OMIMResultMyNCBI[SignIn][Register]Entrez20All DatabasesPubMedNucleotideProteinGenomeStructurePMCTaxonomyOMIM SearchPubMedProteinNucleotideCoreNucleotideGSSESTStructureGenomeBooksCancerChromosomesConservedDomainsdbGaP3DDomainsGeneGenomeProjectGENSATGEOProfilesGEODataSetsHomoloGeneJournalsMeSHNCBIWebSiteNLMCatalogOMIAOMIMPMCPopSetProbeProteinClustersPubChemBioAssayPubChemCompoundPubChemSubstanceSNP SearchPubMedProteinNucleotideCoreNucleotideGSSESTStructureGenomeBooksCancerChromosomesConservedDomainsdbGaP3DDomainsGeneGenomeProjectGENSATGEOProfilesGEODataSetsHomoloGeneJournalsMeSHNCBIWebSiteNLMCatalogOMIAOMIMPMCPopSetProbeProteinClustersPubChemBioAssayPubChemCompoundPubChemSubstanceSNPTaxonomyToolKitUniGeneUniSTSforGoClearLimitsPreview/IndexHistoryClipboardDetails DisplayTitlesDetailedClinicalSynopsisAllelicVariantsASN1XMLLinkOutRelatedEntriesBookLinksGeneLinksGenomeLinksGEOProfileLinksHomoloGeneLinksCoreNucleotideLinksESTLinksGSSLinksNucleotideLinksOMIALinksPubChemBioAssayLinksPMCLinksProteinLinksPubMed(calculated)LinksPubMed(cited)LinksSNPLinksGeneGenotypeLinksStructureLinksUniGeneLinksUniSTSLinksShow5102050100200500SendtoTextFilePrinterClipboard*151690LinksANNEXINA1ANXA1AlternativetitlessymbolsANNEXINIANX1LIPOCORTINILPC1CALPACTINIIGenemaplocus9q11q22TEXTCLONINGTheantiinflammatoryactionofglucocorticoidshasbeenattributedtotheinductionofagroupofproteinscollectivelycalledlipocortinthatinhibitphospholipaseA2TheseproteinsarethoughttocontrolthebiosynthesisofpotentmediatorsofinflammationprostaglandinsandleukotrienesbyinhibitingreleaseoftheircommonprecursorarachidonicacidaprocessthatrequireshydrolysisofphospholipidsbyphospholipaseA2LipocortinlikeproteinshavebeenisolatedfrommonocytesneutrophilsrenalmedullarycellsandothercelltypesThepredominantactiveformhasanapparentrelativemolecularmassof40000PartiallypurifiedlipocortinmimicstheeffectofsteroidsandmediatesantiinflammatoryactivityinvariousinvivomodelsystemsUsingaminoacidsequenceinformationfrompurifiedratlipocortinWallneretal(1986)clonedcDNAforhumanlipocortinandexpressedthegeneinEcoliTheyconfirmedthatLPCisapotentinhibitorofphospholipaseA2LipocortinIbelongstothefamilyofannexinswhicharestructurallyrelatedproteinsthathaveamolecularmassofapproximately35000to40000TheyundergoCa(2+)dependentbindingtophospholipidsthatarepreferentiallylocatedonthecytosolicfaceoftheplasmamembraneTheindividualproteinsinthisfamilyhavebeendiscoveredbyinvestigatorswithvariousgoalsinmindandhavebeengivenavarietyofnames(Kaplanetal1988)Horlicketal(1991)isolatedoverlappingmousegenomicclonesforLipo1Thegeneinthemouseencodesaproteinof346aminoacidresiduesGENESTRUCTUREHorlicketal(1991)demonstratedthatthemouseLipo1genespansabout17kbandisdividedinto13exonsHorlicketal(1991)pointedoutasimilarityingenestructurebetweenmouseLipo1andLipo2(151740)suggestingthattheyhavearecentevolutionaryancestorGENEFAMILYCromptonetal(1988)reviewedthelipocortin/calpactinfamilyofproteinsPepinskyetal(1988)describedthecharacteristicsof3proteinstheycalledlipocortinIIIlipocortinVandlipocortinVILipocortinsIIIandIVareapparentlyidenticalShohatetal(1989)advancedthehypothesisthatfamilialMediterraneanfever(FMF249100)patientsarehomozygousforamutantalleleforoneofthelipocortingenesMAPPINGHuebneretal(19871988)mappedtheANXA1geneto9q11q22bychromosomalinsituhybridizationandsegregationanalysisinsomaticcellhybridsusingacDNAcloneByanalysisofrecombinantinbredstrainsHorlicketal(1991)showedthattheLipo1geneislocatedonmousechromosome19GENEFUNCTIONWaltheretal(2000)showedthatANXA1actsthroughtheformylpeptidereceptor(FPR136537)onhumanneutrophilsPeptidesderivedfromtheuniqueNterminaldomainofANXA1serveasFPRligandsandtriggerdifferentsignalingpathwaysinadosedependentmannerLowerpeptideconcentrationspossiblyfoundininflammatorysituationselicitCa(2+)transientswithoutfullyactivatingthemitogenactivatedproteinkinasepathwayThiscausesaspecificinhibitionofthetransendothelialmigrationofneutrophilsandadesensitizationofneutrophilstowardachemoattractantchallengeThesefindingsidentifiedANXA1peptidesasnovelendogenousFPRligandsandestablishedamechanisticbasisofANXA1mediatedantiinflammatoryeffectsPerrettietal(2002)reportedthatinhibitionofpolymorphonuclearneutrophilinfiltrationbyaspirinanddexamethasoneisapropertysharedbyaspirintriggeredlipoxinsandtheglucocorticoidinducedANXA1derivedpeptidesthatarebothgeneratedinvivoandactatthelipoxinA4receptor(FPRL1136538)tohaltpolymorphonuclearneutrophildiapedesisThesestructurallydiverseligandsspecificallyinteractdirectlywithrecombinanthumanALXRdemonstratedbyspecificradioligandbindingandfunctionaswellasimmunoprecipitationofpolymorphonuclearneutrophilreceptorsInadditionthecombinationofbothaspirintriggeredlipoxinsandANXA1derivedpeptideslimitedpolymorphonuclearneutrophilinfiltrationandreducedproductionofinflammatorymediators(ieprostaglandinsandchemokines)invivoPerrettietal(2002)concludedthattheresultsindicatedfunctionalredundanciesinendogenouslipidandpeptideantiinflammatorycircuitsthatarespatiallyandtemporallyseparatewherebothaspirintriggeredlipoxinsandspecificANXA1derivedpeptidesactinconcertatALXRtodownregulatepolymorphonuclearneutrophilrecruitmenttoinflammatorylociOhetal(2004)describedahypothesisdrivensystemsbiologyapproachtoidentifyingasmallsubsetofproteinsinducedatthetissuebloodinterfacethatareinherentlyaccessibletoantibodiesinjectedintravenouslyTheyusedsubcellularfractionationsubtractiveproteomicsandbioinformaticstoidentifyendothelialcellsurfaceproteinsexhibitingrestrictedtissuedistributionandapparenttissuemodulationExpressionprofilingandgammascintigraphicimagingwithantibodiesestablished2oftheseproteinsaminopeptidaseP(602443)andannexinA1asselectiveinvivotargetsforantibodiesinlungandsolidtumorsrespectivelyRadioimmunotherapytoannexinA1destroyedtumorsandincreasedanimalsurvivalREFERENCES1CromptonMRMossSECrumptonMJDiversityinthelipocortin/calpactinfamilyCell55131988PubMedID29714502HorlickKRChengICWongWTWakelandEKNickHSMouselipocortinIgenestructureandchromosomalassignmentgeneduplicationandtheoriginsofagenefamilyGenomics103653741991PubMedID16769803HuebnerKCannizzaroLACroceCMFreyAZWallnerBPHechtBKHechtFChromosomelocalizationofthehumangenesforlipocortinIandthelipocortinIIfamily(Abstract)CytogenetCellGenet46631only19874HuebnerKCannizzaroLAFreyAZHechtBKHechtFCroceCMWallnerBPChromosomallocalizationofthehumangenesforlipocortinIandlipocortinIIOncogeneRes22993101988PubMedID29694965KaplanRJayeMBurgessWHSchlaepferDDHaiglerHTCloningandexpressionofcDNAforhumanendonexinIIaCa(2+)andphospholipidbindingproteinJBiolChem263803780431988PubMedID29672916OhPLiYYuJDurrEKrasinskaKMCarverLATestaJESchnitzerJESubtractiveproteomicmappingoftheendothelialsurfaceinlungandsolidtumoursfortissuespecifictherapyNature4296296352004PubMedID151903457PepinskyRBTizardRMattalianoRJSinclairLKMillerGTBrowningJLChowEPBurneCHuangKSPrattDWachterLHessionCFreyAZWallnerBPFivedistinctcalciumandphospholipidbindingproteinssharehomologywithlipocortinIJBiolChem26310799108111988PubMedID29689838PerrettiMChiangNLaMFierroIMMarulloSGettingSJSolitoESerhanCNEndogenouslipidandpeptidederivedantiinflammatorypathwaysgeneratedwithglucocorticoidandaspirintreatmentactivatethelipoxinA(4)receptorNatureMed8129613022002PubMedID123689059ShohatMKorenbergJRSchwabeADRotterJIHypothesisfamilialMediterraneanfeverageneticdisorderofthelipocortinfamily?AmJMedGenet341631671989PubMedID253089910WallnerBPMattalianoRJHessionCCateRLTizardRSinclairLKFoellerCChowEPBrowningJLRamachandranKLPepinskyRBCloningandexpressionofhumanlipocortinaphospholipaseA2inhibitorwithpotentialantiinflammatoryactivityNature32077811986PubMedID293696311WaltherARiehemannKGerkeVAnovelligandoftheformylpeptidereceptorannexinIregulatesneutrophilextravasationbyinteractingwiththeFPRMolecCell58318402000PubMedID10882119CONTRIBUTORSAdaHamoshupdated7/26/2004AdaHamoshupdated11/15/2002StylianosEAntonarakisupdated6/21/2000CREATIONDATEVictorAMcKusick6/25/1986EDITHISTORYalopez7/26/2004terry7/26/2004alopez11/18/2002alopez11/18/2002terry11/15/2002mgross6/21/2000mgross9/17/1999terry5/3/1999alopez9/23/1998dkim9/11/1998carol3/20/1998carol9/4/1992supermim3/16/1992carol5/22/1991carol3/20/1991supermim3/20/1990supermim2/9/1990Copyright©19662007JohnsHopkinsUniversityDisclaimerWritetotheHelpDeskPrivacyPolicyNCBINLMNIH