UniProtSummary | FUNCTION:PlaysaroleinleptinsignalingandcontrolofbodyweightBysimilarity.Tyrosinekinaseofthenon-receptortype,involvedininterleukin-3andprobablyinterleukin-23signaltransduction.
CATALYTICACTIVITY:ATP+a[protein]-L-tyrosine=ADP+a[protein]-L-tyrosinephosphate.
SUBUNITSTRUCTURE:InteractswithSIRPAandSH2B1Bysimilarity.InteractswithIL23R,SKB1andSTAM2.
SUBCELLULARLOCATION:Endomembranesystem;PeripheralmembraneproteinBysimilarity.Note:Whollyintracellular,possIBLymembraneassociatedBysimilarity.
TISSUESPECIFICITY:Expressedinblood,bonemarrowandlymphnode.
DOMAIN:Possessestwophosphotransferasedomains.ThesecondoneprobablycontainsthecatalyticdomainBysimilarity,whilethepresenceofslightdifferencessuggestadifferentrolefordomain1.
PTM:Leptinpromotesphosphorylationontyrosineresidues,includingphosphorylationonTyr-813bysimilarity.
INVOLVEMENTINDISEASE:ChromosomalaberrationsinvolvingJAK2arefoundinbothchronicandacuteformsofeosinophilic,lymphoblasticandmyeloidleukemia.Translocationt(8;9)(p22;p24)withPCM1linkstheproteinkinasedomainofJAK2tothemajorportionofPCM1.Translocationt(9;12)(p24;p13)withETV6.DefectsinJAK2areacauseofsusceptibilitytoBudd-Chiarisyndrome[MIM:600880].Budd-Chiarisyndromeisaspectrumofdiseasestates,includinganatomicabnormalitiesandhypercoagulabledisorders,resultinginhepaticvenousoutflowocclusion.Clinicalmanifestationsobservedinthemajorityofpatientsincludehepatomegaly,rightupperquadrantpain,andaBDominalascites.
DefectsinJAK2areassociatedwithpolycythemiavera(PV)[MIM:263300].PV,themostcommonformofprimarypolycythemia,iscausedbysomaticmutationinasinglehematopoieticstemcellleADIngtoclonalhematopoiesis.PVisamyeloproliferativedisordercharacterizedpredominantlybyerythroidhyperplasia,butalsobymyeloidleukocytosis,thrombocytosis,andsplenomegaly.FamilialcasesofPVareveryrareandusuallymanifestinelderlypatients.
DefectsinJAK2genemaybeacauseofessentialthrombocythemia(ET)[MIM:187950].ETischaracterizedbyelevatedplateletlevelsduetosustainedproliferationofmegakaryocytes,andfrequentlyleadtothromboticandhaemorrhagiccomplications.
DefectsinJAK2areassociatedwithfamilialmyelofibrosis[MIM:254450].Myelofibrosiswithmyeloidmetaplasiaisamyeloproliferativediseasewithannualincidenceof0.5-1.5casesper100,000individualsandageatdiagnosisaround60(anincreasedprevalenceisnotedinAshkenaziJews).Clinicalmanifestationsdependonthetypeofbloodcellaffectedandmayincludeanemia,pallor,splenomegaly,hypermetabolicstate,petechiae,ecchymosis,bleeding,lymphadenopathy,hepatomegaly,portalhypertension.
DefectsinJAK2areacauseofacutemyelogenousleukemia(AML)[MIM:601626].AMLisamalignantdiseaseinwhichhematopoieticprecursorsarearrestedinanearlystageofdevelopment.
SEQUENCESIMILARITIES:Belongstotheproteinkinasesuperfamily.Tyrproteinkinasefamily.JAKsubfamily.
Contains1FERMdomain.
Contains1proteinkinasedomain.
Contains1SH2domain. |