InterPro domain: IPR039414

SMG-1 plays a critical role in the mRNA surveillance mechanism known as non-sense mediated mRNA decay (NMD). NMD protects the cells from the accumulation of aberrant mRNAs with premature termination codons (PTCs) generated by genome mutations and by errors during transcription and splicing. SMG-1 phosphorylates Upf1, another central component of NMD, at the C terminus upon recognition of PTCs. The phosphorylation/dephosphorylation cycle of Upf1 is essential for promoting NMD [ 1 ].

In addition to its catalytic domain, SMG-1 contains a FATC (FRAP, ATM and TRRAP, C-terminal) domain at the C terminus. SMG-1 is a member of the phosphoinositide 3-kinase-related protein kinase (PIKK) subfamily. PIKKs have intrinsic serine/threonine kinase activity and are distinguished from other PKs by their unique catalytic domain, similar to that of lipid PI3K, and their large molecular weight (240-470kDa) [ 2 ].

This entry represents the SMG-1 catalytic domain.

1. The role of SMG-1 in nonsense-mediated mRNA decay. Biochim. Biophys. Acta 1754, 305-15
2. Distant N- and C-terminal domains are required for intrinsic kinase activity of SMG-1, a critical component of nonsense-mediated mRNA decay. J. Biol. Chem. 282, 7799-808