
Type:Protein
SpeciesReactivity:H;M;R
B=Bovine;Ca=Cat;Ch=Chicken;D=Dog;EQ=Equine;GP=GuineaPig;H=Human;M=Mouse;P=Porcine;Pr=Primate;R=Rat;Rb=Rabbit;Y=Yeast;Xe=Xenopus;Ze=Zebrafish;;;;NA-NotApplicable;STP=Step-TactinProteins;AllMesencephalicastrocytederivedneurotrophicfactor(MANF),alsoknownasargininerich,mutatedinearlystagetumors(ARMET)andargininerichprotein(ARP),isa20kDamemberoftheARMETfamilyofproteins(1).ThenameARMETcomesfromthefactthattheproteinwasinitiallythoughttobe50aalongerattheNterminusandtocontainanargininerichregion(2-5).Thepresenceofaspecificmutationchangingthepreviouslynumberedcodon50fromATGtoAGG,ordeletionofthatcodon,hasbeenreportedinavarietyofsolidtumors(2-4).
HumanMANFissynthesizedasa179aminoacid(aa)precursorthatcontainsa21aasignalsequenceanda158aamaturechain.MaturehumanMANFis99%,98%and96%aaidenticaltomaturerat,mouseandbovineMANF,respectively.MANFislocalizedtotheendoplasmicreticulum(ER)andGolgiapparatus,andisalsosecreted(5).IntheCNS,MANFselectivelyprotectsnigraldopaminergicneurons,versusGABAergicorSEROtonergicneurons,whichsuggeststhatMANFmaybeindicatedforthetreatmentofParkinson’sdisease(1).MANFisalsooneofthe12commonlyunfoldedproteinresponse(UPR)upregulatedgenes(5).
OnestudyshowedthatMANFplaysanimportantroleinprotectingcellsagainsttunicamycinandthapsigargininducedcelldeath(5).LossofMANFrenderscellsmoresusceptIBLetothosedrugs,butalsoincreasescellproliferationanddecreasescellsize(5).AnotherstudyshowedthatMANFisanendoplasmicreticulumstressresponse(ERSR)geneintheheartthatcanbeinducedandsecretedinresponsetoERstresses,includingischemia,andthatextracellularMANFmayprotectcardiacmyocytesinanautocrineandparacrinemanner(6).