OMIMOnlineMendelianInheritanceinManAll DatabasesPubMedNucleotideProteinGenomeStructurePMCTaxonomyOMIM SearchPubMedProteinNucleotideCoreNucleotideGSSESTStructureGenomeBooksCancerChromosomesConservedDomainsdbGaP3DDomainsGeneGenomeProjectGENSATGEOProfilesGEODataSetsHomoloGeneJournalsMeSHNCBIWebSiteNLMCatalogOMIAOMIMPMCPopSetProbeProteinClustersPubChemBioAssayPubChemCompoundPubChemSubstanceSNPTaxonomyToolKitUniGeneUniSTSLimitsPreview/IndexHistoryClipboardDetailsDisplayTitlesDetailedClinicalSynopsisAllelicVariantsASN1XMLLinkOutRelatedEntriesBookLinksGeneLinksGenomeLinksGEOProfileLinksHomoloGeneLinksNucleotideLinksOMIALinksPubChemBioAssayLinksPMCLinksProteinLinksPubMed(calculated)LinksPubMed(cited)LinksSNPLinksGeneGenotypeLinksStructureLinksUniGeneLinksUniSTSLinksShow5102050100200500SendtoTextFilePrinterClipboardAll1OMIMdbSNP0OMIMUniSTS0*604786LinksADPRIBOSYLATIONFACTORLIKE4ARL4Genemaplocus7qTEXTDESCRIPTIONADPribosylationfactors(ARFsseeARF1103180)regulatediversecellularfunctionssuchasvesicletrafficendocytosisandphospholipaseDactivityARFsandARFlike(ARL)proteinswhichsharesequencesimilaritywithARFsformasubfamilyoftheRasrelatedGTPasesuperfamilyCLONINGSchurmannetal(1994)identifiedmouseArl4asagenethatisabundantlyexpressedindifferentiatedcellsofthepreadipocytecellline3T3L1butisnotdetectablyexpressedinundifferentiated3T3L1cellsByNorthernblotanalysisJacobsetal(1998)foundthatratArl4isexpressedpredominantlyintestisatlowerlevelsinspleenandintestineandatevenlowerlevelsinbrainhearttotalfatliverlungandthymusInsituhybridizationofrattestisshowedthatArl4isexpressedingermcellsofpubertalandadulttestisbutnotinprepubertaltestisJacobsetal(1998)suggestedthatArl4isinvolvedinspermproductionJacobsetal(1999)detectedrecombinantratArl4proteininbothnuclearandextranuclearcompartmentsofmammaliancellsTheydemonstratedthatArl4containsaCterminalnuclearlocalizationsignalRecombinantArl4hadaconsiderablyhigherrateofguaninenucleotideexchangeactivitythanARF1andARP(ARFRP1604699)BysearchingESTdatabasesJacobsetal(1998)identified3humanARL4ESTsthatcontaineda5primeuntranslatedregion(UTR)Thesequenceofthe5primeUTRof1oftheseESTsdifferedfromthesequencesofthe5primeUTRsoftheotherESTsJacobsetal(1998)suggestedthatexpressionofthehumanARL4genelikethatofmouseArl4isdirectedby2separatepromotersThecompletecodingsequenceofthehumanARL4genehasbeendepositedinGenBank(U73960)ThededucedARL4proteinsequenceis99%identicaltothatofthemouseandencodes200aminoacidsByNorthernblotanalysisLinetal(2000)foundthatmurineArl4expressionishighestatembryonicday7butgreatlyreducedbyday11Insituhybridizationanalysisinembryonicmicedetectedexpressionatthe1012somitestage(day85)attheforebrainmidbrainjunctionandatthe2529somitestage(day95)atthejunctionofmidbrainandhindbrainsuggestingarostrocaudalexpressionpatternovertimeInadultmiceexpressionwasdetectedinthebasalregionofseminiferoustubulesincludingSertolicellsbutnotinLeydigcellsImmunofluorescencemicroscopyandWesternblotanalysisdemonstratedfinepunctatenuclearexpressionofanapproximately25kDproteinYeast2hybridandGSTpulldownanalysiswithARL4asbaitrevealedinteractionwithimportinalpha(KPNA2600685)anuclearlocalizationsignalreceptorFunctionalanalysisshowedthatARL4likeARL1(603425)butnotyeastArl3issubjecttomyristoylationUsingimmunohistochemicalanalysisSchurmannetal(2002)detectedexpressionofmouseArl4inspermatocytesandspermatidesbutnotinspermatogoniaandmaturespermatozoaNorthernblotandimmunohistochemicalanalysesofmousetestisat10to30daysofagerevealedArl4expressionbeginningatday16andpeakingatday24GENEFUNCTIONHeoetal(2006)surveyedplasmamembranetargetingmechanismsbyimagingthesubcellularlocalizationof125fluorescentproteinconjugatedRasRabArfandRhoproteinsOf48proteinsthatwerelocalizedtotheplasmamembrane37containedclustersofpositivelychargedaminoacidsTotestwhetherthesepolybasicclustersbindnegativelychargedphosphatidylinositol45bisphosphatelipidsHeoetal(2006)developedachemicalphosphataseactivationmethodtodepleteplasmamembranephosphatidylinositol45bisphosphateUnexpectedlyproteinswithpolybasicclustersdissociatedfromtheplasmamembraneonlywhenbothphosphatidylinositol45bisphosphateandphosphatidylinositol345trisphosphateweredepletedarguingthatbothlipidsecondmessengersjointlyregulateplasmamembranetargetingMAPPINGTheInternationalRadiationHybridMappingConsortiummappedtheARL4genetochromosome7p21p153(stSG30907)Jacobsetal(1998)mappedthemouseArl4genetotheproximalregionofchromosome12whereitislinkedtotheLamb11Hfhbf1andSos2(601247)genesTheproximalregionofmousechromosome12shareshomologyofsyntenywithhumanchromosomes7qand14qANIMALMODELSchurmannetal(2002)generatedmicelackingArl4ThesemicedidnothaveupregulatedexpressionofotherArlgenesintestiswereviableandwereapparentlynormalexceptforreducedtesticularweightandspermcountHowevertheremainingspermhadnormalmotilityandArl4/micewerefertileandsirednormalsizelittersSchurmannetal(2002)proposedthatARL4isrequiredfortheprogressionofcellsthroughmeiosisandthatitsdeletioncausesaretardationoftheformationofhaploidspermatidesREFERENCES1HeoWDInoueTParkWSKimMLParkBOWandlessTJMeyerTPI(345)P(3)andPI(45)P(2)lipidstargetproteinswithpolybasicclusterstotheplasmamembraneScience314145814612006PubMedID170956572JacobsSSchilfCFliegertFKolingSWeberYSchurmannAJoostHGADPribosylationfactor(ARF)like46and7representasubgroupoftheARFfamilycharacterizedbyrapidnucleotideexchangeandanuclearlocalizationsignalFEBSLett4563843881999PubMedID104620493JacobsSSchurmannABeckerWBockersTMCopelandNGJenkinsNAJoostHGThemouseADPribosylationfactorlike4genetwoseparatepromotersdirectspecifictranscriptionintissuesandtesticulargermcellBiochemJ3352592651998PubMedID97617224LinCYHuangPHLiaoWLChengHJHuangCFKuoJCPattonWAMassenburgDMossJLeeFJSARL4anARFlikeproteinthatisdevelopmentallyregulatedandlocalizedtonucleiandnucleoliJBiolChem27537815378232000PubMedID109801935SchurmannABreinerMBeckerWHuppertzCKainulainenHKentrupHJoostHGCloningoftwonovelADPribosylationfactorlikeproteinsandcharacterizationoftheirdifferentialexpressionin3T3L1cellsJBiolChem26915683156881994PubMedID81952196SchurmannAKolingSJacobsSSaftigPKraubSWennemuthGKlugeRJoostHGReducedspermcountandnormalfertilityinmalemicewithtargeteddisruptionoftheADPribosylationfactorlike4(Arl4)geneMolecCellBiol22276127682002PubMedID11909968CONTRIBUTORSAdaHamoshupdated2/6/2007PaulJConverseupdated5/29/2002PaulJConverseupdated2/9/2001CREATIONDATEPattiMSherman4/4/2000EDITHISTORYalopez2/8/2007terry2/6/2007mgross5/29/2002cwells2/13/2001cwells2/9/2001mcapotos4/17/2000psherman4/5/2000Copyright©19662007JohnsHopkinsUniversityDisplayTitlesDetailedClinicalSynopsisAllelicVariantsASN1XMLLinkOutRelatedEntriesBookLinksGeneLinksGenomeLinksGEOProfileLinksHomoloGeneLinksNucleotideLinksOMIALinksPubChemBioAssayLinksPMCLinksProteinLinksPubMed(calculated)LinksPubMed(cited)LinksSNPLinksGeneGenotypeLinksStructureLinksUniGeneLinksUniSTSLinksShow5102050100200500SendtoTextFilePrinterClipboardDisclaimerWritetotheHelpDeskPrivacyPolicyNCBINLMNIH