ID:SMG1_HUMAN DESCRIPTION: RecName: Full=Serine/threonine-protein kinase SMG1; Short=SMG-1; Short=hSMG-1; EC=2.7.11.1; AltName: Full=61E3.4; AltName: Full=Lambda/iota protein kinase C-interacting protein; Short=Lambda-interacting protein; 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. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. COFACTOR: Manganese. ENZYME REGULATION: Inhibited by caffeine, LY294002 and wortmannin. SUBUNIT: 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. Component of the transient SURF (SMG1-UPF1-eRF1-eRF3) complex. Interacts with PRKCI. Interacts with TELO2 and TTI1. Interacts with RUVBL1 and RUVBL2. Interacts with UPF2. INTERACTION: P11940:PABPC1; NbExp=2; IntAct=EBI-1049832, EBI-81531; Q9HAU5:UPF2; NbExp=6; IntAct=EBI-1049832, EBI-372073; SUBCELLULAR LOCATION: Nucleus. Cytoplasm. TISSUE SPECIFICITY: Widely expressed, with highest level in heart and skeletal muscle. Expressed in placenta, brain, lung and spleen, but not in liver. PTM: Autophosphorylated (Probable). Phosphorylated upon DNA damage, probably by ATM or ATR. MISCELLANEOUS: 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. SIMILARITY: Belongs to the PI3/PI4-kinase family. SIMILARITY: Contains 1 FAT domain. SIMILARITY: Contains 1 FATC domain. SIMILARITY: Contains 1 HEAT repeat. SIMILARITY: Contains 1 PI3K/PI4K domain. SEQUENCE CAUTION: Sequence=AAA86535.2; Type=Erroneous initiation; Note=Translation N-terminally extended;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q96Q15
Front
Top
Side
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
