Serine/threonine protein kinase involved in both mRNA surveillance and genotoxic stress response pathways. Recognizes the substrate consensus sequence [ST]-Q. Plays a central role in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons by phosphorylating UPF1/RENT1. Recruited by release factors to stalled ribosomes together with SMG8 and SMG9 (forming the SMG1C protein kinase complex), and UPF1 to form the transient SURF (SMG1-UPF1-eRF1-eRF3) complex. In EJC-dependent NMD, the SURF complex associates with the exon junction complex (EJC) through UPF2 and allows the formation of an UPF1-UPF2-UPF3 surveillance complex which is believed to activate NMD. Also acts as a genotoxic stress-activated protein kinase that displays some functional overlap with ATM. Can phosphorylate p53/TP53 and is required for optimal p53/TP53 activation after cellular exposure to genotoxic stress. Its depletion leads to spontaneous DNA damage and increased sensitivity to ionizing radiation (IR). May activate PRKCI but not PRKCZ. ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein] ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein] Inhibited by caffeine, LY294002 and wortmannin. Component of the SMG1C complex composed of SMG1, SMG8 and SMG9; the recruitment of SMG8 to SMG1 N-terminus induces a large conformational change in the SMG1 C-terminal head domain containing the catalytic domain (PubMed:33205750). Component of the transient SURF (SMG1-UPF1-eRF1-eRF3) complex. Part of a complex composed of SMG1, DHX34 and UPF1; within the complex DHX34 acts as a scaffolding protein to facilitate SMG1 phosphorylation of UPF1 (PubMed:26841701). Interacts with PRKCI. Interacts with TELO2 and TTI1. Interacts with RUVBL1 and RUVBL2 (PubMed:33205750). Interacts with UPF2. Interacts with DHX34 (via C-terminus); the interaction is RNA-independent (PubMed:25220460, PubMed:33205750). Present in the chromatoid body. Widely expressed, with highest level in heart and skeletal muscle. Expressed in placenta, brain, lung and spleen, but not in liver. Autophosphorylated. This gene is located in a region of chromosome 16 that contains 2 segmental duplications. Other genes that are highly related to this exist, but they probably represent pseudogenes. Belongs to the PI3/PI4-kinase family. Truncated N-terminus.