| IED ID | IndEnz0001000894 |
| Enzyme Type ID | amylase000894 |
| Protein Name |
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 |
| Gene Name | ADCY6 KIAA0422 |
| Organism | Homo sapiens (Human) |
| 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 Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MSWFSGLLVPKVDERKTAWGERNGQKRSRRRGTRAGGFCTPRYMSCLRDAEPPSPTPAGPPRCPWQDDAFIRRGGPGKGKELGLRAVALGFEDTEVTTTAGGTAEVAPDAVPRSGRSCWRRLVQVFQSKQFRSAKLERLYQRYFFQMNQSSLTLLMAVLVLLTAVLLAFHAAPARPQPAYVALLACAAALFVGLMVVCNRHSFRQDSMWVVSYVVLGILAAVQVGGALAADPRSPSAGLWCPVFFVYIAYTLLPIRMRAAVLSGLGLSTLHLILAWQLNRGDAFLWKQLGANVLLFLCTNVIGICTHYPAEVSQRQAFQETRGYIQARLHLQHENRQQERLLLSVLPQHVAMEMKEDINTKKEDMMFHKIYIQKHDNVSILFADIEGFTSLASQCTAQELVMTLNELFARFDKLAAENHCLRIKILGDCYYCVSGLPEARADHAHCCVEMGVDMIEAISLVREVTGVNVNMRVGIHSGRVHCGVLGLRKWQFDVWSNDVTLANHMEAGGRAGRIHITRATLQYLNGDYEVEPGRGGERNAYLKEQHIETFLILGASQKRKEEKAMLAKLQRTRANSMEGLMPRWVPDRAFSRTKDSKAFRQMGIDDSSKDNRGTQDALNPEDEVDEFLSRAIDARSIDQLRKDHVRRFLLTFQREDLEKKYSRKVDPRFGAYVACALLVFCFICFIQLLIFPHSTLMLGIYASIFLLLLITVLICAVYSCGSLFPKALQRLSRSIVRSRAHSTAVGIFSVLLVFTSAIANMFTCNHTPIRSCAARMLNLTPADITACHLQQLNYSLGLDAPLCEGTMPTCSFPEYFIGNMLLSLLASSVFLHISSIGKLAMIFVLGLIYLVLLLLGPPATIFDNYDLLLGVHGLASSNETFDGLDCPAAGRVALKYMTPVILLVFALALYLHAQQVESTARLDFLWKLQATGEKEEMEELQAYNRRLLHNILPKDVAAHFLARERRNDELYYQSCECVAVMFASIANFSEFYVELEANNEGVECLRLLNEIIADFDEIISEERFRQLEKIKTIGSTYMAASGLNASTYDQVGRSHITALADYAMRLMEQMKHINEHSFNNFQMKIGLNMGPVVAGVIGARKPQYDIWGNTVNVSSRMDSTGVPDRIQVTTDLYQVLAAKGYQLECRGVVKVKGKGEMTTYFLNGGPSS |
| Enzyme Length | 1168 |
| Uniprot Accession Number | O43306 |
| Absorption | |
| Active Site | |
| Activity Regulation | ACTIVITY REGULATION: Activated by forskolin (PubMed:17916776, PubMed:17110384). Inhibited by calcium ions, already at micromolar concentrations (By similarity). Inhibited by adenosine, AMP and their analogs (By similarity). Activated by GNAS (PubMed:17110384). Is further activated by the complex formed by GNB1 and GNG2 (PubMed:17110384). Phosphorylation by RAF1 results in its activation (By similarity). {ECO:0000250|UniProtKB:P30804, ECO:0000250|UniProtKB:Q01341, ECO:0000250|UniProtKB:Q03343, ECO:0000269|PubMed:17916776}. |
| Binding Site | BINDING 472; /note=ATP; /evidence=ECO:0000250|UniProtKB:P30803; BINDING 1031; /note=ATP; /evidence=ECO:0000250|UniProtKB:P26769; BINDING 1152; /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:17110384, ECO:0000269|PubMed:17916776}; |
| 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:17916776, PubMed:17110384). 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). {ECO:0000250|UniProtKB:Q01341, ECO:0000250|UniProtKB:Q03343, ECO:0000269|PubMed:17110384, ECO:0000269|PubMed:17916776}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | NP_BIND 384..389; /note=ATP; /evidence=ECO:0000250|UniProtKB:P30803; NP_BIND 426..428; /note=ATP; /evidence=ECO:0000250|UniProtKB:P30803; NP_BIND 1105..1107; /note=ATP; /evidence=ECO:0000250|UniProtKB:P26769; NP_BIND 1112..1116; /note=ATP; /evidence=ECO:0000250|UniProtKB:P26769 |
| Features | Alternative sequence (1); Binding site (3); Chain (1); Erroneous initiation (1); Glycosylation (1); Metal binding (5); Modified residue (5); Natural variant (2); Nucleotide binding (4); Topological domain (4); Transmembrane (12) |
| Keywords | ATP-binding;Alternative splicing;Cell membrane;Cell projection;Cilium;Disease variant;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:17110384}; Multi-pass membrane protein {ECO:0000305}. Cell projection, cilium {ECO:0000250|UniProtKB:Q01341}. Cell projection, stereocilium {ECO:0000250|UniProtKB:Q01341}. |
| Modified Residue | MOD_RES 54; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 556; /note="Phosphoserine"; /evidence="ECO:0000250|UniProtKB:Q03343"; MOD_RES 576; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18088087, ECO:0007744|PubMed:23186163"; MOD_RES 662; /note="Phosphoserine"; /evidence="ECO:0000250|UniProtKB:Q03343"; MOD_RES 919; /note="Phosphothreonine"; /evidence="ECO:0000250|UniProtKB:Q03343" |
| Post Translational Modification | PTM: Phosphorylation by RAF1 increases enzyme activity. Phosphorylation by PKA at Ser-662 inhibits the GNAS-mediated increase in catalytic activity. Phosphorylation by PKC at Ser-556, Ser-662 and Thr-919 inhibits catalytic activity. {ECO:0000250|UniProtKB:Q03343}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 10075700; 10318832; 10449730; 11832410; 12058044; 1347957; 13549488; 13680124; 14514350; 15569269; 1658606; 16613843; 16713569; 17230639; 17306374; 17900700; 23209152; 23332756; 24845016; 3104109; 7589461; 7595566; 7641683; 7937899; 8099279; 8119955; 8243272; 8327893; 8663304; 8997178; 9417641; 9707174; 9865521; 9920805; |
| Motif | |
| Gene Encoded By | |
| Mass | 130,615 |
| Kinetics | |
| Metal Binding | METAL 384; /note=Magnesium 1; catalytic; /evidence=ECO:0000255|PROSITE-ProRule:PRU00099; METAL 384; /note=Magnesium 2; catalytic; /evidence=ECO:0000255|PROSITE-ProRule:PRU00099; METAL 385; /note=Magnesium 2; via carbonyl oxygen; catalytic; /evidence=ECO:0000255|PROSITE-ProRule:PRU00099; METAL 428; /note=Magnesium 1; catalytic; /evidence=ECO:0000255|PROSITE-ProRule:PRU00099; METAL 428; /note=Magnesium 2; catalytic; /evidence=ECO:0000255|PROSITE-ProRule:PRU00099 |
| Rhea ID | RHEA:15389 |
| Cross Reference Brenda |