SMG1:UPF1:EJC:Translated mRNP SMG1:Phosphorylated UPF1:EJC:Translated mRNP SMG1 Phosphorylates UPF1 (Enhanced by Exon Junction Complex) Authored: May, B, 2010-08-06 EC Number: 2.7.11 Edited: May, B, 2010-08-06 Pubmed11331269 Pubmed11544179 Pubmed14636577 Pubmed16452507 Pubmed19359157 Pubmed19417104 Pubmed20817927 Reactome Database ID Release 43927889 Reactome, http://www.reactome.org ReactomeREACT_75910 Reviewed: Neu-Yilik, G, 2011-05-19 SMG1 phosphorylates UPF1 in vitro and in vivo (Denning et al. 2001, Yamashita et al. 2001, Kashima et al. 2006). Serines 1073, 1078, 1096, and 1116 in isoform 2 (Serines 1084, 1089, 1107, 1127 in isoform 1) are phosphorylated in vitro and phosphorylation at serines 1078 and 1096 has been confirmed in vivo (Yamashita et al. 2001, Ohnishi et al. 2003, Kashima et al. 2006). UPF1 also contains additional serine and threonine residues that could be phosphorylated. SMG8 and SMG9 associate with SMG1 and regulate the kinase activity of SMG1 (Yamashita et al. 2009). The phosphorylation reaction is rate-limiting in nonsense-mediated decay and is therefore regarded as a licensing step (reviewed in Rebbapragada and Lykke-Andersen 2009). Phosphorylation is enhanced by the exon junction complex, which can interact with UPF1 via UPF2 and/or UPF3 (Kashima et al. 2006, Ivanov et al. 2008) or via Y14:Magoh (Ivanov et al. 2008). SMG8 and SMG9 bind SMG1 and regulate its kinase activity (Yamashita et al. 2009, Fernandez et al. 2011). has a Stoichiometric coefficient of 4