Type:Protein
SpeciesReactivity:H
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;AllNogginisasecretedhomodimericglycoproteinthatisanantagoNISTofbonemorphogeneticproteins(BMPs).1,2HumanNogginCDNAencodesa232aminoacid(aa)precursorprotein;cleavageofa19aasignalpeptidegeneratesthe213aamatureproteinwhichcontainsanN-terminalacidicregion,acentralbasicheparin-bindingsegmentandaC-terminalcysteine-knotstructure.2SecretedNogginprobablyremainsclosetothecellsurfaceduetoitsbindingofheparin-containingproteoglycans.3Nogginisveryhighlyconservedamongvertebrates,suchthatmaturehumanNogginshares99%,99%,98%,97%and89%aasequenceidentitywithmouse,rat,bovine,equineandchickNoggin,respectively.NogginbindssomeBMPssuchasBMP-4withhighaffinityandotherssuchasBMP-7withloweraffinity,antagonizingBMPbioactivitiesbyblockingepitopesonBMPsthatareneededforbindingtobothtypeIandtypeIIreceptors.2,4Duringembryogenesis,NogginantagonizesspecificBMPsatdefinedtimesduringneuraltube,somiteandcardiomyocytegrowthandpatterning.5-7Duringskeletaldevelopment,Nogginpreventschondrocytehyperplasia,thusallowingproperformationofjoints.4Mutationswithinthecysteine-knotregionofhumanNogginarelinkedtomultipletypesofskeletaldysplasiasthatresultinapicaljointfusions.8Nogginisexpressedindefinedareasoftheadultcentralnervoussystemandperipheraltissuessuchaslung,skeletalmuscleandskin.1Duringcultureofhumanembryonicstemcells(hESC)withoutfeederlayersorconditionedmedium,butwithadditionofFGFbasic,additionofNoggintoantagonizeBMPactivityallowshESCtomaintaintheirundifferentiated,pluripotentstate.9,10
References:
1.Valenzuela,D.M.etal.,1995,J.Neurosci.15:6077-6084.6.Itsykson,P.etal.,2005,Mol.Cell.Neurosci.30:24-36.
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