protein
Adenylate cyclase type 6
Gene
ADCY6
Organism
Homo sapiens(9606)
Length
1168 aa
Mass
130,615 Da
Adenylate cyclase type 6 (ADCY6) is a membrane-bound enzyme that catalyzes the formation of cyclic adenosine monophosphate (cAMP), a key second messenger in intracellular signaling downstream of G protein-coupled receptors (UniProt: O43306). The protein functions in diverse physiological processes including β-adrenergic signaling in cardiac and vascular tissues, vasopressin signaling in the kidney, and hormone signaling in the pancreas. ADCY6 mediates cAMP-dependent protein kinase A activation and is important for cardiac contractility and bone mechanotransduction (UniProt: O43306).
ADCY6 is ubiquitously expressed across tissues involved in cardiac, renal, and endocrine function. A rare genetic association exists with lethal congenital contracture syndrome 8 (LCCS8, MIM 616287), an autosomal recessive neuromuscular disorder (UniProt: O43306).
ADCY6 is downregulated in Alzheimer's disease brain tissue. Chaparral AD proteomics analysis of post-mortem AD brain versus age-matched controls detected reduced ADCY6 levels with a mean log2 fold-change of −0.28 across subcellular fractions (Chaparral AD proteomics). This reduction may reflect disrupted cAMP signaling in AD pathology, potentially affecting neuronal plasticity and synaptic function.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↓ Down in ADP3
-0.283
P2
not detected
S2
not detected
S3
not detected
Mean log₂FC across detected fractions: -0.2828 (1 of 4 fractions detected)
Human post-mortem AD brain vs age-matched controls, TMT-labeled, 4 subcellular fractions (P2, P3, S2, S3), DDA proteomics.
Related Publications
Browse all →Tau molecular diversity contributes to clinical heterogeneity in Alzheimer's disease.
Dujardin Simon et al.Nature medicine2020PMID 32572268Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer's Disease Progression.
Bai Bing et al.Neuron2020PMID 31926610A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease.
Seyfried Nicholas T et al.Cell systems2017PMID 27989508Large-scale deep multi-layer analysis of Alzheimer's disease brain reveals strong proteomic disease-related changes not observed at the RNA level.
Johnson Erik C B et al.Nature neuroscience2022PMID 35115731Organization and regulation of gene transcription.
Cramer PatrickNature2019PMID 31462772
Function
Catalyzes the formation of the signaling molecule cAMP downstream of G protein-coupled receptors (PubMed:17110384, PubMed:17916776). Functions in signaling cascades downstream of beta-adrenergic receptors in the heart and in vascular smooth muscle cells (PubMed:17916776). Functions in signaling cascades downstream of the vasopressin receptor in the kidney and has a role in renal water reabsorption. Functions in signaling cascades downstream of PTH1R and plays a role in regulating renal phosphate excretion. Functions in signaling cascades downstream of the VIP and SCT receptors in pancreas and contributes to the regulation of pancreatic amylase and fluid secretion (By similarity). Signaling mediates cAMP-dependent activation of protein kinase PKA. This promotes increased phosphorylation of various proteins, including AKT. Plays a role in regulating cardiac sarcoplasmic reticulum Ca(2+) uptake and storage, and is required for normal heart ventricular contractibility. May contribute to normal heart function (By similarity). Mediates vasodilatation after activation of beta-adrenergic receptors by isoproterenol (PubMed:17916776). Contributes to bone cell responses to mechanical stimuli (By similarity)
Disease associations
Lethal congenital contracture syndrome 8LCCS8
A form of lethal congenital contracture syndrome, an autosomal recessive disorder characterized by degeneration of anterior horn neurons, extreme skeletal muscle atrophy and congenital non-progressive joint contractures. The contractures can involve the upper or lower limbs and/or the vertebral column, leading to various degrees of flexion or extension limitations evident at birth. LCCS8 is an axoglial form of arthrogryposis multiplex congenita, characterized by congenital distal joint contractures, reduced fetal movements, and severe motor paralysis leading to death early in the neonatal period.
Sources
Last updated 5/8/2026, 6:37:03 AM