A14aminoacidpeptidesequencemappingneartheC-terminusofhumanUCP3.||HumanUCP3longform(UCP3L)isa312aamitochondrialuncouplingprotein(1,2).Itisonly57%and73%homologouswithhumanUCP1andUCP2respectively.LikeotherUCPs,UCP3ispredictedtocontain6transmembranedomains.TheUCP3Slacksthe6thtransmembranedomainanditisonly275aalong(2).UCP3haspreferentialexpressioninmuscleanditisunaffectedbycoldacclimation.||Theregulationofbodyweightdependsuponthecalorieintakeandexpenditure.Itisaverycomplexandhighlyregulatedprocess.Itinvolvesmultiplesneuralcircuitswithspecificneuropeptides,neurotransmittertransportersandreceptorsandinfluencedbyperipheralsignals.Theproductofobesegene(Leptin)mayinfluencemanyoftheseprocesses.WhiteandbrownADIposetissues(WATandBAT,respectively)playacentralroleinbodyweightandenergyexpenditure.WATisthemajorsiteforenergystorageviatriglyceridesynthesisandmobilizationvialipolysis.Uncouplingproteins(UCP1-4)areafamilyofmitochondriatransprtproteinsthatplayacriticalroleinThermoregulatoryheatproductionandmaintenanceofbasalmetabolicrate.BATisabletodissipateenergyasheatviauncoupledmitochondrialrespirationbyamitochondrialanioncarrier,uncouplingprotein1(UCP1).UCP1ispredictedtocontain6trans-membrane(TM)domains,aputativepurinenucleotide-bindingdomain(PNBD)andthree-mitochondrialenergytransferproteindomains(ETPDs).BothaminoandC-terminiarepredictedtobecytoplasmic.UCP1isamemberofthemitochondrialcarrierproteinfamily,whichincludestheATP/ADPtranslocator,thephosphate,the2-oxoglutarate/malateandthecitrate(tricarboxylate)carriers.UCP1playsanimportantroleinthermoregulationinhibernatinganimals,neonates,anditcontributestorodentcold-anddietinducedthermogenesis.||BecauseoftherestrictedexpressionofUCP1andthelackofBATinadultanimalsandhumans,UCP1maynotbeimportantinbodyweightregulation/energyexpenditureinadults.RecentlyanovelUCP2,ahomologueofUCP1,hasbeenidentified.IncontrastwithUCP1,UCP2iswidelyexpressedinadulthumantissuesanditisunregulatedinWATinresponsetofatintake.UCP2is59%homologouswithUCP1.IntheWATofob/obanddb/dbmice,UCP2expressionisgreatlyelevatedwhencomparedtoleananimals.Therefore,UCP2hasbeenimplicatedintheregulationofenergybalance,bodyweight,andthermoregulation.Skeletalmusclecontributesupto40%ofwholebodyepinephrine-inducedthermogenesisinhumans.||AnotherhomologueofUCPs,UCP3,hasbeenclonedfromhumanskeletalmuscle.HumanUCP3protein(312aa)has71%and57%homologywithUCP2andUCP1,respectively.Thelong(309aa)andmatureformofUCP3isdesignatedasUCP3L;UCP3slacksthe6thpotentialTMdomainandthePNBDdomainimplicatedinthecontrolofcouplingefficiencyofUCP1.BothformsofUCP3areexpressedinmuscle.UCP3expressionishighlyspecificforskeletalmuscleanditisunaffectedbycoldacclimation.ItisalsoexpressedinBATofanimals.UCP3couldplayacriticalroleinenergyexpenditureanditsregulation.

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