UbiquitinC-terminalhydrolase1(UCHL1)hasseveralothernames,suchasubiquitincarboxylesteraseL1,ubiquitinthiolesterase,neuron-specificproteinPGP9.5andPark5.Theproteinisextremelyabundant,andwasestimatedtobepresentataconcentrationof200-500micrograms/gwetweight,representingamajorproteincomponentofneuronalcytoplasm(1).Thishasbeenclaimedtorepresent1-2%oftotalbrainprotein.
Image:ShowsasectionofratspinalcordstainedwithUCHL1(red)andneurofilamentNF-Hantibody(green).Thelargecellsarea-motorneuronsandUCHL1fillsthecytoplasmoftheirperikaryaanddendrites.TheneurofilamentNF-HantibodybindsprimarilytophosphorylatedaxonalformsofNF-H,andsostainsaxonscoursingbetweenthelargemotorneurons.Protocolondata-sheet.
Theactivityisalsoimportanttoremoveubiquitinfrompartiallydegradedproteins,allowingtheubiquitinmonomertoberecycled.Regulationoftheubiquitinpathwayisveryimportantandmanydiseasestatesareassociatedwithdefectsinthispathway.PointmutationsintheUCHL1geneareassociatedwithsomeformsofhumanParkinson"sdisease.RecentstudiessuggestthatUCHL1alsohasaubiqutinylligaseactivity,beingabletocoupleubiquitinmonomersbylinkingtheC-terminusofonewithlysine63oftheother.SinceUCHL1isheavilyexpressedinneurons,antibodiestoUCHL1canbeusedtoidentifyneuronsinhistologicalsectionsandintissueculture.Thegreatabundanceofthisproteininneuronsmeansthatitisreleasedfromneuronsinlargeamountsfollowinginjuryordegeneration,sothedetectionofofUCHL1inCSFandotherbodilyfluidscanbeusedasabioMarker.UCHL1wasalsodiscoveredasagenemutatedinsomerarefamialformsofParkinson"sdisease.InterestinglyacommonallelicvariantofUCHL1,theS18YpolymorphismisactuallyprotectiveagainstParkinson"sdisease. Itisalsoamarkerfor cellsofthediffuseneuroendocrinesystemandtheirtumors.
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