Affinage

ADA2

Adenosine deaminase 2 · UniProt Q9NZK5

Length
511 aa
Mass
58.9 kDa
Annotated
2026-06-09
100 papers in source corpus 18 papers cited in narrative 18 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

ADA2 (CECR1) is a secreted, heparin-binding adenosine deaminase of the ADGF family that functions extracellularly and within the endolysosomal system to regulate adenosine-dependent signaling, immune cell behavior, and vascular development (PMID:15926889, PMID:24552284). Crystallography established that ADA2 comprises a catalytic domain plus two ADGF/ADA2-specific domains of novel fold that mediate dimerization and cell-surface receptor binding, with extensive glycosylation and a conserved disulfide bond consistent with an extracellular role and a substrate-binding pocket distinct from ADA1 (PMID:20147294); N-linked glycosylation and proper dimerization/secretion are essential for normal function (PMID:29936104). Beyond deaminating free adenosine, ADA2 localizes to lysosomes via glycan-directed targeting and edits deoxyadenosine to deoxyinosine in DNA, thereby modulating TLR9-dependent innate immune sensing (PMID:39441717). Produced largely by monocytes/macrophages, ADA2 binds immune cell subsets lacking the ADA1 receptor CD26 (neutrophils, CD16+ monocytes, NK cells, B cells, regulatory T cells) (PMID:27663683), drives M2 macrophage polarization, and promotes neovascularization by upregulating macrophage PDGFB that activates pericyte PDGFRβ signaling in a paracrine manner (PMID:28534507, PMID:28453746). In development, its deaminase activity acts upstream of adenosine/P1 receptor signaling, and it regulates hematopoietic stem cell emergence through the adenosine A2b receptor pathway by restraining endothelial inflammation (PMID:18032387, PMID:38777862). Biallelic loss-of-function mutations cause the autoinflammatory vasculopathy DADA2, with reduced protein and enzymatic activity, monocyte-driven endothelial damage, and rescue by wild-type CECR1 or gene transfer (PMID:24552284, PMID:35529868); dominant-negative missense variants disrupt dimerization and secretion through Cys408-mediated intracellular disulfide aggregation (PMID:40864493).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2000 Low

    Before any biochemical role was known, the question was what kind of protein CECR1 encodes; sequence and expression analysis linked it to insect growth factors and placed expression in developing cardiovascular and neural structures.

    Evidence Exon trapping, RT-PCR, Northern blot, and in situ hybridization on human embryo

    PMID:10756095

    Open questions at the time
    • No enzymatic activity demonstrated
    • No functional perturbation
    • Developmental role inferred from expression only
  2. 2005 Medium

    It was unknown whether ADA2 was a true enzyme; heparin-affinity purification and activity assays defined it as an ADGF-family adenosine deaminase active at acidic pH and high adenosine concentrations, distinguishing it biochemically from ADA1.

    Evidence Heparin-affinity purification and in vitro enzyme activity assays

    PMID:15926889

    Open questions at the time
    • Physiological substrate not established
    • No structural basis for activity
    • Single lab in vitro characterization
  3. 2005 Medium

    To test whether ADA2 deaminase dosage matters in vivo, transgenic overexpression showed gain-of-function disrupts heart and kidney development, implicating tightly controlled ADA2 activity in organogenesis.

    Evidence Cardiac-specific and ubiquitous promoter-driven transgenic mouse overexpression with histological analysis

    PMID:16145841

    Open questions at the time
    • Mechanism linking deaminase activity to organ phenotype unknown
    • Overexpression may not reflect physiological role
    • Receptor/signaling pathway not defined
  4. 2007 Medium

    Whether the enzyme activity is required for the growth-factor function was open; Xenopus knockdown placed ADA2 deaminase activity upstream of adenosine/P1 receptor signaling in embryogenesis.

    Evidence Morpholino knockdown in Xenopus with recombinant enzyme assay and P1 receptor agonist rescue

    PMID:18032387

    Open questions at the time
    • Specific P1 receptor not identified
    • Ortholog model may not fully reflect human biology
    • Direct receptor binding not shown
  5. 2010 High

    The structural basis of ADA2's distinct activity was unknown; crystal structures revealed a catalytic domain plus two novel ADGF/ADA2-specific dimerization/receptor-binding domains, glycosylation, and a substrate pocket differing from ADA1.

    Evidence X-ray crystallography with transition-state analogue co-crystal and structural comparison to ADA1

    PMID:20147294

    Open questions at the time
    • Cell-surface receptor not identified
    • Functional consequence of dimerization not tested in cells
    • No structure of disease variants
  6. 2014 High

    The pathological role of ADA2 was unknown until biallelic CECR1 loss-of-function mutations were shown to cause vasculopathy, stroke, and inflammation, with zebrafish rescue establishing causality and patient monocytes damaging endothelium.

    Evidence Whole-exome sequencing, enzyme assays, zebrafish morpholino knockdown with human CECR1 rescue, and endothelial co-culture

    PMID:24552284

    Open questions at the time
    • Molecular mechanism of endothelial damage not resolved
    • Link between enzyme loss and inflammation undefined
    • Cell-surface partner unknown
  7. 2016 Medium

    How ADA2 engages immune cells was unclear; binding assays showed it binds CD26-negative subsets distinct from ADA1, indicating a separate cell-surface anchoring function on neutrophils, CD16+ monocytes, NK, B, and regulatory T cells.

    Evidence Flow cytometry binding assays with recombinant ADA2 on patient blood

    PMID:27663683

    Open questions at the time
    • The ADA2 cell-surface receptor is not identified
    • Functional consequence of binding not directly tested
    • Single lab
  8. 2017 Medium

    The mechanism connecting macrophage ADA2 to vasculature was unknown; in glioblastoma, macrophage CECR1 was shown to drive neovascularization by upregulating PDGFB to activate pericyte PDGFRβ, and to promote M2 polarization via MAPK signaling.

    Evidence siRNA knockdown, recombinant stimulation, 3D co-culture angiogenesis and migration assays, qRT-PCR, conditioned medium transfer

    PMID:28453746 PMID:28534507

    Open questions at the time
    • How ADA2 enzymatic activity links to PDGFB induction unclear
    • Tumor context may differ from DADA2 vasculopathy
    • Receptor mediating ADA2 effect on macrophages unknown
  9. 2018 Medium

    Whether post-translational modification governs ADA2 biology was open; a pathogenic variant disrupting an N-glycosylation consensus site established that N-linked glycosylation is essential for ADA2 stability/secretion.

    Evidence Identification of patient variant and biochemical analysis of the glycosylation defect

    PMID:29936104

    Open questions at the time
    • Quantitative effect on secretion vs stability not separated
    • Single variant studied
    • Downstream cellular consequence not assessed
  10. 2022 Medium

    Whether ADA2 loss directly causes the immune/vascular defects was confirmed by lentiviral gene transfer into patient macrophages and HSPCs, which restored enzyme activity and corrected M1 cytokine production and endothelial activation.

    Evidence Lentiviral transduction of patient cells with enzyme, cytokine, endothelial activation, and colony-forming readouts

    PMID:35529868

    Open questions at the time
    • Does not define the molecular substrate driving inflammation
    • In vivo efficacy not tested here
    • Single lab
  11. 2024 Medium

    The physiological substrate and subcellular site of ADA2 action were reconsidered; lysosomal-localized ADA2 was shown to edit deoxyadenosine in DNA to modulate TLR9, suggesting DNA rather than free adenosine is a key substrate.

    Evidence Subcellular fractionation, DNA-binding and DNA deamination assays, TLR9 reporter assays, glycan modification experiments

    PMID:39441717

    Open questions at the time
    • Relative contribution of DNA editing vs adenosine deamination in disease unresolved
    • In vivo relevance of TLR9 modulation not established
    • Single lab
  12. 2024 High

    How ADA2 contributes to blood formation was unknown; a zebrafish cecr1b model showed ADA2 deficiency impairs HSC specification via endothelial inflammation, with rescue by anti-inflammatory agents, A2bR modulation, or recombinant ADA2, placing ADA2 upstream of A2bR signaling.

    Evidence Zebrafish loss-of-function model with multiple independent pharmacological and protein rescue strategies

    PMID:38777862

    Open questions at the time
    • Direct ADA2-A2bR molecular link not shown
    • Human HSC relevance not demonstrated
    • Whether DNA editing or adenosine deamination drives the effect unknown
  13. 2025 Medium

    The molecular basis for dominant inheritance and allele severity was defined; specific missense variants act dominant-negatively by forming Cys408-mediated intracellular disulfide aggregates that block dimerization and secretion, while residual activity tracks with hypomorphic phenotype.

    Evidence Transfected cell expression, enzyme activity assays, western blotting, and aggregation analysis of multiple variants

    PMID:40864493 PMID:41147740

    Open questions at the time
    • Aggregation mechanism shown in overexpression systems
    • In vivo dominant-negative effect not modeled
    • Structural detail of Cys408 bridging not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • The identity of the ADA2 cell-surface receptor on CD26-negative immune subsets and the in vivo balance between free-adenosine deamination, lysosomal DNA editing, and A2bR/PDGFB signaling in driving DADA2 pathology remain unresolved.
  • ADA2 receptor unidentified
  • Dominant substrate in vivo unsettled
  • Mechanistic link between enzyme loss and vasculitis incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 2 GO:0003677 DNA binding 1 GO:0008289 lipid binding 1 GO:0140098 catalytic activity, acting on RNA 1
Localization
GO:0005576 extracellular region 2 GO:0005764 lysosome 2 GO:0005886 plasma membrane 1
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-168256 Immune System 3 R-HSA-162582 Signal Transduction 2 R-HSA-1643685 Disease 2
Partners
PDGFBPDGFRBTLR9
Complex memberships
ADA2 homodimer

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 ADA2 (CECR1) was identified as a member of the ADGF (adenosine deaminase-related growth factor) family and shown to be a heparin-binding protein with adenosine deaminase activity; purification via heparin affinity demonstrated its biochemical properties including activity at acidic pH and elevated adenosine concentrations. Heparin-affinity purification, enzyme activity assays, biochemical characterization The Biochemical journal Medium 15926889
2010 Crystal structures of human ADA2 and ADA2 bound to a transition-state analogue revealed the structural basis of catalytic activity: ADA2 contains a catalytic domain plus two ADGF/ADA2-specific domains of novel folds mediating protein dimerization and binding to cell-surface receptors. Extensive glycosylation and a conserved disulfide bond indicate extracellular function. The substrate-binding pocket of ADA2 differs substantially from ADA1, explaining distinct substrate and inhibitor specificities. X-ray crystallography, transition-state analogue co-crystal structure, structural comparison The Journal of biological chemistry High 20147294
2014 Loss-of-function mutations in CECR1 (encoding ADA2) cause a syndrome of vasculopathy, stroke, and inflammation. Patients had markedly reduced ADA2 protein levels and ADA2-specific enzymatic activity. Morpholino knockdown of zebrafish ADA2 homologue caused intracranial hemorrhages and neutropenia; these phenotypes were rescued by co-injection with wild-type but not mutant human CECR1, establishing a direct causal link. Monocytes from patients induced endothelial cell layer damage in co-culture. Whole-exome sequencing, enzyme activity assay, zebrafish morpholino knockdown, co-culture endothelial damage assay, immunoblotting The New England journal of medicine High 24552284
2016 ADA2 binds to distinct subsets of immune cells that lack CD26 (the ADA1 receptor), including neutrophils, monocytes (preferentially CD16+ monocytes), NK cells, B cells, and CD39+ regulatory T cells; this cell-surface binding is separate from ADA1 binding, suggesting ADA2 regulates activation and survival of immune cells anchored to the cell surface. Flow cytometry binding assays with recombinant ADA2, analysis of patient blood samples Cellular and molecular life sciences : CMLS Medium 27663683
2007 In Xenopus, CECR1/ADGF orthologs exhibit adenosine deaminase activity that is indispensable for their growth factor activity; knockdown caused developmental defects recapitulated by exogenous adenosine or P1 receptor agonists, placing ADA2 function upstream of adenosine/P1 receptor signaling in embryogenesis. Morpholino oligonucleotide knockdown in Xenopus, recombinant protein enzyme assay, adenosine/P1 receptor agonist injection, developmental marker gene expression The Journal of biological chemistry Medium 18032387
2017 In glioblastoma, macrophage-expressed CECR1 (ADA2) promotes neovascularization by upregulating PDGFB mRNA and protein in macrophages, which then activates pericyte PDGFRβ signaling in a paracrine manner, promoting pericyte migration and periostin deposition; siRNA knockdown of CECR1 in macrophages reduced vessel formation in a 3D co-culture system. siRNA knockdown, recombinant protein stimulation, 3D co-culture angiogenesis assay, transwell migration assay, qRT-PCR, immunohistochemistry Oncogene Medium 28534507
2017 CECR1 in M2-like tumor-associated macrophages regulates macrophage M2 polarization and exerts paracrine effects on glioma cells via MAPK signaling; CECR1 knockdown or stimulation of macrophages altered M2 phenotype markers and affected tumor cell proliferation and migration. siRNA knockdown, conditioned medium transfer, flow cytometry, immunohistochemistry, in vitro proliferation and migration assays Neuro-oncology Medium 28453746
2000 CECR1 encodes a protein with sequence similarity to insect growth factors (IDGF from flesh fly, MDGF from sea hare) and is alternatively spliced; it is expressed in developing heart outflow tract, cranial nerve ganglia, and notochord, suggesting a developmental role. Exon trapping, RT-PCR, Northern blot, in situ hybridization on human embryo Genomics Low 10756095
2005 Transgenic overexpression of CECR1 adenosine deaminase in mice under cardiac-specific (myosin heavy chain) or ubiquitous (beta-actin) promoters caused heart enlargement, high rates of embryonic and neonatal lethality, and kidney and eye abnormalities, demonstrating that CECR1 gain-of-function disrupts heart and kidney development. Transgenic mouse generation, cardiac and ubiquitous promoter-driven overexpression, morphological and histological analysis Transgenic research Medium 16145841
2018 A pathogenic mutation in DADA2 affecting a consensus N-linked glycosylation sequence disrupts glycosylation of ADA2, establishing that N-linked glycosylation is essential for normal ADA2 biology (protein stability/secretion). Identification of novel mutation, biochemical analysis of glycosylation defect The Journal of allergy and clinical immunology Medium 29936104
2024 ADA2 localizes within lysosomes (targeted via glycan modifications) and interacts with DNA molecules, editing deoxyadenosine (dA) to deoxyinosine (dI) in DNA; this lysosomal DNA-editing activity modulates TLR9 activation, regulating innate immune sensing of nucleic acids. Data suggest DNA rather than free adenosine is the physiological substrate. Subcellular fractionation/localization studies, DNA-binding assays, in vitro deamination assays on DNA substrates, TLR9 reporter assays, glycan modification experiments Cell reports Medium 39441717
2024 In a zebrafish cecr1b loss-of-function model, ADA2 deficiency disrupts hematopoietic stem cell specification and causes defective hematopoiesis via induction of inflammation in the vascular endothelium; pharmacological blockade of inflammation, modulation of the adenosine A2 receptor (A2bR) pathway, or administration of recombinant human ADA2 corrected these hematopoietic defects, placing ADA2 upstream of A2bR signaling in hematopoiesis regulation. Zebrafish cecr1b loss-of-function model, pharmacological rescue (A2R pathway modulation, anti-inflammatory agents), recombinant human ADA2 administration, hematopoietic assays Communications biology High 38777862
2025 Specific ADA2 missense variants (p.G47A, p.G47R, p.G47V, p.R169Q, p.E328K, p.H424N, p.Y453C) exert dominant-negative effects on ADA2 enzymatic activity, dimerization, and/or secretion; in vitro analysis showed these variants form large intracellular protein aggregates via disulfide bond formation at Cys408. Transfected cell expression assays, enzyme activity assays, western blotting, protein aggregation analysis The Journal of experimental medicine Medium 40864493
2024 Dominant-negative ADA2 missense variants disrupt ADA2 enzymatic activity, dimerization, and/or secretion; these variants can cause DADA2 in heterozygous carriers, demonstrating that ADA2 protein function requires proper dimerization and secretion. Overexpression in 293T cells, enzyme activity assay, western blotting, patient cohort analysis medRxivpreprint Low 39711711
2025 In vitro analysis of DADA2-associated ADA2 missense variants shows that residual ADA2 activity correlates with hypomorphic alleles; variants can synergistically disrupt protein function via intracellular aggregate formation mediated by disulfide bonds at Cys408. Overexpression in 293T cells, enzyme activity assay, western blotting Arthritis & rheumatology Medium 41147740
2021 CECR1-encoded ADA2 plays a role in butyrate-modulated M2 macrophage polarization; siRNA knockdown of CECR1 in THP-1 cells impaired butyrate-induced M2 polarization in LPS-stimulated cells, and ADA2 levels in pleural fluid correlated with TGF-β and IL-22 (anti-inflammatory markers) and inversely with CCL21 and CCL25. siRNA knockdown in THP-1 macrophages, flow cytometry, ELISA of pleural fluid International immunopharmacology Low 33857806
2025 ADA2 localizes to endolysosomes within macrophages; intracellular ADA2 concentration decreases in cells secreting TNF-α, suggesting ADA2 functions as a lysosomal adenosine deaminase that regulates TNF-α expression. Secreted ADA2 can bind to apoptotic cells and reduce extracellular adenosine levels to activate immune cells. Subcellular localization imaging, correlation of intracellular ADA2 with TNF-α secretion, binding assay on apoptotic cells, bronchoalveolar lavage analysis Frontiers of medicine Low 39832022
2022 Lentiviral-mediated ADA2 gene transfer into patient-derived macrophages and CD34+ HSPCs restored ADA2 protein expression and enzymatic activity, ameliorated M1 macrophage cytokine production (IFN-γ, phospho-STAT1), and reduced macrophage-mediated endothelial activation, demonstrating that ADA2 loss-of-function is the direct cause of these immune and vascular defects. Lentiviral transduction of patient cells, enzyme activity assay, western blotting, cytokine measurement, endothelial activation assay, colony-forming unit assay Frontiers in immunology Medium 35529868

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Early-onset stroke and vasculopathy associated with mutations in ADA2. The New England journal of medicine 640 24552284
1992 Genetic isolation of ADA2: a potential transcriptional adaptor required for function of certain acidic activation domains. Cell 395 1638630
1994 Functional similarity and physical association between GCN5 and ADA2: putative transcriptional adaptors. The EMBO journal 236 7957049
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 185 28522451
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
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 153 15926889
2016 Phenotypic variability in patients with ADA2 deficiency due to identical homozygous R169Q mutations. Rheumatology (Oxford, England) 125 26867732
2010 Structural basis for the growth factor activity of human adenosine deaminase ADA2. The Journal of biological chemistry 112 20147294
1997 Identification of native complexes containing the yeast coactivator/repressor proteins NGG1/ADA3 and ADA2. The Journal of biological chemistry 105 9038164
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 98 27663683
2014 Mutations in CECR1 associated with a neutrophil signature in peripheral blood. Pediatric rheumatology online journal 97 25278816
2016 Monogenic polyarteritis: the lesson of ADA2 deficiency. Pediatric rheumatology online journal 94 27609179
1997 ADA1, a novel component of the ADA/GCN5 complex, has broader effects than GCN5, ADA2, or ADA3. Molecular and cellular biology 93 9154821
2003 Two Drosophila Ada2 homologues function in different multiprotein complexes. Molecular and cellular biology 88 12697829
2003 Two different Drosophila ADA2 homologues are present in distinct GCN5 histone acetyltransferase-containing complexes. Molecular and cellular biology 77 12482983
2017 CECR1-mediated cross talk between macrophages and vascular mural cells promotes neovascularization in malignant glioma. Oncogene 67 28534507
2015 Dermatologic Features of ADA2 Deficiency in Cutaneous Polyarteritis Nodosa. JAMA dermatology 66 26131734
2017 Activation of CECR1 in M2-like TAMs promotes paracrine stimulation-mediated glial tumor progression. Neuro-oncology 64 28453746
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
2000 The human homolog of insect-derived growth factor, CECR1, is a candidate gene for features of cat eye syndrome. Genomics 57 10756095
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 55 23796864
2003 A novel human Ada2 homologue functions with Gcn5 or Brg1 to coactivate transcription. Molecular and cellular biology 52 12972612
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 49 30224453
2016 ADA2 deficiency: case report of a new phenotype and novel mutation in two sisters. RMD open 47 27252897
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
2001 The invertebrate growth factor/CECR1 subfamily of adenosine deaminase proteins. Gene 37 11311551
2020 The Ada2/Ada3/Gcn5/Sgf29 histone acetyltransferase module. Biochimica et biophysica acta. Gene regulatory mechanisms 36 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
2022 Distinct Roles of Adenosine Deaminase Isoenzymes ADA1 and ADA2: A Pan-Cancer Analysis. Frontiers in immunology 31 35663977
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
2007 The extracellular adenosine deaminase growth factor, ADGF/CECR1, plays a role in Xenopus embryogenesis via the adenosine/P1 receptor. The Journal of biological chemistry 29 18032387
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
2001 Characterization of the adenosine deaminase-related growth factor (ADGF) gene family in Drosophila. Gene 27 11738815
2024 Lysine acetylation of histone acetyltransferase adaptor protein ADA2 is a mechanism of metabolic control of chromatin modification in plants. Nature plants 26 38326652
2018 Diagnosis and management of ADA2 deficient polyarteritis nodosa. International journal of rheumatic diseases 24 29624883
2003 Genetic analysis of the ADGF multigene family by homologous recombination and gene conversion in Drosophila. Genetics 24 14573477
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
2005 Transgenic expression of CECR1 adenosine deaminase in mice results in abnormal development of heart and kidney. Transgenic research 19 16145841
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
2022 ELISA based assays to measure adenosine deaminases concentration in serum and saliva for the diagnosis of ADA2 deficiency and cancer. Frontiers in immunology 14 35967411
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
2021 A Novel LC-MS/MS-Based Method for the Diagnosis of ADA2 Deficiency from Dried Plasma Spot. Molecules (Basel, Switzerland) 13 34577178
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
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
2024 ADA2 regulates inflammation and hematopoietic stem cell emergence via the A2bR pathway in zebrafish. Communications biology 10 38777862
2019 A homozygote novel L451W mutation in CECR1 gene causes deficiency of adenosine deaminase 2 in a pediatric patient representing with chronic lymphoproliferation and cytopenia. Pediatric hematology and oncology 8 31522599
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
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
2025 Dominant negative ADA2 mutations cause ADA2 deficiency in heterozygous carriers. The Journal of experimental medicine 4 40864493
2023 Ada2 and Ada3 Regulate Hyphal Growth, Asexual Development, and Pathogenicity in Beauveria bassiana by Maintaining Gcn5 Acetyltransferase Activity. Microbiology spectrum 4 37052485
2023 The AMP deaminase of the mollusk Helix pomatia is an unexpected member of the adenosine deaminase-related growth factor (ADGF) family. PloS one 4 37471401
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
2021 Proerythroblast Cells of Diamond-Blackfan Anemia Patients With RPS19 and CECR1 Mutations Have Similar Transcriptomic Signature. Frontiers in physiology 4 34177624
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
2025 Structural basis for the substrate specificity of Helix pomatia AMP deaminase and a chimeric ADGF adenosine deaminase. The Journal of biological chemistry 2 40505866
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 Structural basis of substrate specificity of Helix pomatia AMP deaminase and a chimeric ADGF adenosine deaminase. bioRxiv : the preprint server for biology 1 40196538
2025 Diagnostic Implications and Correlates of Plasma Adenosine Deaminase 2 Activity and ADA2 Variants. Arthritis & rheumatology (Hoboken, N.J.) 1 41147740
2023 Elevated ADA2 Enzyme Activity at the Onset of Chronic Graft-versus-Host Disease in Children. Transplantation and cellular therapy 1 36804932
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

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