Affinage

ADCY5

Adenylate cyclase type 5 · UniProt O95622

Length
1261 aa
Mass
138.9 kDa
Annotated
2026-06-09
76 papers in source corpus 18 papers cited in narrative 19 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ADCY5 (AC5) is a membrane-anchored adenylyl cyclase that converts ATP to cAMP and serves as a signal-integration node coupling G-protein-coupled receptor activation to downstream cAMP-PKA effectors in striatal neurons, pancreatic β-cells, glia, and secretory cells (PMID:30772269, PMID:16537460, PMID:24740569). Its catalytic core is bidirectionally regulated: Gαs stimulation drives cAMP production while D2 dopamine receptors impose Giα-mediated inhibition, and Ca²⁺ exerts both high- and low-affinity inhibition by acting at the Mg²⁺-binding sites of the catalytic domain (PMID:30772269, PMID:12065575). Cryo-EM of the AC5–Gβγ complex shows Gβγ binding to a coiled-coil linking the transmembrane region to the catalytic core and to the C1b regulatory hub, where it modulates the catalytic core and AC5 dimerization (PMID:38589608). Spatial organization and feedback control are provided by AKAP79/150, which binds the AC5 N-terminus to scaffold the cyclase to synaptic AMPA receptors and PKA and to enable PKA-mediated inhibition of AC activity (PMID:20231277). Gain-of-function missense mutations (R418W, R418Q, A726T, M1029K), several mapping to the Gβγ interface, increase Gαs-stimulated cAMP and reduce D2-mediated inhibition, causing familial dyskinesia (PMID:38589608, PMID:24700542, PMID:30772269). Physiologically, AC5 is required for glucose-coupled (but not GLP-1-coupled) insulin secretion in human islets and mediates mu/delta opioid receptor signaling and the behavioral effects of morphine in striatum (PMID:16537460, PMID:24740569). Additional roles include Ca²⁺-dependent suppression of renin secretion, adrenergic/CPEB3/GluA1-dependent structural plasticity in Bergmann glia, and cAMP-PKA-driven melanosome transport (PMID:17068292, PMID:32229518, PMID:36430661).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2002 High

    Established where Ca²⁺ inhibits AC5, resolving whether calcium acts on the catalytic core or accessory domains — a key question for understanding feedback control of cAMP output.

    Evidence Site-directed mutagenesis, domain deletions, and AC5/AC2 chimeras with activity assays using divalent cations

    PMID:12065575

    Open questions at the time
    • Does not map the structural basis of the Mg²⁺/Ca²⁺ site at atomic resolution
    • Physiological Ca²⁺ thresholds in native cells not addressed
  2. 2006 High

    Placed AC5 downstream of mu/delta but not kappa opioid receptors in striatal cAMP signaling, defining its role in the behavioral pharmacology of morphine.

    Evidence AC5 knockout mice with behavioral pharmacology and striatal membrane adenylyl cyclase assays using selective agonists

    PMID:16537460

    Open questions at the time
    • Does not resolve which downstream effectors transmit the cAMP signal to behavior
    • Striatal cell-type specificity not dissected
  3. 2006 High

    Identified AC5 (with AC6) as the calcium-sensitive intermediary explaining the renin secretion calcium paradox in juxtaglomerular cells.

    Evidence siRNA knockdown of AC5/AC6 in primary and As4.1 cells with cAMP and renin secretion readouts plus perfused kidney

    PMID:17068292

    Open questions at the time
    • Relative contributions of AC5 vs AC6 not separated
    • Does not establish the calcium sensor upstream of the cyclases
  4. 2010 High

    Defined AKAP79/150 as the scaffold tethering AC5 to synaptic AMPA receptors and PKA, providing the spatial framework for localized cAMP signaling and PKA feedback inhibition.

    Evidence Reciprocal Co-IP, live-cell FRET, competitive peptide displacement, membrane AC assays, and AKAP150 knockout mouse brain

    PMID:20231277

    Open questions at the time
    • Stoichiometry of the AC5–AKAP–PKA–AMPAR complex unresolved
    • Whether scaffolding alters basal vs stimulated activity not fully separated
  5. 2010 Medium

    Linked striatal AC5 cAMP signaling to alcohol sensitivity and consumption, extending its behavioral role beyond opioids.

    Evidence AC5 knockout mice with ethanol preference, hypothermia, and sedation assays

    PMID:21193983

    Open questions at the time
    • Single lab, no direct biochemical mechanism for ethanol effects
    • Brain-region and cell-type contributions undefined
  6. 2012 Medium

    Clarified that heterologous sensitization of AC5 by chronic D2 activation depends on vesicular trafficking and signalosome assembly rather than direct Gβγ–AC5 contact.

    Evidence Gαs mutants in Gαs-deficient cells, cAMP sensitization assays, and dominant-negative trafficking inhibitors

    PMID:22523680

    Open questions at the time
    • Single lab with limited replication
    • Identity of the trafficking-dependent signalosome components not defined
  7. 2014 High

    Demonstrated that ADCY5 missense mutations are gain-of-function, increasing β-adrenergic-stimulated cAMP and providing the molecular basis for familial dyskinesia.

    Evidence Intracellular cAMP accumulation assays comparing wild-type and mutant ADCY5 under stimulatory/inhibitory conditions

    PMID:24700542

    Open questions at the time
    • Does not establish the structural mechanism of activation
    • Neuronal consequences not directly assayed
  8. 2014 High

    Established ADCY5 as indispensable for coupling glucose specifically to insulin secretion in human islets, with additional metabolism-independent roles in Ca²⁺ signaling and β-cell connectivity.

    Evidence siRNA silencing in human islets with cAMP/Ca²⁺ imaging, glucose metabolism assays, and connectivity analysis

    PMID:24740569

    Open questions at the time
    • Mechanism distinguishing glucose from GLP-1 coupling unresolved
    • Basis of metabolism-independent Ca²⁺ effects not defined
  9. 2014 High

    Showed that excess AC5 activity is proarrhythmic in heart by driving SR Ca²⁺ overload and CaMKII-dependent RyR hyperactivation.

    Evidence AC5 transgenic mice with Ca²⁺ imaging, action potential recordings, and biochemistry of SERCA2a/CaMKII/RyR

    PMID:25485900

    Open questions at the time
    • Overexpression model may not reflect endogenous AC5 levels
    • Direct cAMP-to-CaMKII oxidation link not fully mapped
  10. 2017 High

    Identified a functional islet enhancer harboring the T2D risk variant rs11708067 that controls ADCY5 expression and insulin secretion, connecting GWAS signal to a regulatory mechanism.

    Evidence ChIP-seq, luciferase reporters, CRISPR enhancer deletion in 832/13 cells, qRT-PCR, and insulin secretion assays

    PMID:28684635

    Open questions at the time
    • Identity of the allele-specific nuclear binding factor not determined
    • Human β-cell validation in vivo not addressed
  11. 2019 High

    Expanded the gain-of-function variant panel and showed mutants combine enhanced Gαs stimulation with reduced D2 inhibition, increasing downstream transcription and exhibiting selective P-site inhibitor sensitivity — establishing pharmacological tractability.

    Evidence CRISPR AC-deficient cell lines, membrane and whole-cell cAMP assays, transcriptional reporters, and SQ22536 inhibition

    PMID:30772269

    Open questions at the time
    • In vivo efficacy of P-site inhibitors not tested
    • Neuronal circuit-level consequences not assessed
  12. 2019 Medium

    Identified PP2A (PPP2CB) and NAPA as AC5 modulators in medium spiny neurons, with PP2A acting as a persistent regulator of cyclase activity.

    Evidence BiFC interaction screening with functional knockdown and cAMP assays in neuronal lines and primary MSNs

    PMID:31752385

    Open questions at the time
    • Single lab; reciprocal biochemical validation limited
    • Whether PP2A acts directly on AC5 or on pathway components unresolved
  13. 2020 High

    Placed AC5 in an adrenergic/AC5/CPEB3/GluA1 axis governing stress-induced suppression of GluA1 translation and structural plasticity in cerebellar Bergmann glia.

    Evidence AC5 and CPEB3 knockout mice with β-adrenergic pharmacology, electrophysiology, and immunoblotting

    PMID:32229518

    Open questions at the time
    • Direct biochemical link from cAMP to CPEB3 not mapped
    • Generalizability beyond Bergmann glia unknown
  14. 2022 Medium

    Demonstrated AC5 (with AC3a) drives melanosome dispersion via cAMP-PKA control of kinesin-1 and dynein-1 downstream of α-MSH/MC1R, linking AC5 to motor-driven organelle transport.

    Evidence Zebrafish single/double CRISPR mutants with PKA rescue, in vivo melanosome imaging, and melanin pathway marker analysis

    PMID:36430661

    Open questions at the time
    • Ortholog study in zebrafish; human relevance not confirmed
    • Direct PKA targets on motor regulation not identified
  15. 2024 High

    Resolved the structural basis of Gβγ regulation, showing Gβγ engages the coiled-coil and C1b hub and that dyskinesia mutations cluster at this interface with altered conditional activation.

    Evidence Cryo-EM of AC5–Gβγ with cell-based and pulldown validation and functional mutant characterization

    PMID:38589608

    Open questions at the time
    • Functional consequence of the observed AC5 dimer in cells not established
    • How Gβγ binding integrates with Gαs and Ca²⁺ inputs not fully resolved
  16. 2023 Medium

    Showed adenosine receptor antagonists (caffeine, theophylline, istradefylline) preferentially suppress cAMP from the R418W gain-of-function mutant, indicating a candidate therapeutic strategy for ADCY5 dyskinesia.

    Evidence cAMP quantification in wild-type vs R418W ADCY5-overexpressing cells after compound treatment

    PMID:36867608

    Open questions at the time
    • Mechanism of preferential inhibition of mutant not resolved
    • Overexpression system; endogenous and in vivo effects untested
  17. 2021 Medium

    Identified miR-18a-3p as a direct repressor of ADCY5 controlling osteogenic differentiation of human bone marrow mesenchymal stem cells.

    Evidence Dual luciferase reporter, RNA pull-down, and ADCY5 overexpression/miRNA mimic functional osteogenesis assays in hBMSCs

    PMID:33684620

    Open questions at the time
    • Single lab; in vivo bone phenotype not tested
    • Downstream cAMP effectors in osteogenesis not defined
  18. 2025 Low

    Proposed Adcy5 as upstream of a Gch1-BH4-dopamine biosynthesis axis mediating artemisinin protection in a Parkinson's disease model.

    Evidence Molecular docking, midbrain proteomics/metabolomics, and Adcy5 inhibitor rescue experiments in rat PD model

    PMID:40908481

    Open questions at the time
    • Relies on docking and pharmacological inhibition rather than direct binding/genetic evidence
    • Single lab, single study
    • Direct Adcy5-Gch1 mechanistic link not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the distinct regulatory inputs to AC5 — Gαs stimulation, Giα/D2 inhibition, Gβγ allostery, Ca²⁺ inhibition, and PKA feedback — are integrated structurally and dynamically at the catalytic core in native cells remains unresolved.
  • No integrated structural model combining Gαs, Gβγ, and Ca²⁺ inputs
  • Cell-type-specific signalosome composition incompletely defined
  • Functional role of AC5 dimerization in vivo unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0009975 cyclase activity 4 GO:0016740 transferase activity 3 GO:0060089 molecular transducer activity 2
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-1643685 Disease 4 R-HSA-112316 Neuronal System 3 R-HSA-162582 Signal Transduction 3 R-HSA-1430728 Metabolism 1
Partners
AKAP5GNB1GNG2NAPAPPP2CB

Evidence

Reading pass · 19 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2024 Cryo-EM structure of AC5 in complex with Gβγ revealed that Gβγ binds to a coiled-coil domain linking the AC5 transmembrane region to its catalytic core and to the C1b regulatory hub. Gain-of-function mutations associated with familial dyskinesia are located at the AC5–Gβγ interface and show reduced conditional activation by Gβγ. A dimeric form of AC5 was also observed, and the proposed mechanism is that Gβγ either prevents AC5 dimerization or allosterically modulates the coiled-coil domain to regulate the catalytic core. Cryo-electron microscopy structure determination; cell-based and pulldown assays confirming Gβγ interaction; functional characterization of dyskinesia-associated gain-of-function mutants Nature structural & molecular biology High 38589608
2014 Missense mutations in ADCY5 (p.R418W, inherited de novo; p.A726T, inherited) cause a statistically significant increase in β-adrenergic receptor agonist-stimulated intracellular cAMP accumulation compared with wild-type protein, establishing these as gain-of-function mutations that increase adenylyl cyclase activity. Intracellular cAMP accumulation assay under stimulatory and inhibitory conditions in cells expressing wild-type vs. mutant ADCY5 Annals of neurology High 24700542
2019 A panel of ADCY5 gain-of-function variants identified in dyskinesia patients (including R418W, R418Q, A726T, M1029K) exhibit enhanced adenylyl cyclase activity in response to Gαs-mediated stimulation in both cell-based and membrane assays, and show significantly reduced inhibition following D2 dopamine receptor activation. The elevated cAMP response at the membrane translates into increased downstream gene transcription in a neuronal model. The P-site inhibitor SQ22536 preferentially inhibits the overactive gain-of-function mutants. CRISPR-Cas9-generated adenylyl cyclase-deficient cell lines; membrane and whole-cell cAMP assays; downstream transcriptional reporter assays; pharmacological inhibition Biochemical pharmacology High 30772269
2002 Both high-affinity and low-affinity Ca²⁺ inhibition of AC5 are exerted at the Mg²⁺-binding sites within the catalytic domain. Mg²⁺ activation decreases the absolute amount of high-affinity Ca²⁺ inhibition without changing its Ki, while decreasing the Ki for low-affinity inhibition, proportional to Mg²⁺ sensitivity of the mutant. Deletion of the N-terminus and C1b domain and chimeras with AC2 confirmed that the catalytic domain alone is responsible for high-affinity inhibition. Site-directed mutagenesis of the catalytic domain; adenylyl cyclase activity assays with Ca²⁺, Sr²⁺, Ba²⁺; domain deletion and AC5/AC2 chimeric constructs The Journal of biological chemistry High 12065575
2010 AKAP79/150 directly interacts with AC5 (and AC6 and AC9) through the N-terminal regions of these cyclases. The reciprocal binding surface on AKAP79 was mapped to residues 77–108. Deletion of AKAP79(77–108) abolished AC5–AKAP79 interaction in living cells (FRET). Addition of the AKAP79(77–153) polypeptide uncoupled AC5/6 from the anchoring protein and prevented PKA-mediated inhibition of AC activity in membranes. Loss of AKAP150 in mouse brain resulted in decreased AMPA receptor-associated AC activity, indicating that AKAP79/150 scaffolds AC5 to synaptic AMPA receptors. Co-immunoprecipitation; intensity- and lifetime-based FRET in living cells; competitive peptide displacement; membrane AC activity assays; AKAP150 knockout mouse brain extracts The Journal of biological chemistry High 20231277
2006 AC5 is an essential mediator of mu and delta opioid receptor signaling in the striatum. In AC5 knockout mice, all major behavioral effects of morphine (locomotor activation, analgesia, tolerance, reward, physical dependence/withdrawal) were attenuated. The ability of mu or delta (but not kappa) opioid receptor agonists to suppress striatal adenylyl cyclase activity was absent in AC5⁻/⁻ mice, placing AC5 downstream of mu/delta opioid receptors in striatal cAMP signaling. AC5 knockout mice; behavioral pharmacology assays; striatal membrane adenylyl cyclase activity assays with selective opioid receptor agonists Proceedings of the National Academy of Sciences of the United States of America High 16537460
2006 Calcium suppresses renin exocytosis from juxtaglomerular cells by inhibiting adenylate cyclases AC5 and AC6, thereby reducing intracellular cAMP. siRNA-mediated knockdown of AC5 and/or AC6 in renin-producing cells prevented calcium-dependent suppression of cAMP levels and renin release. Clamping cAMP with membrane-permeable analogs bypassed the calcium inhibition, confirming that AC5/AC6 are the critical intermediaries of the calcium paradox in renin secretion. siRNA knockdown of AC5 and AC6 in primary juxtaglomerular cells and As4.1 cell line; cAMP measurement; renin secretion assays; isolated perfused mouse kidney Circulation research High 17068292
2014 ADCY5 is indispensable for coupling glucose (but not GLP-1) to insulin secretion in human islets. ADCY5 silencing impaired glucose-induced cAMP increases and blocked glucose metabolism toward ATP at >8 mmol/L glucose. Calcium transient generation and functional connectivity between β-cells were sharply inhibited at all glucose concentrations after ADCY5 knockdown, indicating additional metabolism-independent roles. Calcium rises were unaffected in ADCY5-depleted islets exposed to GLP-1. siRNA silencing of ADCY5 in human islets; in situ imaging of cAMP and calcium with recombinant probes; glucose metabolism assays; functional connectivity analysis Diabetes High 24740569
2017 An islet enhancer overlapping rs11708067 regulates ADCY5 expression. The type 2 diabetes risk allele (rs11708067-A) showed reduced H3K27ac marks, lower transcriptional activity in reporter assays, and increased nuclear protein binding. Homozygous deletion of the orthologous enhancer region in 832/13 cells caused a 64% reduction in Adcy5 expression (but not adjacent Sec22a) and a 39% reduction in insulin secretion, establishing this variant as a functional regulatory element for ADCY5 in β-cells. ChIP-seq; luciferase reporter assays in rodent β-cells; CRISPR-Cas9 enhancer deletion in 832/13 cells; qRT-PCR; insulin secretion assays Diabetes High 28684635
2012 Heterologous sensitization of AC5 by chronic D2 dopamine receptor activation requires signalosome assembly. Gαs is required for D2-induced sensitization of AC5, but neither Gαs palmitoylation nor Gαs–Gβγ interactions are necessary. Coexpression of βARKct-CD8 or dominant-negative Sar1(H79G) blocked heterologous sensitization, implicating vesicular trafficking and proper signalosome assembly rather than direct Gβγ–AC5 interaction as the mechanism. Expression of Gαs mutants in Gαs-deficient cells; cAMP sensitization assays; dominant-negative trafficking inhibitors Journal of signal transduction Medium 22523680
2019 BiFC screening identified two novel AC5 modulators in striatal medium spiny neurons: PP2A catalytic subunit (PPP2CB) and the intracellular trafficking protein NAPA (NSF attachment protein alpha). Knockdown of PPP2CB reduced both acute and sensitized adenylyl cyclase activity, establishing PP2A as a persistent regulator of AC5 activity. NAPA knockdown effects were activity-dependent. Both interactions were validated in D1 and D2 dopamine receptor-expressing MSNs. Bimolecular fluorescence complementation (BiFC) protein–protein interaction screening; genetic knockdown; cAMP activity assays in neuronal cell lines and primary MSNs from CAMPER mice Cells Medium 31752385
2020 AC5 mediates stress-induced suppression of GluA1 protein synthesis and structural plasticity in cerebellar Bergmann glial cells. Acute stress reduced GluA1 protein levels and AMPA receptor-mediated currents in these glia; deletion of adenylyl cyclase 5 prevented GluA1 suppression, placing AC5 downstream of β-adrenergic receptor activation and upstream of CPEB3-dependent translational repression in an adrenergic/adenylyl cyclase/CPEB3/GluA1 pathway. AC5 knockout mice; β-adrenergic receptor blocker pharmacology; CPEB3 knockout mice; electrophysiology; immunoblotting in cerebellar Bergmann glial cells The Journal of neuroscience High 32229518
2014 AC5 overexpression in transgenic mice creates a proarrhythmic substrate by inducing SR Ca²⁺ overload and hyperactivation of ryanodine receptors through CaMKII phosphorylation. AC5Tg myocytes showed higher SR Ca²⁺ content, longer action potential duration, and spontaneous Ca²⁺ waves that induced afterdepolarizations and triggered action potentials. Increased SERCA2a, oxidized CaMKII, and CaMKII-site phosphorylation of RyR were observed, especially after isoproterenol. AC5 transgenic mice; intracellular Ca²⁺ imaging (fluo-4 AM); action potential recordings; immunoblotting for SERCA2a, CaMKII oxidation, RyR phosphorylation; ROS measurement; in vivo arrhythmia induction American journal of physiology. Heart and circulatory physiology High 25485900
2010 AC5 knockout mice show increased ethanol consumption and preference and reduced ethanol sensitivity (attenuated hypothermia and sedation/behavioral sleep responses to high-dose ethanol), establishing AC5 as a regulator of alcohol sensitivity and preference in the striatal cAMP pathway. AC5 knockout mice; two-bottle free-choice ethanol preference; ethanol-induced hypothermia; sedation/loss-of-righting-reflex assay Psychopharmacology Medium 21193983
2022 In zebrafish, Adcy3a and Adcy5 double mutants display defects in melanosome dispersion (but not melanoblast differentiation or regeneration). Mechanistically, Adcy3a and Adcy5 regulate melanosome dispersion by activating kinesin-1 while inhibiting cytoplasmic dynein-1, acting through cAMP-PKA signaling downstream of α-MSH/MC1R. In adults, deletion of both cyclases inhibits melanin production by reducing Mitfa and melanin synthesis enzymes (Tyr, Dct, Trp1b). Zebrafish single and double CRISPR/Cas9 mutants; PKA activator rescue experiments; in vivo imaging of melanosome dispersion; molecular marker analysis of melanin synthesis pathway International journal of molecular sciences Medium 36430661
2023 All three purine derivatives caffeine, theophylline, and istradefylline reduce cAMP production by ADCY5-overexpressing cells. The most pronounced cAMP reduction was observed for the gain-of-function ADCY5 R418W mutant compared to wild-type, demonstrating that these adenosine receptor antagonists preferentially suppress elevated cAMP signaling from the overactive mutant. ADCY5 wild-type and R418W overexpressing cell lines; cAMP quantification assay following treatment with caffeine, theophylline, and istradefylline PloS one Medium 36867608
2021 ADCY5 acts upstream of CPEB3 and GluA1 translation in cerebellar Bergmann glia during stress response, placing it in an adrenergic/AC5/CPEB3/GluA1 signaling axis. AC5 deletion prevented GluA1 suppression and the associated retraction of glial lateral processes, establishing a direct role for AC5 in glial structural plasticity via translational regulation. AC5 knockout mice; CPEB3 knockout mice; β-adrenergic pharmacology; immunoblotting; electrophysiology The Journal of neuroscience High 32229518
2021 miR-18a-3p directly targets ADCY5 mRNA as demonstrated by dual luciferase reporter assay and RNA pull-down, suppressing ADCY5 expression and thereby inhibiting osteogenic differentiation of human bone marrow mesenchymal stem cells. Overexpression of ADCY5 increased calcium deposition, ALP activity, and osteoblast protein expression, while miR-18a-3p mimic partially reversed these effects. Dual luciferase reporter assay; RNA pull-down; ADCY5 overexpression and miR-18a-3p mimic transfection in hBMSCs; ALP activity assay; calcium deposition assay Biochemical and biophysical research communications Medium 33684620
2025 Artemisinin was shown by molecular docking to directly bind to Adcy5 in rat midbrain. In rescue experiments in vitro, inhibition of Adcy5 abolished artemisinin-generated increases in DA, BH4, and Gch1 expression. In vivo, suppression of Adcy5 aggravated Parkinson's disease manifestations and decreased midbrain DA, BH4, and Gch1 expression, placing Adcy5 upstream of a Gch1-BH4-dopamine biosynthesis axis. Molecular docking; midbrain proteomics; non-targeted metabolomics; Adcy5 inhibitor rescue experiments in vitro and in vivo in rat Parkinson's disease model Genome biology Low 40908481

Source papers

Stage 0 corpus · 76 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 ADCY5 couples glucose to insulin secretion in human islets. Diabetes 122 24740569
2016 Phenotypic insights into ADCY5-associated disease. Movement disorders : official journal of the Movement Disorder Society 105 27061943
2015 ADCY5-related dyskinesia: Broader spectrum and genotype-phenotype correlations. Neurology 102 26537056
2014 Gain-of-function ADCY5 mutations in familial dyskinesia with facial myokymia. Annals of neurology 101 24700542
2010 AKAP79 interacts with multiple adenylyl cyclase (AC) isoforms and scaffolds AC5 and -6 to alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptors. The Journal of biological chemistry 95 20231277
2006 Adenylyl cyclase type 5 (AC5) is an essential mediator of morphine action. Proceedings of the National Academy of Sciences of the United States of America 94 16537460
2015 The AC5 protein encoded by Mungbean yellow mosaic India virus is a pathogenicity determinant that suppresses RNA silencing-based antiviral defenses. The New phytologist 80 26010321
2011 The effect of including Lactobacillus reuteri KUB-AC5 during post-hatch feeding on the growth and ileum microbiota of broiler chickens. Poultry science 72 22080014
2015 ADCY5 mutations are another cause of benign hereditary chorea. Neurology 71 26085604
2017 ADCY5-related movement disorders: Frequency, disease course and phenotypic variability in a cohort of paediatric patients. Parkinsonism & related disorders 66 28511835
2006 The calcium paradoxon of renin release: calcium suppresses renin exocytosis by inhibition of calcium-dependent adenylate cyclases AC5 and AC6. Circulation research 65 17068292
2014 A de novo ADCY5 mutation causes early-onset autosomal dominant chorea and dystonia. Movement disorders : official journal of the Movement Disorder Society 64 25545163
2017 A Type 2 Diabetes-Associated Functional Regulatory Variant in a Pancreatic Islet Enhancer at the ADCY5 Locus. Diabetes 51 28684635
2021 An Update on the Phenotype, Genotype and Neurobiology of ADCY5-Related Disease. Movement disorders : official journal of the Movement Disorder Society 46 33934385
2022 Efficacy of Caffeine in ADCY5-Related Dyskinesia: A Retrospective Study. Movement disorders : official journal of the Movement Disorder Society 42 35384065
2019 ADCY5-Related Dyskinesia: Improving Clinical Detection of an Evolving Disorder. Movement disorders clinical practice 38 31538084
2019 Identification of Novel Adenylyl Cyclase 5 (AC5) Signaling Networks in D1 and D2 Medium Spiny Neurons using Bimolecular Fluorescence Complementation Screening. Cells 38 31752385
2016 Treatment of ADCY5-Associated Dystonia, Chorea, and Hyperkinetic Disorders With Deep Brain Stimulation: A Multicenter Case Series. Journal of child neurology 38 27052971
2002 A critical interplay between Ca2+ inhibition and activation by Mg2+ of AC5 revealed by mutants and chimeric constructs. The Journal of biological chemistry 38 12065575
2019 Functional characterization of AC5 gain-of-function variants: Impact on the molecular basis of ADCY5-related dyskinesia. Biochemical pharmacology 37 30772269
2012 Aluminum carboxymethyl cellulose-rice bran microcapsules: enhancing survival of Lactobacillus reuteri KUB-AC5. Carbohydrate polymers 37 24751013
2018 Protective effect of Lactobacillus reuteri KUB-AC5 against Salmonella Enteritidis challenge in chickens. Beneficial microbes 34 30406695
2017 ADCY5-related dyskinesia presenting as familial myoclonus-dystonia. Neurogenetics 31 28229249
2018 PDE10A and ADCY5 mutations linked to molecular and microstructural basal ganglia pathology. Movement disorders : official journal of the Movement Disorder Society 30 30345538
2010 Mice lacking adenylyl cyclase type 5 (AC5) show increased ethanol consumption and reduced ethanol sensitivity. Psychopharmacology 26 21193983
2019 Autosomal recessive ADCY5-Related dystonia and myoclonus: Expanding the genetic spectrum of ADCY5-Related movement disorders. Parkinsonism & related disorders 25 30975617
2023 Scoping Review on ADCY5-Related Movement Disorders. Movement disorders clinical practice 24 37476318
2020 Deep brain stimulation reduces (nocturnal) dyskinetic exacerbations in patients with ADCY5 mutation: a case series. Journal of neurology 22 32647899
2014 Overexpression of adenylyl cyclase type 5 (AC5) confers a proarrhythmic substrate to the heart. American journal of physiology. Heart and circulatory physiology 21 25485900
2020 Polymorphic variants of bovine ADCY5 gene identified in GWAS analysis were significantly associated with ovarian morphological related traits. Gene 19 32949694
2005 Probing the reorganization of the nicotinic acetylcholine receptor during desensitization by time-resolved covalent labeling using [3H]AC5, a photoactivatable agonist. Molecular pharmacology 18 16269537
2024 Structure of adenylyl cyclase 5 in complex with Gβγ offers insights into ADCY5-related dyskinesia. Nature structural & molecular biology 17 38589608
2020 Emotional Stress Induces Structural Plasticity in Bergmann Glial Cells via an AC5-CPEB3-GluA1 Pathway. The Journal of neuroscience : the official journal of the Society for Neuroscience 17 32229518
2014 Enhancement of Lactobacillus reuteri KUB-AC5 survival in broiler gastrointestinal tract by microencapsulation with alginate-chitosan semi-interpenetrating polymer networks. Journal of applied microbiology 16 24712513
2017 Facial twitches in ADCY5-associated disease - Myokymia or myoclonus? An electromyography study. Parkinsonism & related disorders 15 28442302
2023 Development of high cell density Limosilactobacillus reuteri KUB-AC5 for cell factory using oxidative stress reduction approach. Microbial cell factories 14 37120528
2018 The group I alphabaculovirus-specific protein, AC5, is a novel component of the occlusion body but is not associated with ODVs or the PIF complex. The Journal of general virology 14 29465345
2018 Depression and psychosis in ADCY5-related dyskinesia-part of the phenotypic spectrum? Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 13 30172639
2022 Probing Genome-Scale Model Reveals Metabolic Capability and Essential Nutrients for Growth of Probiotic Limosilactobacillus reuteri KUB-AC5. Biology 12 35205160
2017 Combined effects of holy basil essential oil and inlet temperature on lipid peroxidation and survival of Lactobacillus reuteri KUB-AC5 during spray drying. Food research international (Ottawa, Ont.) 12 28873688
2021 ADCY5, CAPN10 and JAZF1 Gene Polymorphisms and Placental Expression in Women with Gestational Diabetes. Life (Basel, Switzerland) 11 34440550
2020 Efficacy of Istradefylline for the Treatment of ADCY5-Related Disease. Movement disorders clinical practice 10 33043083
2025 Treatment Efficacy of Theophylline in ADCY5-Related Dyskinesia: A Retrospective Case Series Study. Movement disorders : official journal of the Movement Disorder Society 9 40079709
2023 Effects of theophylline on ADCY5 activation-From cellular studies to improved therapeutic options for ADCY5-related dyskinesia patients. PloS one 9 36867608
2022 AC5 protein encoded by squash leaf curl China virus is an RNA silencing suppressor and a virulence determinant. Frontiers in microbiology 9 36060769
2021 Homozygous ADCY5 mutation causes early-onset movement disorder with severe intellectual disability. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 9 33704598
2021 Effects of Whole-Body Adenylyl Cyclase 5 (Adcy5) Deficiency on Systemic Insulin Sensitivity and Adipose Tissue. International journal of molecular sciences 9 33919448
2012 Dopamine D(2) Receptor-Mediated Heterologous Sensitization of AC5 Requires Signalosome Assembly. Journal of signal transduction 9 22523680
2011 Absence of birth-weight lowering effect of ADCY5 and near CCNL, but association of impaired glucose-insulin homeostasis with ADCY5 in Asian Indians. PloS one 9 21712988
2020 Common genetic variants in ADCY5 and gestational glycemic traits. PloS one 8 32163478
2023 DNA methylation alterations of ADCY5, MICAL2, and PLEKHG2 during the developmental stage of cryptogenic hepatocellular carcinoma. Hepatology research : the official journal of the Japan Society of Hepatology 7 37906571
2022 Type 2 diabetes is more closely associated with risk of colorectal cancer based on elevated DNA methylation levels of ADCY5. Oncology letters 7 35720494
2019 Antimicrobial peptide presenting potential strain-specific real time polymerase chain reaction assay for detecting the probiotic Lactobacillus reuteri KUB-AC5 in chicken intestine. Poultry science 7 32416839
2024 Probiotic Limosilactobacillus reuteri KUB-AC5 decreases urothelial cell invasion and enhances macrophage killing of uropathogenic Escherichia coli in vitro study. Frontiers in cellular and infection microbiology 6 39091675
2021 By inhibiting ADCY5, miR-18a-3p promotes osteoporosis and possibly contributes to spinal fracture. Biochemical and biophysical research communications 6 33684620
2019 Hyperphosphorylated Tau, Increased Adenylate Cyclase 5 (ADCY5) Immunoreactivity, but No Neuronal Loss in ADCY5-Dyskinesia. Movement disorders clinical practice 6 31970214
2024 ADCY5-related dyskinesia - case series with literature review. Neurologia i neurochirurgia polska 5 38230756
2022 Requirement of Zebrafish Adcy3a and Adcy5 in Melanosome Dispersion and Melanocyte Stripe Formation. International journal of molecular sciences 5 36430661
2022 Early-life low-level lead exposure alters anxiety-like behavior, voluntary alcohol consumption and AC5 protein content in adult male and female C57BL/6 J mice. Neurotoxicology and teratology 3 36539102
2021 Integrative growth physiology and transcriptome profiling of probiotic Limosilactobacillus reuteri KUB-AC5. PeerJ 3 34707932
2025 ADCY5 Gene Affects Seasonal Reproduction in Dairy Goats by Regulating Ovarian Granulosa Cells Steroid Hormone Synthesis. International journal of molecular sciences 2 40004085
2024 ADCY5 act as a putative tumor suppressor in glioblastoma: An integrated analysis. Heliyon 2 39319137
2025 Pearls & Oy-sters: ADCY5-Related Dyskinesia: From a Longstanding Misdiagnosis of Drug-Resistant Epilepsy. Neurology 1 40300124
2023 Case report: Diagnosis of ADCY5-related dyskinesia explaining the entire phenotype in a patient with atypical citrullinemia type I. Frontiers in neurology 1 38020658
2022 ADCY5 gene mutation: a case report. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 1 36112278
2020 [ADCY5-associated dyskinesia in young children: a case report of a family and an updated review]. Revista de neurologia 1 32627162
2015 ADCY5 Mutations and Benign Hereditary Chorea. Pediatric neurology briefs 1 26933606
1999 Accumulation of ζ-carotene in Chlamydomonas reinhardtii under control of the ac5 nuclear gene. Plant cell reports 1 30754756
2026 Nocturnal Ballistic Bouts in ADCY5-Related Movement Disorder. Cureus 0 41705003
2026 [Autosomal dominant dyskinesia associated with the ADCY5 gene]. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova 0 41782543
2026 Mixed Movement Disorder Caused by ADCY5 Pathogenic Variant Successfully Treated With Caffeine: A Case From Ukraine. Case reports in neurological medicine 0 41799247
2026 Distinct Brain Drivers and Shared Cerebello-Cortical Input in ADCY5 and SGCE Hyperkinetic Movements. Movement disorders : official journal of the Movement Disorder Society 0 42063207
2026 Parkinsonism in Childhood, a Clue to Autosomal Recessive ADCY5-Related Movement Disorder? Movement disorders clinical practice 0 42120309
2025 Generation of an induced pluripotent stem cell line (UCLi026-A) from a patient with ADCY5-related disease carrying the heterozygous variant c.1253G > A; (p. Arg418Gln). Stem cell research 0 39919432
2025 Artemisinin alleviates Parkinson's disease by targeting Adcy5-Gch1 axis to trigger a cascade generation of BH4 and dopamine in rats. Genome biology 0 40908481
2024 A Single-Arm, Prospective Study of a Proprietary Synthetic Acellular Self-Assembling Peptide Wound Matrix, AC5® Advanced Wound System, for Treatment of Hard-to-Heal Wounds. Surgical technology international 0 39546632

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