
Type:Protein
SpeciesReactivity:H;R
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;AllSortilin(neurotensinreceptor3,glycoprotein95)isa95kDaTypeItransmembranemonomericglycoproteinthatisoneoffiveknownmembersofthemammalianvacuolarproteinsorting10pdomain(Vps10pD)familyofsortingreceptors(1,2).Humanpreprosortilinisprocessedbysignalsequencecleavagefollowedbypropeptidecleavageatafurinrecognitionsite.ThecationicpropeptideexhibitspHdependenthighaffinitybindingthatblockstheSortilinligandbindingsitebothpreandpostcleavage(3).Theextracellular/luminalsequencecomprisestheVps10pdomain,including10conservedcysteines(10CC)essentialforligandbinding(2).Thecytoplasmicdomainsortingmotifsconferalltraffickingduringsynthesis,targetingtolysosomes,endocytosisandGolgiendosometransport;aslittleas10%maybefoundonthecellsurface(4).MaturehumanSortilinshares91%aaidentitywithmouseandratSortilinand93%aaidentitywithdog.Duringmurinedevelopment,sortilinismainlyexpressedinthenervoussystem(5)whereitisareceptorforneuropeptidesincludingneurotensin,nervegrowthfactor(NGF)andbrainderivedneurotrophicfactor(BDNF)(69).ProNGF(ortheNGFpropeptidealone)bindssortilinwithmuchhigheraffinity(Kd~58nM)thandoesmatureNGF(Kd~90nM).Thecomplexofsortilin,proNGFandthereceptorp75ntrresultsinendocytosisofproNGFandinductionofapoptosis(7).SimilarresultshavebeenobtainedwithproBDNFandBDNF(8,9).Sortilinisexpressedinothertissuesincludingtestis,skeletalmuscleandfat(1,10).ItisessentialandsufficientforbiogenesisofGlut4storagevesiclesnecessaryforinsulinresponsivenessinADIpocytes(10).Sortilinalsobindslipoproteinlipase(11),apoE(2)andRAP(1,11).Bindingiscompetitive,indicatingthatalthoughunrelated,targetslikelybindthesamesite.