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商品描述
Description | |
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CatalogueNumber | AB9658 |
BrandFamily | Chemicon® |
TradeName |
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Description | Anti-TauphosphoSerine396Antibody |
BackgroundInformation | Tauisaneuronalmicrotubule-associatedproteinfoundpredominantlyonaxonsandfunctionstopromotetubulinpolymerizationandstABIlizemicrotubules.Tau,initshyperphosphorylatedform,isthemajorcomponentofpairedhelicalfilaments(PHF),thebuildingblockofneurofibrillarylesionsinAlzheimer"sdisease(AD)brain.HyperphosphorylatedTauisalsofoundinneurofibrillarylesionsinarangeofothercentralnervoussystemdisorders.HyperphosphorylationimpairsthemicrotubulebindingfunctionofTau,resultinginthedestabilizationofmicrotubulesinADbrains,ultimatelyleADIngtothedegenerationoftheaffectedneurons.Numerousserine/threoninekinases,includingGSK-3beta,proteinkinaseA(PKA),cyclin-dependentkinase5(cdk5)andcaseinkinaseII(CK2),phosphorylateTau.Serine396isphosphorylatedbyGSK-3betaandcdk5invitroandinvivo. |
ProductInformation | |
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Format | AffinityPurified |
Presentation | Affinitypurifiedimmunoglobulin.LiquidinDulbecco"sPBS(withoutMg2+andCa2+),pH7.3,50%glycerolwith1.0mg/mLBSAand0.05%sodiumazide. |
StorageandShippingInformation | |
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StorageConditions | Maintainat-20°Cinundilutedforupto6monthsafterdateofreceipt.Avoidrepeatedfreeze/thawcycles.Donotstoreinaselfdefrostingfreezer. |
BIOLOGicalInformation | |
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Immunogen | SyntheticpeptideofaminoacidssurroundingthephosphoSerine396siteofhumanTau. |
Host | Rabbit |
Specificity | TauphosphoSerine396.TheantibodyrecognizesTaupSerine396insamplesofrecombinanthumanTautreatedwithGSK-3betafor45minutes.ThereactivityoftheantibodyisblockedwiththepSerine396peptidebutnotthenon-phosphopeptideoragenericphosphoSerine-containingpeptide. |
SpeciesReactivity |
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SpeciesReactivityNote | Theimmunogenisconservedinrat,mouse rhesusmonkey,goat,bovineandbaboon. |
AntibodyType | PolyclonalAntibody |
EntrezGeneNumber | |
EntrezGeneSummary | Thisgeneencodesthemicrotubule-associatedproteintau(MAPT)whosetranscriptundergoescomplex,regulatedalternativesplicing,givingrisetoseveralmRNAspecies.MAPTtranscriptsaredifferentiallyexpressedinthenervoussystem,dependingonstageofneuronalmaturationandneurontype.MAPTgenemutationshavebeenassociatedwithseveralneurodegenerativedisorderssuchasAlzheimer"sdisease,Pick"sdisease,frontotemporaldementia,cortico-basaldegenerationandprogressivesupranuclearpalsy. |
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UniProtNumber | |
UniProtSummary | FUNCTION:SwissProt:P10636#Promotesmicrotubuleassemblyandstability,andmightbeinvolvedintheestablishmentandmaintenanceofneuronalpolarity.TheC-terminusbindsaxonalmicrotubuleswhiletheN-terminusbindsneuralplasmamembranecomponents,suggestingthattaufunctionsasalinkerproteinbetweenboth.Axonalpolarityispredeterminedbytaulocalization(intheneuronalcell)inthedomainofthecellbodydefinedbythecentrosome.TheshortisoformsallowplasticityoftheCytoskeletonwhereasthelongerisoformsmaypreferentiallyplayaroleinitsstabilization. SIZE:758aminoacids;78878Da SUBUNIT:InteractswithPSMC2throughSQSTM1(Bysimilarity).InteractswithSQSTM1whenpolyubiquitinated. SUBCELLULARLOCATION:Cytoplasm,cytosol.Cellmembrane.Note=Mostlyfoundintheaxonsofneurons,inthecytosolandinassociationwithplasmamembranecomponents. TISSUESPECIFICITY:Expressedinneurons.IsoformPNS-tauisexpressedintheperipheralnervoussystemwhiletheothersareexpressedinthecentralnervoussystem.DEVELOPMENTALSTAGE:Four-repeat(typeII)tauisexpressedinanadult-specificmannerandisnotfoundinfetalbrain,whereasthree-repeat(typeI)tauisfoundinbothadultandfetalbrain. DOMAIN:SwissProt:P10636Thetau/MAPrepeatbindstotubulin.TypeIisoformscontain3repeatswhiletypeIIisoformscontain4repeats. PTM:PhosphorylationatserineandthreonineresiduesinS-PorT-Pmotifsbyproline-directedproteinkinases(PDPK:CDC2,CDK5,GSK-3,MAPK)(only2-3sitesperproteinininterphase,seven-foldincreaseinmitosis,andinPHF-tau),andatserineresiduesinK-X-G-SmotifsbyMAP/microtubuleaffinity-regulatingkinase(MARK)inAlzheimerdiseasedbrains.Phosphorylationdecreaseswithage.Phosphorylationwithintau"srepeatdomainorinflankingregionsseemstoreducetau"sinteractionwith,respectively,microtubulesorplasmamembranecomponents.PhosphorylationonSer-610,Ser-622,Ser-641andSer-673inseveralisoformsduringmitosis.&Polyubiquitinated.RequiresfunctionalTRAF6andmayprovokeSQSTM1-dependentdegradationbytheproteasome(Bysimilarity).PHF-taucanbemodifiedbythreedifferentformsofpolyubiquitination."Lys-48"-linkedpolyubiquitinationisthemajorform,"Lys-6"-linkedand"Lys-11"-linkedpolyubiquitinationalsooccur.&GlycationofPHF-tau,butnotnormalbraintau.Glycationisanon-enzymaticpost-translationalmodificationthatinvolvesacovalentlinkagebetweenasugarandanaminogroupofaproteinmoleculeformingketoamine.Subsequentoxidation,fragmentationand/orcross-linkingofketoamineleadstotheproductionofadvancedglycationendproducts(AGES).GlycationmayplayaroleinstabilizingPHFaggregationleadingtotangleformationinAD. DISEASE:SwissProt:P10636#InAlzheimerdisease,theneuronalcytoskeletoninthebrainisprogressivelydisruptedandreplacedbytanglesofpairedhelicalfilaments(PHF)andstraightfilaments,mainlycomposedofhyperphosphorylatedformsofTAU(PHF-TAUorADP-TAU).&DefectsinMAPTareacauseoffrontotemporaldementiaandparkinsonismlinkedtochromosome17(FTDP17)[MIM:600274,172700];alsocalledfrontotemporaldementia(FTD)orhistoricallytermedPickcomplex.Thisformoffrontotemporaldementiaischaracterizedbypreseniledementiawithbehavioralchanges,deteriorationofcognitivecapacitiesandlossofmemory.Insomecases,parkinsoniansymptomsareprominent.Neuropathologicalchangesincludefrontotemporalatrophyoftenassociatedwithatrophyofthebasalganglia,substantianigra,amygdala.Inmostcases,proteintaudepositsarefoundinglialcellsand/orneurons.&DefectsinMAPTareacauseofpallido-ponto-nigraldegeneration(PPND)[MIM:168610].Theclinicalfeaturesincludeocularmotilityabnormalities,dystoniaandurinaryincontinence,besidesprogressiveparkinsonismanddementia.&DefectsinMAPTareacauseofcorticobasaldegeneration(CBD).Itismarkedbyextrapyramidalsignsandapraxiaandcanbeassociatedwithmemoryloss.NeuropathologicfeaturesmayoverlapAlzheimerdisease,progressivesupranuclearpalsy,andParkinsondisease.&DefectsinMAPTareacauseofprogressivesupranuclearpalsy(PSP)[MIM:601104,260540];alsoknownasSteele-Richardson-Olszewskisyndrome.PSPischaracterizedbyakinetic-rigidsyndrome,supranucleargazepalsy,pyramidaltractdysfunction,pseudobulbarsignsandcognitivecapacitiesdeterioration.Neurofibrillarytanglesandgliosisbutnoamyloidplaquesarefoundindiseasedbrains.Mostcasesappeartobesporadic,withasignificantassociationwithacommonhaplotypeincludingtheMAPTgeneandtheflankingregions.Familialcasesshowanautosomaldominantpatternoftransmissionwithincompletepenetrance;geneticanalysisofafewcasesshowedtheoccurrenceoftaumutations,includingadeletionofAsn-613.&DefectsinMAPTmaybeacauseofhereditarydysphasicdisinhibitiondementia(HDDD)[MIM:607485].HDDDisafrontotemporaldementiacharacterizedbyprogressivecognitivedeficitswithmemorylossandpersonalitychanges,severedysphasicdisturbancesleadingtomutism,andhyperphagia. SIMILARITY:Contains4Tau/MAPrepeats. |
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