SMG1

Description

The SMG1 (SMG1 nonsense mediated mRNA decay associated PI3K related kinase) is a protein-coding gene located on chromosome 16.

SMG1 (SMG-1, hSMG-1) is a serine/threonine-protein kinase encoded by the SMG1 gene in humans. It belongs to the phosphatidylinositol 3-kinase-related kinase protein family. SMG1 plays a key role in nonsense-mediated mRNA decay (NMD) as part of the mRNA surveillance complex. It possesses kinase activity and is believed to phosphorylate the regulator of nonsense transcripts 1 protein (UPF1) during NMD. SMG1 has been shown to interact with PRKCI and UPF1.

SMG1 is a serine/threonine protein kinase that plays a key role in both mRNA surveillance and genotoxic stress response pathways. It recognizes the substrate consensus sequence [ST]-Q. In mRNA surveillance, SMG1 is central to nonsense-mediated decay (NMD) of mRNAs containing premature stop codons. It achieves this by phosphorylating UPF1/RENT1. SMG1 is recruited by release factors to stalled ribosomes, forming the SMG1C protein kinase complex with SMG8 and SMG9, and the transient SURF (SMG1-UPF1-eRF1-eRF3) complex with UPF1. In EJC-dependent NMD, the SURF complex interacts with the exon junction complex (EJC) via UPF2, facilitating the formation of an UPF1-UPF2-UPF3 surveillance complex believed to activate NMD. SMG1 also functions as a genotoxic stress-activated protein kinase, exhibiting some functional overlap with ATM. It can phosphorylate p53/TP53, contributing to optimal p53/TP53 activation following exposure to genotoxic stress. Depletion of SMG1 results in spontaneous DNA damage and increased sensitivity to ionizing radiation (IR). SMG1 may activate PRKCI but not PRKCZ.

SMG1 is also known as 61E3.4, ATX, LIP.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing