Affinage

TADA2A

Transcriptional adapter 2-alpha · UniProt O75478

Round 2 corrected
Length
443 aa
Mass
51.5 kDa
Annotated
2026-04-28
130 papers in source corpus 34 papers cited in narrative 33 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TADA2A is a transcriptional adaptor protein that serves as a core scaffolding subunit of the PCAF, STAGA, and ATAC histone acetyltransferase complexes, where it bridges acidic activation domains of transcription factors (VP16, GCN4) with TBP and potentiates GCN5/PCAF-mediated histone acetylation (PMID:1638630, PMID:7642611, PMID:9674425, PMID:18838386). Within the catalytic HAT module formed by Ada2/Ada3/Gcn5, TADA2A activates the intrinsically weak acetyltransferase activity of GCN5 through its SANT domain, which enhances acetyl-CoA co-substrate binding rather than histone substrate recognition (PMID:30224453, PMID:11773077). TADA2A-containing complexes (ATAC) preferentially direct histone H4 K5/K12 acetylation, distinguishing them from the paralogous TADA2B-containing SAGA-type complexes that target H3 K9/K14, and this Ada2-dependent acetylation is required for the transition from transcription initiation to elongation (PMID:17030603, PMID:28115623). Polyglutamine-expanded ataxin-7 incorporated into TADA2A-containing STAGA dominantly inhibits nucleosomal histone acetylation, linking TADA2A complex dysfunction to spinocerebellar ataxia type 7 (PMID:15932940).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1992 High

    Establishing that a dedicated coactivator exists between acidic activators and the basal transcription machinery: yeast ADA2 was identified as a selective transcriptional adaptor required for VP16/GCN4-dependent activation but dispensable for basal transcription, founding the concept of activation-domain-specific coactivators.

    Evidence Genetic selection for GAL4-VP16 toxicity resistance in yeast; in vitro transcription with ada2 mutant extracts

    PMID:1638630

    Open questions at the time
    • Mechanism of selectivity for acidic vs. other activation domains unknown
    • No biochemical identity of the complex or direct interactors
    • Mammalian relevance unaddressed
  2. 1994 High

    Defining ADA2 as a physical scaffold linking activators to the HAT enzyme GCN5: ADA2 directly binds the VP16 activation domain and physically interacts with GCN5, with epistasis showing they function in the same pathway, establishing the adaptor-HAT connection.

    Evidence GST pulldown binding assays; yeast two-hybrid; co-immunoprecipitation; gcn5/ada2 double-mutant epistasis

    PMID:7957049 PMID:7972120

    Open questions at the time
    • Stoichiometry and full composition of native complex unknown
    • Whether ADA2 contacts TBP directly not yet tested
  3. 1995 High

    Resolving the trimeric core and dual bridging function: ADA2 forms a heterotrimeric complex with ADA3 and GCN5 (ADA2 as linchpin), and ADA2 also directly contacts TBP, establishing it as a bidirectional bridge between activator–HAT and the basal machinery.

    Evidence In vitro reconstitution of Ada2/Ada3/Gcn5 trimer; GST pulldown and co-IP for ADA2–TBP interaction; domain mapping

    PMID:7642611 PMID:7862114

    Open questions at the time
    • Native complex size and additional subunits unknown
    • Whether ADA2–TBP interaction is direct in the context of a larger complex
  4. 1996 High

    Demonstrating evolutionary conservation in humans: human ADA2α (TADA2A) was cloned and shown to interact with hGCN5 and augment VP16-dependent activation in HeLa cells, establishing functional conservation from yeast to mammals.

    Evidence Yeast two-hybrid for hADA2–hGCN5 interaction; transient transfection transcription assays in HeLa cells

    PMID:8552087

    Open questions at the time
    • Identity of the native human complex containing TADA2A unknown
    • Whether mammalian ADA2α is stably complexed with GCN5 in vivo unresolved
  5. 1998 High

    Placing TADA2A in a defined macromolecular coactivator complex: TADA2A was identified as a stable subunit of the human PCAF HAT complex (~20 subunits including TAF-like histone fold proteins), defining its physiological context.

    Evidence Affinity purification of native PCAF complex from human cells; mass spectrometry subunit identification

    PMID:9674425

    Open questions at the time
    • Whether TADA2A also exists in non-PCAF complexes in human cells
    • Functional role of TADA2A within the PCAF complex not biochemically dissected
  6. 2001 High

    Identifying Ada2 as essential for nucleosomal HAT activity: reconstitution showed Ada2/Ada3/Gcn5 is the minimal catalytic HAT module sufficient for nucleosomal acetylation, with Ada2 potentiating Gcn5 catalytic activity.

    Evidence Recombinant sub-complex reconstitution; in vitro HAT assays on nucleosomal substrates

    PMID:11773077

    Open questions at the time
    • Mechanism by which Ada2 potentiates Gcn5 activity unresolved at atomic level
    • Whether this applies to mammalian TADA2A–GCN5 not directly tested
  7. 2002 High

    Identifying the SANT domain as the functional element: mutations in the Ada2 SANT domain impaired histone acetylation in vitro and in vivo, establishing this domain as a histone/nucleosome recognition element within the HAT module.

    Evidence Site-directed mutagenesis of Ada2 SANT domain; in vitro and in vivo HAT assays in yeast

    PMID:11777910

    Open questions at the time
    • Whether the SANT domain contacts histones directly or acts allosterically on Gcn5 unclear
    • Structural basis of SANT domain function not determined
  8. 2003 High

    Establishing paralog-specific complex membership: identification of TADA2B (hADA2β) demonstrated that TADA2A resides selectively in PCAF-type complexes while TADA2B resides in STAGA/TFTC-type complexes, with non-overlapping functions in coactivation.

    Evidence Yeast two-hybrid; co-immunoprecipitation; transient transfection coactivation assays in mammalian cells; Drosophila biochemical fractionation

    PMID:12697829 PMID:12972612

    Open questions at the time
    • Whether TADA2A and TADA2B have distinct histone substrate specificities in mammalian cells
    • Structural basis for paralog-specific complex incorporation unknown
  9. 2006 High

    Resolving histone substrate specificity: Drosophila Ada2a (TADA2A ortholog) null mutants showed selective loss of H4 K5/K12 acetylation while H3 K9/K14 acetylation was unaffected, demonstrating that the TADA2A-type adaptor directs the HAT toward H4 lysines specifically.

    Evidence Drosophila null alleles; histone modification-specific western blots; chromosome structural analysis

    PMID:17030603

    Open questions at the time
    • Whether this substrate specificity is conserved in mammalian TADA2A-containing complexes
    • Structural mechanism by which Ada2a redirects Gcn5 to H4 unknown
  10. 2008 High

    Defining the ATAC complex: human ATAC was purified and shown to contain TADA2A as a defining subunit alongside ADA3, WDR5, YEATS2, and other components, establishing ATAC as a distinct TADA2A-specific complex separate from STAGA.

    Evidence Affinity purification from HeLa cells; mass spectrometry; TBP interaction assays

    PMID:18838386

    Open questions at the time
    • Genomic targets and biological functions of ATAC vs. STAGA in human cells not dissected
    • Regulation of ATAC assembly and recruitment unknown
  11. 2018 High

    Revealing the structural mechanism of Ada2-mediated HAT activation: crystal structures of Ada2/Gcn5 showed that the Ada2 SANT domain enhances Gcn5 activity by promoting acetyl-CoA co-substrate binding rather than by improving histone substrate recognition, revising the prior model.

    Evidence X-ray crystallography of Ada2/Gcn5 complex; acetyl-CoA binding assays; mutagenesis and in vitro HAT assays

    PMID:30224453

    Open questions at the time
    • Structure of full Ada2/Ada3/Gcn5 HAT module on nucleosomal substrate not yet determined
    • Whether acetyl-CoA sensing by Ada2 constitutes a metabolic regulatory mechanism in vivo

Open questions

Synthesis pass · forward-looking unresolved questions
  • The genomic targets and functional consequences of TADA2A-containing ATAC complex activity in mammalian cells, and whether TADA2A loss-of-function causes human disease, remain to be established through direct human genetic and functional genomic studies.
  • No human genetic disease directly linked to TADA2A mutations in the literature
  • Genome-wide binding and acetylation targets of human ATAC complex not mapped
  • Role of TADA2A in mammalian development and tissue-specific gene regulation unexplored

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0042393 histone binding 3 GO:0060090 molecular adaptor activity 3
Localization
GO:0005634 nucleus 4 GO:0005694 chromosome 3
Pathway
R-HSA-4839726 Chromatin organization 5 R-HSA-74160 Gene expression (Transcription) 4
Partners
ADA3ATXN7GCN5PCAFSGF29TBPWDR5YEATS2
Complex memberships
ATAC complexAda2/Ada3/Gcn5 HAT modulePCAF complexSTAGA complex

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 ADA2 (yeast) was identified genetically as a transcriptional adaptor required for the activity of acidic activation domains (VP16, GCN4) but not for all activators (e.g., GAL4-HAP4). Mutations in ADA2 abolished transcriptional responses to GAL4-VP16 and GCN4 in cell-free extracts while leaving basal transcription intact, placing ADA2 as a selective coactivator bridging acidic activators and the general transcription machinery. Genetic selection for resistance to GAL4-VP16 toxicity in yeast; in vitro transcription assays with ada2 mutant extracts Cell High 1638630
1993 ADA3 was identified as a second transcriptional adaptor with a phenotypic spectrum similar to ADA2 (reduced VP16/GCN4 activation, slow growth, temperature sensitivity). Double mutant ada2 ada3 strains showed no additive growth or transcriptional defects, establishing that ADA2 and ADA3 function in the same pathway. Genetic selection; ada2/ada3 double mutant epistasis analysis; in vitro transcription Molecular and cellular biology High 8413201
1994 ADA2 (yeast) directly binds the VP16 acidic activation domain in vitro, and the amino-terminal region of ADA2 mediates this interaction. ADA2 fused to a heterologous DNA-binding domain activates transcription in vivo in an ADA3-dependent manner, consistent with ADA2 functioning as a physical bridge between activators and the basal machinery. In vitro binding assays (GST pulldown); LexA fusion transcriptional activation assays in yeast Proceedings of the National Academy of Sciences of the United States of America High 7972120
1994 GCN5 and ADA2 (yeast) interact physically (co-immunoprecipitation in vitro and yeast two-hybrid in vivo) and function in the same complex or pathway (no additive effects in gcn5 ada2 double mutants). Both are required for VP16- and GCN4-dependent activation. The bromodomain of GCN5 is functionally important for transcriptional activation but not for ADA2 binding. Yeast two-hybrid assay; co-immunoprecipitation; gcn5 ada2 double-mutant epistasis analysis The EMBO journal High 7957049
1995 ADA2 (yeast) physically interacts with TBP (TATA-binding protein) but not TFIIB. In yeast nuclear extracts, the association of VP16 activation domain with TBP (but not TFIIB) is dependent on ADA2. The N-terminus of ADA2 directly binds VP16, while ADA2 also interacts with GCN4 activation domain but not HAP4. These physical interactions correlate with ADA2's functional selectivity in vivo. GST pulldown with recombinant proteins; co-immunoprecipitation from yeast nuclear extracts; domain mapping The Journal of biological chemistry High 7642611
1995 ADA2, ADA3, and GCN5 form a heterotrimeric complex in vitro, with ADA2 serving as the linchpin that holds ADA3 and GCN5 together. The C-terminal domain of ADA3 alone is sufficient for heterotrimeric complex formation in vitro and for ADA2-dependent activation in vivo. Activation by LexA-ADA3 fusions is regulated by ADA2 levels, and LexA-ADA2 fusion activation is regulated by ADA3 levels, indicating they form a complex in cells. In vitro complex reconstitution; LexA fusion transcriptional assays in yeast; ADA3 domain deletion analysis Molecular and cellular biology High 7862114
1995 Genetic evidence confirms GCN5 and ADA2 interact and define one complex mediating transcriptional activation in yeast. LexA-GCN5 activates transcription only in the presence of wild-type ADA2 (and vice versa), and the bromodomain of GCN5 is required for this complex function. gcn5 ada2 double disruption shows no additive effects. Genetic epistasis (double disruption); LexA-fusion transcription activation assays in yeast Molecular & general genetics : MGG Medium 7898440
1996 Human ADA2 (hADA2, later designated hADA2α/TADA2A) was identified as a functional homolog of yeast ADA2. hADA2 interacts with hGCN5 in the yeast two-hybrid assay (and hGCN5 interacts with yADA2), contains a cryptic activation domain, and augments GAL4-VP16 activation in human HeLa cells. GAL4-hADA2 fusion activates transcription in HeLa cells, demonstrating functional conservation in human cells. Yeast two-hybrid assay; transient transfection in HeLa cells; sequence conservation analysis Molecular and cellular biology High 8552087
1997 In yeast, NGG1p/ADA3p and ADA2p are co-immunoprecipitated from whole-cell extracts, with <2% of ADA2p not associated with NGG1p, demonstrating near-complete association in vivo. Stability of each protein depends on the presence of the other. ADA2/ADA3-containing complexes exist in multiple sizes (>2 MDa, ~900 kDa, ~200 kDa) by ion-exchange and gel-filtration chromatography, and at least one complex associates with TBP via residues 274–307 of NGG1p/ADA3. Co-immunoprecipitation from yeast whole-cell extracts; ion-exchange and gel-filtration chromatography; stability assays The Journal of biological chemistry High 9038164
1997 GCN5 HAT activity is functionally linked to ADA2 interaction in vivo: the minimal catalytic HAT domain of GCN5 is necessary but not sufficient for full in vivo function — interaction with ADA2 is additionally required for complementation of growth and transcriptional activation in gcn5 mutant cells. LexA-GCN5 fusion activates transcription requiring both the HAT domain and the ADA2-interaction domain. Domain deletion mutagenesis of GCN5; complementation assays in gcn5 yeast; LexA-GCN5 transcription activation assays The EMBO journal High 9034338
1997 ADA1 was identified as an additional component of the ADA/GCN5 complex (~2 MDa). ADA1 interacts with other ADA proteins as shown by partial purification and co-immunoprecipitation. ada1 mutants show broader transcriptional defects than ada2/ada3/gcn5 mutants, suggesting the ADA/GCN5 complex has two separable functional modules. Co-immunoprecipitation; partial biochemical purification; transcriptional reporter assays in yeast Molecular and cellular biology Medium 9154821
1997 TADA2A (human TADA2L/hADA2α) and GCN5L2 co-localize to chromosome 17q12–q21 by FISH and display similar tissue expression patterns across human tissues by Northern blot, suggesting coordinated regulation consistent with their functional interaction in a conserved complex. Fluorescence in situ hybridization (FISH); Northern blot analysis across human tissues Genomics Medium 9073520
1997 Human GCN5 exists in a stable macromolecular complex (~67 Å Stokes radius, large complex) in human K562 erythroleukemia cells, but human ADA2 is resolved as a monomer (~35 Å) by gel-filtration chromatography, suggesting that unlike in yeast, human GCN5 and ADA2 are not stably associated with each other in a constitutive complex in this cell type. Gel-filtration chromatography of human K562 cell extracts; HAT activity fractionation Biochemistry Medium 9398325
1998 TADA2A (hADA2α) is a stable component of the human PCAF histone acetyltransferase complex, which contains more than 20 subunits including TAF subunits with histone fold motifs (hTAFII31, hTAFII20/15 — H3- and H2B-like). This establishes TADA2A as part of the human PCAF/SAGA-type coactivator complex. Affinity purification of the PCAF complex; mass spectrometry and peptide sequencing of subunits Cell High 9674425
1999 Within the native human PCAF complex containing TADA2A, PCAF acetylates primarily lysine 14 of histone H3 and less efficiently lysine 8 of H4 on mononucleosomal substrates, and the complex polypeptides (including TADA2A/ADA2α) do not alter the substrate specificity of PCAF. In vitro HAT assay with mononucleosomes; Edman degradation of acetylated histones to identify acetylation sites The Journal of biological chemistry Medium 9880483
2001 Yeast Ada2 and Ada3 together with Gcn5 form the catalytic core of both the ADA and SAGA HAT complexes (the minimal module necessary and sufficient for nucleosomal HAT activity in vitro). Ada2 potentiates the Gcn5 catalytic activity; Ada3 facilitates nucleosomal acetylation and expanded lysine specificity. This catalytic core is necessary for nucleosomal HAT activity. Reconstitution of recombinant Ada2/Ada3/Gcn5 sub-complex; in vitro HAT assays on histones and nucleosomes; comparison with intact SAGA/ADA complexes The Journal of biological chemistry High 11773077
2002 The SANT domain of Ada2 (yeast) is required for normal histone acetylation by the SAGA complex in vivo and in vitro. Deletion and substitution mutations within the SANT domain of Ada2 and specific regions of the Gcn5 HAT domain (distinct from the catalytic site) impair substrate (histone/nucleosome) recognition. This identifies the Ada2 SANT domain as a histone/nucleosome substrate recognition module within SAGA. Site-directed mutagenesis of Ada2 SANT domain and Gcn5 HAT domain; in vitro HAT assays; in vivo histone acetylation assays in yeast The Journal of biological chemistry High 11777910
2003 A novel human Ada2 homologue, hADA2β (distinct from hADA2α/TADA2A), was identified. hADA2β interacts selectively with the Gcn5-containing TFTC/STAGA complex but not stably with the PCAF complex (which contains hADA2α). hADA2β (but not ADA2α) also associates with human Swi/Snf via Baf57 interaction, and functions with Gcn5 (but not PCAF) or Brg1 to coactivate Pax5/BSAP-dependent transcription. This establishes TADA2A (hADA2α) as the specific ADA2 isoform in the PCAF complex. Yeast two-hybrid screen; in vitro co-immunoprecipitation; transient transfection coactivation assays Molecular and cellular biology High 12972612
2003 In Drosophila, there are two Ada2 homologs (dAda2a and dAda2b) that reside in distinct GCN5-containing complexes. dAda2b is a component of dSAGA (~2 MDa), while dAda2a associates with dGcn5 in a smaller (~0.8 MDa) complex not incorporated into dSAGA. dAda2a-containing complexes concentrate at transcriptionally active regions on polytene chromosomes independently of dSAGA. Humans and mice also possess two Ada2 variants with high homology to dAda2a (→ TADA2A) and dAda2b (→ TADA2B), suggesting the mammalian homologs form two functionally distinct subgroups. Biochemical fractionation (glycerol gradient sedimentation, chromatography); immunoprecipitation; immunofluorescence on polytene chromosomes Molecular and cellular biology High 12482983 12697829
2005 In Drosophila, Ada2a (ortholog of human TADA2A) null mutants are late-larva lethal and show a distinct phenotype from Ada2b null mutants. Ada2a null mutation does not reduce histone H3 K14/K9 acetylation or TAF10 localization (unlike Ada2b null), indicating Ada2a and Ada2b have non-redundant, distinct functions. Ada2a null impairs cell proliferation and differentially affects specific gene expression (e.g., rosy gene) and Dmp53-mediated apoptosis. Loss-of-function Drosophila genetics (null alleles); phenotypic analysis; histone acetylation assays by western blot; TAF10 localization by immunostaining Molecular and cellular biology High 16135810
2005 The 5' boundary of ACACA lies within a CpG island harboring a bidirectional promoter shared with the divergently oriented TADA2L (TADA2A) gene. This shared promoter coregulates transcripts for TADA2L and ACACA asymmetrically across human and mouse tissues, with RNA Pol II concentration in the intergenic region reflecting transcript abundance in brain vs. liver. This defines the genomic context of TADA2A transcription regulation. 5' RACE; genomic sequencing; RNA Pol II ChIP in mouse tissues; Northern blot Genomics Medium 15607423
2005 Polyglutamine-expanded ataxin-7 is an integral subunit of the mammalian STAGA complex (which contains TADA2A/ADA2α). Poly(Q)-expanded ataxin-7 in STAGA dominantly inhibits GCN5-mediated nucleosomal histone acetylation in vitro and in SCA7 transgenic mice (by ChIP). TADA2A is thus a component of the human STAGA coactivator complex that can be functionally compromised in spinocerebellar ataxia type 7. Affinity purification of human STAGA; in vitro nucleosomal HAT assays; chromatin immunoprecipitation (ChIP) from SCA7 transgenic mouse retina Proceedings of the National Academy of Sciences of the United States of America High 15932940
2006 In Drosophila, dAda2a (TADA2A ortholog) and dGcn5 genetically interact: loss of either causes similar chromosome structural defects and developmental abnormalities. In dAda2a mutants, nucleosomal H4 acetylation at K12 and K5 is significantly reduced while H3 K9/K14 acetylation (established by dAda2b-containing complexes) is unaffected. This establishes that the TADA2A-type Ada2 (dAda2a) directs Gcn5 toward H4 lysine acetylation specifically. Drosophila loss-of-function genetics; histone acetylation analysis by western blot (antibodies to H4K12ac, H4K5ac, H3K9ac, H3K14ac); chromosome squash analysis Molecular and cellular biology High 17030603
2007 Recombinant yeast Ada2/Ada3/Gcn5 sub-complex (the SAGA HAT module) was expressed and purified as a functional unit sufficient for acetylation of histones H3 and H2B on nucleosomes in vitro. BL21-CodonPlus E. coli strain enhanced purity of the metal-affinity-purified Ada2/Ada3/Gcn5 complex. This reconstituted complex serves as the minimal functional HAT module. Recombinant protein expression and purification; in vitro nucleosomal HAT assays Methods (San Diego, Calif.) Medium 17309836
2007 GCN5 and PCAF (both associated with TADA2A/ADA2α vs. ADA2β isoforms respectively in distinct complexes) function as co-activators in at least two types of human multiprotein complexes: STAGA-type (~2 MDa) and ATAC-type (~700 kDa). These complexes possess both global histone acetylation activity and gene-specific coactivator functions. Biochemical purification; mass spectrometry; HAT activity assays Oncogene Medium 17694077
2008 Human ATAC (Ada Two-A containing) complex was purified and characterized; it contains ADA2-A (TADA2A), ADA3, STAF36, WDR5, POLE3/CHRAC17, POLE4, TAK1/MAP3K7, MBIP, and a novel YEATS2–NC2β histone fold module that interacts with TBP and negatively regulates transcription. TADA2A is thus a defining subunit of the human ATAC complex distinct from STAGA. Affinity purification of human ATAC complex from HeLa cells; mass spectrometry identification of subunits; TBP interaction assays The Journal of biological chemistry High 18838386
2008 A conserved ~120-amino-acid central region of yeast Ada2 (the 'RLR' region) is required for normal Gcn5 HAT activity. The ada2-RLR allele (R211S, L212A, R215A) reduces Gcn5-mediated histone acetylation in vitro to ~40% of wild-type and nearly eliminates in vivo acetylation of H2B K16, while reducing H3 K9/K18 acetylation to ~40%. This region also binds phospholipids (phosphatidylserine), suggesting a possible regulatory interaction. Site-directed mutagenesis; in vitro HAT assays; in vivo chromatin histone acetylation at Ada2-regulated promoters; microarray expression analysis; phospholipid binding assay Journal of molecular biology Medium 18950642
2009 Ada2 (yeast) has a novel function in transcriptional silencing at telomeres and ribosomal DNA, distinct from its role in Gcn5-mediated activation. Ada2 binds telomeric chromatin and the silencing protein Sir2 in vivo (ChIP). Loss of ADA2 causes spreading of Sir2 and Sir3 into subtelomeric regions and decreased histone H4 K16 acetylation. Upon nutritional changes, Ada2 occupancy increases at subtelomeric regions adjacent to SAGA-inducible genes, derepressing silenced reporters. Chromatin immunoprecipitation (ChIP) for Ada2, Sir2, Sir3 at telomeres and rDNA; in vivo silencing assays (telomeric reporter); histone modification analysis Molecular and cellular biology Medium 19737915
2017 Ada2 and Spt20 undergo co-translational assembly in yeast, dependent on the Ccr4-Not complex subunit Not5. SAGA mRNAs encoding a core set of subunits (including Ada2) are tethered together for co-translational assembly. Disruption of this co-translational assembly (via not5 deletion) impairs SAGA integrity, reducing histone acetylation. mRNA co-immunoprecipitation; polysome profiling; SAGA complex integrity assays; histone acetylation assays in yeast not5 mutants Nucleic acids research Medium 28180299
2017 Ada2(Gcn5)-dependent histone H3K14 acetylation (along with Sas3) is required for transcription elongation at the de-repressed FLO1 gene in yeast. In the absence of H3K14 acetylation, Swi/Snf recruitment and histone eviction proceed but RNAP II is absent from the coding region, demonstrating that Ada2-dependent H3 acetylation is required specifically for the transition from initiation to elongation. Chromatin immunoprecipitation (ChIP) for RNAP II, Swi/Snf, histone modifications; transcription kinetics assays in histone mutant and ada2 yeast strains Nucleic acids research Medium 28115623
2018 Crystal structures of a yeast Ada2/Gcn5 complex were determined using Fab antibody crystallization chaperones. Structural and biochemical analysis revealed that the Ada2 SANT domain activates Gcn5 HAT activity not by directly affecting histone peptide binding as previously proposed, but by enhancing Gcn5 binding to the enzymatic co-substrate acetyl-CoA. This suggests a mechanism for regulating chromatin modification enzyme activity by controlling co-substrate rather than substrate binding. X-ray crystallography of Ada2/Gcn5 complex; in vitro HAT activity assays; acetyl-CoA binding assays; mutagenesis Proceedings of the National Academy of Sciences of the United States of America High 30224453
2005 Large-scale yeast two-hybrid screening of human proteins detected protein-protein interactions involving TADA2A (TADA2L), placing it in the human binary interactome network and identifying novel interaction partners consistent with its role in coactivator complexes. High-throughput yeast two-hybrid assay (CCSB-HI1 dataset); co-affinity purification validation Nature Low 16189514
2020 The Ada2/Ada3/Gcn5/Sgf29 HAT module of SAGA is the minimal unit for Gcn5-mediated histone H3 acetylation at multiple positions. Structural and biochemical studies demonstrate that Ada2 activates Gcn5's intrinsically weak HAT activity, Ada3 facilitates nucleosomal acetylation and expanded lysine specificity, and Sgf29 binds H3K4me3 to recruit the module to active gene promoters. Two Ada2 isoforms (TADA2A and TADA2B) define distinct SAGA-related complexes with different histone substrate preferences. Review integrating structural studies, reconstitution biochemistry, and genetic data from multiple laboratories Biochimica et biophysica acta. Gene regulatory mechanisms High 32890768

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Towards a proteome-scale map of the human protein-protein interaction network. Nature 2090 16189514
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2012 Quantitative analysis of HSP90-client interactions reveals principles of substrate recognition. Cell 708 22939624
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2014 Early-onset stroke and vasculopathy associated with mutations in ADA2. The New England journal of medicine 630 24552284
1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene 492 8125298
1998 Histone-like TAFs within the PCAF histone acetylase complex. Cell 462 9674425
2015 Widespread macromolecular interaction perturbations in human genetic disorders. Cell 454 25910212
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2016 Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing. Cell 423 26871637
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
1992 Genetic isolation of ADA2: a potential transcriptional adaptor required for function of certain acidic activation domains. Cell 395 1638630
2008 The putative cancer stem cell marker USP22 is a subunit of the human SAGA complex required for activated transcription and cell-cycle progression. Molecular cell 355 18206973
1999 Overlapping but distinct patterns of histone acetylation by the human coactivators p300 and PCAF within nucleosomal substrates. The Journal of biological chemistry 343 9880483
2007 Distinct GCN5/PCAF-containing complexes function as co-activators and are involved in transcription factor and global histone acetylation. Oncogene 316 17694077
2013 GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer. Nature genetics 294 23535730
1994 Functional similarity and physical association between GCN5 and ADA2: putative transcriptional adaptors. The EMBO journal 236 7957049
2007 hORFeome v3.1: a resource of human open reading frames representing over 10,000 human genes. Genomics 222 17207965
2016 A High-Density Map for Navigating the Human Polycomb Complexome. Cell reports 216 27705803
2011 Toward an understanding of the protein interaction network of the human liver. Molecular systems biology 207 21988832
2018 An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations. Nature communications 201 29568061
2011 Next-generation sequencing to generate interactome datasets. Nature methods 200 21516116
2005 Polyglutamine-expanded ataxin-7 inhibits STAGA histone acetyltransferase activity to produce retinal degeneration. Proceedings of the National Academy of Sciences of the United States of America 197 15932940
2001 Role of the Ada2 and Ada3 transcriptional coactivators in histone acetylation. The Journal of biological chemistry 190 11773077
1997 Histone acetyltransferase activity and interaction with ADA2 are critical for GCN5 function in vivo. The EMBO journal 189 9034338
2017 ADA2 deficiency (DADA2) as an unrecognised cause of early onset polyarteritis nodosa and stroke: a multicentre national study. Annals of the rheumatic diseases 183 28522451
2008 Human ATAC Is a GCN5/PCAF-containing acetylase complex with a novel NC2-like histone fold module that interacts with the TATA-binding protein. The Journal of biological chemistry 176 18838386
1995 Characterization of physical interactions of the putative transcriptional adaptor, ADA2, with acidic activation domains and TATA-binding protein. The Journal of biological chemistry 167 7642611
2019 H4K20me0 recognition by BRCA1-BARD1 directs homologous recombination to sister chromatids. Nature cell biology 162 30804502
1996 Identification of human proteins functionally conserved with the yeast putative adaptors ADA2 and GCN5. Molecular and cellular biology 161 8552087
1995 ADA3, a putative transcriptional adaptor, consists of two separable domains and interacts with ADA2 and GCN5 in a trimeric complex. Molecular and cellular biology 158 7862114
2005 Human ADA2 belongs to a new family of growth factors with adenosine deaminase activity. The Biochemical journal 152 15926889
1998 The 400 kDa subunit of the PCAF histone acetylase complex belongs to the ATM superfamily. Molecular cell 145 9885574
2016 Phenotypic variability in patients with ADA2 deficiency due to identical homozygous R169Q mutations. Rheumatology (Oxford, England) 124 26867732
2010 Structural basis for the growth factor activity of human adenosine deaminase ADA2. The Journal of biological chemistry 111 20147294
1997 Identification of native complexes containing the yeast coactivator/repressor proteins NGG1/ADA3 and ADA2. The Journal of biological chemistry 105 9038164
2006 Physical and functional interactions of Arabidopsis ADA2 transcriptional coactivator proteins with the acetyltransferase GCN5 and with the cold-induced transcription factor CBF1. Biochimica et biophysica acta 103 16603259
1994 Yeast ADA2 protein binds to the VP16 protein activation domain and activates transcription. Proceedings of the National Academy of Sciences of the United States of America 102 7972120
1993 ADA3: a gene, identified by resistance to GAL4-VP16, with properties similar to and different from those of ADA2. Molecular and cellular biology 102 8413201
2002 The SANT domain of Ada2 is required for normal acetylation of histones by the yeast SAGA complex. The Journal of biological chemistry 100 11777910
2016 Human adenosine deaminases ADA1 and ADA2 bind to different subsets of immune cells. Cellular and molecular life sciences : CMLS 96 27663683
1997 ADA1, a novel component of the ADA/GCN5 complex, has broader effects than GCN5, ADA2, or ADA3. Molecular and cellular biology 93 9154821
2016 Monogenic polyarteritis: the lesson of ADA2 deficiency. Pediatric rheumatology online journal 92 27609179
2003 Two Drosophila Ada2 homologues function in different multiprotein complexes. Molecular and cellular biology 87 12697829
2003 Two different Drosophila ADA2 homologues are present in distinct GCN5 histone acetyltransferase-containing complexes. Molecular and cellular biology 76 12482983
2015 Dermatologic Features of ADA2 Deficiency in Cutaneous Polyarteritis Nodosa. JAMA dermatology 66 26131734
2005 The homologous Drosophila transcriptional adaptors ADA2a and ADA2b are both required for normal development but have different functions. Molecular and cellular biology 66 16135810
1995 Genetic evidence for the interaction of the yeast transcriptional co-activator proteins GCN5 and ADA2. Molecular & general genetics : MGG 60 7898440
2017 Autoimmune phenotype with type I interferon signature in two brothers with ADA2 deficiency carrying a novel CECR1 mutation. Pediatric rheumatology online journal 59 28830446
1989 Serum adenosine deaminase activity in HIV positive subjects. A hypothesis on the significance of ADA2. Panminerva medica 56 2689968
2013 Evaluating pleural ADA, ADA2, IFN-γ and IGRA for diagnosing tuberculous pleurisy. The Journal of infection 54 23796864
2006 The Drosophila histone acetyltransferase Gcn5 and transcriptional adaptor Ada2a are involved in nucleosomal histone H4 acetylation. Molecular and cellular biology 52 17030603
2003 A novel human Ada2 homologue functions with Gcn5 or Brg1 to coactivate transcription. Molecular and cellular biology 52 12972612
2020 CircRNA TADA2A relieves idiopathic pulmonary fibrosis by inhibiting proliferation and activation of fibroblasts. Cell death & disease 49 32694556
2018 Structural basis for activation of SAGA histone acetyltransferase Gcn5 by partner subunit Ada2. Proceedings of the National Academy of Sciences of the United States of America 48 30224453
2016 ADA2 deficiency: case report of a new phenotype and novel mutation in two sisters. RMD open 47 27252897
2008 Two Arabidopsis orthologs of the transcriptional coactivator ADA2 have distinct biological functions. Biochimica et biophysica acta 45 18929690
2019 Variable Clinical Phenotypes and Relation of Interferon Signature with Disease Activity in ADA2 Deficiency. The Journal of rheumatology 44 30647181
2006 Pair of unusual GCN5 histone acetyltransferases and ADA2 homologues in the protozoan parasite Toxoplasma gondii. Eukaryotic cell 44 16400169
2019 ALPS-Like Phenotype Caused by ADA2 Deficiency Rescued by Allogeneic Hematopoietic Stem Cell Transplantation. Frontiers in immunology 39 30692987
2018 Deletion of ADA2 Increases Antifungal Drug Susceptibility and Virulence in Candida glabrata. Antimicrobial agents and chemotherapy 38 29311082
2017 Not5-dependent co-translational assembly of Ada2 and Spt20 is essential for functional integrity of SAGA. Nucleic acids research 37 28180299
2020 The Ada2/Ada3/Gcn5/Sgf29 histone acetyltransferase module. Biochimica et biophysica acta. Gene regulatory mechanisms 35 32890768
2017 Sas3 and Ada2(Gcn5)-dependent histone H3 acetylation is required for transcription elongation at the de-repressed FLO1 gene. Nucleic acids research 35 28115623
2004 PfADA2, a Plasmodium falciparum homologue of the transcriptional coactivator ADA2 and its in vivo association with the histone acetyltransferase PfGCN5. Gene 33 15246536
2021 Sequence-Based Screening of Patients With Idiopathic Polyarteritis Nodosa, Granulomatosis With Polyangiitis, and Microscopic Polyangiitis for Deleterious Genetic Variants in ADA2. Arthritis & rheumatology (Hoboken, N.J.) 32 33021335
2004 Interaction of maize Opaque-2 and the transcriptional co-activators GCN5 and ADA2, in the modulation of transcriptional activity. Plant molecular biology 32 15604678
2020 Dysregulation in B-cell responses and T follicular helper cell function in ADA2 deficiency patients. European journal of immunology 31 32707604
2018 Novel Mutation in CECR1 Leads to Deficiency of ADA2 with Associated Neutropenia. Journal of clinical immunology 31 29564582
2018 Disrupted N-linked glycosylation as a disease mechanism in deficiency of ADA2. The Journal of allergy and clinical immunology 30 29936104
2022 Distinct Roles of Adenosine Deaminase Isoenzymes ADA1 and ADA2: A Pan-Cancer Analysis. Frontiers in immunology 28 35663977
2007 Expression and purification of recombinant yeast Ada2/Ada3/Gcn5 and Piccolo NuA4 histone acetyltransferase complexes. Methods (San Diego, Calif.) 28 17309836
2018 ADA2 Deficiency Mimicking Idiopathic Multicentric Castleman Disease. Pediatrics 27 30139808
2009 The SAGA subunit Ada2 functions in transcriptional silencing. Molecular and cellular biology 27 19737915
2005 Asymmetric expression of transcripts derived from the shared promoter between the divergently oriented ACACA and TADA2L genes. Genomics 24 15607423
2018 Diagnosis and management of ADA2 deficient polyarteritis nodosa. International journal of rheumatic diseases 23 29624883
2024 Lysine acetylation of histone acetyltransferase adaptor protein ADA2 is a mechanism of metabolic control of chromatin modification in plants. Nature plants 22 38326652
2019 ADA2 Deficiency: Case Series of Five Patients with Varying Phenotypes. Journal of clinical immunology 21 31848804
2017 [Multiple facets of ADA2 deficiency: Vasculitis, auto-inflammatory disease and immunodeficiency: A literature review of 135 cases from literature]. La Revue de medecine interne 21 29273180
2014 SAGA/ADA complex subunit Ada2 is required for Cap1- but not Mrr1-mediated upregulation of the Candida albicans multidrug efflux pump MDR1. Antimicrobial agents and chemotherapy 21 24936593
2011 Analysis of serum adenosine deaminase (ADA) and ADA1 and ADA2 isoenzyme activities in HIV positive and HIV-HBV co-infected patients. Clinical biochemistry 21 21640091
2021 The Histone Acetyltransferase GCN5 and the Associated Coactivators ADA2: From Evolution of the SAGA Complex to the Biological Roles in Plants. Plants (Basel, Switzerland) 20 33562796
2024 ADA2 is a lysosomal deoxyadenosine deaminase acting on DNA involved in regulating TLR9-mediated immune sensing of DNA. Cell reports 19 39441717
2021 Circular RNA TADA2A promotes proliferation and migration via modulating of miR‑638/KIAA0101 signal in non‑small cell lung cancer. Oncology reports 19 34296306
1997 Human histone acetyltransferase GCN5 exists in a stable macromolecular complex lacking the adapter ADA2. Biochemistry 18 9398325
2020 Two siblings presenting with novel ADA2 variants, lymphoproliferation, persistence of large granular lymphocytes, and T-cell perturbations. Clinical immunology (Orlando, Fla.) 16 32659374
2020 Two cases of ADA2 deficiency presenting as childhood polyarteritis nodosa: novel ADA2 variant, atypical CNS manifestations, and literature review. Clinical rheumatology 15 32535845
2020 ADA2 deficiency complicated by EBV-driven lymphoproliferative disease. Clinical immunology (Orlando, Fla.) 14 32353633
2022 Lentiviral Mediated ADA2 Gene Transfer Corrects the Defects Associated With Deficiency of Adenosine Deaminase Type 2. Frontiers in immunology 13 35529868
1998 Enzymes (isoenzyme system) as homeostatic mechanisms the isoenzyme (ADA2) of adenosine deaminase of human monocytes-macrophages as a regulator of the 2'deoxyadenosine. Biochemistry and molecular biology international 13 9818088
2023 A Cohort Study on Deficiency of ADA2 from China. Journal of clinical immunology 12 36807221
2022 ELISA based assays to measure adenosine deaminases concentration in serum and saliva for the diagnosis of ADA2 deficiency and cancer. Frontiers in immunology 12 35967411
2021 Novel Adenosine Deaminase 2 (ADA2) Mutations Associated With Hematological Manifestations. Journal of investigative medicine high impact case reports 12 34845942
2008 A conserved central region of yeast Ada2 regulates the histone acetyltransferase activity of Gcn5 and interacts with phospholipids. Journal of molecular biology 12 18950642
2021 A Novel LC-MS/MS-Based Method for the Diagnosis of ADA2 Deficiency from Dried Plasma Spot. Molecules (Basel, Switzerland) 11 34577178
1997 The human transcriptional adaptor genes TADA2L and GCN5L2 colocalize to chromosome 17q12-q21 and display a similar tissue expression pattern. Genomics 9 9073520
2024 ADA2 regulates inflammation and hematopoietic stem cell emergence via the A2bR pathway in zebrafish. Communications biology 8 38777862
2023 Selective ADA2 inhibition for enhancing anti-tumor immune response in glioma: Insights from computational screening of flavonoid compounds. International journal of biological macromolecules 7 37844820
2022 ADA2 deficiency (DADA2) misdiagnosed as systemic onset juvenile idiopathic arthritis in a child carrying a novel compound heterozygous ADA2 mutation: a case report. Translational pediatrics 7 36798931
2021 What a difference ADA2 makes: Insights into the pathophysiology of ADA2 deficiency from single-cell RNA sequencing of monocytes. Journal of leukocyte biology 7 34137068
2019 ADA2 deficiency in a patient with Noonan syndrome-like disorder with loose anagen hair: The co-occurrence of two rare syndromes. American journal of medical genetics. Part A 7 31584751
2018 Identification of co-occurrence in a patient with Dent's disease and ADA2-deficiency by exome sequencing. Gene 7 29391272
2005 Intimate relationship between the genes of two transcriptional coactivators, ADA2a and PIMT, of Drosophila. Gene 6 15777699
2023 The Gcn5-Ada2-Ada3 histone acetyltransferase module has divergent roles in pathogenesis of Candida glabrata. Medical mycology 5 36715154
2023 A new CECR1 mutation associated with severe hematological involvement in ADA2 deficiency. Immunity, inflammation and disease 5 37647436
2022 Atypical presentation of adenosine deaminase 2 deficiency with bi-allelic ADA2 mutation. Clinical case reports 5 35261770
2023 Ada2 and Ada3 Regulate Hyphal Growth, Asexual Development, and Pathogenicity in Beauveria bassiana by Maintaining Gcn5 Acetyltransferase Activity. Microbiology spectrum 4 37052485
2022 A Report of 2 Cases of Kidney Involvement in ADA2 Deficiency: Different Disease Phenotypes and the Tissue Response to Type I Interferon. American journal of kidney diseases : the official journal of the National Kidney Foundation 4 35817275
2025 Dominant negative ADA2 mutations cause ADA2 deficiency in heterozygous carriers. The Journal of experimental medicine 3 40864493
2024 Central retinal artery occlusion in a child with ADA2 deficiency: a case report. Annals of medicine and surgery (2012) 3 38576931
2024 Dominant negative ADA2 mutations cause ADA2 deficiency in heterozygous carriers. medRxiv : the preprint server for health sciences 3 39711711
2025 Intracellular concentration of ADA2 is a marker for monocyte differentiation and activation. Frontiers of medicine 2 39832022
2023 A case with febrile attacks and vasculopathy associated with ADA2 and MEFV pathogenic variants. Modern rheumatology case reports 2 37542433
2021 A Novel Germline Mutation of ADA2 Gene in Two "Discordant" Homozygous Female Twins Affected by Adenosine Deaminase 2 Deficiency: Description of the Bone-Related Phenotype. International journal of molecular sciences 2 34361096
2021 Increased Agrobacterium-mediated transformation of Saccharomyces cerevisiae after deletion of the yeast ADA2 gene. Letters in applied microbiology 2 34816457
2025 ADA2 Forms Nuclear Condensates with GCN5 and ATP-Citrate Lyase (ACL) to Modulate H3K9 Acetylation at Genes Functioning in Rice Meristems. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 1 41221643
2024 Misdiagnosed for 14 Years: Adenosine Deaminase 2 (ADA2) Deficiency in a Teen Mimicking Polyarteritis Nodosa. Clinical case reports 1 39588247
2023 Elevated ADA2 Enzyme Activity at the Onset of Chronic Graft-versus-Host Disease in Children. Transplantation and cellular therapy 1 36804932
2022 A novel frameshift variant in the ADA2 gene of a patient with a neurological phenotype: a case report. Pediatric rheumatology online journal 1 36528591
2021 The role of CECR1 in the immune-modulatory effects of butyrate and correlation between ADA2 and M1/M2 chemokines in tuberculous pleural effusion. International immunopharmacology 1 33857806
1997 [Adenosine deaminase: isoenzymes ADA1 and ADA2]. Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego 1 9523470
2025 Early-onset neutropenia and mixed phenotype in ADA2 deficiency: diagnostic and therapeutic challenges. Frontiers in immunology 0 41112235
2025 Diagnostic Implications and Correlates of Plasma Adenosine Deaminase 2 Activity and ADA2 Variants. Arthritis & rheumatology (Hoboken, N.J.) 0 41147740