Affinage

AICDA

Single-stranded DNA cytosine deaminase · UniProt Q9GZX7

Length
198 aa
Mass
24.0 kDa
Annotated
2026-06-09
100 papers in source corpus 34 papers cited in narrative 34 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AICDA (AID) is a B cell single-stranded DNA cytidine deaminase that initiates antibody diversification, serving as the obligate trigger for both class switch recombination (CSR) and somatic hypermutation (SHM) — processes that are completely abolished in its absence and underlie autosomal recessive hyper-IgM syndrome type 2 in humans (PMID:11007474, PMID:11007475). Mechanistically, AID converts deoxycytidine to deoxyuridine in DNA, not RNA, producing a mutator phenotype that is amplified by loss of uracil excision; this generates uracil lesions physically detectable on both strands of Ig variable and switch DNA, whose processing yields the AID-dependent, UNG-dependent double-strand breaks at WRC/GYW hotspots that drive recombination (PMID:12097915, PMID:16103411, PMID:21151102). Catalysis is restricted to single-stranded DNA and is coupled to transcription, which exposes ssDNA; the enzyme acts processively, tracking unidirectionally with RNA polymerase on transcription bubbles and preferentially deaminating the exposed non-transcribed strand at 5'-WRC motifs (PMID:12692563, PMID:12819663, PMID:26681117). Crystallographic analysis reveals a bifurcated substrate-binding surface that engages two adjacent ssDNA overhangs and favors G-quadruplex substrates mimicking switch regions, with G4-induced cooperative oligomerization required for CSR (PMID:28757211). Substrate access to double-stranded DNA additionally requires PKA phosphorylation at Ser38, which enables RPA association, and phosphorylation at Thr140 contributes preferentially to SHM, allowing the two arms of antibody diversification to be genetically separated (PMID:16251902, PMID:18838546, PMID:21258321). AID is targeted to its genomic substrates by noncoding RNA: intronic switch RNA acting in trans via G-quadruplex structures, and RNA-exosome-regulated antisense/divergent transcripts that mark ssDNA-forming loci (PMID:25119026, PMID:25957684). Because AID is a promiscuous mutagen, its activity is constrained by transcriptional control (Pax5/E-box activators, c-Myb/E2f silencers in the first intron, BCR-calmodulin inhibition of E2A, estrogen-receptor and NF-κB induction, and BATF/TET-dependent superenhancer activity) and by cell-cycle-regulated nuclear-cytoplasmic shuttling that limits genotoxic nuclear exposure to G1 (PMID:18203819, PMID:19139166, PMID:19966806, PMID:26355458, PMID:31028100, PMID:16439679). Beyond immunity, AID mediates active DNA demethylation at OCT4 and NANOG during reprogramming and shapes epigenetic methylation heterogeneity in lymphomas (PMID:20027182, PMID:29335468). Its off-target activity causes c-myc/IgH translocations and germinal-center-derived lymphomas, and deamination of 5-methylcytosine can generate oncogenic mutations such as EGFR T790M (PMID:12732658, PMID:18066064, PMID:17724134, PMID:30333118, PMID:26276629).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2000 High

    Establishing that a single factor controls antibody diversification, AID was shown to be required for both CSR and SHM and causally linked to a human immunodeficiency, defining the gene's central physiological role.

    Evidence AID-/- mouse knockout with CSR/SHM defects, transgenic overexpression in CH12F3-2 cells, and genetic sequencing of HIGM2 patients

    PMID:11007474 PMID:11007475

    Open questions at the time
    • Did not define the biochemical substrate (DNA vs RNA)
    • Did not establish enzymatic mechanism or targeting
  2. 2002 High

    Resolving the long-debated substrate question, AID was shown to act as a DNA cytidine deaminase rather than an RNA-editing enzyme, and to be sufficient to drive hypermutation of a transcribed reporter in non-lymphoid cells.

    Evidence E. coli mutator assay with UNG-deficiency epistasis, Ig gene conversion rescue in DT40 cells, and ectopic AID expression with a GFP reporter in fibroblasts

    PMID:11847344 PMID:12065838 PMID:12097915

    Open questions at the time
    • Did not show strand or sequence preference of purified enzyme
    • Did not address how transcription exposes substrate in vivo
  3. 2003 High

    Defining the enzyme's intrinsic biochemistry, purified AID was shown to deaminate ssDNA processively at WRC hotspots and to access dsDNA only when coupled to transcription, explaining its transcription dependence in vivo.

    Evidence In vitro deamination assays on ssDNA/dsDNA, transcription-coupled deamination, mutation spectrum and processivity analysis with purified AID

    PMID:12692563 PMID:12819663

    Open questions at the time
    • Did not explain genomic targeting specificity to Ig loci
    • Did not identify cofactors or post-translational regulation
  4. 2005 High

    Connecting signaling to enzymatic access, PKA phosphorylation at Ser38 was shown to enable RPA association and dsDNA deamination, providing a regulatable switch for CSR distinct from intrinsic ssDNA catalysis.

    Evidence Recombinant PKA phosphorylation assay, AID-RPA co-IP, site-directed mutagenesis, and in vivo CSR assays; complemented by LM-PCR detection of AID/UNG-dependent switch-region DSBs

    PMID:15607819 PMID:16103411 PMID:16251902

    Open questions at the time
    • Did not map all phosphosites or their division of labor between CSR and SHM
    • Did not resolve how phosphorylation is spatially restricted
  5. 2008 Medium

    Refining the regulatory code, a second phosphosite (Thr140) was identified that preferentially supports SHM, and BCR-calmodulin-E2A signaling was shown to repress AID transcription, revealing layered control of a dangerous mutator.

    Evidence Mass spectrometry phosphosite mapping with alanine-substitution mice, plus BCR stimulation, calmodulin overexpression, and E2A mutagenesis

    PMID:18203819 PMID:18838546

    Open questions at the time
    • Did not establish kinase identity for T140
    • Mechanistic separation of CSR vs SHM functions remained partial
  6. 2010 High

    Extending function beyond immunity, AID was shown to be required for active DNA demethylation at pluripotency promoters during reprogramming, and AID-generated uracil was directly detected in Ig DNA, confirming the deamination-then-repair model in vivo.

    Evidence siRNA knockdown in heterokaryons with promoter methylation/binding analysis, and direct uracil detection by UDG/abasic-endonuclease assays in stimulated B cells

    PMID:20027182 PMID:21151102

    Open questions at the time
    • Direct demethylation mechanism (5mC deamination vs indirect) not fully resolved
    • Did not define how AID is targeted to non-Ig developmental loci
  7. 2015 High

    Solving the genomic targeting problem, noncoding RNAs were shown to recruit AID to ssDNA-forming sites — intronic switch RNA via G-quadruplexes in trans, and RNA-exosome-regulated antisense/divergent transcripts — while single-molecule and cell-cycle studies defined how AID moves with RNAPII and is spatially restricted.

    Evidence RNA-AID binding and G4 biochemistry with mutagenesis and CSR rescue; conditional Exosc3 KO with AID recruitment/ChIP; smFRET of AID on transcription bubbles; cell-cycle degradation-tag and localization studies

    PMID:25119026 PMID:25957684 PMID:26355458 PMID:26681117

    Open questions at the time
    • RNA-binding interface on AID not fully mapped structurally
    • How ncRNA and phosphorylation cues are integrated remains unresolved
  8. 2016 Medium

    Linking oligomeric state to cofactor selection, the AID C-terminus was shown to control dimerization, with monomers and dimers engaging distinct hnRNP cofactors in an RNA-dependent manner, partitioning DNA cleavage from recombination functions.

    Evidence BiFC, glycerol gradient fractionation, and co-immunoprecipitation

    PMID:26929374

    Open questions at the time
    • Co-IP without reciprocal/structural validation of individual hnRNP contacts
    • Functional consequences of each cofactor association not dissected in vivo
  9. 2017 High

    Providing atomic-resolution mechanism, crystal structures revealed a bifurcated substrate-binding surface capturing two adjacent ssDNA overhangs and a preference for G-quadruplex switch substrates that drives cooperative oligomerization required for CSR.

    Evidence X-ray crystallography of MBP-AID alone and with dCMP, in vitro deamination, structure-guided mutagenesis, and in vivo splenic-B-cell CSR assays

    PMID:28757211

    Open questions at the time
    • No structure of full-length AID bound to physiological RNA/DNA complexes
    • Structural basis of phosphoregulation and RPA contact not resolved
  10. 2022 Medium

    Connecting chromatin state to mutational targeting, SETD2/H3K36me3 was shown to constrain AID-induced SHM on the nontemplate strand, demonstrating that chromatin modifications tune the genomic consequences of AID activity, alongside roles in oncogenic mutation and translocation.

    Evidence Heterozygous Setd2 KO mice with H3K36me3 and RNAPII ChIP-seq, whole-genome mutation analysis; complemented by lymphoma models linking AID to c-myc/IgH translocations, GC-derived lymphomagenesis, methylation heterogeneity, and EGFR T790M

    PMID:12732658 PMID:17724134 PMID:18066064 PMID:19139166 PMID:19966806 PMID:26276629 PMID:29335468 PMID:30333118 PMID:31028100 PMID:35443279

    Open questions at the time
    • How chromatin marks are mechanistically read by the AID/repair machinery is unclear
    • Determinants of on- vs off-target genomic specificity remain incompletely defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how the structural, phosphoregulatory, ncRNA-targeting, cofactor, and chromatin inputs are integrated into a single coherent rule that directs AID to physiological Ig loci while limiting genome-wide off-target mutagenesis.
  • No unified model linking RNA targeting, phosphorylation, and chromatin state
  • Structure of full-length AID engaged with in vivo targeting RNA/protein partners lacking
  • Mechanism distinguishing Ig-locus from genome-wide deamination undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140097 catalytic activity, acting on DNA 5 GO:0003677 DNA binding 4 GO:0016787 hydrolase activity 3 GO:0003723 RNA binding 2
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 2
Pathway
R-HSA-1643685 Disease 5 R-HSA-168256 Immune System 4 R-HSA-4839726 Chromatin organization 4 R-HSA-73894 DNA Repair 2
Partners
HNRNP KHNRNP LHNRNP URPASERBP1

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 AID is required for both class switch recombination (CSR) and somatic hypermutation (SHM) in B cells; AID-/- mice show complete defects in both processes, and overexpression of AID in CH12F3-2 cells augments class switching without cytokine stimulation. Knockout mouse model, transgenic overexpression, in vitro B cell stimulation assays Cell High 11007474 11007475
2000 Mutations in the human AICDA gene cause autosomal recessive hyper-IgM syndrome type 2 (HIGM2), characterized by absence of CSR, lack of somatic hypermutation, and lymph node hyperplasia with giant germinal centers. Genetic sequencing of HIGM2 patients, phenotypic characterization Cell High 11007475
2002 AID functions by deaminating dC residues in DNA (not RNA); expression of AID in E. coli produces a mutator phenotype with C/G transitions that is enhanced by UNG deficiency, demonstrating a DNA deamination mechanism. E. coli mutator assay, UNG-deficient bacteria, context-dependent mutation analysis Nature High 12097915
2002 AID is required for immunoglobulin gene conversion in chicken DT40 B cells; disruption of AID completely blocks Ig gene conversion, and reintroduction of AID cDNA rescues this block. Gene disruption in DT40 cells, complementation with AID cDNA Science High 11847344
2002 Ectopic expression of AID alone is sufficient to induce somatic hypermutation in an actively transcribed GFP reporter in NIH 3T3 fibroblasts; mutation frequency correlates with transcription level. Ectopic AID expression in fibroblasts, GFP reporter mutation assay, transcription-level correlation Science High 12065838
2003 AID deaminates cytidines specifically on single-stranded DNA (ssDNA) but not double-stranded DNA (dsDNA) in vitro; dsDNA can be deaminated when the reaction is coupled to transcription, which generates ssDNA secondary structures, and this transcriptional orientation-dependence matches in vivo CSR requirements. In vitro cytidine deaminase assay on ssDNA and dsDNA substrates, transcription-coupled deamination assay Nature High 12692563
2003 Purified AID catalyzes processive C-to-U deamination on ssDNA preferentially at 5' WRC hotspot sequences; AID introduces multiple deaminations per DNA strand (10–70 per clone) rather than distributively; AID shows 15-fold preference for the non-transcribed strand exposed by RNA polymerase. In vitro deamination assay with purified AID on ssDNA, mutation spectrum analysis, transcribed dsDNA substrate assay Nature High 12819663
2003 Constitutive ubiquitous expression of AID in transgenic mice causes T cell lymphomas and epithelial micro-adenomas; point mutations are massively introduced in TCR and c-myc genes, demonstrating AID can mutate non-Ig oncogenes. AID transgenic mouse model, tumor sequencing, mutation analysis of TCR and c-myc genes The Journal of experimental medicine High 12732658
2005 AID is phosphorylated on Ser38 by protein kinase A (PKA) in B cells; phosphorylation enables AID to associate with replication protein A (RPA) and promotes deamination of transcribed dsDNA; mutation of the PKA site preserves ssDNA deamination but markedly reduces RPA-dependent dsDNA deamination and severely impairs CSR in vivo. Biochemical phosphorylation assay with recombinant PKA, AID-RPA co-immunoprecipitation, site-directed mutagenesis, in vivo CSR assay Nature High 16251902
2005 DNA double-strand breaks (DSBs) in Ig switch regions during CSR are AID-dependent and UNG-dependent, occur preferentially at WRC/GYW AID hotspot motifs, and AID attacks cytosines on both DNA strands. Ligation-mediated PCR detection of DSBs in splenic B cells, AID-/- and UNG-/- genetic ablation The Journal of experimental medicine High 16103411
2005 5-methylcytosine (methylated CpG) is protected from AID-mediated deamination in vitro; unmethylated cytidines adjacent to CpGs are not protected, indicating methylation does not provide broader protection. In vitro deamination assay on methylated and unmethylated plasmid substrates with purified AID Molecular immunology Medium 15607819
2007 AID deficiency prevents Bcl6-dependent germinal center-derived B cell lymphoma in mouse models, but has no impact on pre-GC Myc-driven lymphomas, demonstrating AID is required specifically for GC-derived lymphomagenesis through CSR/SHM-mediated genetic alterations. Genetic cross of AID-/- mice with Bcl6-, Myc-, and Myc/Bcl6-transgenic lymphoma models Nature genetics High 18066064
2007 AID is required for c-myc to IgH variable-region (V-JH) chromosomal translocations in IL-6 transgenic mice; these translocations are absent in AID-/- IL-6 transgenic mice. Genetic cross of AID-/- mice with IL-6 transgenic model, translocation detection by PCR The Journal of experimental medicine High 17724134
2008 AID is phosphorylated at both Ser38 and Thr140; mutation of either site does not affect catalytic activity but impairs CSR and somatic hypermutation in vivo, with T140 phosphorylation preferentially affecting somatic mutation. Mass spectrometry identification of phosphorylation sites, alanine substitution mutagenesis, in vivo CSR and SHM assays in haploinsufficient mice The Journal of experimental medicine High 18838546
2008 BCR engagement inhibits AID gene expression through Ca2+/calmodulin-dependent inhibition of the E2A transcription factor; calmodulin overexpression inhibits AID expression, and calmodulin-binding-site-mutated E2A renders AID expression resistant to BCR-mediated inhibition. BCR stimulation assays, calmodulin overexpression, E2A mutagenesis, AID expression analysis Proceedings of the National Academy of Sciences Medium 18203819
2009 The estrogen-estrogen receptor complex binds directly to the AID promoter, enhancing AID mRNA and protein expression, leading to increases in SHM and CSR at the Ig locus, and enhanced c-myc translocations. Promoter binding assay (ChIP/reporter), AID mRNA/protein expression analysis, functional CSR and SHM assays, translocation analysis The Journal of experimental medicine High 19139166
2009 B cell-specific and stimulation-responsive enhancer elements in the Aicda first intron overcome silencer elements to derepress AID expression; the intron contains binding sites for ubiquitous silencers c-Myb and E2f and B cell-specific activators Pax5 and E-box-binding proteins. Reporter assay, phylogenetic footprinting, histone acetylation mapping, mutagenesis of regulatory elements in CH12F3-2 cells Nature immunology Medium 19966806
2010 AID (AICDA) is required for active DNA demethylation at OCT4 and NANOG promoters during reprogramming toward pluripotency; AID protein binds methylated silent promoters in fibroblasts but not active demethylated promoters in ES cells; siRNA knockdown of AID prevents promoter demethylation and induction of OCT4 and NANOG. siRNA knockdown in human-mouse heterokaryons, promoter methylation analysis, AID protein binding assay, gene expression analysis Nature High 20027182
2010 Uracil residues generated by AID deamination are physically present in immunoglobulin variable and switch region DNA of stimulated B cells; they are present on both strands, replace mainly cytosine, appear within 24 hours of stimulation, and are AID-dependent. Uracil-DNA glycosylase sensitivity assay, abasic endonuclease assay, multiple detection methods in AID-/- and wild-type B cells Nature immunology High 21151102
2011 A knock-in AID(G23S) mutation selectively impairs somatic hypermutation while preserving normal immunoglobulin levels; AID(G23S) mice develop germinal center hyperplasia and defective mucosal defense, demonstrating SHM has a distinct function from CSR in intestinal homeostasis. Knock-in point mutation mouse model, Ig quantification, germinal center analysis, bacterial challenge assays Nature immunology High 21258321
2014 RNA exosome regulation of noncoding RNA (xTSS-RNAs) recruits AID to single-stranded DNA-forming sites of antisense and divergent transcription; Exosc3-deficient B cells have impaired CSR and SHM; divergently transcribed ncRNA-associated genomic loci accumulate AID-mediated mutations and translocations. Conditional Exosc3 KO mouse model, transcriptome analysis, AID recruitment assay, ChIP, SSB structure analysis Nature High 25119026
2015 Intronic switch RNA (generated after lariat debranching) acts in trans to target AID to switch region DNA via G-quadruplex structures formed by the RNA; AID binds directly to switch RNA; mutation of a key residue in AID's putative RNA-binding domain impairs AID recruitment to S regions and abolishes CSR; inhibition of RNA lariat processing similarly disrupts AID localization and CSR. RNA-AID binding assay, G-quadruplex biochemical analysis, AID mutagenesis, RNA lariat processing inhibition, AID ChIP, CSR functional assay Cell High 25957684
2015 AID undergoes nuclear degradation more slowly in G1 phase than in S or G2-M phase; enforced nuclear localization of AID in G1 accelerates SHM and CSR and is well-tolerated, while nuclear AID in S-G2/M phase compromises cell viability; regulatory phosphorylation and catalytic activity mutations alter AID nuclear stability. High content screening microscopy, cell cycle-specific degradation tag fusions, CSR and SHM functional assays, AID stability measurements PLoS genetics Medium 26355458
2015 AID binds to transcribed dsDNA and translocates unidirectionally in concert with RNA polymerase on moving transcription bubbles, while increasing the fraction of stalled bubbles; when constrained in a model bubble, AID scans randomly; on unconstrained ssDNA, AID moves bidirectionally in short slides/hops. Single-molecule FRET analysis of AID on transcribed dsDNA and ssDNA substrates Nature communications High 26681117
2016 The AID C terminus is required for stable dimer formation; AID monomers associate with DNA cleavage cofactor hnRNP K, whereas AID dimers associate with recombination cofactors hnRNP L, hnRNP U, and Serpine mRNA-binding protein 1; all AID/ribonucleoprotein associations are RNA-dependent. Bimolecular fluorescence complementation (BiFC), glycerol gradient fractionation, co-immunoprecipitation Proceedings of the National Academy of Sciences Medium 26929374
2017 Crystal structures of human AID (MBP-fused) alone and in complex with deoxycytidine monophosphate reveal a bifurcated substrate-binding surface that captures two adjacent single-stranded overhangs simultaneously; G-quadruplex substrates mimicking Ig switch regions are preferred AID substrates; G4 substrates induce cooperative AID oligomerization; structure-based mutations disrupting bifurcated substrate recognition or oligomerization both compromise CSR in splenic B cells. X-ray crystallography, in vitro deamination assays, site-directed mutagenesis, in vivo CSR assay in splenic B cells Molecular cell High 28757211
2018 EGFR T790M resistance mutation is acquired through AICDA-mediated deamination of 5-methylcytosine at position c.2369; EGFR TKI treatment activates NFκB which induces AICDA expression; pharmacologic inhibition of NFκB or AICDA knockout prevents T790M mutation development. AICDA knockout, NFκB inhibition, 5-methylcytosine deamination assay, mutation frequency analysis in lung cancer cells Cancer research Medium 30333118
2019 TET2 and TET3 enhance AID (Aicda) expression in B cells by depositing 5-hydroxymethylcytosine (5hmC) and maintaining chromatin accessibility at two superenhancer elements (TetE1, TetE2) in the Aicda locus; BATF facilitates TET recruitment to TetE1; TET-dependent Aicda expression regulates CSR. Conditional Tet2/Tet3 KO in B cells, 5hmC mapping (ChIP-seq), ATAC-seq, BATF-deficient B cells, Aicda expression and CSR assays Science immunology High 31028100
2004 AID protein is predominantly localized in the cytoplasm of normal germinal center centroblasts and malignant B cells (Burkitt lymphoma), as detected using specific antibodies; cytoplasmic localization suggests additional regulatory mechanisms for its nuclear function. Immunohistochemistry and immunofluorescence with specific anti-AID antibodies in normal and neoplastic B cells Blood Medium 15304391
2006 Nuclear AID is detected in ~2.5% of germinal center cells specifically in the dark zone and outer zone (but not light zone); AID is relocalized to the nucleus in cycling CDKN1B-/CCNB1- GC blasts and in extrafollicular large B cells (14% with nuclear AID); nuclear/cytoplasmic distribution is consistent with the topography of SHM and CSR. Immunohistochemistry, immunofluorescence, co-staining with cell cycle markers in human tonsil GC sections Blood Medium 16439679
2012 APOBEC3B nuclear import requires an N-terminal motif analogous to AID's nuclear localization determinant, and A3B interacts with the same subset of importin proteins as AID, suggesting mechanistic conservation of nuclear import between AID and A3B. Mutagenesis of nuclear localization determinant, importin co-immunoprecipitation, nuclear localization assays Journal of molecular biology Medium 22446380
2015 Chronic Plasmodium infection prolongs germinal center expansion and AID expression, leading to widespread DNA damage in GC B cells and chromosome translocations; AID-dependent mature B cell lymphomas with translocations are favored by malaria infection. Mouse Plasmodium chabaudi chronic infection model, GC analysis, DNA damage assays, AID-/- genetic ablation, lymphoma characterization Cell High 26276629
2018 AICDA overexpression drives increased cytosine methylation heterogeneity in BCL2-driven murine lymphomas without increasing somatic mutation burden; AICDA depletion in normal GC B cells reduces cytosine methylation heterogeneity, identifying AICDA as a driver of epigenetic heterogeneity. AICDA transgenic overexpression and shRNA depletion in mouse lymphoma models, whole-genome bisulfite sequencing for methylation heterogeneity analysis Nature communications Medium 29335468
2022 SETD2 haploinsufficiency enhances AICDA-induced somatic hypermutation selectively on the nontemplate DNA strand; H3K36me3 loss (from SETD2 deficiency) is associated with greater RNA polymerase II processivity and increased mutational burden; SETD2-mediated H3K36me3 is required for proper sensing of AID-induced cytosine deamination. Heterozygous Setd2 KO mouse model, ChIP-seq for H3K36me3, RNAPII ChIP-seq, whole genome sequencing for mutation analysis, AICDA-dependent SHM strand analysis Cancer discovery Medium 35443279

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme. Cell 2694 11007474
2000 Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the Hyper-IgM syndrome (HIGM2). Cell 1254 11007475
2002 AID mutates E. coli suggesting a DNA deamination mechanism for antibody diversification. Nature 703 12097915
2003 Transcription-targeted DNA deamination by the AID antibody diversification enzyme. Nature 607 12692563
2010 Reprogramming towards pluripotency requires AID-dependent DNA demethylation. Nature 542 20027182
2003 Processive AID-catalysed cytosine deamination on single-stranded DNA simulates somatic hypermutation. Nature 527 12819663
2015 The auxin-inducible degradation (AID) system enables versatile conditional protein depletion in C. elegans. Development (Cambridge, England) 518 26552885
2008 The AID/APOBEC family of nucleic acid mutators. Genome biology 439 18598372
2003 Constitutive expression of AID leads to tumorigenesis. The Journal of experimental medicine 364 12732658
2002 Requirement of the activation-induced deaminase (AID) gene for immunoglobulin gene conversion. Science (New York, N.Y.) 357 11847344
2007 AID is required for germinal center-derived lymphomagenesis. Nature genetics 304 18066064
2002 AID enzyme-induced hypermutation in an actively transcribed gene in fibroblasts. Science (New York, N.Y.) 294 12065838
2009 Estrogen directly activates AID transcription and function. The Journal of experimental medicine 210 19139166
2007 Regulation of AID expression in the immune response. The Journal of experimental medicine 209 17452520
2005 The AID antibody diversification enzyme is regulated by protein kinase A phosphorylation. Nature 208 16251902
2022 Functions and consequences of AID/APOBEC-mediated DNA and RNA deamination. Nature reviews. Genetics 204 35256818
2011 Mice carrying a knock-in mutation of Aicda resulting in a defect in somatic hypermutation have impaired gut homeostasis and compromised mucosal defense. Nature immunology 201 21258321
2013 The use of carbohydrates during exercise as an ergogenic aid. Sports medicine (Auckland, N.Z.) 185 23846824
2014 Noncoding RNA transcription targets AID to divergently transcribed loci in B cells. Nature 167 25119026
2010 AID and somatic hypermutation. Advances in immunology 167 20510733
2004 Expression of the AID protein in normal and neoplastic B cells. Blood 155 15304391
2015 Non-coding RNA Generated following Lariat Debranching Mediates Targeting of AID to DNA. Cell 154 25957684
2004 AID: how does it aid antibody diversity? Immunity 154 15189732
2009 Balancing AID and DNA repair during somatic hypermutation. Trends in immunology 153 19303358
2017 AID Recognizes Structured DNA for Class Switch Recombination. Molecular cell 152 28757211
2016 Mutations, kataegis and translocations in B cells: understanding AID promiscuous activity. Nature reviews. Immunology 146 26898111
2005 Inducible DNA breaks in Ig S regions are dependent on AID and UNG. The Journal of experimental medicine 143 16103411
2015 Plasmodium Infection Promotes Genomic Instability and AID-Dependent B Cell Lymphoma. Cell 138 26276629
2006 AID in somatic hypermutation and class switch recombination. Current opinion in immunology 138 16464563
2007 DNA deamination in immunity: AID in the context of its APOBEC relatives. Advances in immunology 130 17560271
2006 Nuclear and cytoplasmic AID in extrafollicular and germinal center B cells. Blood 127 16439679
2020 AID in Antibody Diversification: There and Back Again. Trends in immunology 110 32434680
2011 AID targeting in antibody diversity. Advances in immunology 108 21762814
2008 Regulation of class switch recombination and somatic mutation by AID phosphorylation. The Journal of experimental medicine 107 18838546
2010 Uracil residues dependent on the deaminase AID in immunoglobulin gene variable and switch regions. Nature immunology 105 21151102
2009 B cell-specific and stimulation-responsive enhancers derepress Aicda by overcoming the effects of silencers. Nature immunology 104 19966806
2013 Regulation of AID, the B-cell genome mutator. Genes & development 103 23307864
2007 Role of AID in tumorigenesis. Advances in immunology 102 17560277
2013 Regulation of Aicda expression and AID activity. Autoimmunity 99 23181381
2015 AID/APOBEC deaminases and cancer. Oncoscience 95 26097867
2019 TET enzymes augment activation-induced deaminase (AID) expression via 5-hydroxymethylcytosine modifications at the Aicda superenhancer. Science immunology 84 31028100
2007 Regulation of aicda expression and AID activity: relevance to somatic hypermutation and class switch DNA recombination. Critical reviews in immunology 83 18197815
2012 APOBEC3B and AID have similar nuclear import mechanisms. Journal of molecular biology 76 22446380
2005 AID to overcome the limitations of genomic information. Nature immunology 75 15970938
2007 Immunohistochemistry as a diagnostic aid in cervical pathology. Pathology 69 17365826
2007 A role for AID in chromosome translocations between c-myc and the IgH variable region. The Journal of experimental medicine 69 17724134
2014 AID and APOBECs span the gap between innate and adaptive immunity. Frontiers in microbiology 67 25352838
2011 Tagging recombinant proteins to enhance solubility and aid purification. Methods in molecular biology (Clifton, N.J.) 67 20978965
2005 Methylation protects cytidines from AID-mediated deamination. Molecular immunology 65 15607819
2005 Differential expression of activation-induced cytidine deaminase (AID) in nodular lymphocyte-predominant and classical Hodgkin lymphoma. The Journal of pathology 65 15732141
2018 AICDA drives epigenetic heterogeneity and accelerates germinal center-derived lymphomagenesis. Nature communications 64 29335468
2014 AID expression in B-cell lymphomas causes accumulation of genomic uracil and a distinct AID mutational signature. DNA repair 61 25486549
2013 The AID-induced DNA damage response in chromatin. Molecular cell 60 23664375
2003 What role for AID: mutator, or assembler of the immunoglobulin mutasome? Nature immunology 56 12830138
2021 MIR-NATs repress MAPT translation and aid proteostasis in neurodegeneration. Nature 48 34012113
2015 AID targeting: old mysteries and new challenges. Trends in immunology 48 26254147
2009 Clinical and laboratory findings in hyper-IgM syndrome with novel CD40L and AICDA mutations. Journal of clinical immunology 48 19575287
2015 MicroRNA 155 control of p53 activity is context dependent and mediated by Aicda and Socs1. Molecular and cellular biology 47 25645925
2008 Glycophorin A: Band 3 aid. Blood cells, molecules & diseases 46 18304844
2012 Activation-induced cytidine deaminase (AID) linking immunity, chronic inflammation, and cancer. Cancer immunology, immunotherapy : CII 43 22527246
2016 PrimPol prevents APOBEC/AID family mediated DNA mutagenesis. Nucleic acids research 42 26926109
2003 Class-switch recombination: after the dawn of AID. Current opinion in immunology 41 12633669
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
2023 ASGARD is A Single-cell Guided Pipeline to Aid Repurposing of Drugs. Nature communications 39 36813801
2014 Ammonium metabolism enzymes aid Helicobacter pylori acid resistance. Journal of bacteriology 39 24936052
2004 Cloning and expression of the AID gene in the channel catfish. Developmental and comparative immunology 38 15043936
2013 Reporter enzyme inhibitor study to aid assembly of orthogonal reporter gene assays. ACS chemical biology 37 23485150
2014 Biological function of activation-induced cytidine deaminase (AID). Biomedical journal 36 25163501
2012 AID targeting is dependent on RNA polymerase II pausing. Seminars in immunology 36 22784681
2008 B-cell receptor activation inhibits AID expression through calmodulin inhibition of E-proteins. Proceedings of the National Academy of Sciences of the United States of America 36 18203819
2018 The EGFR T790M Mutation Is Acquired through AICDA-Mediated Deamination of 5-Methylcytosine following TKI Treatment in Lung Cancer. Cancer research 34 30333118
2011 Aberrant expression and mutation-inducing activity of AID in human lung cancer. Annals of surgical oncology 34 21290192
2007 Oncogenic events triggered by AID, the adverse effect of antibody diversification. Carcinogenesis 34 17804422
2005 Identification of a ubiquitously active promoter of the murine activation-induced cytidine deaminase (AICDA) gene. Molecular immunology 33 16005067
2011 AID and partners: for better and (not) for worse. Current opinion in immunology 32 21439803
2016 Functional requirements of AID's higher order structures and their interaction with RNA-binding proteins. Proceedings of the National Academy of Sciences of the United States of America 31 26929374
2015 Activation-induced deoxycytidine deaminase (AID) co-transcriptional scanning at single-molecule resolution. Nature communications 31 26681117
2007 AID-initiated purposeful mutations in immunoglobulin genes. Advances in immunology 31 17560274
2014 Could dopamine agonists aid in drug development for anorexia nervosa? Frontiers in nutrition 30 25988121
2013 Hormones and AID: balancing immunity and autoimmunity. Autoimmunity 28 23181348
2022 SETD2 Haploinsufficiency Enhances Germinal Center-Associated AICDA Somatic Hypermutation to Drive B-cell Lymphomagenesis. Cancer discovery 27 35443279
2016 UNG protects B cells from AID-induced telomere loss. The Journal of experimental medicine 27 27697833
2015 RNA Exosome Regulates AID DNA Mutator Activity in the B Cell Genome. Advances in immunology 27 26073986
2008 Effects of L-carnitine on obesity, diabetes, and as an ergogenic aid. Asia Pacific journal of clinical nutrition 27 18296364
2008 Aberrant AID expression and human cancer development. The international journal of biochemistry & cell biology 27 18329947
2021 Helicase-AID: A novel molecular device for base editing at random genomic loci. Metabolic engineering 26 34411701
2015 Cell Cycle Regulates Nuclear Stability of AID and Determines the Cellular Response to AID. PLoS genetics 26 26355458
2014 AID-induced remodeling of immunoglobulin genes and B cell fate. Oncotarget 26 24851241
2023 Challenges and advances in serological and molecular tests to aid leprosy diagnosis. Experimental biology and medicine (Maywood, N.J.) 25 38059475
2021 A Review on Microfluidics: An Aid to Assisted Reproductive Technology. Molecules (Basel, Switzerland) 25 34299629
2014 AID and APOBEC deaminases: balancing DNA damage in epigenetics and immunity. Epigenomics 25 25333851
2012 The AID dilemma: infection, or cancer? Advances in cancer research 25 22429851
2022 AID function in somatic hypermutation and class switch recombination. Acta biochimica et biophysica Sinica 24 35975606
2020 Estrogen Reverses HDAC Inhibitor-Mediated Repression of Aicda and Class-Switching in Antibody and Autoantibody Responses by Downregulation of miR-26a. Frontiers in immunology 23 32265934
2004 Transcription-coupled mutagenesis by the DNA deaminase AID. Genome biology 23 15003109
2019 HIV-1 Tat protein induces aberrant activation of AICDA in human B-lymphocytes from peripheral blood. Journal of cellular physiology 21 30701532
2016 Enrichment of rare variants in population isolates: single AICDA mutation responsible for hyper-IgM syndrome type 2 in Finland. European journal of human genetics : EJHG 21 27142677
2014 IL-10 regulates Aicda expression through miR-155. Journal of leukocyte biology 21 25381386
2018 Heterologous expression, characterization and possible functions of the chitin deacetylases, Cda1 and Cda2, from mushroom Coprinopsis cinerea. Glycobiology 20 29370398
2012 AID and Apobec3G haphazard deamination and mutational diversity. Cellular and molecular life sciences : CMLS 20 23178850

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