645, PMID:15480992, PMID:19386592, PMID:25100733). APOBEC1 also deaminates cytosines in single-stranded DNA in a sequence-context-dependent manner that is suppressed by RPA binding, and its homodimeric structure—mediated by a unique C-terminal hydrophobic domain—governs substrate selectivity between RNA and DNA (PMID:12697753, PMID:33094286, PMID:33330905).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1995 High

    Defining the catalytic architecture of APOBEC1 established that zinc-coordinating residues (H61, E63, C93, C96) are essential for deaminase activity, a leucine-rich region is required for editing but not deamination, and an RNA-binding domain mediates AU-rich RNA recognition—resolving how a single protein couples substrate binding to catalysis.

    Evidence Site-directed mutagenesis of GST-APOBEC1 with in vitro deaminase, UV cross-linking, and EMSA assays in McA 7777 cells

    PMID:7782342 PMID:7782343

    Open questions at the time
    • No three-dimensional structure available at this stage
    • Cofactor requirements for site-specific editing not yet defined
  2. 1996 High

    Knockout of Apobec1 in mice abolished all apoB mRNA editing and apoB48 production in every tissue, proving APOBEC1 is the sole essential catalytic subunit with no redundant paralog, while overexpression studies revealed dose-dependent promiscuous editing at additional mooring-sequence-dependent cytidines.

    Evidence Gene targeting in mice with apoB editing and protein assays; stable overexpression in rat hepatoma cells with dose-response editing analysis

    PMID:8621694 PMID:8626621 PMID:8824235

    Open questions at the time
    • Identity of the obligate cofactor unknown
    • Mechanism controlling editing fidelity versus promiscuity unresolved
  3. 1997 High

    Demonstration that APOBEC1 functions as a homodimer—with catalytically inactive dimers acting as dominant negatives—and identification of auxiliary binding partners (ABBP-1) established that editosome assembly involves regulated multimerization.

    Evidence Co-immunoprecipitation of epitope-tagged mutants, adenoviral delivery to mice, yeast two-hybrid and immunodepletion for ABBP-1

    PMID:8999813 PMID:8999814

    Open questions at the time
    • Structural basis of dimerization unknown
    • Stoichiometry and order of assembly not defined
  4. 1999 High

    Discovery that APOBEC1 binds a UUUN[A/U]U consensus motif in AU-rich 3′ UTRs and stabilizes c-myc mRNA revealed a second, editing-independent function—mRNA stabilization—broadening APOBEC1's biological role beyond site-specific deamination.

    Evidence Filter binding, circular-permutation analysis, actinomycin D chase in transfected F442A cells with RNA-binding mutant controls

    PMID:10688645

    Open questions at the time
    • Full repertoire of stabilized mRNAs unknown
    • Mechanism distinguishing editing from stabilization unclear
  5. 2000 High

    Identification of ACF as the obligate RNA-binding cofactor that recognizes the mooring sequence and constitutes, with APOBEC1, the minimal editing holoenzyme resolved the long-standing question of what confers site specificity, while GRY-RBP was shown to negatively regulate editing by sequestering ACF.

    Evidence Protein purification and peptide sequencing, UV cross-linking, co-IP, immunodepletion, in vitro reconstitution; GRY-RBP identified by two-hybrid with competition and knockdown assays

    PMID:10669759 PMID:11134005

    Open questions at the time
    • Structural basis of ACF–APOBEC1 interaction unknown
    • In vivo requirement of ACF versus other cofactors not tested genetically
  6. 2001 Medium

    Identification of additional editosome regulators—CUGBP2 as a dose-dependent inhibitor and ABBP-2/Hsp40 as an ATP-dependent activator—demonstrated that the holoenzyme is a dynamically regulated multiprotein assembly, not a simple binary complex; APOBEC1 was also shown to edit NF1 mRNA, extending its target repertoire.

    Evidence Co-fractionation, co-IP, reconstituted editing with purified components, antisense knockdown; NF1 editing by adenoviral APOBEC1 in HepG2 cells

    PMID:11577082 PMID:11584023 PMID:11727199

    Open questions at the time
    • Relative contributions of each auxiliary factor in vivo undetermined
    • NF1 editing not validated in Apobec1 knockout mice
  7. 2003 High

    Demonstration that APOBEC1 deaminates cytosines in single-stranded DNA in a sequence-context-dependent manner established it as a dual RNA/DNA deaminase, raising the possibility of genomic mutagenesis.

    Evidence In vitro deamination assay with partially purified APOBEC1 on ssDNA substrates; confirmed in E. coli rifampicin-resistance mutation assay

    PMID:12453430 PMID:12697753

    Open questions at the time
    • In vivo relevance of DNA deamination in mammalian cells not yet shown
    • No structural explanation for dual substrate activity
  8. 2005 High

    NMR structure of the apoB mRNA stem-loop showed that C6666 is buried in the loop, and ACF melts the stem-loop to expose the target cytidine, providing the first structural mechanism for how cofactor-mediated RNA remodeling enables site-specific editing.

    Evidence NMR structure determination of 31-nt apoB RNA, binding assays with APOBEC1 ± ACF

    PMID:15659357

    Open questions at the time
    • No co-crystal structure of the ternary APOBEC1–ACF–RNA complex
    • Kinetic mechanism of stem-loop melting not characterized
  9. 2006 High

    PKC-mediated phosphorylation of ACF at S154 and S368 was shown to regulate editosome assembly and ethanol-stimulated editing, providing a signal transduction mechanism that modulates APOBEC1 activity in response to metabolic cues.

    Evidence In vitro kinase assays, phosphomimetic and phosphodead mutagenesis, editing assays in primary hepatocytes

    PMID:16820530 PMID:17229474

    Open questions at the time
    • Upstream signaling pathway linking ethanol to PKC activation not fully defined
    • Whether phosphorylation regulates ACF shuttling is unknown
  10. 2011 High

    Transcriptome-wide RNA-Seq revealed dozens of novel APOBEC1-dependent C-to-U editing sites, all in 3′ UTR AU-rich regions, and APOBEC1 was shown to restrict LINE-1 and LTR retrotransposition through partially deamination-independent mechanisms, expanding its functional scope beyond mRNA editing.

    Evidence Comparative RNA-Seq of APOBEC1-expressing vs. control cells with Sanger validation; cell-based retrotransposition assays with catalytic mutants

    PMID:21258325 PMID:21398638

    Open questions at the time
    • Functional consequences of most 3′ UTR editing events unknown
    • Deamination-independent retrotransposon restriction mechanism undefined
  11. 2014 High

    Identification of RBM47 as a cofactor that is necessary and sufficient for APOBEC1-mediated editing in vivo, and demonstration that APOBEC1 induces genomic DNA mutations in vertebrate cells, resolved two key questions: the in vivo cofactor identity and whether DNA deamination has physiological mutagenic consequences.

    Evidence Rbm47 KO mice with editing quantification plus in vitro reconstitution; reporter gene inactivation in DT40 cells and imatinib resistance assay in CML cells

    PMID:24916387 PMID:25085003

    Open questions at the time
    • Relative contribution of RBM47 vs. A1CF across tissues not resolved at this point
    • Frequency and spectrum of APOBEC1-induced DNA mutations in normal tissues unknown
  12. 2017 High

    Conditional A1cf knockout mice showed no editing deficiency, demonstrating A1CF is dispensable in vivo, while loss of APOBEC1 editing function in microglia caused progressive neurodegeneration—revealing an unexpected role in maintaining microglial homeostasis.

    Evidence Conditional A1cf KO with systematic editing quantification; APOBEC1 editing-deficient mouse model with histological, behavioral, and inflammatory readouts

    PMID:28069890 PMID:29167375

    Open questions at the time
    • Specific mRNA targets mediating the microglial phenotype not identified
    • Whether RBM47 fully compensates for A1CF loss in all contexts unclear
  13. 2018 High

    Genetic epistasis with tissue-specific double knockouts of A1cf and Rbm47 demonstrated that these cofactors function independently but collaborate in a tissue-specific manner, with the double KO eliminating apoB editing in liver—clarifying the cofactor hierarchy.

    Evidence Tissue-specific conditional KO mice (liver and intestine) with systematic RNA editing quantification

    PMID:30309881

    Open questions at the time
    • Structural basis of RBM47 vs. A1CF preference for different editing sites unknown
    • Mechanistic basis of tissue-specific cofactor utilization not defined
  14. 2020 High

    The crystal structure of APOBEC1 revealed a unique C-terminal hydrophobic domain (A1HD) that mediates stable dimerization and forms a positively charged β-sheet surface that directs RNA versus DNA substrate selectivity and cofactor interactions, finally providing structural explanations for dimerization and dual substrate activity.

    Evidence X-ray crystallography with structure-guided mutagenesis and substrate selectivity assays

    PMID:33094286

    Open questions at the time
    • No structure of APOBEC1 in complex with ACF/RBM47 or RNA substrate
    • Conformational dynamics during catalysis not captured
  15. 2021 Medium

    RPA was shown to suppress APOBEC1 DNA deamination activity by outcompeting it for ssDNA binding, providing a mechanistic explanation for why APOBEC1 expression causes limited genomic damage despite its intrinsic DNA mutator activity.

    Evidence In vitro deamination assays with RPA competition; γH2AX foci measurement in lung cancer cells

    PMID:33330905

    Open questions at the time
    • In vivo validation of RPA protection against APOBEC1-mediated mutagenesis lacking
    • Whether replication stress or RPA depletion unmasks APOBEC1 DNA damage in physiological settings is untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • A high-resolution structure of the complete APOBEC1–RBM47(or A1CF)–RNA ternary complex is needed to understand how cofactor binding remodels the RNA substrate and positions the target cytidine in the active site, and the physiological significance of APOBEC1-mediated DNA deamination in normal somatic tissues remains unresolved.
  • No ternary complex structure available
  • In vivo contribution of APOBEC1 to somatic mutagenesis in healthy tissues unknown
  • Full functional consequences of 3′ UTR editing on mRNA fate and translation not systematically characterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140098 catalytic activity, acting on RNA 7 GO:0003723 RNA binding 4 GO:0140097 catalytic activity, acting on DNA 3 GO:0016787 hydrolase activity 2
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 2
Pathway
R-HSA-8953854 Metabolism of RNA 6 R-HSA-1430728 Metabolism 1
Partners
A1CFABBP-1CUGBP2DNAJB1GRY-RBPRBM47SYNCRIP
Complex memberships
apoB mRNA editosome

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 APOBEC1 contains distinct functional domains: a zinc-coordinating catalytic domain (H61, E63, C93, C96) required for cytidine deaminase activity and apoB RNA editing, a leucine-rich region (LRR) required for RNA editing but not deaminase activity, and an RNA-binding domain; mutation of H61→Arg abolishes RNA binding while E63→Gln and C96→Ser mutants retain RNA binding but lose editing activity. Overexpression acts as a dominant negative when RNA binding is eliminated. Site-directed mutagenesis of GST-APOBEC1 fusion protein, in vitro cytidine deaminase assays, UV cross-linking RNA binding assays, transient transfection in McA 7777 cells The Journal of biological chemistry High 7782343
1995 Recombinant APOBEC1 binds with high specificity to apoB RNA in AU-rich sequences, demonstrated by UV cross-linking and EMSA; binding is competed by poly(U) and poly(A,U) but not poly(A); binding specificity for the RNA template is distinct from editing specificity. UV cross-linking, electrophoretic mobility shift assay (EMSA), RNA competition assays with recombinant GST-APOBEC1 The Journal of biological chemistry High 7782342
1996 Targeted disruption of mouse apobec-1 abolishes all apoB mRNA editing and eliminates apoB48 production in all tissues, demonstrating APOBEC1 is the essential catalytic subunit with no functional gene duplication. Gene targeting/knockout mice, apoB mRNA editing assay, Western blot for apoB48 The Journal of biological chemistry High 8626621 8824235
1996 Overexpression of APOBEC1 in stable rat hepatoma cell lines results in promiscuous RNA editing of cytidines 5' of the mooring sequence in addition to the wild-type site, and this promiscuous editing is mooring sequence-dependent and increases with APOBEC1 expression level. Stable cell lines overexpressing APOBEC1, apoB RNA editing assays, sequence analysis The Journal of biological chemistry High 8621694
1996 APOBEC1 requires a 65-kDa complementing protein (later identified as ACF) for apoB mRNA editing activity in vitro; this protein interacts directly with APOBEC1 in the absence of apoB mRNA, as demonstrated by APOBEC1 affinity chromatography. Affinity chromatography using immobilized recombinant His6-APOBEC1, size exclusion chromatography, glycerol gradient sedimentation, functional in vitro editing assay The Journal of biological chemistry High 8910449
1997 APOBEC1 functions as a homodimer; a catalytically inactive mutant (H61K/C93S/C96S) that retains dimerization capacity acts as a dominant negative inhibitor of wild-type APOBEC1 editing activity in vivo, while mutants that dimerize poorly do not inhibit. In vitro editing assay, co-immunoprecipitation of epitope-tagged APOBEC1 mutants, adenoviral delivery to mice The Journal of biological chemistry High 8999814
1997 ABBP-1, an hnRNP-type RNA-binding protein, interacts with APOBEC1 via its glycine-rich C-terminal domain and binds apoB mRNA; immunodepletion of ABBP-1 from editing extracts inhibits editing activity. Yeast two-hybrid screening, deletion mapping, UV cross-linking, immunodepletion, antisense knockdown in HepG2 cells The Journal of biological chemistry Medium 8999813
1999 APOBEC1 exhibits a consensus high-affinity binding site for AU-rich RNA of sequence UUUN[A/U]U; binding to the c-myc 3'UTR containing this motif stabilizes c-myc mRNA (half-life increased from 90 to 240 min), an effect dependent on APOBEC1 RNA-binding activity. Filter binding assays, circular-permutation analysis, actinomycin D mRNA turnover assays in transfected F442A cells with RNA-binding mutants Molecular and cellular biology High 10688645
2000 ACF (apobec-1 complementation factor), a 65-kDa protein with three RNA recognition motifs, is identified as the obligate RNA-binding subunit of the minimal apoB mRNA editing holoenzyme; ACF binds the mooring sequence of apoB mRNA, interacts with APOBEC1, and together they constitute the minimal editing complex. Protein purification, peptide sequencing, molecular cloning, UV cross-linking, co-immunoprecipitation, immunodepletion from liver extracts, in vitro reconstitution of editing Molecular and cellular biology High 10669759
2000 GRY-RBP is an apoB RNA-binding protein that interacts with both APOBEC1 and ACF; it competitively inhibits ACF binding to apoB mRNA and C-to-U editing by sequestering ACF, and antisense knockdown of GRY-RBP increases apoB RNA editing. Two-hybrid screening, recombinant protein pulldowns, RNA binding assays, immunodepletion, antisense oligonucleotide knockdown, confocal colocalization The Journal of biological chemistry High 11134005
2000 APOBEC1-mediated apoB mRNA editing can occur in the cytoplasm when APOBEC1 is overexpressed; under normal conditions editing is restricted to the nucleus. ACF distributes to both nucleus and cytoplasm, providing auxiliary protein support in both compartments. Reporter RNA assays with intron-containing constructs, immunolocalization of ACF and APOBEC1 in McArdle cells, ethanol stimulation experiments The Journal of biological chemistry Medium 10833526
2001 CUGBP2, a 54-kDa RNA-binding protein, is a component of the apoB mRNA editing holoenzyme; it co-fractionates with ACF, binds apoB RNA upstream of the edited cytidine, and dose-dependently inhibits C-to-U editing in a reconstituted system, rescued by addition of APOBEC1 or ACF. Co-fractionation, co-immunoprecipitation, RNA binding assays, reconstituted editing system, antisense knockdown The Journal of biological chemistry High 11577082
2001 ARCD-1, an apobec-1 homologue, heterodimerizes with both APOBEC1 and ACF, exhibits cytidine deaminase and apoB RNA binding activity but cannot catalyze C-to-U RNA editing; it acts as a dominant negative inhibitor of APOBEC1-mediated editing. Co-immunoprecipitation, in vitro editing assays, cytidine deaminase assays, subcellular localization by immunofluorescence American journal of physiology. Cell physiology Medium 11698249
2001 ABBP-2, a DnaJ/Hsp40 family protein, binds APOBEC1 via its J domain and neighboring G/F domain; Hsp70/ABBP-2 interaction (requiring ATP) is necessary for apoB mRNA editing activity in vitro extracts, and ABBP-2 knockdown inhibits endogenous editing. Yeast two-hybrid, co-immunoprecipitation, in vitro editing assays with ATP depletion, ATPase stimulation assays, antisense knockdown The Journal of biological chemistry Medium 11584023
2001 ACF localizes predominantly to the nucleus; the NH2-terminal 380 residues containing RNA recognition motifs define both apoB RNA binding and APOBEC1-interacting domains. ACF cotransfection with APOBEC1 results in nuclear colocalization and nuclear import of APOBEC1 via protein-protein interaction. Deletion mutagenesis, co-immunoprecipitation, RNA binding assays, confocal microscopy, transfection The Journal of biological chemistry High 11571303
2002 APOBEC1 and its homologs APOBEC3C and APOBEC3G exhibit potent DNA mutator activity in an E. coli assay through dC deamination, with each protein showing distinct local target sequence specificity. E. coli rifampicin resistance mutation assay, sequence analysis of mutations Molecular cell High 12453430
2002 ACF requires N-terminal pre-RRM regions and all three RRMs for apoB mRNA binding and complementing activity; the RG-rich auxiliary domain is required for apobec-1 interaction and complementing activity; RRM1 and RRM2 mutations reduce binding affinity by 100-fold while RRM3 reduces it 13-fold. Deletion mutagenesis, point mutagenesis, RNA binding assays measuring Kd, in vitro complementation editing assays RNA (New York, N.Y.) High 11871661
2003 APOBEC1 can deaminate cytosine to uracil in single-stranded DNA in vitro, with activity dependent on local sequence context; this establishes APOBEC1 as a dual RNA and DNA cytosine deaminase. In vitro deamination assay using partially purified APOBEC1 from E. coli with ssDNA substrates The Journal of biological chemistry High 12697753
2003 A novel 41-residue motif (ANS) in the auxiliary domain of ACF functions as an authentic nuclear localization signal; ACF nuclear accumulation is transcription-dependent and reversible, and ACF shuttles between nucleus and cytoplasm via binding to the carrier protein transportin 2. GFP/beta-gal chimera localization, actinomycin D treatment, leptomycin B (CRM1 inhibitor), heterokaryon assays, co-immunoprecipitation with transportin 2, confocal microscopy The Journal of biological chemistry High 12896982
2004 Crystal structure of yeast CDD1 (APOBEC1 ortholog) at 2.0 Å reveals a central active site 'flap' that accommodates large substrates (RNA or DNA) and models of APOBEC1 and AID suggest both are equally likely to bind ssDNA or RNA; the structure explains dimerization and need for trans-acting loops in active site formation. X-ray crystallography at 2.0 Å, comparative structural modeling of APOBEC1 and AID Proceedings of the National Academy of Sciences of the United States of America High 15148397
2004 Apobec-1 binds AU-rich sequences in the 3'UTR of cyclooxygenase-2 (COX-2) mRNA and stabilizes it; deletion of apobec-1 in mice reduces COX-2 mRNA stabilization after irradiation, reducing intestinal stem cell survival through loss of prostaglandin E2-mediated radioprotection. EMSA, UV cross-linking with recombinant APOBEC1, luciferase-COX-2 3'UTR reporter assays, apobec-1 knockout mice with gamma irradiation, clonogenic intestinal crypt survival assay Gastroenterology High 15480992
2004 APOBEC1 apoenzyme alone has residual editing activity on minimal apoB mRNA substrate without auxiliary factors; ACF broadens the temperature range of APOBEC1 activity and lowers the optimal temperature, likely by promoting a conformational transition in the RNA substrate. In vitro editing assays with purified recombinant APOBEC1, optimization by incomplete factorial and response surface experiments, steady-state kinetic analysis with and without ACF RNA (New York, N.Y.) High 15273326
2005 NMR structure of the 31-nt apoB mRNA stem-loop reveals the edited C6666 is stacked in an octa-loop; APOBEC1 alone does not specifically bind apoB mRNA and requires ACF for specific editing; ACF recognizes the flexible mooring sequence and then melts the stem-loop to expose C6666 for deamination. NMR structure determination of apoB mRNA stem-loop, RNA binding assays with APOBEC1 and ACF RNA (New York, N.Y.) High 15659357
2006 ACF is a metabolically regulated phosphoprotein; serine phosphorylation of ACF (by protein phosphatase I-sensitive kinase) is restricted to nuclear extracts where it co-sediments with editing-competent 27S complexes; ethanol stimulation of editing is associated with 2-3 fold increased ACF phosphorylation; alkaline phosphatase treatment reduces APOBEC1 co-immunoprecipitation with ACF and inhibits editing. Co-immunoprecipitation, alkaline phosphatase treatment, 2D phosphoamino acid analysis, protein phosphatase inhibitors, metabolic stimulation experiments Nucleic acids research High 16820530
2006 PKC phosphorylates ACF at S154 and S368; S154A/S368A mutations inhibit ethanol-stimulated editing while S154D/S368D phosphomimetic mutations stimulate editing to levels comparable to ethanol treatment; PKA has no effect on editing or ACF phosphorylation. In vitro phosphorylation with purified kinases, site-directed mutagenesis, editing assays in primary hepatocytes and McArdle cells Biochimica et biophysica acta High 17229474
2006 APOBEC1 and AID are nucleo-cytoplasmic shuttling proteins, whereas APOBEC3G is strongly retained in the cytoplasm through mechanisms involving both N- and C-terminal regions. Nucleo-cytoplasmic shuttling assays, subcellular fractionation, domain deletion analysis Biochemical and biophysical research communications Medium 16999936
2009 APOBEC1 binds AU-rich sequences in the 3'UTR of Cyp7a1 mRNA (containing UUUN[A/U]U consensus motif) as demonstrated by UV cross-linking and in vivo RNA co-immunoprecipitation, and post-transcriptionally regulates Cyp7a1 expression; apobec-1 deletion decreases Cyp7a1 mRNA without altering transcription, increasing gallstone susceptibility. UV cross-linking with recombinant APOBEC1, in vivo RNA co-immunoprecipitation, apobec-1 knockout mice, adenoviral rescue, hepatocyte nuclear transcription assay The Journal of biological chemistry High 19386592
2011 APOBEC1 edits 32 previously undescribed mRNA targets located in AU-rich segments of transcript 3'UTRs, as identified by transcriptome-wide comparative RNA sequencing of APOBEC1-expressing versus control cells. Comparative RNA-Seq (transcriptome-wide), Sanger sequencing validation Nature structural & molecular biology High 21258325
2011 APOBEC1 restricts LINE-1 retrotransposition through a deamination-independent mechanism, and inhibits LTR retrotransposons (IAP, MusD) through a mechanism requiring deaminase activity, as demonstrated in cell culture retrotransposition assays. Cell culture-based retrotransposition assays with wild-type and catalytic mutant APOBEC1, subcellular localization analysis Nucleic acids research Medium 21398638
2014 RBM47 is a novel RNA-binding protein that interacts with APOBEC1 and A1CF, can substitute for A1CF in complementing APOBEC1 for C-to-U RNA editing in vitro, and is necessary and sufficient for APOBEC1-mediated editing in vivo as shown by Rbm47-deficient mice with impaired editing. Co-immunoprecipitation, in vitro editing reconstitution, Rbm47 knockout mice, editing assays EMBO reports High 24916387
2014 APOBEC1 expression induces a mutator phenotype in vertebrate cells through direct targeting of genomic DNA; it increases inactivation of a stably inserted reporter gene in chicken cells lacking other AID/APOBEC proteins and increases imatinib-resistant clones in a human CML model through BCR-ABL1 mutations. Reporter gene inactivation assay in DT40 chicken cells, imatinib resistance clonogenic assay in human CML cells, sequence analysis of mutations Genome biology High 25085003
2014 Genome-wide deep sequencing identifies 56 novel Apobec-1-dependent C-to-U editing sites in intestinal mRNAs and 22 in liver mRNAs, all in 3'UTRs; editing changes lead to corresponding changes in mRNA and protein levels for 11 genes; cell-free editing validated by wild-type but not Apobec-1-deficient mouse extracts. Deep RNA sequencing of wild-type and Apobec-1-/- mice, Sanger validation, polysome profiling, cell-free editing assays, adenoviral rescue, transgenic overexpression Genome biology High 24946870
2017 A1CF is dispensable for APOBEC1-mediated C-to-U RNA editing in vivo in adult mice; conditional A1cf knockout mice show no changes in RNA editing efficiency for multiple targets including ApoB in intestine, liver, or kidney. Conditional knockout mice (A1cf floxed allele), RNA editing quantification by sequencing of multiple targets RNA (New York, N.Y.) High 28069890
2017 APOBEC1-mediated RNA editing in microglia maintains their resting state; loss of APOBEC1 editing function in microglia leads to progressive age-related neurodegeneration characterized by clustering of activated microglia, aberrant myelination, increased inflammation, and lysosomal anomalies with behavioral and motor deficits. APOBEC1 editing-deficient mouse model, histological analysis, behavioral assays, protein abundance analysis Proceedings of the National Academy of Sciences of the United States of America Medium 29167375
2018 A1CF and RBM47 function independently yet interact in a tissue-specific manner to regulate APOBEC1-dependent C-to-U RNA editing; intestinal-specific Rbm47 KO nearly eliminates editing while liver-specific Rbm47 KO reduces a subset; double A1cf/Rbm47 KO in liver eliminates apoB editing and eliminates editing of most targets, beyond the effect of either single KO. Tissue-specific conditional knockout mice (liver and intestine), RNA editing quantification, adenoviral APOBEC1 administration RNA (New York, N.Y.) High 30309881
2020 Crystal structure of APOBEC1 reveals a typical APOBEC deaminase core plus a unique well-folded hydrophobic C-terminal domain (A1HD) that forms a stable dimer via hydrophobic interactions creating a four-stranded β-sheet positively charged surface; structure-guided mutagenesis shows A1HD directs RNA and cofactor interactions and governs RNA versus DNA substrate selectivity. X-ray crystallography, structure-guided mutagenesis, substrate selectivity assays NAR cancer High 33094286
2021 RPA (replication protein A) suppresses APOBEC1 cytosine deaminase activity on ssDNA by competing for ssDNA binding; APOBEC1 cannot efficiently compete with RPA in vitro, correlating with low levels of genomic DNA damage in lung cancer cells expressing APOBEC1. In vitro deamination assays with RPA competition, γH2AX foci measurement in lung cancer cell line Nucleic acids research Medium 33330905
2014 hnRNPQ isoform 6 (hnRNPQ6) is required for efficient interaction of APOBEC1 with IL-8 mRNA; APOBEC1 binding to AU-rich elements in the IL-8 3'UTR extends IL-8 mRNA half-life and increases IL-8 production in a cell type-specific, hnRNPQ6-dependent manner. RNA co-immunoprecipitation/microarray, mRNA half-life assays, yeast two-hybrid, siRNA screen, luciferase reporter with IL-8 3'UTR The Journal of biological chemistry Medium 25100733
2001 C-to-U RNA editing of neurofibromatosis 1 (NF1) mRNA by APOBEC1 occurs preferentially in transcripts containing alternatively spliced exon 23A; adenovirus-mediated APOBEC1 expression in HepG2 cells induces NF1 transcript editing with preference for exon 23A-containing forms, demonstrating APOBEC1 as the catalytic deaminase for this non-apoB target. In vitro editing assays with recombinant APOBEC1 on synthetic NF1 RNA templates, adenoviral transduction of HepG2 cells, editing quantification by sequencing American journal of human genetics Medium 11727199

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 RNA editing enzyme APOBEC1 and some of its homologs can act as DNA mutators. Molecular cell 478 12453430
2000 Molecular cloning of apobec-1 complementation factor, a novel RNA-binding protein involved in the editing of apolipoprotein B mRNA. Molecular and cellular biology 215 10669759
2011 Transcriptome-wide sequencing reveals numerous APOBEC1 mRNA-editing targets in transcript 3' UTRs. Nature structural & molecular biology 194 21258325
2007 Recombinant antibodies to an oxidized low-density lipoprotein epitope induce rapid regression of atherosclerosis in apobec-1(-/-)/low-density lipoprotein receptor(-/-) mice. Journal of the American College of Cardiology 137 18068040
1996 Targeted disruption of the mouse apobec-1 gene abolishes apolipoprotein B mRNA editing and eliminates apolipoprotein B48. The Journal of biological chemistry 129 8626621
2003 In vitro deamination of cytosine to uracil in single-stranded DNA by apolipoprotein B editing complex catalytic subunit 1 (APOBEC1). The Journal of biological chemistry 114 12697753
1995 Mutagenesis of apobec-1, the catalytic subunit of the mammalian apolipoprotein B mRNA editing enzyme, reveals distinct domains that mediate cytosine nucleoside deaminase, RNA binding, and RNA editing activity. The Journal of biological chemistry 112 7782343
1995 apobec-1, the catalytic subunit of the mammalian apolipoprotein B mRNA editing enzyme, is a novel RNA-binding protein. The Journal of biological chemistry 108 7782342
2010 APOBEC-1-mediated RNA editing. Wiley interdisciplinary reviews. Systems biology and medicine 102 20836050
2014 C to U RNA editing mediated by APOBEC1 requires RNA-binding protein RBM47. EMBO reports 94 24916387
1995 Alternative mRNA splicing and differential promoter utilization determine tissue-specific expression of the apolipoprotein B mRNA-editing protein (Apobec1) gene in mice. Structure and evolution of Apobec1 and related nucleoside/nucleotide deaminases. The Journal of biological chemistry 93 7768898
2014 The RNA editing enzyme APOBEC1 induces somatic mutations and a compatible mutational signature is present in esophageal adenocarcinomas. Genome biology 85 25085003
2000 Identification of GRY-RBP as an apolipoprotein B RNA-binding protein that interacts with both apobec-1 and apobec-1 complementation factor to modulate C to U editing. The Journal of biological chemistry 85 11134005
2001 Novel role for RNA-binding protein CUGBP2 in mammalian RNA editing. CUGBP2 modulates C to U editing of apolipoprotein B mRNA by interacting with apobec-1 and ACF, the apobec-1 complementation factor. The Journal of biological chemistry 84 11577082
1997 Cloning of an Apobec-1-binding protein that also interacts with apolipoprotein B mRNA and evidence for its involvement in RNA editing. The Journal of biological chemistry 83 8999813
1996 Overexpression of APOBEC-1 results in mooring sequence-dependent promiscuous RNA editing. The Journal of biological chemistry 83 8621694
1996 Complete phenotypic characterization of apobec-1 knockout mice with a wild-type genetic background and a human apolipoprotein B transgenic background, and restoration of apolipoprotein B mRNA editing by somatic gene transfer of Apobec-1. The Journal of biological chemistry 83 8824235
2014 Genome-wide identification and functional analysis of Apobec-1-mediated C-to-U RNA editing in mouse small intestine and liver. Genome biology 82 24946870
2004 The structure of a yeast RNA-editing deaminase provides insight into the fold and function of activation-induced deaminase and APOBEC-1. Proceedings of the National Academy of Sciences of the United States of America 74 15148397
2000 An AU-rich sequence element (UUUN[A/U]U) downstream of the edited C in apolipoprotein B mRNA is a high-affinity binding site for Apobec-1: binding of Apobec-1 to this motif in the 3' untranslated region of c-myc increases mRNA stability. Molecular and cellular biology 74 10688645
2008 Murine APOBEC1 is a powerful mutator of retroviral and cellular RNA in vitro and in vivo. Journal of molecular biology 63 18983852
1997 Apobec-1 and apolipoprotein B mRNA editing. Biochimica et biophysica acta 58 9084497
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1999 Psoriasis upregulated phorbolin-1 shares structural but not functional similarity to the mRNA-editing protein apobec-1. The Journal of investigative dermatology 53 10469298
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2001 C-->U editing of neurofibromatosis 1 mRNA occurs in tumors that express both the type II transcript and apobec-1, the catalytic subunit of the apolipoprotein B mRNA-editing enzyme. American journal of human genetics 52 11727199
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1996 Hepatic expression of the catalytic subunit of the apolipoprotein B mRNA editing enzyme (apobec-1) ameliorates hypercholesterolemia in LDL receptor-deficient rabbits. Human gene therapy 50 8727508
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