UniProtSummary | FUNCTION:RasproteinsbindGDP/GTPandpossessintrinsicGTPaseactivity. Enzymeregulation:AlternatebetweenaninactiveformboundtoGDPandanactiveformboundtoGTP.Activatedbyaguaninenucleotide-exchangefactor(GEF)andinactivatedbyaGTPase-activatingprotein(GAP). SIZE:189aminoacids;21,656Da SUBUNIT:InteractswithPHLPP(Bysimilarity). SUBCELLULARLOCATION:Cellmembrane;Lipid-anchor;Cytoplasmicside. Involvementindisease: DefectsinKRASareacauseofacutemyelogenousleukemia(AML)[MIM:601626].AMLisamalignantdiseaseinwhichhematopoieticprecursorsarearrestedinanearlystageofdevelopment.
DefectsinKRASareacauseofjuvenilemyelomonocyticleukemia(JMML)[MIM:607785].JMMLisapediatricmyelodysplasticsyndromethatconstitutesapproximately30%ofchildhoodcasesofmyelodysplasticsyndrome(MDS)and2%ofleukemia.ItischaracterizedbyleukocytosiswithtissueinfiltrationandinvitrohypersensitivityofmyeloidProgenitorstogranulocyte-macrophagecolonystimulatingfactor.
DefectsinKRASarethecauseofNoonansyndrome3(NS3)[MIM:609942].Noonansyndrome(NS)[MIM:163950]isadisordercharacterizedbydysmorphicfacialfeatures,shortstature,hypertelorism,cardiacanomalies,deafness,motordelay,andableedingdiathesis.Itisageneticallyheterogeneousandrelativelycommonsyndrome,withanestimatedincidenceof1in1000-2500livebirths.Rarely,NSisassociatedwithjuvenilemyelomonocyticleukemia(JMML).NS3inheritanceisautosomaldominant.
DefectsinKRASareacauseofcardiofaciocutaneoussyndrome(CFCsyndrome)[MIM:115150];alsoknownascardio-facio-cutaneoussyndrome.CFCsyndromeischaracterizedbyadistinctivefacialappearance,heartdefectsandmentalretardation.Heartdefectsincludepulmonicstenosis,atrialseptaldefectsandhypertrophiccardiomyopathy.Someaffectedindividualspresentwithectodermalabnormalitiessuchassparse,friablehair,hyperkeratoticskinlesionsandageneralizedichthyosis-likecondition.TypicalfacialfeaturesaresimilartoNoonansyndrome.Theyincludehighforeheadwithbitemporalconstriction,hypoplasticsupraorbitalridges,downslantingpalpebralfissures,adepressednasalbridge,andposteriorlyangulatedearswithprominenthelices.TheinheritanceofCFCsyndromeisautosomaldominant.
KRASmutationsareinvolvedincancerdevelopment. |