SMG1
Function
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.
Post-translational modifications
Autophosphorylated.
Sequence Similarities
Belongs to the PI3/PI4-kinase family.
Tissue Specificity
Widely expressed, with highest level in heart and skeletal muscle. Expressed in placenta, brain, lung and spleen, but not in liver.
Cellular localization
- Nucleus
- Cytoplasm
- Present in the chromatoid body.
Alternative names
ATX, KIAA0421, LIP, SMG1, Serine/threonine-protein kinase SMG1, SMG-1, hSMG-1, Lambda/iota protein kinase C-interacting protein, Nonsense mediated mRNA decay-associated PI3K-related kinase SMG1, Lambda-interacting protein