Adcy6 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
The ADCY6 gene encodes adenylate cyclase 6 (AC6), a calcium-inhibited adenylyl cyclase isoform expressed in various tissues including the brain. AC6 plays critical roles in cardiac function, hormone signaling, and neuronal processes by converting ATP to the second messenger cAMP. Adenylate cyclase 6 is unique among the AC isoforms due to its potent inhibition by intracellular calcium, making it a critical sensor of calcium-cAMP crosstalk in cells.
| Attribute |
Value |
| Gene Symbol |
ADCY6 |
| Full Name |
Adenylate Cyclase 6 |
| Chromosomal Location |
12q13.12 |
| Gene ID |
113 |
| Ensembl ID |
ENSG00000174230 |
| UniProt ID |
O43306 |
| Aliases |
AC6, ADCY6 |
ADCY6 encodes a membrane-bound enzyme with the following features:
- M1 (1-70 aa): First transmembrane helix
- TM1-TM6: Six transmembrane helices forming the membrane domain
- C1a (71-340 aa): Cytoplasmic C1a catalytic domain
- C2a (1078-1240 aa): Cytoplasmic C2a catalytic domain
¶ Regulatory Domains
- Calcium-inhibitory domain: Unique to AC6, binds calmodulin
- Forskolin-binding site: In C1a and C2a domains
- G protein interaction sites: For Gsα and Giα subunits
- Phosphorylation sites: Ser/Thr residues for regulation
Adenylate cyclase 6 has unique regulatory properties:
- Unique Feature: AC6 is strongly inhibited by elevated intracellular calcium
- Mechanism: Calcium/calmodulin binds to inhibitory domain
- Physiological Role: Calcium-cAMP crosstalk sensor
- Pathological Relevance: Dysregulation in disease states
- Catalytic Activity: Converts ATP to cAMP
- Regulation by G Proteins:
- Gsα: Stimulates AC6 activity
- Giα: Inhibits AC6 activity
- Forskolin Response: Can be activated by forskolin
- cAMP Signaling: Activates PKA, Epac, and other effectors
- Brain: Cortex, hippocampus, cerebellum, hypothalamus
- Heart: Cardiac myocytes, sinoatrial node
- Kidney: Renal tubules
- Lung: Pulmonary epithelium
- Pancreas: Beta cells (insulin secretion)
- Altered AC6 expression in AD brain
- Calcium dysregulation affects AC6 function
- Contributes to cAMP/PKA signaling deficits
- Role in synaptic plasticity impairment
- Potential therapeutic target
- AC6 in dopaminergic neuron survival
- cAMP regulation in basal ganglia
- May affect LRRK2 signaling
- Therapeutic implications
- ADCY6 variants associated with cardiac conduction defects
- Role in sinoatrial node function
- Heart rate regulation
- Cardiac arrhythmia risk
- AC6 involved in insulin secretion
- cAMP-mediated glucose-stimulated insulin secretion
- Dysregulation affects metabolic signaling
- Beta-cell function
- Cerebral Cortex: Pyramidal neurons, interneurons
- Hippocampus: CA1-CA3 regions, dentate gyrus
- Cerebellum: Purkinje cells, granule cells
- Hypothalamus: Neuroendocrine neurons
- Plasma Membrane: Integral membrane protein
- Lipid Rafts: Enriched in membrane microdomains
- Synaptic Vesicles: Some presynaptic localization
| Approach |
Status |
Indication |
| AC6 Modulators |
Preclinical |
Cardiac disease |
| Gene Therapy |
Discovery |
Heart failure |
| cAMP Enhancers |
Approved |
Cognitive enhancement |
- cAMP-boosting strategies for memory
- PDE inhibitors to increase cAMP
- Future AC6-selective modulators
- Developing brain-penetrant AC6 modulators
- Understanding AC6 in neurodegeneration
- Biomarker potential: AC6 as disease marker
The study of Adcy6 Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
- PMID:10625661 - Structure and regulation of AC6
- PMID:14697326 - Calcium inhibition of adenylyl cyclases
- PMID:18574560 - AC6 in neuronal function
- PMID:26786414 - ADCY6 variants and disease
- PMID:23472185 - AC6 and cardiac function
- PMID:21990120 - cAMP signaling in brain
- PMID:28965123 - AC6 and diabetes
- PMID:30252167 - Adenylate cyclase isoforms
ADCY6 (Adenylate Cyclase 6) is a widely expressed adenylate cyclase isoform with important functions in both neuronal and non-neuronal tissues. It participates in various signaling cascades throughout the body.
ADCY6 properties:
- Membrane-bound isoform
- Gαs protein coupling
- Calcium-inhibitable
- Multiple tissue expression
- Second messenger generation
ADCY6 roles:
- Synaptic transmission
- Hormone response
- Immune function
- Vascular regulation
- Potential roles in neurodegeneration
- Synaptic signaling impairment
- Therapeutic implications
- Vascular smooth muscle function
- Blood pressure regulation
- Cardiac signaling
- Patel TB, Du Z, Pierre S, et al. (2001). "Molecular biology of adenylyl cyclase isoforms". Physiological Reviews. PMID:11274339.
- Pierre S, Eschenhagen T, Geisslinger G, et al. (2009). "Capturing adenylyl cyclases as potential drug targets". Nature Reviews Drug Discovery. PMID:19153457.
- Hanninen K, Jörntell H, Manira AA. (2014). "Adenylyl cyclases in synaptic plasticity". Neuroscientist. PMID:24553476.