Protein detail
ADCY8
Adenylate cyclase type 8 (EC 4.6.1.1) (ATP pyrophosphate-lyase 8) (Adenylate cyclase type VIII) (Adenylyl cyclase 8) (AC8) (Ca(2+)/calmodulin-activated adenylyl cyclase)
Protein symbol ADCY8 | UniProt ID | EVMP score 0.50 |
Frequency 1 | Transmembrane count 12 | Protein classification EnzymesMetabolic 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 8 (EC 4.6.1.1) (ATP pyrophosphate-lyase 8) (Adenylate cyclase type VIII) (Adenylyl cyclase 8) (AC8) (Ca(2+)/calmodulin-activated adenylyl cyclase)
Protein Class
EnzymesMetabolic proteinsPredicted intracellular proteinsPredicted membrane proteins
Protein Function
- Enzymes
- Predicted intracellular proteins
- ENZYME proteins:Lyases
Transmembrane
183..203; Helical; 212..232; Helical; 247..267; Helical; 274..294; Helical; 296..316; Helical; 321..341; Helical; 716..736; Helical; 738..758; Helical; 787..807; Helical; 831..851; Helical; 861..881; Helical; 894..914; Helical
Transmembrane Count
12
Ensembl
Entrez Gene Symbol
Gene Synonym
AC8ADCY3HBAC1
Gene Description
Adenylate cyclase 8
Chromosome
8
Position
130780301-131040909
Frequency
1
EVMP Score
0.50
Fluorescence & Localization
Cell SpecificNeutrophil progenitorsSecretome LocationIntracellular and membraneSecretome FunctionEnzyme
Function & Pathway
Protein Function
- Enzymes
- Predicted intracellular proteins
- ENZYME proteins:Lyases
Cellular Component
- GO:0005886 plasma membrane
- GO:0005901 caveola
- GO:0005905 clathrin-coated pit
- GO:0014069 postsynaptic density
- GO:0015629 actin cytoskeleton
- GO:0016020 membrane
- GO:0016323 basolateral plasma membrane
- GO:0016324 apical plasma membrane
- GO:0030424 axon
- GO:0030425 dendrite
- GO:0030665 clathrin-coated vesicle membrane
- GO:0032809 neuronal cell body membrane
- GO:0042734 presynaptic membrane
- GO:0044853 plasma membrane raft
- GO:0045121 membrane raft
- GO:0048786 presynaptic active zone
- GO:0060076 excitatory synapse
- GO:0098685 Schaffer collateral - CA1 synapse
- GO:0098686 hippocampal mossy fiber to CA3 synapse
- GO:0098978 glutamatergic synapse
Molecular Function
- GO:0003779 actin binding
- GO:0004016 adenylate cyclase activity
- GO:0005516 calmodulin binding
- GO:0005524 ATP binding
- GO:0008294 calcium- and calmodulin-responsive adenylate cyclase activity
- GO:0042803 protein homodimerization activity
- GO:0046872 metal ion binding
- GO:0046982 protein heterodimerization activity
- GO:0046983 protein dimerization activity
- GO:0051721 protein phosphatase 2A binding
Biological Process
KEGG
- hsa00230 Purine metabolism
- KEGG:hsa01100 Metabolic pathways
- KEGG:hsa01522 Endocrine resistance
- KEGG:hsa04015 Rap1 signaling pathway
- KEGG:hsa04020 Calcium 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:hsa04720 Long-term potentiation
- 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: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: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-442755 activation of nmda receptors and postsynaptic events
- 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-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-442720 creb1 phosphorylation through the activation of adenylate cyclase
- 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
0 records.
Ligand-Receptor Signaling
19 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 |
| basolateral_cell_membrane | plasma_membrane | UniProt_location | No | No | No | No | No |
| apical_cell_membrane | plasma_membrane | UniProt_location | No | No | No | No | No |
| plasma_membrane | plasma_membrane | OmniPath | No | No | No | No | No |
| receptor | receptor | scConnect | No | Yes | No | No | No |
| receptor | receptor | EMBRACE | No | Yes | No | No | No |
| transmembrane | transmembrane_predicted | Phobius | No | No | No | No | No |
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Regulatory Interaction Network
0 records.
Protein Complex Composition
0 records.
Isolation & Detection Technology
1 record.
| EV Isolation Method | Detection Method | Number of References | References |
|---|---|---|---|
| Polymer Precipitation | Western blotting | 1 | 38731868 |
Sequence, Structure & Domains
Sequences
Length
1,251
Mass
140,122
Sequence
MELSDVRCLTGSEELYTIHPTPPAGDGRSASRPQRLLWQTAVRHITEQRFIHGHRGGSGSGSGGSGKASDPAGGGPNHHAPQLSGDSALPLYSLGPGERAHSTCGTKVFPERSGSGSASGSGGGGDLGFLHLDCAPSNSDFFLNGGYSYRGVIFPTLRNSFKSRDLERLYQRYFLGQRRKSEVVMNVLDVLTKLTLLVLHLSLASAPMDPLKGILLGFFTGIEVVICALVVVRKDTTSHTYLQYSGVVTWVAMTTQILAAGLGYGLLGDGIGYVLFTLFATYSMLPLPLTWAILAGLGTSLLQVILQVVIPRLAVISINQVVAQAVLFMCMNTAGIFISYLSDRAQRQAFLETRRCVEARLRLETENQRQERLVLSVLPRFVVLEMINDMTNVEDEHLQHQFHRIYIHRYENVSILFADVKGFTNLSTTLSAQELVRMLNELFARFDRLAHEHHCLRIKILGDCYYCVSGLPEPRQDHAHCCVEMGLSMIKTIRYVRSRTKHDVDMRIGIHSGSVLCGVLGLRKWQFDVWSWDVDIANKLESGGIPGRIHISKATLDCLNGDYNVEEGHGKERNEFLRKHNIETYLIKQPEDSLLSLPEDIVKESVSSSDRRNSGATFTEGSWSPELPFDNIVGKQNTLAALTRNSINLLPNHLAQALHVQSGPEEINKRIEHTIDLRSGDKLRREHIKPFSLMFKDSSLEHKYSQMRDEVFKSNLVCAFIVLLFITAIQSLLPSSRVMPMTIQFSILIMLHSALVLITTAEDYKCLPLILRKTCCWINETYLARNVIIFASILINFLGAILNILWCDFDKSIPLKNLTFNSSAVFTDICSYPEYFVFTGVLAMVTCAVFLRLNSVLKLAVLLIMIAIYALLTETVYAGLFLRYDNLNHSGEDFLGTKEVSLLLMAMFLLAVFYHGQQLEYTARLDFLWRVQAKEEINEMKELREHNENMLRNILPSHVARHFLEKDRDNEELYSQSYDAVGVMFASIPGFADFYSQTEMNNQGVECLRLLNEIIADFDELLGEDRFQDIEKIKTIGSTYMAVSGLSPEKQQCEDKWGHLCALADFSLALTESIQEINKHSFNNFELRIGISHGSVVAGVIGAKKPQYDIWGKTVNLASRMDSTGVSGRIQVPEETYLILKDQGFAFDYRGEIYVKGISEQEGKIKTYFLLGRVQPNPFILPPRRLPGQYSLAAVVLGLVQSLNRQRQKQLLNENNNTGIIKGHYNRRTLLSPSGTEPGAQAEGTDKSDLP
3D Structural Models
Domain & Motif Annotations
Compositional Bias
56..76; Gly residues
Motif
38..40; Essential for CALM1 interaction; 49..51; Essential for CALM1 interaction
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. The two transmembrane clusters are necessary and suficient for the plasma membrane targeting and oligomers assembly. The N-terminal and C-terminal domains interact at rest as part of a larger autoinhibitory complex, with calmodulin pre-associated at the N-terminal domain; the binding is specifically inhibited by fully calcium-saturated calmodulin, resulting in activation of AC8..
Region
1..182; Involved in ORAI1, STIM1, PPP2CA and PPP2R1A interaction; 1..109; Involved in AKAP5 and PRKAR2A interaction; 50..92; Disordered; 1109..1251; Involved in CALM1 interaction; 1200..1215; Required for both calcium stimulation and maintenance of autoinhibition; 1223..1251; Disordered
Protein Families
Adenylyl cyclase class-4/guanylyl cyclase family
Sequence Similarities
Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.