Protein detail
ADCY6
Adenylate cyclase type 6 (EC 4.6.1.1) (ATP pyrophosphate-lyase 6) (Adenylate cyclase type VI) (Adenylyl cyclase 6) (Ca(2+)-inhibitable adenylyl cyclase)
Entry name ADCY6 | UniProt ID | EVMP score 0.47 |
Frequency 12 | Transmembrane count 12 | Protein classification Disease related genesEnzymesHuman disease related genesMetabolic proteinsPredicted intracellular proteinsPredicted membrane proteins |
EVMP score: annotation confidence score.
Extremely high >= 0.85High >= 0.70Medium >= 0.55Low >= 0.40
Basic Information
Protein Names
Adenylate cyclase type 6 (EC 4.6.1.1) (ATP pyrophosphate-lyase 6) (Adenylate cyclase type VI) (Adenylyl cyclase 6) (Ca(2+)-inhibitable adenylyl cyclase)
Protein Class
Disease related genesEnzymesHuman disease related genesMetabolic proteinsPredicted intracellular proteinsPredicted membrane proteins
Protein Function
- Predicted intracellular proteins
- Human disease related genes:Congenital malformations:Congenital malformations of the musculoskeletal system
- ENZYME proteins:Lyases
- Enzymes
- Disease related genes
Transmembrane
152..168; Helical; 181..197; Helical; 214..230; Helical; 239..255; Helical; 259..275; Helical; 289..305; Helical; 674..691; Helical; 702..718; Helical; 743..759; Helical; 820..836; Helical; 839..855; Helical; 897..913; Helical
Transmembrane Count
12
Ensembl
Entrez Gene Symbol
Gene Synonym
AC6
Gene Description
Adenylate cyclase 6
Chromosome
12
Position
48766194-48789089
Frequency
12
EVMP Score
0.47
Fluorescence & Localization
Tissue Specificlymphoid tissueCell SpecificcDCSingle-Nuclei Brain Specificcentral nervous system macrophage
Function & Pathway
Protein Function
- Predicted intracellular proteins
- Human disease related genes:Congenital malformations:Congenital malformations of the musculoskeletal system
- ENZYME proteins:Lyases
- Enzymes
- Disease related genes
Cellular Component
Molecular Function
Biological Process
KEGG
- hsa00230 Purine metabolism
- KEGG:hsa01100 Metabolic pathways
- KEGG:hsa01522 Endocrine resistance
- KEGG:hsa04015 Rap1 signaling pathway
- KEGG:hsa04022 cGMP-PKG signaling pathway
- KEGG:hsa04024 cAMP signaling pathway
- KEGG:hsa04062 Chemokine signaling pathway
- KEGG:hsa04072 Phospholipase D signaling pathway
- KEGG:hsa04081 Hormone signaling
- KEGG:hsa04082 Neuroactive ligand signaling
- KEGG:hsa04114 Oocyte meiosis
- KEGG:hsa04211 Longevity regulating pathway
- KEGG:hsa04213 Longevity regulating pathway - multiple species
- KEGG:hsa04261 Adrenergic signaling in cardiomyocytes
- KEGG:hsa04270 Vascular smooth muscle contraction
- KEGG:hsa04371 Apelin signaling pathway
- KEGG:hsa04540 Gap junction
- KEGG:hsa04611 Platelet activation
- KEGG:hsa04713 Circadian entrainment
- KEGG:hsa04714 Thermogenesis
- KEGG:hsa04723 Retrograde endocannabinoid signaling
- KEGG:hsa04724 Glutamatergic synapse
- KEGG:hsa04725 Cholinergic synapse
- KEGG:hsa04727 GABAergic synapse
- KEGG:hsa04742 Taste transduction
- KEGG:hsa04750 Inflammatory mediator regulation of TRP channels
- KEGG:hsa04911 Insulin secretion
- KEGG:hsa04912 GnRH signaling pathway
- KEGG:hsa04913 Ovarian steroidogenesis
- KEGG:hsa04914 Progesterone-mediated oocyte maturation
- KEGG:hsa04915 Estrogen signaling pathway
- KEGG:hsa04916 Melanogenesis
- KEGG:hsa04918 Thyroid hormone synthesis
- KEGG:hsa04921 Oxytocin signaling pathway
- KEGG:hsa04923 Regulation of lipolysis in adipocytes
- KEGG:hsa04924 Renin secretion
- KEGG:hsa04925 Aldosterone synthesis and secretion
- KEGG:hsa04926 Relaxin signaling pathway
- KEGG:hsa04927 Cortisol synthesis and secretion
- KEGG:hsa04928 Parathyroid hormone synthesis, secretion and action
- KEGG:hsa04934 Cushing syndrome
- KEGG:hsa04935 Growth hormone synthesis, secretion and action
- KEGG:hsa04961 Endocrine and other factor-regulated calcium reabsorption
- KEGG:hsa04962 Vasopressin-regulated water reabsorption
- KEGG:hsa04970 Salivary secretion
- KEGG:hsa04971 Gastric acid secretion
- KEGG:hsa04972 Pancreatic secretion
- KEGG:hsa04976 Bile secretion
- KEGG:hsa05032 Morphine addiction
- KEGG:hsa05163 Human cytomegalovirus infection
- KEGG:hsa05166 Human T-cell leukemia virus 1 infection
- KEGG:hsa05200 Pathways in cancer
- KEGG:hsa05207 Chemical carcinogenesis - receptor activation
- KEGG:hsa05414 Dilated cardiomyopathy
Reactome
- R-hsa-170660 adenylate cyclase activating pathway
- R-hsa-170670 adenylate cyclase inhibitory pathway
- R-hsa-9660821 adora2b mediated anti inflammatory cytokines production
- R-hsa-400042 adrenaline noradrenaline inhibits insulin secretion
- R-hsa-9662851 anti inflammatory response favouring leishmania parasite infection
- R-hsa-445717 aquaporin mediated transport
- R-hsa-111996 ca dependent events
- R-hsa-9855142 cellular responses to mechanical stimuli
- R-hsa-8953897 cellular responses to stimuli
- R-hsa-1489509 dag and ip3 signaling
- R-hsa-9664323 fcgr3a mediated il10 synthesis
- R-hsa-977444 gaba b receptor activation
- R-hsa-977443 gaba receptor activation
- R-hsa-381676 glucagon like peptide 1 glp1 regulates insulin secretion
- R-hsa-163359 glucagon signaling in metabolic regulation
- R-hsa-9634597 gper1 signaling
- R-hsa-418594 g alpha i signalling events
- R-hsa-418555 g alpha s signalling events
- R-hsa-418597 g alpha z signalling events
- R-hsa-112040 g protein mediated events
- R-hsa-5610787 hedgehog off state
- R-hsa-9856530 high laminar flow shear stress activates signaling by piezo1 and pecam1 cdh5 kdr in endothelial cells
- R-hsa-5663205 infectious disease
- R-hsa-163685 integration of energy metabolism
- R-hsa-9006925 intracellular signaling by second messengers
- R-hsa-9658195 leishmania infection
- R-hsa-112316 neuronal system
- R-hsa-112314 neurotransmitter receptors and postsynaptic signal transmission
- R-hsa-111885 opioid signalling
- R-hsa-164378 pka activation in glucagon signalling
- R-hsa-111931 pka mediated phosphorylation of creb
- R-hsa-422356 regulation of insulin secretion
- R-hsa-372790 signaling by gpcr
- R-hsa-5358351 signaling by hedgehog
- R-hsa-112315 transmission across chemical synapses
- R-hsa-382551 transport of small molecules
- R-hsa-432040 vasopressin regulates renal water homeostasis via aquaporins
Mediation Categories
Clinical-translation mediationFusion and delivery mediationMetabolism mediationReceptor-signaling mediation
Relations & Evidence
Enzyme-Mediated Modification
4 records.
| Substrate Gene Symbol | Enzyme Gene Symbol | Enzyme UniProt ID | Residue Type | Residue Offset | Modification | Database | References |
|---|---|---|---|---|---|---|---|
| ADCY6 | CDK1 | P06493 | S | 54 | phosphorylation | KEA | KEA:17570479 |
| ADCY6 | GSK3B | P49841 | S | 54 | phosphorylation | KEA | KEA:17570479 |
| ADCY6 | MAPK1 | P28482 | S | 54 | phosphorylation | KEA | KEA:17570479 |
| ADCY6 | MAPK8 | P45983 | S | 54 | phosphorylation | KEA | KEA:17570479 |
Ligand-Receptor Signaling
18 records.
| Category | Parent | Database | Transmitter | Receiver | Secreted | Plasma Membrane (Transmembrane) | Plasma Membrane (Peripheral) |
|---|---|---|---|---|---|---|---|
| transmembrane | transmembrane | Ramilowski_location | No | No | No | No | No |
| transmembrane | transmembrane | OmniPath | No | No | No | No | No |
| plasma_membrane | plasma_membrane | UniProt_location | No | No | No | No | No |
| plasma_membrane | plasma_membrane | OmniPath | No | No | No | No | No |
| cell_surface | cell_surface | Surfaceome | No | No | No | No | No |
| cell_surface | cell_surface | OmniPath | No | No | No | No | No |
| receptor | receptor | scConnect | No | Yes | No | No | No |
| transmembrane | transmembrane_predicted | Phobius | No | No | No | No | No |
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Regulatory Interaction Network
5 records.
| Source Protein Symbol | Source UniProt ID | Target Protein Symbol | Target UniProt ID | Is Directed | Is Stimulation | Is Inhibition | Database | References |
|---|---|---|---|---|---|---|---|---|
| ADCY6 | O43306 | CAMP | P49913 | Yes | No | No | SignaLink3TCRcuration_SignaLink3 | SignaLink3:23109003SignaLink3:15539636SignaLink3:16460834SignaLink3:7935349 |
| GNAI1 | P63096 | ADCY6 | O43306 | Yes | No | Yes | KEGG-MEDICUSSIGNORSignaLink3WangTCRcuration_SignaLink3 | SIGNOR:8119955SignaLink3:7935349SignaLink3:23109003SignaLink3:11376933SignaLink3:15539636SignaLink3:16460834 |
| GNAI2 | P04899 | ADCY6 | O43306 | Yes | No | Yes | KEGG-MEDICUSSIGNORSignaLink3WangTCRcuration_SignaLink3 | SIGNOR:8119955SignaLink3:7935349SignaLink3:23109003SignaLink3:11376933SignaLink3:15539636SignaLink3:16460834 |
| GNAI3 | P08754 | ADCY6 | O43306 | Yes | No | Yes | KEGG-MEDICUSSIGNORSignaLink3WangTCRcuration_SignaLink3 | SIGNOR:8119955SignaLink3:7935349SignaLink3:23109003SignaLink3:11376933SignaLink3:15539636SignaLink3:16460834 |
| COMPLEX:P59768_P62873 | ADCY6 | O43306 | Yes | No | Yes | SIGNOR | SIGNOR:9707174 |
Protein Complex Composition
0 records.
Isolation & Detection Technology
1 record.
| EV Isolation Method | Detection Method | Number of References | References |
|---|---|---|---|
| Differential UltracentrifugationSize Exclusion Chromatography | Mass spectrometry | 1 | 31737616 |
Sequence, Structure & Domains
Sequences
Length
1,168
Mass
130,615
Sequence
MSWFSGLLVPKVDERKTAWGERNGQKRSRRRGTRAGGFCTPRYMSCLRDAEPPSPTPAGPPRCPWQDDAFIRRGGPGKGKELGLRAVALGFEDTEVTTTAGGTAEVAPDAVPRSGRSCWRRLVQVFQSKQFRSAKLERLYQRYFFQMNQSSLTLLMAVLVLLTAVLLAFHAAPARPQPAYVALLACAAALFVGLMVVCNRHSFRQDSMWVVSYVVLGILAAVQVGGALAADPRSPSAGLWCPVFFVYIAYTLLPIRMRAAVLSGLGLSTLHLILAWQLNRGDAFLWKQLGANVLLFLCTNVIGICTHYPAEVSQRQAFQETRGYIQARLHLQHENRQQERLLLSVLPQHVAMEMKEDINTKKEDMMFHKIYIQKHDNVSILFADIEGFTSLASQCTAQELVMTLNELFARFDKLAAENHCLRIKILGDCYYCVSGLPEARADHAHCCVEMGVDMIEAISLVREVTGVNVNMRVGIHSGRVHCGVLGLRKWQFDVWSNDVTLANHMEAGGRAGRIHITRATLQYLNGDYEVEPGRGGERNAYLKEQHIETFLILGASQKRKEEKAMLAKLQRTRANSMEGLMPRWVPDRAFSRTKDSKAFRQMGIDDSSKDNRGTQDALNPEDEVDEFLSRAIDARSIDQLRKDHVRRFLLTFQREDLEKKYSRKVDPRFGAYVACALLVFCFICFIQLLIFPHSTLMLGIYASIFLLLLITVLICAVYSCGSLFPKALQRLSRSIVRSRAHSTAVGIFSVLLVFTSAIANMFTCNHTPIRSCAARMLNLTPADITACHLQQLNYSLGLDAPLCEGTMPTCSFPEYFIGNMLLSLLASSVFLHISSIGKLAMIFVLGLIYLVLLLLGPPATIFDNYDLLLGVHGLASSNETFDGLDCPAAGRVALKYMTPVILLVFALALYLHAQQVESTARLDFLWKLQATGEKEEMEELQAYNRRLLHNILPKDVAAHFLARERRNDELYYQSCECVAVMFASIANFSEFYVELEANNEGVECLRLLNEIIADFDEIISEERFRQLEKIKTIGSTYMAASGLNASTYDQVGRSHITALADYAMRLMEQMKHINEHSFNNFQMKIGLNMGPVVAGVIGARKPQYDIWGNTVNVSSRMDSTGVPDRIQVTTDLYQVLAAKGYQLECRGVVKVKGKGEMTTYFLNGGPSS
Alternative Products
Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=O43306-1; Sequence=Displayed; Name=2; IsoId=O43306-2; Sequence=VSP_000244
Alternative Sequence
762..814; Missing (in isoform 2)
3D Structural Models
Domain & Motif Annotations
Domain (CC)
The protein contains two modules with six transmembrane helices each; both are required for catalytic activity. Isolated N-terminal or C-terminal guanylate cyclase domains have no catalytic activity, but when they are brought together, enzyme activity is restored. The active site is at the interface of the two domains. Both contribute substrate-binding residues, but the catalytic metal ions are bound exclusively via the N-terminal guanylate cyclase domain.
Protein Families
Adenylyl cyclase class-4/guanylyl cyclase family
Sequence Similarities
Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.
Clinical Relevance
Disease Involvement
Disease variant
Antibody