Affinage

APOBEC3G

DNA dC->dU-editing enzyme APOBEC-3G · UniProt Q9HC16

Length
384 aa
Mass
46.4 kDa
Annotated
2026-06-09
100 papers in source corpus 52 papers cited in narrative 49 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

APOBEC3G is a cytoplasmically retained single-stranded DNA/RNA cytidine deaminase that functions as an intrinsic restriction factor against HIV-1 and retroelements (PMID:12808466, PMID:12808465, PMID:16999936). It is built from two zinc-coordinating domains with division of labor: the catalytic C-terminal domain (CD2) carries out C-to-U deamination, while the non-catalytic N-terminal domain (CD1) mediates RNA binding, oligomerization, and virion encapsidation (PMID:15668174, PMID:15721369, PMID:18288108, PMID:25984970). Packaged into assembling virions through interaction with the nucleocapsid domain of Gag and selective binding of host 7SL RNA (PMID:15159405, PMID:15358144, PMID:17881443), A3G restricts HIV-1 by two genetically separable routes: processive 3'→5' deamination of minus-strand viral cDNA producing lethal G-to-A hypermutation (with edited uracils subsequently targeted by uracil base excision repair) (PMID:12808466, PMID:12808465, PMID:16622407, PMID:29158605), and deaminase-independent impedance of reverse transcription — blocking elongation and strand transfer by competing with RT for ssDNA, directly binding RT, and forming oligomeric roadblocks on the template (PMID:17855362, PMID:17942420, PMID:22301159, PMID:23761443, PMID:28928403). Its enzymatic state is governed by RNA, which both competitively and allosterically suppresses ssDNA deaminase activity and drives dimer/oligomer dissociation from DNA (PMID:21856286, PMID:26424853). HIV-1 Vif neutralizes A3G by nucleating a CBF-β–CUL5–ELOB–ELOC–RBX E3 ubiquitin ligase that polyubiquitinates A3G for proteasomal degradation, an interaction in which RNA serves as molecular glue at the Vif–A3G N-terminal-domain interface (PMID:14564014, PMID:14528300, PMID:14528301, PMID:14527406, PMID:22190037, PMID:36754086, PMID:36598981). Beyond antiviral defense, A3G performs site-specific C-to-U editing of cellular mRNAs at stem-loop substrates under cellular stress and restricts Alu retrotransposition by sequestering Alu RNAs in cytoplasmic high-molecular-mass ribonucleoprotein complexes (PMID:17030807, PMID:27974822, PMID:29230368).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2003 High

    Established the molecular basis of A3G antiviral activity: that it is a cytidine deaminase acting on nascent viral DNA, answering how a host factor could mutationally cripple retroviral replication.

    Evidence Retroviral infection and hypermutation analysis of viral DNA

    PMID:12808465 PMID:12808466

    Open questions at the time
    • Did not resolve whether deamination is the sole restriction mechanism
    • Directionality and processivity of editing unaddressed
  2. 2003 High

    Defined the viral countermeasure: Vif binds A3G and assembles a Cullin5-based E3 ubiquitin ligase to drive its proteasomal degradation and exclude it from virions, explaining Vif's essentiality.

    Evidence Co-IP, ubiquitination/proteasome inhibitor assays, virion fractionation, species-specificity controls

    PMID:12859895 PMID:14527406 PMID:14528300 PMID:14528301 PMID:14564014

    Open questions at the time
    • Full ligase composition not yet complete (CBF-β unknown)
    • Structural basis of Vif–A3G recognition unresolved
    • Reported translational inhibition of A3G mRNA needed independent mechanistic support
  3. 2004 High

    Determined how A3G enters virions, showing packaging depends on the Gag nucleocapsid domain and a defined A3G region (aa 104-156), establishing encapsidation as a prerequisite for restriction.

    Evidence Co-IP, VLP fractionation, deletion mutagenesis

    PMID:15159405 PMID:15358144

    Open questions at the time
    • RNA dependence of packaging not yet defined
    • Whether packaging requires oligomerization unknown
  4. 2005 High

    Resolved the functional architecture of A3G's two domains, dissociating CD1-mediated antiviral/encapsidation function from CD2-mediated catalysis and demonstrating deaminase-independent restriction.

    Evidence Active-site and deletion mutagenesis with infectivity, RNA-binding, encapsidation, and deaminase readouts

    PMID:15668174 PMID:15721369

    Open questions at the time
    • Molecular nature of deaminase-independent restriction not defined
    • Structures of either domain not yet available
  5. 2006 High

    Characterized the biochemical mode of editing and the resting state of A3G, showing processive 3'→5' scanning on ssDNA and residence in cytoplasmic HMM RNP complexes with Argonautes/P-bodies/stress granules.

    Evidence In vitro processivity assays, TAP-MS, confocal microscopy

    PMID:16622407 PMID:16999936 PMID:17030807 PMID:17166910

    Open questions at the time
    • Functional relevance of P-body/stress-granule localization unclear
    • How RNA gates catalytic activity in HMM complexes unknown
  6. 2007 High

    Demonstrated deaminase-independent inhibition of reverse transcription, showing A3G blocks elongation and strand transfer by out-competing RT for ssDNA, with selective 7SL RNA co-packaging supporting virion loading.

    Evidence Endogenous RT assays in cell-free virions, in vitro primer extension, fluorescence anisotropy, single-molecule stretching, encapsidation assays

    PMID:17855362 PMID:17881443 PMID:17942420 PMID:19057663

    Open questions at the time
    • Whether A3G directly contacts RT not yet shown
    • Relative contribution of editing vs. physical blockade in vivo unquantified
  7. 2008 High

    Provided the first atomic view of the catalytic domain and identified post-translational and transcriptional regulators, defining the active-site DNA-binding model and PKA/Thr32 phosphorylation that modulates Vif susceptibility.

    Evidence NMR structure with DNA titration, in vitro kinase assays, mutagenesis, transcription factor/reporter studies

    PMID:15297452 PMID:16982890 PMID:17517765 PMID:18288108 PMID:18836454

    Open questions at the time
    • N-terminal/Vif-binding domain structure still lacking
    • Physiological signals controlling these regulatory inputs in vivo unclear
  8. 2009 High

    Established that A3G oligomerization is RNA-dependent and mapped to CD1 residues (Y124/W127) that double as packaging determinants, linking oligomeric state to encapsidation and Vif translational control.

    Evidence Y2H, Co-IP, crosslinking, homology modeling, mutagenesis, in vitro RNA-binding/translation assays

    PMID:19266078 PMID:19910370

    Open questions at the time
    • Stoichiometry of functional oligomers unresolved
    • How oligomerization toggles catalytic vs. blocking activity unknown
  9. 2010 High

    Connected oligomeric state to enzymatic behavior and uncovered an additional restriction output, showing CD1 governs processivity and 3'→5' polarity and that A3G impairs integration by generating a 6-bp U5 LTR extension.

    Evidence MALS, AFM, mutagenesis, Southern blot of viral cDNA, integration assays

    PMID:20212048 PMID:20219927

    Open questions at the time
    • Integration defect mechanism's in vivo weight unclear
    • Whether monomer or oligomer is the antiviral unit unresolved
  10. 2011 High

    Defined RNA as a direct negative regulator of A3G catalysis, showing RNA forms RNP complexes that block ssDNA binding and that CBF-β is an obligate component of the Vif degradation machinery.

    Evidence In vitro deaminase assays with defined RNA, native PAGE, AP-MS, reconstituted in vitro ubiquitination, RNAi rescue

    PMID:21856286 PMID:22190037

    Open questions at the time
    • Whether RNA inhibition is purely competitive or allosteric not yet distinguished
    • Structural role of CBF-β in the ligase unknown
  11. 2012 Medium

    Identified a direct A3G–RT interaction (A3G aa 65-132) underlying deaminase-independent inhibition and revealed a nuclear, DNA-repair-associated role of A3G at double-strand breaks.

    Evidence Cell-based Co-IP, deletion analysis, competitive peptide disruption; nuclear fractionation, DSB foci IF, repair assays, AFM

    PMID:22301159 PMID:22645179

    Open questions at the time
    • RT interaction lacks in vitro reconstitution
    • Reconciliation of nuclear DSB role with predominantly cytoplasmic localization unresolved
  12. 2013 High

    Built a dynamic model of A3G action on DNA, showing monomers bind ssDNA rapidly then oligomerize into slow-dissociating roadblocks, and that RNA binding via W94/W127 is specifically required for deaminase-independent restriction.

    Evidence Single-molecule DNA stretching, fluorescence anisotropy, oligomerization mutants, RNA-binding mutants with infectivity/RT/integration readouts; P-body disruption assays

    PMID:23761443 PMID:23926332 PMID:24345943

    Open questions at the time
    • Direct structural snapshot of the oligomeric roadblock lacking
    • Quantitative split between editing and roadblocking in primary cells unclear
  13. 2015 High

    Solved the N-terminal Vif-binding domain structure and dissected mechanisms of RNA-mediated inhibition, mapping distinct ssDNA- and RNA-binding surfaces and the Vif-interacting loops, alongside discovery of A3G-stabilizing factors HDAC6 and ASK1.

    Evidence NMR structure, crosslinking MS, fluorescence anisotropy, native PAGE, Co-IP domain mapping, autophagy/complex-assembly assays

    PMID:25901786 PMID:25984970 PMID:26105074 PMID:26424853

    Open questions at the time
    • Full-length A3G structure still unresolved
    • In vivo significance of HDAC6/ASK1 regulation in infection uncertain
  14. 2016 High

    Provided crystallographic detail of the CD1 dimerization interface bound to ssDNA and established A3G as a transcriptome-wide site-specific mRNA C-to-U editor requiring both catalytic domains.

    Evidence X-ray crystallography of CD1 ± ssDNA, mutagenesis, RNA-seq, RNA co-purification

    PMID:27480941 PMID:27974822

    Open questions at the time
    • Physiological function of cellular mRNA editing unknown
    • How CD1 catalytic residues contribute to RNA editing mechanistically unclear
  15. 2017 High

    Refined substrate selectivity rules and the inhibition-by-oligomerization model, defining the preferred CCCA ssDNA and stem-loop RNA substrates and showing UBER enzymes cleave A3G-edited viral cDNA.

    Evidence Crystallography with Pot1-fusion ssDNA anchoring, single-molecule biophysics, RNA editing substrate mutagenesis, deep sequencing of RT products in T cells, UBER inhibitor assays

    PMID:28928403 PMID:29158605 PMID:29230368 PMID:29596531

    Open questions at the time
    • In vivo balance between hypermutation and UBER-mediated degradation of edited cDNA unquantified
    • Determinants of RNA vs DNA substrate choice not fully separated
  16. 2019 Medium

    Extended A3G's editing biology to physiological cell states and identified a deubiquitinase counter-regulator, showing stress/hypoxia-driven mRNA editing in NK cells and USP49-mediated stabilization of A3G via a Vif/cullin-independent degradation pathway.

    Evidence RNA-seq in primary NK cells with metabolic inhibitors and HIF-1α KO; Co-IP, in vitro deubiquitination, pathway dissection

    PMID:30791937 PMID:31397674

    Open questions at the time
    • Functional consequence of NK-cell mRNA editing unknown
    • Identity of the Vif-independent E3 ligase opposed by USP49 unresolved
  17. 2020 High

    Delivered full-length A3G structures revealing inter-domain packing and a positive electrostatic RNA-binding surface, contextualizing oligomerization and packaging behavior.

    Evidence Cryo-EM and X-ray crystallography of full-length rhesus A3G, mutagenesis, virion packaging assays

    PMID:32005813

    Open questions at the time
    • Conformational changes during catalysis vs. RNA binding not captured
    • Determinants of packaging beyond the electrostatic surface unclear
  18. 2023 High

    Resolved the complete Vif degradation complex bound to A3G, demonstrating that RNA acts as molecular glue at the Vif–A3G N-terminal interface while the catalytic domain is poised for ubiquitin transfer, unifying the structural basis of restriction antagonism.

    Evidence Cryo-EM of A3G–Vif–CBF-β–CUL5-RING complex with biochemical binding and mutagenesis, independently confirmed

    PMID:36598981 PMID:36754086

    Open questions at the time
    • Mechanism of the ubiquitin-independent Vif repression mode incompletely defined
    • How this complex assembles on packaged vs. cytoplasmic A3G in cells unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • The physiological role of A3G's cellular mRNA editing and its nuclear DNA-repair activity, and how A3G's enzymatic and deaminase-independent restriction modes are quantitatively balanced in vivo, remain unresolved.
  • Biological purpose of transcriptome-wide C-to-U editing unknown
  • Relative in vivo contribution of hypermutation vs. physical RT blockade unquantified
  • Mechanism and physiological trigger of nuclear DSB recruitment unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 4 GO:0140098 catalytic activity, acting on RNA 4 GO:0003677 DNA binding 3 GO:0140097 catalytic activity, acting on DNA 3 GO:0016787 hydrolase activity 2
Localization
GO:0031410 cytoplasmic vesicle 3 GO:0005634 nucleus 1 GO:0005829 cytosol 1
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-1643685 Disease 3 R-HSA-8953854 Metabolism of RNA 3 R-HSA-168256 Immune System 2
Partners
CBFBCUL5ELOBELOCHDAC6RBX1USP49VIF
Complex memberships
P-body / stress granule RNPVif–CBF-β–CUL5–ELOB–ELOC–RBX E3 ubiquitin ligase (substrate)high-molecular-mass cytoplasmic ribonucleoprotein complex

Evidence

Reading pass · 49 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 APOBEC3G exerts its antiviral effect during reverse transcription by triggering G-to-A hypermutation in nascent retroviral DNA, acting as a cytidine deaminase that converts dC to dU in minus-strand reverse transcripts. Retroviral infection assays, hypermutation analysis of viral DNA Nature High 12808465 12808466
2003 HIV-1 Vif interacts with cellular proteins Cul5, elongins B and C, and Rbx1 to form an SCF-like E3 ubiquitin ligase complex that induces polyubiquitination and proteasomal degradation of APOBEC3G. Co-immunoprecipitation, ubiquitination assays, proteasome inhibitor studies Science High 14528300 14528301 14564014
2003 HIV-1 Vif prevents APOBEC3G incorporation into progeny virions and induces its proteasomal degradation via ubiquitination, thereby allowing infection to proceed without viral DNA deamination. Virion fractionation, proteasome inhibitor assays, immunoprecipitation Nature medicine High 14527406 14528300 14528301
2003 HIV-1 Vif physically binds APOBEC3G and forms a complex with it; species-specific differences in this interaction explain why HIV-1 Vif does not efficiently complex with mouse APOBEC3G. Co-immunoprecipitation, virion encapsidation assays Cell High 12859895 14528301
2003 Vif impairs both the translation of APOBEC3G mRNA and accelerates posttranslational degradation of the protein by the 26S proteasome, acting through direct physical interaction with APOBEC3G. Western blot with proteasome inhibitors, pulse-chase analysis, immunoprecipitation, endogenous APOBEC3G-specific antiserum Molecular cell High 14527406
2004 APOBEC3G is recruited to the membrane and packaged into HIV-1 Gag virus-like particles through interaction with the nucleocapsid (NC) domain of Gag; amino acids 104-156 of APOBEC3G are required for this incorporation, and Gag alone (without other viral proteins) is sufficient for packaging. Co-immunoprecipitation, virus-like particle fractionation, deletion mutagenesis Journal of Biological Chemistry High 15159405 15358144
2004 APOBEC3G is a single-stranded DNA cytidine deaminase that deaminates cDNA independently of reverse transcriptase; deamination requires the cDNA to be free of its RNA template (RNase H-dependent exposure of ssDNA). In vitro deaminase assay with baculovirus-derived APOBEC3G, RNase H-deficient RT experiments Nucleic acids research High 15121899
2005 APOBEC3G antiviral activity can be dissociated from cytidine deaminase activity: the N-terminal domain (CD1) can confer antiviral function without DNA mutator activity, whereas the C-terminal domain (CD2) is essential for deaminase activity. Only the C-terminal catalytic motif is required for DNA hypermutation. Site-directed mutagenesis of catalytic motifs, infectivity assays, deaminase activity assays Current Biology High 15668174
2005 APOBEC3G's N-terminal domain (CD1) mediates RNA binding and virion encapsidation through zinc-coordination residues and conserved aromatic residues, while the C-terminal domain (CD2) mediates cytidine deaminase activity; the two domains have complementary but non-redundant functions. Deletion and point mutagenesis, RNA binding assays, virion encapsidation assays Virology High 15721369
2006 APOBEC3G acts processively on single-stranded DNA in the 3'→5' direction by a combination of jumping and sliding mechanisms, without requiring a nucleotide cofactor, explaining the G-to-A mutational gradient observed in viral DNA. In vitro biochemical deamination assays, processivity measurements on ssDNA substrates Nature structural & molecular biology High 16622407
2006 APOBEC3G localizes to P bodies and stress granules as part of high-molecular-weight ribonucleoprotein (RNP) complexes; it associates with Argonaute 1 and Argonaute 2 in an RNase-resistant manner, and redistributes to stress granules upon cellular stress. Tandem affinity purification/mass spectrometry, confocal microscopy, RNase treatment co-immunoprecipitation Journal of virology High 17166910
2006 High-molecular-mass (HMM) APOBEC3G complexes, which contain Staufen-containing RNA-transporting granules and Ro RNP complexes loaded with Alu and small Y RNAs, restrict Alu retrotransposition by sequestering Alu RNAs in cytoplasmic HMM complexes rather than by inhibiting L1 reverse transcriptase function. Tandem affinity purification/MS, Alu retrotransposition reporter assay, RNA analysis PNAS High 17030807
2007 APOBEC3G inhibits HIV-1 minus- and plus-strand DNA transfer steps during reverse transcription independently of its editing activity; this inhibition correlates with its ability to prevent RNase H degradation of the RNA template. In vivo viral cDNA intermediate analysis, in vitro strand transfer assay Journal of Biological Chemistry Medium 17855362
2007 7SL RNA selectively interacts with APOBEC3G and is preferentially packaged into HIV-1 particles via the nucleocapsid domain of Gag; APOBEC3G mutants with reduced 7SL RNA binding are packaged poorly and have impaired antiviral activity. RNA-binding assays, virion encapsidation assays, SRP19 overexpression to competitively reduce 7SL RNA Journal of virology Medium 17881443
2007 APOBEC3G inhibits HIV-1 reverse transcription elongation in a deaminase-independent manner; in cell-free virions, A3G impedes elongation of cDNA products without requiring target cell factors. Endogenous reverse transcriptase assay in cell-free virions PLoS pathogens Medium 19057663
2007 APOBEC3G inhibits RT-catalyzed DNA elongation reactions in a deaminase-independent manner by competing with RT for ssDNA binding; NC has faster nucleic acid association/dissociation kinetics than A3G, while RT binds ssDNA with much lower affinity than A3G. In vitro primer extension assays, fluorescence anisotropy, single-molecule DNA stretching Nucleic acids research High 17942420
2008 The solution structure of the APOBEC3G catalytic (C-terminal) domain reveals five alpha-helices arranged over a hydrophobic beta-strand platform with a zinc-coordinating active site; NMR DNA titration and mutagenesis define a DNA-binding model with positively charged residues positioning the target cytosine for catalysis. NMR structure determination, DNA titration NMR, computational modelling, E. coli-based activity assays Nature High 18288108
2008 Protein kinase A (PKA) binds and phosphorylates APOBEC3G at Thr32 in vitro and in vivo; this phosphorylation reduces A3G binding to Vif, diminishes Vif-induced ubiquitination and degradation, and promotes antiviral activity. In vitro kinase assay, co-immunoprecipitation, mutagenesis, structural modeling Nature structural & molecular biology Medium 18836454
2008 APOBEC3G is exclusively retained in the cytoplasm and does not undergo nucleo-cytoplasmic shuttling; this cytoplasmic retention requires both the N- and C-terminal regions of the protein. Live-cell imaging, subcellular fractionation, heterokaryon assays Biochemical and biophysical research communications Medium 16999936
2009 APOBEC3G oligomerization is RNA-dependent and requires tyrosine-124 and tryptophan-127 in the N-terminal CDA domain; these oligomerization-mediating residues also coincide with virion packaging determinants. Arginine residues at positions 24, 30, and 136 in a positively charged pocket promote RNA-dependent oligomerization and virion packaging. Yeast two-hybrid, co-immunoprecipitation, chemical crosslinking, homology modeling, mutational analysis PLoS pathogens High 19266078
2009 HIV-1 Vif directly binds to APOBEC3G mRNA (with higher affinity for the 3'UTR) and inhibits its translation by two mechanisms: a time-independent process requiring the 5'UTR and an additional UTR-independent process. Filter binding assays, fluorescence titration, RNase footprinting, in vitro translation assays Nucleic acids research Medium 19910370
2010 APOBEC3G inhibits HIV-1 DNA integration by generating a 6-bp extension at the viral U5 end of the 3'-LTR (a poor substrate for integration), dependent on a functional C-terminal catalytic domain; this mechanism is distinct from that of APOBEC3F. Southern blot analysis of viral cDNA processing, integration assays, mutational analysis Journal of virology Medium 20219927
2010 APOBEC3G exists as monomers, dimers, tetramers, and higher-order oligomers; the CD1 domain is essential for both processivity and 3'→5' deamination polarity. A CD1-CD1 dimer interface mutant (F126A/W127A) predominantly converts A3G to a monomer that retains ssDNA binding, Alu RNA binding, and processive deaminase activity. Multiangle light scattering, atomic force microscopy, mutagenesis, deaminase activity assays Journal of Biological Chemistry High 20212048
2011 Vif additionally recruits the transcription cofactor CBF-β to the Vif-CUL5-ELOC-ELOB-RBX ubiquitin ligase complex; CBF-β is required for Vif-mediated APOBEC3G degradation and a reconstituted six-protein assembly elicits specific polyubiquitination of APOBEC3G but not APOBEC3A. Affinity tag/purification mass spectrometry, RNA knockdown, genetic complementation, reconstituted in vitro ubiquitination assay Nature High 22190037
2012 APOBEC3G directly interacts with HIV-1 reverse transcriptase (RT); the RT-binding region of A3G maps to amino acids 65-132. This interaction disrupts RT function and plays an important role in A3G's deaminase-independent inhibition of reverse transcription. Cell-based co-immunoprecipitation, deletion analysis, overexpression of binding-domain peptide to competitively disrupt interaction Journal of virology Medium 22301159
2012 APOBEC3G accumulates transiently in the nucleus in response to ionizing radiation, is recruited to DNA double-strand break (DSB) repair foci, and promotes DSB repair in a deaminase-dependent manner; AFM shows that A3G multimers associate with ssDNA termini at DSBs. Nuclear fractionation, immunofluorescence recruitment to DSB foci, siRNA knockdown with DSB repair assay, reporter cassette, atomic force microscopy Blood Medium 22645179
2013 APOBEC3G initially binds ssDNA with rapid on-off rates and subsequently converts to a slowly dissociating mode through oligomerization; an oligomerization-deficient mutant does not exhibit the slow off rate, suggesting catalytically active monomers/dimers oligomerize on the viral genome to inhibit reverse transcription. Single-molecule DNA stretching, fluorescence anisotropy, oligomerization mutant analysis Nature chemistry High 24345943
2013 RNA binding by APOBEC3G (via tryptophan residues W94 and W127 in the N-terminal domain) is specifically required for deamination-independent restriction of retroviruses, including inhibition of late reverse transcript accumulation and prevention of proviral DNA integration; deaminase activity does not significantly contribute to restriction of these processes. Mutagenesis of RNA-binding residues, retroviral infectivity assays, RT product quantification, integration assays Nucleic acids research Medium 23761443
2013 APOBEC3G and P-body localization to processing bodies is not required for virion incorporation or antiviral activity; sucrose gradient analysis shows the majority of A3G is in high-molecular-mass RNA-protein complexes distinct from canonical P-body markers. DDX6 knockdown to disrupt P bodies, SRP19 overexpression to deplete A3G from P bodies, sucrose gradient sedimentation Journal of virology Medium 23926332
2015 NMR structure of the APOBEC3G N-terminal (Vif-binding) domain reveals a smaller zinc-coordinating pocket and altered helical packing compared to the catalytic domain; the Vif-interacting surface is formed by loops α1-β1, β2-α2, and β4-α4, identified by mutagenesis and biochemical binding experiments. NMR structure determination (evolution- and structure-guided solubilizing mutations), mutagenesis, biochemical binding assays Nature structural & molecular biology High 25984970
2015 HDAC6 directly interacts with APOBEC3G through its C-terminal BUZ domain and co-distributes along microtubules; HDAC6 also interacts with Vif and promotes its autophagic degradation (requiring HDAC6 deacetylase activity), thereby stabilizing A3G and increasing its incorporation into virions. Co-immunoprecipitation, domain mapping, autophagy inhibitor assays, virion fractionation Retrovirology Medium 26105074
2015 ASK1 (apoptosis signal-regulating kinase 1) binds the BC-box of Vif, disrupting assembly of the Vif-ubiquitin ligase complex, thereby stabilizing A3G and promoting its incorporation into viral particles; AZT treatment induces ASK1 expression, restoring A3G antiviral activity. Co-immunoprecipitation, ubiquitin ligase complex assembly assays, virion fractionation, viral infectivity assays Nature communications Medium 25901786
2016 Crystal structure of a primate A3G N-terminal domain (CD1) alone and in complex with ssDNA shows the dimerization interface and reveals conformational changes in loops around the zinc-coordinated center upon DNA binding; the CD1 dimerization interface is important for oligomerization, nucleic acid binding, and Vif-mediated degradation. X-ray crystallography, mutagenesis, functional assays Nature communications High 27480941
2016 APOBEC3G causes site-specific C-to-U editing of mRNAs from over 600 genes, requiring conserved catalytic residues in both N-terminal and C-terminal cytidine deaminase domains; APOBEC3G co-purifies with highly edited mRNA substrates. Transcriptome-wide RNA-seq, active-site mutagenesis of both catalytic domains, RNA co-purification Scientific reports Medium 27974822
2017 Deep sequencing of HIV-1 reverse transcripts in infected T cells demonstrates that A3G inhibits reverse transcription in a site- and sequence-independent manner that requires direct interaction with reverse transcriptase; cellular uracil base excision repair (UBER) enzymes target and cleave A3G-edited uridine-containing viral cDNA. Deep sequencing of nascent reverse transcription products, A3G-RT interaction studies, UBER inhibitor assays Nature microbiology High 29158605
2017 APOBEC3G first binds ssDNA as a catalytically active monomer, then forms N-terminal domain-mediated dimers whose dissociation from DNA is reduced and deaminase activity is inhibited; this dimerization-to-inactivation mechanism may create enzymatically deficient roadblocks that inhibit reverse transcription. Single-molecule DNA stretching, fluorescence assays with wild-type and oligomerization-deficient A3G mutants Nature communications Medium 28928403
2019 APOBEC3G induces widespread site-specific C-to-U mRNA editing in natural killer cells and lymphoma cell lines under conditions of cellular crowding and hypoxia (mimicked by mitochondrial respiration inhibition), independently of HIF-1α; this editing is enriched for genes involved in mRNA translation and ribosome function. RNA-seq in primary NK cells, mitochondrial inhibitors, HIF-1α knockout controls, metabolic assays Genome biology Medium 30791937
2019 USP49 directly interacts with APOBEC3G and efficiently removes ubiquitin from it, stabilizing A3G protein expression and enhancing its anti-HIV-1 activity; A3G degradation also occurs via a Vif- and cullin-ring-independent pathway that USP49 counteracts. Co-immunoprecipitation, in vitro deubiquitination assay, proteasome pathway dissection, clinical sample correlation eLife Medium 31397674
2020 Full-length rhesus macaque A3G cryo-EM/crystal structures reveal different inter-domain packing through a short linker and refolding of CD2; A3G dimerization generates a surface with intensified positive electrostatic potential for RNA binding and dimer stabilization, though mutating this surface does not abolish virion packaging. Cryo-EM and X-ray crystallography of full-length A3G, mutagenesis, virion packaging assays Nature communications High 32005813
2023 Cryo-EM structure of human APOBEC3G bound to HIV-1 Vif in complex with CBF-β and the CUL5-RING E3 ubiquitin ligase reveals that RNA acts as molecular glue for the Vif-A3G interaction; Vif makes contact primarily through A3G's non-catalytic N-terminal domain while the catalytic domain is positioned for ubiquitin transfer. Vif can repress A3G by both ubiquitin-dependent and ubiquitin-independent mechanisms. Cryo-electron microscopy structure determination, biochemical binding assays, mutagenesis Nature High 36598981 36754086
2004 Transcription of APOBEC3G in human T lymphocytes is controlled by the PKCα/βI–MEK–ERK protein kinase cascade; PKCα/βI/MEK/ERK pathway inhibitors reduce both basal and induced APOBEC3G mRNA/protein levels, and this pathway is activated by phorbol myristate acetate. Pharmacological inhibitor studies, luciferase reporter assays, RT-PCR and western blot Journal of Biological Chemistry Medium 15297452
2007 Basal transcription of the APOBEC3G gene is regulated by transcription factors Sp1 and Sp3 through a GC-box element at position -87/-78 relative to the major transcriptional start site; mutation of this GC-box abolishes promoter activity. Luciferase reporter assays, EMSA, chromatin immunoprecipitation (ChIP), 5' RACE Nucleic acids research Medium 17517765
2006 IFN-α induces APOBEC3G expression in liver cells and macrophages but not in T cells or epithelial cells; this induction is STAT1-independent but STAT2-dependent in liver cells, revealing a non-canonical IFN-α signaling pathway for A3G regulation. Cytokine treatment, pathway inhibitors (Rottlerin), STAT1-deficient cells, western blot/RT-PCR Journal of immunology Medium 16982890
2008 The prolyl isomerase Pin1 interacts with APOBEC3G and reduces its expression and incorporation into HIV-1 virions; HIV-1 infection modulates Pin1 phosphorylation state, enhancing its ability to decrease A3G activity. Co-immunoprecipitation, virion incorporation assays, HIV infection modulation of Pin1 Journal of virology Low 18684817
2011 RNA directly suppresses APOBEC3G ssDNA deaminase activity in a concentration-dependent manner; RNA forms RNP complexes with A3G that prevent ssDNA substrates from binding; RNAs as short as 25 nt and of diverse sequences are effective inhibitors. In vitro deaminase assay with defined RNA concentrations, native PAGE gel-shift analysis Biochemical and biophysical research communications High 21856286
2015 RNA stochastically dissociates APOBEC3G dimers and higher-order oligomers from ssDNA; mass spectrometry cross-linking maps distinct A3G peptide surfaces for ssDNA binding (aa 181-194, 314-320, 345-374) versus RNA binding (same surfaces plus additional N-terminal peptides aa 15-29, 41-52, 83-99), suggesting RNA inhibition occurs through both competitive and allosteric mechanisms. Native PAGE, fluorescence anisotropy, cross-linking mass spectrometry peptide mapping Nucleic acids research High 26424853
2017 Both APOBEC3A and APOBEC3G prefer RNA substrates with a stem-loop structure where the reactive cytidine is at the 3'-end of the loop; loop size, nucleotides 5' of the target C, and stem stability all influence editing efficiency. Mutagenesis of endogenous RNA substrates, RNA editing assays PeerJ Medium 29230368
2018 Crystal structure of APOBEC3G catalytic domain in complex with ssDNA (via Pot1-fusion anchoring strategy) reveals a unique conformation of catalytic-site loops; nucleotide-binding pockets at the -1 and active-site positions influence each other in selecting the preferred CCCA substrate sequence. X-ray crystallography with Pot1-fusion strategy, biochemical deaminase assays, HIV infectivity assays PLoS one Medium 29596531
2017 APOBEC3G-mediated C-to-U mRNA editing requires stem-loop RNA secondary structure with the target cytidine at the 3'-end of the loop, and APOBEC3G edits sites largely distinct from those targeted by APOBEC3A. Transcriptome RNA-seq, mutagenesis of RNA substrates PeerJ Medium 29230368

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts. Nature 1238 12808466
2003 Induction of APOBEC3G ubiquitination and degradation by an HIV-1 Vif-Cul5-SCF complex. Science (New York, N.Y.) 1008 14564014
2003 The cytidine deaminase CEM15 induces hypermutation in newly synthesized HIV-1 DNA. Nature 914 12808465
2003 The antiretroviral enzyme APOBEC3G is degraded by the proteasome in response to HIV-1 Vif. Nature medicine 799 14528300
2003 Species-specific exclusion of APOBEC3G from HIV-1 virions by Vif. Cell 763 12859895
2003 HIV-1 Vif protein binds the editing enzyme APOBEC3G and induces its degradation. Nature medicine 680 14528301
2003 HIV-1 Vif blocks the antiviral activity of APOBEC3G by impairing both its translation and intracellular stability. Molecular cell 607 14527406
2005 Antiviral function of APOBEC3G can be dissociated from cytidine deaminase activity. Current biology : CB 421 15668174
2004 Ancient adaptive evolution of the primate antiviral DNA-editing enzyme APOBEC3G. PLoS biology 371 15269786
2011 Vif hijacks CBF-β to degrade APOBEC3G and promote HIV-1 infection. Nature 313 22190037
2011 Human and rhesus APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H demonstrate a conserved capacity to restrict Vif-deficient HIV-1. Journal of virology 297 21835787
2003 The human immunodeficiency virus type 1 Vif protein reduces intracellular expression and inhibits packaging of APOBEC3G (CEM15), a cellular inhibitor of virus infectivity. Journal of virology 274 14557625
2005 Complementary function of the two catalytic domains of APOBEC3G. Virology 273 15721369
2007 Deaminase-independent inhibition of HIV-1 reverse transcription by APOBEC3G. Nucleic acids research 272 17942420
2008 APOBEC3G inhibits elongation of HIV-1 reverse transcripts. PLoS pathogens 268 19057663
2006 APOBEC3G DNA deaminase acts processively 3' --> 5' on single-stranded DNA. Nature structural & molecular biology 252 16622407
2006 Antiviral protein APOBEC3G localizes to ribonucleoprotein complexes found in P bodies and stress granules. Journal of virology 232 17166910
2004 The interaction between HIV-1 Gag and APOBEC3G. The Journal of biological chemistry 217 15159405
2006 High-molecular-mass APOBEC3G complexes restrict Alu retrotransposition. Proceedings of the National Academy of Sciences of the United States of America 207 17030807
2008 Structure of the DNA deaminase domain of the HIV-1 restriction factor APOBEC3G. Nature 185 18288108
2004 APOBEC3G is a single-stranded DNA cytidine deaminase and functions independently of HIV reverse transcriptase. Nucleic acids research 178 15121899
2003 The enzymatic activity of CEM15/Apobec-3G is essential for the regulation of the infectivity of HIV-1 virion but not a sole determinant of its antiviral activity. The Journal of biological chemistry 159 12970355
2008 Exosomes packaging APOBEC3G confer human immunodeficiency virus resistance to recipient cells. Journal of virology 147 18987139
2009 RNA-dependent oligomerization of APOBEC3G is required for restriction of HIV-1. PLoS pathogens 143 19266078
2007 7SL RNA mediates virion packaging of the antiviral cytidine deaminase APOBEC3G. Journal of virology 136 17881443
2006 Distinct patterns of cytokine regulation of APOBEC3G expression and activity in primary lymphocytes, macrophages, and dendritic cells. The Journal of biological chemistry 133 17110377
2007 APOBEC3G inhibits DNA strand transfer during HIV-1 reverse transcription. The Journal of biological chemistry 130 17855362
2005 APOBEC3G hypermutates genomic DNA and inhibits Ty1 retrotransposition in yeast. Proceedings of the National Academy of Sciences of the United States of America 124 16000409
2006 Anti-viral protein APOBEC3G is induced by interferon-alpha stimulation in human hepatocytes. Biochemical and biophysical research communications 121 16426578
2005 APOBEC3G targets human T-cell leukemia virus type 1. Retrovirology 118 15943885
2008 Characterization of conserved motifs in HIV-1 Vif required for APOBEC3G and APOBEC3F interaction. Journal of molecular biology 117 18619467
2010 APOBEC3G generates nonsense mutations in human T-cell leukemia virus type 1 proviral genomes in vivo. Journal of virology 103 20463074
2005 APOBEC3G/CEM15 (hA3G) mRNA levels associate inversely with human immunodeficiency virus viremia. Journal of virology 101 16103203
2010 Structural model for deoxycytidine deamination mechanisms of the HIV-1 inactivation enzyme APOBEC3G. The Journal of biological chemistry 100 20212048
2010 APOBEC3F and APOBEC3G inhibit HIV-1 DNA integration by different mechanisms. Journal of virology 98 20219927
2004 APOBEC3G targets specific virus species. Journal of virology 98 15254195
2012 The cellular antiviral protein APOBEC3G interacts with HIV-1 reverse transcriptase and inhibits its function during viral replication. Journal of virology 90 22301159
2011 The activity spectrum of Vif from multiple HIV-1 subtypes against APOBEC3G, APOBEC3F, and APOBEC3H. Journal of virology 87 22013041
2004 HIV-1 and MLV Gag proteins are sufficient to recruit APOBEC3G into virus-like particles. Biochemical and biophysical research communications 86 15358144
2006 STAT1-independent cell type-specific regulation of antiviral APOBEC3G by IFN-alpha. Journal of immunology (Baltimore, Md. : 1950) 84 16982890
2017 Deep sequencing of HIV-1 reverse transcripts reveals the multifaceted antiviral functions of APOBEC3G. Nature microbiology 83 29158605
2016 The double-domain cytidine deaminase APOBEC3G is a cellular site-specific RNA editing enzyme. Scientific reports 78 27974822
2008 Restriction of retroviral replication by APOBEC3G/F and TRIM5alpha. Trends in microbiology 75 18976920
2015 Structure of the Vif-binding domain of the antiviral enzyme APOBEC3G. Nature structural & molecular biology 72 25984970
2013 Binding of RNA by APOBEC3G controls deamination-independent restriction of retroviruses. Nucleic acids research 72 23761443
2007 Analysis of the contribution of cellular and viral RNA to the packaging of APOBEC3G into HIV-1 virions. Retrovirology 70 17631688
2016 Crystal structures of APOBEC3G N-domain alone and its complex with DNA. Nature communications 69 27480941
2004 Transcriptional regulation of APOBEC3G, a cytidine deaminase that hypermutates human immunodeficiency virus. The Journal of biological chemistry 67 15297452
2008 Phosphorylation of APOBEC3G by protein kinase A regulates its interaction with HIV-1 Vif. Nature structural & molecular biology 65 18836454
2008 Interactions of murine APOBEC3 and human APOBEC3G with murine leukemia viruses. Journal of virology 64 18448535
2019 Mitochondrial hypoxic stress induces widespread RNA editing by APOBEC3G in natural killer cells. Genome biology 63 30791937
2009 HIV-1 Vif binds to APOBEC3G mRNA and inhibits its translation. Nucleic acids research 63 19910370
2017 Stem-loop structure preference for site-specific RNA editing by APOBEC3A and APOBEC3G. PeerJ 62 29230368
2009 Tumultuous relationship between the human immunodeficiency virus type 1 viral infectivity factor (Vif) and the human APOBEC-3G and APOBEC-3F restriction factors. Microbiology and molecular biology reviews : MMBR 62 19487726
2004 Exhaustive genotyping of the CEM15 (APOBEC3G) gene and absence of association with AIDS progression in a French cohort. The Journal of infectious diseases 62 15609224
2023 The structural basis for HIV-1 Vif antagonism of human APOBEC3G. Nature 60 36754086
2013 Oligomerization transforms human APOBEC3G from an efficient enzyme to a slowly dissociating nucleic acid-binding protein. Nature chemistry 60 24345943
2012 APOBEC3G-induced hypermutation of human immunodeficiency virus type-1 is typically a discrete "all or nothing" phenomenon. PLoS genetics 60 22457633
2012 APOBEC3G enhances lymphoma cell radioresistance by promoting cytidine deaminase-dependent DNA repair. Blood 60 22645179
2004 Analysis of HIV-1 viral infectivity factor-mediated proteasome-dependent depletion of APOBEC3G: correlating function and subcellular localization. The Journal of biological chemistry 58 15537645
2016 APOBEC3G Expression Correlates with T-Cell Infiltration and Improved Clinical Outcomes in High-grade Serous Ovarian Carcinoma. Clinical cancer research : an official journal of the American Association for Cancer Research 57 27016308
2015 Identification of the HIV-1 Vif and Human APOBEC3G Protein Interface. Cell reports 51 26628364
2015 The HDAC6/APOBEC3G complex regulates HIV-1 infectiveness by inducing Vif autophagic degradation. Retrovirology 50 26105074
2010 Differential anti-APOBEC3G activity of HIV-1 Vif proteins derived from different subtypes. The Journal of biological chemistry 50 20833716
2006 Biochemical differentiation of APOBEC3F and APOBEC3G proteins associated with HIV-1 life cycle. The Journal of biological chemistry 49 17142455
2015 Development of benzimidazole derivatives to inhibit HIV-1 replication through protecting APOBEC3G protein. European journal of medicinal chemistry 48 25847768
2009 APOBEC3G mRNA expression in exposed seronegative and early stage HIV infected individuals decreases with removal of exposure and with disease progression. Retrovirology 48 19254362
2008 APOBEC3G encapsidation into HIV-1 virions: which RNA is it? Retrovirology 47 18597677
2016 APOBEC3G-Mediated G-to-A Hypermutation of the HIV-1 Genome: The Missing Link in Antiviral Molecular Mechanisms. Frontiers in microbiology 44 28066353
2013 Retroviral restriction factor APOBEC3G delays the initiation of DNA synthesis by HIV-1 reverse transcriptase. PloS one 40 23717565
2009 Stochastic properties of processive cytidine DNA deaminases AID and APOBEC3G. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 40 19022738
2009 APOBEC3G: an intracellular centurion. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 39 19008196
2008 Human immunodeficiency virus type 1 replication and regulation of APOBEC3G by peptidyl prolyl isomerase Pin1. Journal of virology 39 18684817
2020 Understanding the structural basis of HIV-1 restriction by the full length double-domain APOBEC3G. Nature communications 37 32005813
2017 Dimerization regulates both deaminase-dependent and deaminase-independent HIV-1 restriction by APOBEC3G. Nature communications 36 28928403
2013 Mov10 and APOBEC3G localization to processing bodies is not required for virion incorporation and antiviral activity. Journal of virology 36 23926332
2009 Differences in APOBEC3G expression in CD4+ T helper lymphocyte subtypes modulate HIV-1 infectivity. PLoS pathogens 36 19197360
2012 APOBEC3G expression and hypermutation are inversely associated with human immunodeficiency virus type 1 (HIV-1) burden in vivo. Virology 35 22579353
2011 Direct evidence that RNA inhibits APOBEC3G ssDNA cytidine deaminase activity. Biochemical and biophysical research communications 35 21856286
2012 Small-molecule APOBEC3G DNA cytosine deaminase inhibitors based on a 4-amino-1,2,4-triazole-3-thiol scaffold. ChemMedChem 34 23180603
2014 Small molecules that inhibit Vif-induced degradation of APOBEC3G. Virology journal 33 24986077
2021 Dysregulated APOBEC3G causes DNA damage and promotes genomic instability in multiple myeloma. Blood cancer journal 32 34625538
2015 ASK1 restores the antiviral activity of APOBEC3G by disrupting HIV-1 Vif-mediated counteraction. Nature communications 31 25901786
2015 RNA binding to APOBEC3G induces the disassembly of functional deaminase complexes by displacing single-stranded DNA substrates. Nucleic acids research 30 26424853
2023 The Cytidine Deaminase APOBEC3G Contributes to Cancer Mutagenesis and Clonal Evolution in Bladder Cancer. Cancer research 29 36480186
2012 Emerging complexities of APOBEC3G action on immunity and viral fitness during HIV infection and treatment. Retrovirology 29 22546055
2009 High level expression of the anti-retroviral protein APOBEC3G is induced by influenza A virus but does not confer antiviral activity. Retrovirology 29 19371434
2008 Vpr14-88-Apobec3G fusion protein is efficiently incorporated into Vif-positive HIV-1 particles and inhibits viral infection. PloS one 29 18414671
2008 Expression and regulation of antiviral protein APOBEC3G in human neuronal cells. Journal of neuroimmunology 29 19027180
2006 Inhibition of HIV-1 replication by simian restriction factors, TRIM5alpha and APOBEC3G. Gene therapy 29 16943852
2018 Insights into DNA substrate selection by APOBEC3G from structural, biochemical, and functional studies. PloS one 28 29596531
2017 Hepatitis B virus X protein is capable of down-regulating protein level of host antiviral protein APOBEC3G. Scientific reports 28 28098260
2007 Sp1 and Sp3 regulate basal transcription of the human APOBEC3G gene. Nucleic acids research 28 17517765
2023 Structural basis for HIV-1 antagonism of host APOBEC3G via Cullin E3 ligase. Science advances 27 36598981
2019 USP49 potently stabilizes APOBEC3G protein by removing ubiquitin and inhibits HIV-1 replication. eLife 27 31397674
2010 Inhibition of LINE-1 and Alu retrotransposition by exosomes encapsidating APOBEC3G and APOBEC3F. Virology 27 20153011
2006 APOBEC-1 and AID are nucleo-cytoplasmic trafficking proteins but APOBEC3G cannot traffic. Biochemical and biophysical research communications 27 16999936
2020 Long non-coding RNA ESCCAL-1 promotes esophageal squamous cell carcinoma by down regulating the negative regulator of APOBEC3G. Cancer letters 25 32905814
2015 Identification of an HIV-1 replication inhibitor which rescues host restriction factor APOBEC3G in Vif-APOBEC3G complex. Antiviral research 25 26241003
2006 High expression of APOBEC3G in patients infected with hepatitis C virus. Journal of molecular histology 24 17036163

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