OMIMOnlineMendelianInheritanceinManAll DatabasesPubMedNucleotideProteinGenomeStructurePMCTaxonomyOMIM SearchPubMedProteinNucleotideCoreNucleotideGSSESTStructureGenomeBooksCancerChromosomesConservedDomainsdbGaP3DDomainsGeneGenomeProjectGENSATGEOProfilesGEODataSetsHomoloGeneJournalsMeSHNCBIWebSiteNLMCatalogOMIAOMIMPMCPopSetProbeProteinClustersPubChemBioAssayPubChemCompoundPubChemSubstanceSNPTaxonomyToolKitUniGeneUniSTSLimitsPreview/IndexHistoryClipboardDetailsDisplayTitlesDetailedClinicalSynopsisAllelicVariantsASN1XMLLinkOutRelatedEntriesBookLinksGeneLinksGenomeLinksGEOProfileLinksHomoloGeneLinksNucleotideLinksOMIALinksPubChemBioAssayLinksPMCLinksProteinLinksPubMed(calculated)LinksPubMed(cited)LinksSNPLinksGeneGenotypeLinksStructureLinksUniGeneLinksUniSTSLinksShow5102050100200500SendtoTextFilePrinterClipboardAll1OMIMdbSNP0OMIMUniSTS0*103070LinksADENYLATECYCLASE8ADCY8AlternativetitlessymbolsADCY8ADENYLYLCYCLASEBRAINTYPEIADENYLATECYCLASE3FORMERLYADCY3FORMERLYGenemaplocus8q242TEXTDESCRIPTIONAdenylylcyclase(EC4611)catalyzesthetransformationofATPintocyclicAMPTheenzymaticactivityisunderthecontrolofseveralhormonesanddifferentpolypeptidesparticipateinthetransductionofthesignalfromthereceptortothecatalyticmoietyStimulatoryorinhibitoryreceptors(RsandRi)interactwithGproteins(GsandGi)thatexhibitGTPaseactivityandtheymodulatetheactivityofthecatalyticsubunitoftheadenylylcyclase(Parmaetal1991)CLONINGParmaetal(1991)clonedacDNAcorrespondingtohumanbrainadenylylcyclasesymbolizedbythemasHBAC1SequencingoftheisolatedcDNAsrevealed2polyadenylationsignalsbutnonecontainedthe5primecodingregionofHBACThededuced675aminoacidCterminalportioncontains6putativetransmembranesegmentsfollowedbyalongcytoplasmictailThelatterdomaincontainsa250aminoacidregionhighlysimilartobovineandratadenylateandguanylatecyclasesandnonmammalianadenylatecyclasesNorthernblotanalysisdetectedtranscriptsof105and52inhumanbrainByscreeningahumannewbornbrainstemcDNAlibraryDeferetal(1994)obtainedfulllengthADCY8Thededuced1251aminoacidproteinhasacalculatedmolecularmassof140kDIthas12membranespanningsegmentsgroupedinto2transmembranedomainsanduniquelylongNandCterminaltailsIthas2putativeNglycosylationsitesbetweenmembranespanningregions9and10anotherNglycosylationsitebetweenmembranespanningregions11and12andithasapotentialproteinkinaseA(seePRKACA601639)phosphorylationsiteinthefirstcytoplasmicloopByscreeningatestiscDNAlibraryDeferetal(1994)identifiedapartialADCY8splicevariantwitha90bpdeletionleadingtolossofaregionbetweenmembranespans9and10including2potentialNglycosylationsitesBysemiquantitativeRTPCRLudwigandSeuwen(2002)foundweakexpressionofADCY8inbrainandtestisandnoexpressioninanyothertissueexaminedByanalyzingratandbovineAdcy8isoformsGuandCooper(1999)identifiedNandCterminalcalmodulin(seeCALM1114180)bindingsitesinmammalianADCY8GENESTRUCTUREDeferetal(1994)foundthattheregionupstreamoftheADCY8startcodonwashighlyGCrichLudwigandSeuwen(2002)determinedthattheADCY8genecontains18exonsandspans2623kbGENEFUNCTIONCa(2+)stimulationofADCY8occursthroughlooselyboundcalmodulinBymutationanalysisoftheNterminalcalmodulinbindingdomainofmammalianAdcy8GuandCooper(1999)determinedthatthisdomainmakesaminorcontributiontotheCa(2+)stimulationofAdcy8activityalthoughitmaybeinvolvedincalmodulintrappingMutagenesisandfunctionalassaysoftheCterminalcalmodulinbindingsiteindicatedthatthissiteislargelyresponsiblefortheCa(2+)stimulationofAdcy8RemovaloftheCterminalcalmodulinbindingregionresultedinahyperactivatedenzymeandlossofCa(2+)sensitivitySimpsonetal(2006)foundthattheNterminalcalmodulinbindingdomainofrodentAdcy8hadaroleinrecruitingcalmodulinandthatthisrecruitmentwasessentialforstimulationbyCa(2+)invivoAmong304SwissindividualstestedandgenotypeddeQuervainandPapassotiropoulos(2006)foundasignificantassociation(p=000008)betweenshorttermepisodicmemoryperformanceandgeneticvariationsina7geneclusterconsistingoftheADCY8PRKACG(176893)CAMK2G(602123)GRIN2A(138253)GRIN2B(138252)GRM3(601115)andPRKCA(176960)genesallofwhichhavewellestablishedmolecularandbiologicfunctionsinanimalmemoryFunctionalMRIstudiesinanindependentsetof32individualswithsimilarmemoryperformanceshowedacorrelationbetweenactivationinmemoryrelatedbrainregionsincludingthehippocampusandparahippocampalgyrusandgeneticvariabilityinthe7geneclusterDeQuervainandPapassotiropoulos(2006)concludedthatthese7genesencodeproteinsofthememoryformationsignalingcascadethatareimportantforhumanmemoryfunctionMAPPINGByinsituhybridizationtometaphasechromosomalspreadsusingthehumanbraincDNAprobeStengeletal(1992)showedthattheADCY8geneislocatedonchromosome8q242AhighlyhomologousgeneADCY2(103071)wasassignedto5p153bythesamemethodANIMALMODELWeietal(2002)foundthatwildtypeAdcy1(103072)nullAdcy8nullandAdcy1Adcy8doubleknockoutmicewereindistinguishableintheirresponsetoacutepainHoweverbehavioralresponsestoinflammatorystimuliweresignificantlyreducedinmicelackingAdcy1orAdcy8andmoreprofoundlycompromisedinAdcy1andAdcy8doubleknockoutmiceBothAdcy1andAdcy8wereexpressedathighlevelsin2painrelatedforebrainareastheanteriorcingulatecortexandtheinsularcortexandatalowlevelinthespinalcordInjectionofanadenylatecyclaseactivatorintheanteriorcingulatecortexrescuedtheresponsetonoxiousstimuliinAdcy1Adcy8doubleknockoutmiceREFERENCES1DeferNMarinxOStengelDDanisovaAIourgenkoVMatsuokaICaputDHanouneJMolecularcloningofthehumantypeVIIIadenylylcyclaseFEBSLett3511091131994PubMedID80766762deQuervainDJFPapassotiropoulosAIdentificationofageneticclusterinfluencingmemoryperformanceandhippocampalactivityinhumansProcNatAcadSci103427042742006PubMedID165375203GuCCooperDMFCalmodulinbindingsitesonadenylylcyclasetypeVIIIJBiolChem274801280211999PubMedID100757004LudwigMGSeuwenKCharacterizationofthehumanadenylylcyclasegenefamilycDNAgenestructureandtissuedistributionofthenineisoformsJReceptSignalTransductRes22791102002PubMedID125036095ParmaJStengelDGannageMHPoyardMBaroukiRHanouneJSequenceofahumanbrainadenylylcyclasepartialcDNAevidenceforaconsensuscyclasedomainBiochemBiophysResCommun1794554621991PubMedID17156956SimpsonRECiruelaACooperDMFTheroleofcalmodulinrecruitmentinCa(2+)stimulationofadenylylcyclasetype8JBiolChem28117379173892006PubMedID166138437StengelDParmaJGannageMHRoeckelNMatteiMGBaroukiRHanouneJDifferentchromosomallocalizationoftwoadenylylcyclasegenesexpressedinhumanbrainHumGenet901261301992PubMedID14277688WeiFQiuCSKimSJMugliaLMaasJWJrPinedaVVXuHMChenZFStormDRMugliaLJZhuoMGeneticeliminationofbehavioralsensitizationinmicelackingcalmodulinstimulatedadenylylcyclasesNeuron367137262002PubMedID12441059CONTRIBUTORSPatriciaAHartzupdated10/11/2006CassandraLKniffinupdated4/3/2006CREATIONDATEVictorAMcKusick12/4/1992EDITHISTORYcarol10/12/2006terry10/11/2006wwang4/17/2006ckniffin4/3/2006carol7/9/1999carol9/19/1994carol5/27/1993carol5/26/1993carol1/12/1993carol12/30/1992carol12/4/1992Copyright©19662007JohnsHopkinsUniversityDisplayTitlesDetailedClinicalSynopsisAllelicVariantsASN1XMLLinkOutRelatedEntriesBookLinksGeneLinksGenomeLinksGEOProfileLinksHomoloGeneLinksNucleotideLinksOMIALinksPubChemBioAssayLinksPMCLinksProteinLinksPubMed(calculated)LinksPubMed(cited)LinksSNPLinksGeneGenotypeLinksStructureLinksUniGeneLinksUniSTSLinksShow5102050100200500SendtoTextFilePrinterClipboardDisclaimerWritetotheHelpDeskPrivacyPolicyNCBINLMNIH