| IED ID | IndEnz0001000212 |
| Enzyme Type ID | amylase000212 |
| Protein Name |
Adenylate cyclase type 6 EC 4.6.1.1 ATP pyrophosphate-lyase 6 Adenylate cyclase type VI Adenylyl cyclase 6 AC6 Ca 2+ -inhibitable adenylyl cyclase |
| Gene Name | Adcy6 |
| Organism | Mus musculus (Mouse) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Mus Mus Mus musculus (Mouse) |
| Enzyme Sequence | MSWFSGLLVPKVDERKTAWGERNGQKRPRHANRASGFCAPRYMSCLKNAEPPSPTPAAHTRCPWQDEAFIRRAGPGRGVELGLRSVALGFDDTEVTTPMGTAEVAPDTSPRSGPSCWHRLVQVFQSKQFRSAKLERLYQRYFFQMNQSSLTLLMAVLVLLMAVLLTFHAAPAQPQPAYVALLTCASVLFVVLMVVCNRHSFRQDSMWVVSYVVLGILAAVQVGGALAANPHSPSAGLWCPVFFVYITYTLLPIRMRAAVLSGLGLSTLHLILAWQLNSSDPFLWKQLGANVVLFLCTNAIGVCTHYPAEVSQRQAFQETRGYIQARLHLQHENRQQERLLLSVLPQHVAMEMKEDINTKKEDMMFHKIYIQKHDNVSILFADIEGFTSLASQCTAQELVMTLNELFARFDKLAAENHCLRIKILGDCYYCVSGLPEARADHAHCCVEMGVDMIEAISLVREVTGVNVNMRVGIHSGRVHCGVLGLRKWQFDVWSNDVTLANHMEAGGGRRIHITRATLQYLNGDYEVEPGRGGERNAYLKEQCIETFLILGASQKRKEEKAMLAKLQRTRANSMEGLMPRWVPDRAFSRTKDSKAFRQMGIDDSSKDNRGAQDALNPEDEVDEFLGRAIDARSIDQLRKDHVRRFLLTFQREDLEKKYSRKVDPRFGAYVACALLVFCFICFIQLLVFPYSTLILGIYAAIFLLLLVTVLICAVCSCGSFFPKALQRLSRNIVRSRVHSTAVGIFSVLLVFISAIANMFTCNHTPIRTCAARMLNLTPADVTACHLQQLNYSLGLDAPLCEGTAPTCSFPEYFVGNVLLSLLASSVFLHISSIGKLAMTFILGFTYLVLLLLGPPAAIFDNYDLLLGVHGLASSNETFDGLDCPAVGRVALKYMTPVILLVFALALYLHAQQVESTARLDFLWKLQATGEKEEMEELQAYNRRLLHNILPKDVAAHFLARERRNDELYYQSCECVAVMFASIANFSEFYVELEANNEGVECLRLLNEIIADFDEIISEERFRQLEKIKTIGSTYMAASGLNASTYDQVGRSHITALADYAMRLMEQMKHINEHSFNNFQMKIGLNMGPVVAGVIGARKPQYDIWGNTVNVSSRMDSTGVPDRIQVTTDLYQVLAAKGYQLECRGVVKVKGKGEMTTYFLNGGPSS |
| Enzyme Length | 1165 |
| Uniprot Accession Number | Q01341 |
| Absorption | |
| Active Site | |
| Activity Regulation | ACTIVITY REGULATION: Activated by forskolin (PubMed:18071070, PubMed:20466003, PubMed:20864687, PubMed:23753526, PubMed:24363043). Inhibited by calcium ions, already at micromolar concentrations (PubMed:1379717, PubMed:18071070). Inhibited by adenosine, AMP and their analogs (By similarity). Activated by GNAS. Is further activated by the complex formed by GNB1 and GNG2 (By similarity). Phosphorylation by RAF1 results in its activation (By similarity). {ECO:0000250|UniProtKB:P30804, ECO:0000250|UniProtKB:Q03343, ECO:0000269|PubMed:1379717, ECO:0000269|PubMed:18071070, ECO:0000269|PubMed:20466003, ECO:0000269|PubMed:20864687, ECO:0000269|PubMed:23753526, ECO:0000269|PubMed:24363043}. |
| Binding Site | BINDING 470; /note=ATP; /evidence=ECO:0000250|UniProtKB:P30803; BINDING 1028; /note=ATP; /evidence=ECO:0000250|UniProtKB:P26769; BINDING 1149; /note=ATP; /evidence=ECO:0000250|UniProtKB:P26769 |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=ATP = 3',5'-cyclic AMP + diphosphate; Xref=Rhea:RHEA:15389, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:58165; EC=4.6.1.1; Evidence={ECO:0000269|PubMed:1379717, ECO:0000269|PubMed:18071070, ECO:0000269|PubMed:20466003, ECO:0000269|PubMed:20864687, ECO:0000269|PubMed:23753526, ECO:0000269|PubMed:24363043, ECO:0000269|PubMed:24854272}; |
| DNA Binding | |
| EC Number | 4.6.1.1 |
| Enzyme Function | FUNCTION: Catalyzes the formation of the signaling molecule cAMP downstream of G protein-coupled receptors (PubMed:18071070, PubMed:24363043). Functions in signaling cascades downstream of beta-adrenergic receptors in the heart and in vascular smooth muscle cells (PubMed:18071070). Functions in signaling cascades downstream of the vasopressin receptor in the kidney and has a role in renal water reabsorption (PubMed:20466003, PubMed:20864687). Functions in signaling cascades downstream of PTH1R and plays a role in regulating renal phosphate excretion (PubMed:24854272). Functions in signaling cascades downstream of the VIP and SCT receptors in pancreas and contributes to the regulation of pancreatic amylase and fluid secretion (PubMed:23753526). Signaling mediates cAMP-dependent activation of protein kinase PKA and promotes increased phosphorylation of various proteins, including AKT (PubMed:18071070, PubMed:23753526). Plays a role in regulating cardiac sarcoplasmic reticulum Ca(2+) uptake and storage, and is required for normal heart ventricular contractibility (PubMed:18071070). May contribute to normal heart function (PubMed:18071070, PubMed:20359598). Mediates vasodilatation after activation of beta-adrenergic receptors by isoproterenol (By similarity). Contributes to bone cell responses to mechanical stimuli (PubMed:20371630, PubMed:24277577). {ECO:0000250|UniProtKB:O43306, ECO:0000269|PubMed:1379717, ECO:0000269|PubMed:18071070, ECO:0000269|PubMed:20359598, ECO:0000269|PubMed:20371630, ECO:0000269|PubMed:20466003, ECO:0000269|PubMed:20864687, ECO:0000269|PubMed:23753526, ECO:0000269|PubMed:24277577, ECO:0000269|PubMed:24363043, ECO:0000269|PubMed:24854272}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | NP_BIND 382..387; /note=ATP; /evidence=ECO:0000250|UniProtKB:P30803; NP_BIND 424..426; /note=ATP; /evidence=ECO:0000250|UniProtKB:P30803; NP_BIND 1102..1104; /note=ATP; /evidence=ECO:0000250|UniProtKB:P26769; NP_BIND 1109..1113; /note=ATP; /evidence=ECO:0000250|UniProtKB:P26769 |
| Features | Binding site (3); Chain (1); Glycosylation (3); Metal binding (5); Modified residue (5); Nucleotide binding (4); Sequence conflict (6); Topological domain (4); Transmembrane (12) |
| Keywords | ATP-binding;Cell membrane;Cell projection;Cilium;Glycoprotein;Lyase;Magnesium;Manganese;Membrane;Metal-binding;Nucleotide-binding;Phosphoprotein;Reference proteome;Repeat;Transmembrane;Transmembrane helix;cAMP biosynthesis |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:1379717, ECO:0000269|PubMed:20466003, ECO:0000269|PubMed:21670265}; Multi-pass membrane protein {ECO:0000269|PubMed:21670265}. Cell projection, cilium {ECO:0000269|PubMed:20371630, ECO:0000269|PubMed:20466003, ECO:0000269|PubMed:21670265}. Cell projection, stereocilium {ECO:0000269|PubMed:17567809}. |
| Modified Residue | MOD_RES 53; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:O43306; MOD_RES 553; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q03343; MOD_RES 573; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:21183079; MOD_RES 659; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q03343; MOD_RES 916; /note=Phosphothreonine; /evidence=ECO:0000250|UniProtKB:Q03343 |
| Post Translational Modification | PTM: Phosphorylation by RAF1 increases enzyme activity. Phosphorylation by PKA on Ser-659 inhibits the GNAS-mediated increase in catalytic activity. Phosphorylation by PKC on Ser-553, Ser-659 and Thr-916 inhibits catalytic activity. {ECO:0000250|UniProtKB:Q03343}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 11805091; 12297500; 12466851; 14610273; 14681479; 15007069; 15582152; 16141072; 16602821; 16615126; 17068292; 17110384; 17229090; 17593019; 17597072; 18835269; 19734365; 19889965; 20056751; 20164376; 20348281; 20431059; 20562336; 20861226; 21195051; 21282557; 21937603; 21986494; 22832924; 22952279; 23123217; 23264685; 23587598; 23609114; 23726959; 24194600; 24218452; 24431204; 24944202; 24994926; 25205328; 26932446; 27643574; 28405619; 28767701; 28870220; 29903911; 29941522; 30301777; 30624615; 31009605; 31162142; 31173603; 31918924; 32683324; 32702291; 7766992; 9611134; |
| Motif | |
| Gene Encoded By | |
| Mass | 130,319 |
| Kinetics | |
| Metal Binding | METAL 382; /note=Magnesium 1; catalytic; /evidence=ECO:0000255|PROSITE-ProRule:PRU00099; METAL 382; /note=Magnesium 2; catalytic; /evidence=ECO:0000255|PROSITE-ProRule:PRU00099; METAL 383; /note=Magnesium 2; via carbonyl oxygen; catalytic; /evidence=ECO:0000255|PROSITE-ProRule:PRU00099; METAL 426; /note=Magnesium 1; catalytic; /evidence=ECO:0000255|PROSITE-ProRule:PRU00099; METAL 426; /note=Magnesium 2; catalytic; /evidence=ECO:0000255|PROSITE-ProRule:PRU00099 |
| Rhea ID | RHEA:15389 |
| Cross Reference Brenda | 4.6.1.1; |