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Millipore/MAB348-100UL | Anti-APP A4 Antibody, a.a. 66-81 of APP (NT), clone 22C11/MAB348-100UL/100 µL
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Millipore/MAB348-100UL | Anti-APP A4 Antibody, a.a. 66-81 of APP (NT), clone 22C11/MAB348-100UL/100 µL
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密理博
货号 / 
MAB348-100UL
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Description
CatalogueNumberMAB348-100UL
BrandFamilyChemicon®
TradeName
  • Chemicon
DescriptionAnti-APPA4Antibody,a.a.66-81ofAPP(NT),clone22C11
AlternateNames
  • APP
BackgroundInformationAmyloidPrecursorProtein(APP)isexpressedinthebrain,kidney,heart,andspleenoffetaltissues;itisinducedduringneuronaldifferentiation.Themost-substantiatedroleforAPPisinsynapticformationandrepair;itsexpressionisupregulatedduringneuronaldifferentiationandafterneuralinjury.Inadultbrain,highestexpressionofAPPisfoundinthefrontallobeofthecortex.Moderateexpressionisobservedinthecerebellarcortex,theposteriorperisylviancortex-operculargyriandthetemporalassociatedcortex.DefectsinAPPareacauseofautosomaldominantAlzheimer"sdisease(AD).DepositsofamyloidproteininsenileplaquesnearnerveprocessesarefoundinthebrainsofagedhumansandincasesofAlzheimer"sdisease.Theprinciplecomponentofthisextracellularamyloidisbeta/A4,a4kDapeptidederivedfromthelargerAPP.Thecreation,transportandfunctionoftheseproteinsarecurrentlyunderinvestigation.
ProductInformation
FormatAscites
Control
  • Braintissue.
PresentationUnpurifiedascitesmousemonoclonalIgG1containingnopreservatives.
StorageandShippingInformation
StorageConditionsStablefor1yearat-20ºCfromdateofreceipt.
Applications
ApplicationAnti-APPA4Antibody,a.a.66-81ofAPP(N-terminus),clone22C11detectslevelofAlzheimerPrecursorProteinA4&hasbeenpublished&validatedforuseinIF,IH,IH(P)&WB.
KeyApplications
  • Immunofluorescence
  • Immunohistochemistry
  • Immunohistochemistry(Paraffin)
  • WesternBlotting
ApplicationNotesImmunohistochemistry:
PreviouslottestedImmunohistochemistryon4%paraformaldehyde/15%picricacidperfusedandfixed,frozenandparaffinembeddedsections.

Optimalworkingdilutionsmustbedeterminedbytheenduser.
BIOLOGicalInformation
ImmunogenPurifiedrecombinantAlzheimerprecursorA4(preA4695)fusionprotein.
Epitopea.a.66-81ofAPP(N-terminus)
Clone22C11
ConcentrationPleaserefertotheCertificateofAnalysisforthelot-specificconcentration.
HostMouse
SpecificityReactswithpre-A4.TheantibodyrecognizesaN-terminalepitopeonthepre-A4molecule
IsotypeIgG1
SpeciesReactivity
  • Human
  • Mouse
  • Rat
  • Monkey
  • Pig
  • Fish
AntibodyTypeMonoclonalAntibody
EntrezGeneNumber
EntrezGeneSummaryThisgeneencodesacellsurfacereceptorandtransmembraneprecursorproteinthatiscleavedbysecretasestoformanumberofpeptides.SomeofthesepeptidesaresecretedandcanbindtotheacetyltransferasecomplexAPBB1/TIP60topromotetranscriptionalactivation,whileothersformtheproteinbasisoftheamyloidplaquesfoundinthebrainsofpatientswithAlzheimerdisease.MutationsinthisgenehavebeenimplicatedinautosomaldominantAlzheimerdiseaseandcerebroarterialamyloidosis(cerebralamyloidangiopathy).Multipletranscriptvariantsencodingseveraldifferentisoformshavebeenfoundforthisgene.
GeneSymbol
  • APP
  • PN-II
  • AD1
  • ABETA
  • CTFgamma
  • APPI
  • ABPP
  • A4
  • CVAP
  • PN2
  • PreA4
  • AAA
PurificationMethodUnpurified
UniProtNumber
UniProtSummaryFUNCTION:SwissProt:P05067#Thegamma-CTFpeptidesaswellasthecaspase-cleavedpeptides,includingC31,arepotentenhancersofneuronalapoptosis.
SIZE:770aminoacids;86943Da
SUBUNIT:Binds,viaitsC-terminus,tothePIDdomainofseveralcytoplasmicproteins,includingAPBBfamilymembers,theAPBAfamily,MAPK8IP1,SHC1and,NumbandDab1(Bysimilarity).BindingtoDab1inhibitsitsserinephosphorylation(Bysimilarity).AlsointeractswithGPCR-likeproteinBPP,FPRL1,APPBP1,IB1,KNS2(viaitsTPRdomains)(Bysimilarity),APPBP2(viaBaSS)andDDB1.Invitro,itbindsMAPTviatheMT-bindingdomains(Bysimilarity).AssociateswithmicrotubulesinthepresenceofATPandinakinesin-dependentmanner(Bysimilarity).Interacts,throughaC-terminaldomain,withGNAO1.Amyloidbeta-42bindsCHRNA7inhippocampalneurons.Beta-amyloidassociateswithHADH2.SolubleAPPbinds,viaitsN-terminalhead,toFBLN1.InteractswithCPEB1(Bysimilarity).
SUBCELLULARLOCATION:Membrane;Single-passtypeImembraneprotein.Note=Cellsurfaceproteinthatrapidlybecomesinternalizedviaclathrin-coatedpits.Duringmaturation,theimmatureAPP(N-glycosylatedintheendoplasmicreticulum)movestotheGolgicomplexwherecompletematurationoccurs(O-glycosylatedandsulfated).Afteralpha-secretasecleavage,solubleAPPisreleasedintotheextracellularspaceandtheC-terminalisinternalizedtoendosomesandlysosomes.SomeAPPaccumulatesinsecretorytransportvesiclesleavingthelateGolgicompartmentandreturnstothecellsurface.Gamma-CTF(59)peptideislocatedtoboththecytoplasmandnucleiofneurons.ItcanbetranslocatedtothenucleusthroughassociationwithFe65.Beta-APP42associateswithFRPL1atthecellsurfaceandthecomplexisthenrapidlyinternalized.APPsortstothebasolateralsurfaceinepithelialcells.Duringneuronaldifferentiation,theThr-743phosphorylatedformislocatedmainlyingrowthcones,moderatelyinneuritesandsparinglyinthecellbody.Caseinkinasephosphorylationcanoccureitheratthecellsurfaceorwithinapost-Golgicompartment.
TISSUESPECIFICITY:Expressedinallfetaltissuesexaminedwithhighestlevelsinbrain,kidney,heartandspleen.Weakexpressioninliver.Inadultbrain,highestexpressionfoundinthefrontallobeofthecortexandintheanteriorperisylviancortex-operculargyri.Moderateexpressioninthecerebellarcortex,theposteriorperisylviancortex-operculargyriandthetemporalassociatedcortex.Weakexpressionfoundinthestriate,extra-striateandmotorcortices.IsoformAPP695isthepredominantforminneuronaltissue,isoformAPP751andisoformAPP770arewidelyexpressedinnon-neuronalcells.IsoformAPP751isthemostabundantforminT-lymphocytes.Appicanisexpressedinastrocytes.
DOMAIN:SwissProt:P05067Thebasolateralsortingsignal(BaSS)isrequiredforsortingofmembraneproteinstothebasolateralsurfaceofepithelialcells.&TheNPXYsequencemotiffoundinmanytyrosine-phosphorylatedproteinsisrequiredforthespecificbindingofthePIDdomain.However,additionalaminoacidseitherN-orC-terminaltotheNPXYmotifareoftenrequiredforcompleteinteraction.ThePIDdomain-containingproteinswhichbindAPPrequiretheYENPTYmotifforfullinteraction.Theseinteractionsareindependentofphosphorylationontheterminaltyrosineresidue.TheNPXYsiteisalsoinvolvedinclathrin-mediatedendocytosis.
PTM:Proteolyticallyprocessedundernormalcellularconditions.Cleavagebyalpha-secretaseoralternativelybybeta-secretaseleadstogenerationandextracellularreleaseofsolubleAPPpeptides,S-APP-alphaandS-APP-beta,respectively,andtheretentionofcorrespondingmembrane-anchoredC-terminalfragments,C83andC99.SubsequentprocessingofC83bygamma-secretaseyieldsP3peptides.Thisisthemajorsecretorypathwayandisnon-amyloidogenic.Alternatively,presenilin/nicastrin-mediatedgamma-secretaseprocessingofC99releasestheamyloidbetaproteins,amyloid-beta40(Abeta40)andamyloid-beta42(Abeta42),majorcomponentsofamyloidplaques,andthecytotoxicC-terminalfragments,gamma-CTF(50),gamma-CTF(57)andgamma-CTF(59).&Proteolyticallycleavedbycaspasesduringneuronalapoptosis.CleavageatAsp-739byeithercaspase-6,-8or-9resultsintheproductionoftheneurotoxicC31peptideandtheincreasedproductionofbeta-amyloidpeptides.&N-andO-glycosylated.O-linkageofchondroitinsulfatetotheL-APPisoformsproducestheAPPproteoglycancoreproteins,theappicans.Thechondroitinsulfatechainofappicanscontains4-O-sulfatedgalactoseinthelinkageregionandchondroitinsulfateEintherepeateddisaccharideregion(Bysimilarity).&PhosphorylationintheC-terminalontyrosine,threonineandserineresiduesisneuron-specific.PhosphorylationcanaffectAPPprocessing,neuronaldifferentiationandinteractionwithotherproteins.PhosphorylatedonThr-743inneuronalcellsbyCdc5kinaseandMapk10,individingcellsbyCdc2kinaseinacell-cycledependentmannerwithmaximallevelsattheG2/Mphaseand,invitro,byGSK-3-beta.TheThr-743phosphorylatedformcausesaconformationalchangewhichreducesbindingofFe65familymembers.PhosphorylationonTyr-757isrequiredforSHCbinding.Phosphorylatedintheextracellulardomainbycaseinkinasesonbothsolubleandmembrane-boundAPP.Thisphosphorylationisinhibitedbyheparin.&Extracellularbindingandreductionofcopper,resultsinacorrespondingoxidationofCys-144andCys-158,andtheformationofadisulfidebond.Invitro,theAPP-Cu(+)complexinthepresenceofhydrogenperoxideresultsinanincreasedproductionofbeta-amyloid-containingpeptides.
DISEASE:SwissProt:P05067#DefectsinAPPareacauseofautosomaldominantAlzheimerdisease(AD)[MIM:104300].ADisthemostprevelantformofdementia,characterizedbyneurofibrillarytanglesandamyloidplaquesdepositioninthebrain.IdenticallesionsoccurintheneuronsofagedDownsyndromebutatanearlieragethaninAD.Themajorconstituentoftheseneuriticplaquesistheneurotoxicamyloid-beta-APP40-42peptide(s),derivedproteolyticallyfromthetransmembraneprecursorproteinAPPbysequentialsecretaseprocessing.Mutationsoccurringatthebeta-amyloidN-terminal,suchastheSwedishdoublemutation,appeartoincreaselevelsofbeta-amyloidbyfacilitatingbeta-secretasecleavageresultinginelevatedlevelsofbothbeta-APP42andbeta-APP40.ThecytotoxicC-terminalfragments(CTFs)andthecaspase-cleavedproductssuchasC31,arealsoimplicatedinADneuronaldeath.AlzheimerdiseasecausedbymutationsinAPPisarareoccurrenceandusuallycausesthefamilialorearly-onsetformofthedisease(FAD).Flemish-typeADischaracterizedby,inadditiontopreseniledementia,cerebralhemorrhagingduetocerebralamyloidangiopathywhichissimilarto,butdistinctfrom,cerebroarterialamyloidosisDutchtype.Onlyabout5%ofallcasesofAlzheimerdiseasearecausedbyFADmutations,therestaresporADIc.&DefectsinAPParethecauseofhereditarycerebralhemorrhagewithamyloidosisDutchtype(HCHWAD)[MIM:609065].HCHWADischaracterizedbyamyloiddepositsincerebralvessels.Theprincipalclinicalcharacteristicsarerecurringcerebralhemorrhages,sometimesprecededbymigrainousheadachesormentalcleavage.Beta-APP40isthepredominantformofcerebrovascularamyloid.&DefectsinAPParethecauseofhereditarycerebroarterialamyloidosisIowatype[MIM:605714].HereditarycerebroarterialamyloidosisIowatypeisanautosomaldominantdementiabeginninginthesixthorseventhdecadeoflife.Thepatientshaveprogressiveaphasicdementia,leukoencephalopathy,andoccipitalcalcifications.Theydonotpresentcerebralhemorrhaging.
SIMILARITY:BelongstotheAPPfamily.&Contains1BPTI/Kunitzinhibitordomain.
MISCELLANEOUS:Chelationofmetalions,notablycopper,ironandzinc,caninducehistidine-bridgingbetweenbeta-amyloidmoleculesresultinginbeta-amyloid-metalaggregates.Theaffinityforcopperismuchhigherthanforothertransientmetalsandisincreasedunderacidicconditions.Extracellularzinc-bindingincreasesbindingofheparintoAPPandinhibitscollagen-binding.
PhysicochemicalInformation
Dimensions
MaterialsInformation
MaterialsInformation

2006年,在完成了对Chemicon、Upstate、Linco等著名品牌的收购之后,密理博生物科学部除了提供传统的除菌过滤、超滤、蛋白质转印、免疫诊断、环境监测等分离纯化产品和技术之外,更增加了实验室研究所需的各种检测试剂、细胞培养产品,主要覆盖干细胞、神经生物学、肿瘤、细胞信号转导、药物开发等领域,从而成为生命科学领域的策略性供应商,为您提供更广泛的研发工具,同步共享全球专业技术,提升您的科研平台,加速您的科研进程。该部门拥有的著名品牌有:Millex、Millicell、Amicon、Durapore、Multiscreen、Montage、Multiplex、Stericup、Chemicon、Upstate、4G10、Luminex、Catch、Release和Beadlyte等。

密理博(Millipore)公司成立于1954年,总部位于美国麻省,在全世界设有47个办事处,为100多个国家提供产品和技术服务。目前全球雇员超过5800人,在美国、法国和日本等国家拥有7家大型生产工厂,主要生产过滤膜及膜过滤产品。

20世纪80年代,密理博公司进入中国市场。先后在香港、北京、上海、广州及成都设立了办事机构,并于2000年4月在上海浦东外高桥保税区建立了密理博(上海)贸易有限公司。

为了更好地满足中国用户的需求,密理博中国主页(www.millipore.com/cn)于2006年11月向广大用户开放,介绍密理博中国有限公司的最新动态,力求为用户打造专业的产品与服务信息交流平台。

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目前,密理博实验室纯水设备在行业内占据绝对主导地位。从经典的MIlli-Q超纯水系列,Elix纯水系统,RiOs反渗透纯水系统,到新型的Simplicity、Direct-Q等小流量应用系统,密理博的纯水生产设备已成为实验室纯水行业的金标准。膜技术则为免疫诊断试纸条、免疫浓缩检测装置的生产提供全套膜材料,并提供各种材质、孔径的过滤膜及即用式过滤装置,还有专为医疗设备配套的批量供应的一次性过滤器。密理博生命科学的过滤、超滤产品及蛋白印迹系列产品也得到广泛应用,蛋白质组、基因组系列试剂盒以及用于新药开发的多孔滤膜板日益得到用户的认可。2006年,密理博在生命科学领域又迈出了重要一步,完成了对Serologicals公司的合并,这一举措使得产品涉及的广度明显增强,大大加强了Millipore全面服务各个领域的能力,从而进一步确立了密理博的行业领先地位。

除实验室产品外,密理博同样为生物工程和制药企业提供高品质的纯化设备与服务。密理博的滤器、超滤器、反渗透系统、层析系统、层析柱及层析填料,用于药品及生物制品的澄清、分离、纯化、浓缩,和最终产品的除菌、除热原、除病毒,可以满足从小试、中试到大规模生产的各种需求;并可以帮助用户进行过滤、超滤系统的设计、评估及GMP要求的设备验证。此外还提供制药行业、食品饮料行业,微电子行业全面的质量控制产品与服务。

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