PP2A (Aalpha:B55alpha:Calpha) Phosphorylated UPF1:SMG5:SMG7:SMG6:PP2A:Translated mRNP SMG1:Phosphorylated UPF1:EJC:Translated mRNP Phosphorylated UPF1 Recruits SMG5, SMG7, SMG6, and PP2A Authored: May, B, 2010-08-06 Edited: May, B, 2010-08-06 Pubmed12554878 Pubmed14636577 Pubmed15546618 Pubmed15721257 Pubmed17053788 Pubmed17893241 Pubmed18423202 Pubmed19060897 Pubmed20023408 Pubmed20930030 Reactome Database ID Release 43927813 Reactome, http://www.reactome.org ReactomeREACT_75891 Reviewed: Neu-Yilik, G, 2011-05-19 SMG6, SMG5 and SMG7 contain 14-3-3 domains which are believed to bind phosphorylated SQ motifs in UPF1 (Chiu et al. 2003, Ohnishi et al. 2003, Unterholzner and Izaurralde 2004, Fukuhara et al. 2005, Durand et al. 2007). SMG7 has been shown to bind UPF1 directly, target UPF1 for dephosphorylation by PP2A, and recruit enzymes that degrade RNA (Ohnishi et al. 2003, Unterholzner and Izaurralde 2004, Fukuhara et al. 2005). UPF3AS (the small isoform of UPF3A) also associates with the complex (Ohnishi et al. 2003). SMG6 is an endoribonuclease that cleaves the mRNA bound by UPF1 and also recruits phosphatase PP2A to dephosphorylate UPF1 (Chiu et al. 2003, Glavan et al. 2006, Eberle et al. 2009) .<br>Though immunofluorescence in vivo indicates that SMG5 and SMG7 exist in separate complexes from SMG6 (Unterholzner and Izaurralde 2004) immunoprecipitation shows that SMG6 is present in complexes that also contain SMG5, SMG7, UPF1, UPF2, Y14, Magoh, and PABP (Kashima et al. 2010). SMG5, SMG6, and SMG7 are therefore represented here together in the same RNP complex. It is possible that some complexes contain only SMG6 or SMG5:SMG7 (reviewed in Nicholson et al. 2010, Muhlemann and Lykke-Andersen 2010). Note that "Smg5/7a" in Chiu et al. 2003 actually refers to SMG6.<br>Phosphorylated UPF1 also inhibits translation initiation by inhibiting conversion of 40S:tRNAmet:mRNA to 80S:tRNAmet:mRNA complexes (Isken et al. 2008)