OMIMOnlineMendelianInheritanceinManAll DatabasesPubMedNucleotideProteinGenomeStructurePMCTaxonomyOMIM SearchPubMedProteinNucleotideCoreNucleotideGSSESTStructureGenomeBooksCancerChromosomesConservedDomainsdbGaP3DDomainsGeneGenomeProjectGENSATGEOProfilesGEODataSetsHomoloGeneJournalsMeSHNCBIWebSiteNLMCatalogOMIAOMIMPMCPopSetProbeProteinClustersPubChemBioAssayPubChemCompoundPubChemSubstanceSNPTaxonomyToolKitUniGeneUniSTSforLimitsPreview/IndexHistoryClipboardDetailsDisplayTitlesDetailedClinicalSynopsisAllelicVariantsASN1XMLLinkOutRelatedEntriesBookLinksGeneLinksGenomeLinksGEOProfileLinksHomoloGeneLinksNucleotideLinksOMIALinksPubChemBioAssayLinksPMCLinksProteinLinksPubMed(calculated)LinksPubMed(cited)LinksSNPLinksGeneGenotypeLinksStructureLinksUniGeneLinksUniSTSLinksShow5102050100200500<>SendtoTextFilePrinterClipboardAll1OMIMdbSNP0OMIMUniSTS0*605250605250][GeneViewindbSNPhttp//wwwncbinlmnihgov/SNP/CGI/genesnpviewcgi?fromdb=omim&id=605250][UniGenehttp//wwwncbinlmnihgov/entrez/queryfcgi?itool=omim_Detailed&db=omim&cmd=Display&dopt=omim_unigene&from_uid=605250][RelatedEntrieshttp//wwwncbinlmnihgov/entrez/queryfcgi?itool=omim_Detailed&db=omim&cmd=Display&dopt=omim_omim&from_uid=605250][Nucleotidehttp//wwwncbinlmnihgov/entrez/queryfcgi?itool=omim_Detailed&db=omim&cmd=Display&dopt=omim_nucleotide&from_uid=605250][Proteinhttp//wwwncbinlmnihgov/entrez/queryfcgi?itool=omim_Detailed&db=omim&cmd=Display&dopt=omim_protein&from_uid=605250][LinkOuthttp//wwwncbinlmnihgov/entrez/queryfcgi?itool=omim_Detailed&cmd=Retrieve&db=omim&list_uids=605250&dopt=ExternalLink]]//>LinksATPBINDINGCASSETTESUBFAMILYCMEMBER4ABCC4AlternativetitlessymbolsMULTIDRUGRESISTANCEASSOCIATEDPROTEIN4MRP4MULTISPECIFICORGANICANIONTRANSPORTERBMOATBGenemaplocus13q32TEXTCancercellsthatoverproducedrugtransportingproteinsmaybecomeresistanttoawidespectrumofdrugswithdifferentstructuresorcellulartargetsaphenomenoncalledmultidrugresistance(MDR)MDR/ATPbindingcassette(ABC)membraneproteinsareinvolvedinenergydependenttransportofawidevarietyofsubstratesByESTdatabasesearchingwithNterminalPGY1(ABCB1171050)andCFTR(602421)asprobesAllikmetsetal(1996)isolated21cDNAsincludingacDNAencodinga65aminoacidfragmentofABCC4UsingasimilarstrategywithCterminalMRP1(ABCC1158343)andCMOAT(ABCC2601107)asprobesKooletal(1997)obtainedcDNAsencodingtheCterminalportionofMRP3(ABCC3604323)ABCC4andMRP5(ABCC5605251)BydegenerativePCRbasedontheNterminalsequencesofMRP1followedbyplaquehybridizationofbreastandovarianbacteriophagelibrariesLeeetal(1998)obtainedacDNAencodingABCC4whichtheytermedMOATBSequenceanalysispredictedthatthe1325aminoacidproteinlikeotherABCtransporterscontainsnucleotidebindingfoldsand12transmembranespanninghelicesin2hydrophobicdomainsNorthernblotanalysisrevealedubiquitousexpressionofanapproximately60kbtranscriptthatishighestinprostateandlowestinliverandperipheralbloodleukocytes(Leeetal1998)RNaseprotectionanalysisshowedonlylowlevelexpressioninafewtissues(Kooletal1997)UnlikeABCC2whichisoverexpressedinseveralMDRcelllinesABCC3andABCC5areoverexpressedinonlyafewsuchcelllinesandABCC4isoverexpressedinnone(Kooletal1997)Schuetzetal(1999)foundthatMRP4confersresistancetoacyclicnucleosidemonophosphatessuchas9(2phosphonylmethoxyethyl)guanine(PMEG)andtotheantiHIVdrug9(2phosphonylmethoxyethyl)adenine(PMEA)Lambaetal(2003)isolatedanABCC4cDNAencodinganonfunctionalproteinduetoaninsertionandsubsequentlydeterminedtheABCC4genestructureTheinsertionwasattributedto2additionalexonsthatproducedprematureterminationcodons(PTCs)Theexonsdesignated1aand1bwere113and153bpinlengthrespectivelyAcomparisonofhumanmonkeyandrodentABCC4genesrevealedthatthesesamePTCproducingexonswerealsohighlyconservedinevolutionInvitroinhibitionofproteinsynthesis(usingpuromycinoranisomycin)selectivelyreducednonsensemediatedmRNAdecayofPTCcontainingABCC4transcriptsinallcelllinestestedLambaetal(2003)concludedthatthehighlyconservedPTCcontainingexonsoftheABCC4genemaydictateitsexpressionByradiationhybridanalysisKooletal(1997)mappedtheABCC4genetochromosome13UsingFISHLeeetal(1998)refinedthelocalizationto13q32REFERENCES1AllikmetsRGerrardBHutchinsonADeanMCharacterizationofthehumanABCsuperfamilyisolationandmappingof21newgenesusingtheexpressedsequencetagsdatabaseHumMolecGenet5164916551996PubMedID88947022KoolMdeHaasMSchefferGLScheperRJvanEijkMJJuijnJABaasFBorstPAnalysisofexpressionofcMOAT(MRP2)MRP3MRP4andMRP5homologuesofthemultidrugresistanceassociatedproteingene(MRP1)inhumancancercelllinesCancerRes57353735471997PubMedID92700263LambaJKAdachiMSunDTammurJSchuetzEGAllikmetsRSchuetzJDNonsensemediateddecaydownregulatesconservedalternativelysplicedABCC4transcriptsbearingnonsensecodonsHumMolecGenet12991092003PubMedID124993914LeeKBelinskyMGBellDWTestaJRKruhGDIsolationofMOATBawidelyexpressedmultidrugresistanceassociatedprotein/canalicularmultispecificorganicaniontransporterrelatedtransporterCancerRes58274127471998PubMedID96618855SchuetzJDConnellyMCSunDPaibirSGFlynnPMSrinivasRVKumarAFridlandAMRP4apreviouslyunidentifiedfactorinresistancetonucleosidebasedantiviraldrugsNatureMed5104810511999PubMedID10470083CONTRIBUTORSGeorgeETillerupdated10/26/2004VictorAMcKusickupdated9/1/2000CREATIONDATEPaulJConverse8/31/2000EDITHISTORYtkritzer11/2/2004terry10/26/2004carol9/1/2000Copyright©19662007JohnsHopkinsUniversityDisplayTitlesDetailedClinicalSynopsisAllelicVariantsASN1XMLLinkOutRelatedEntriesBookLinksGeneLinksGenomeLinksGEOProfileLinksHomoloGeneLinksNucleotideLinksOMIALinksPubChemBioAssayLinksPMCLinksProteinLinksPubMed(calculated)LinksPubMed(cited)LinksSNPLinksGeneGenotypeLinksStructureLinksUniGeneLinksUniSTSLinksShow5102050100200500<>SendtoTextFilePrinterClipboardDisclaimerWritetotheHelpDeskPrivacyPolicyNCBINLMNIH