| Protein Name | Adenylate Cyclase 5 |
|---|---|
| Gene | [ADCY5](/genes/adcy5) |
| UniProt ID | O95622 |
| Protein Size | 1,224 amino acids (~138 kDa) |
| Subcellular Localization | Plasma membrane; intracellular compartments |
| Protein Family | Adenylyl cyclase family (ADCY) |
| PDB Structures | 1CJK, 1CJM |
Adenylate Cyclase 5 (ADCY5) is a membrane-bound enzyme that catalyzes the conversion of ATP to cyclic AMP (cAMP), a crucial second messenger involved in numerous signaling pathways in the brain. ADCY5 is particularly important in dopaminergic signaling and motor control.
ADCY5 is a large transmembrane enzyme with complex domain organization:
The protein has a "M-shaped" structure with transmembrane helices forming the base and cytoplasmic catalytic domains forming the arms.
ADCY5 performs essential signaling functions:
cAMP Production: Catalyzes ATP → cAMP, the central second messenger in G-protein-coupled receptor (GPCR) signaling.
Dopaminergic Signaling: ADCY5 is highly expressed in striatal medium spiny neurons where it couples D1 dopamine receptor signaling to cAMP production[1].
Motor Control: cAMP production in basal ganglia regulates movement initiation and motor learning.
Synaptic Plasticity: cAMP modulates synaptic strength and long-term potentiation.
Gene Expression: cAMP activates PKA and CREB, regulating transcription of plasticity-related genes.
Dominant ADCY5 mutations cause the most common form of genetic dystonia, characterized by rapid, involuntary muscle contractions and abnormal postures[2]. Mutations lead to:
ADCY5 mutations cause a distinct syndrome with paroxysmal dyskinesias and facial myokymia.
ADCY5 expression is altered in AD brains:
Dysregulated cAMP signaling in dopaminergic neurons is implicated in PD pathogenesis, and ADCY5 may be relevant to L-DOPA-induced dyskinesias.
ADCY5 and its downstream signaling are therapeutic targets:
ADCY5 interacts with: