Table 2.
Key characteristics of core human NMD factors
| NMD Factor (Uniprot ID)a | Cal.MW (kDa) | Length (aminoacids) | Alternative names | Major cellular localization | Direct NMD interactors | Functions in NMD |
|---|---|---|---|---|---|---|
| UPF1 (Q92900-2) | 123 | 1118 | NORF1, RENT1, smg-2 | Steady state cytoplasmic, nucleocytoplasmic shuttling | UPF2, SMG1, SMG6, SMG7 | Direct RNA binding; helicase activity; (phosphorylated) N- and C-terminus are binding platforms for SMG5-7, PNRC2 and decapping factors |
| UPF2 (Q9HAU5-1) | 148 | 1272 | RENT2, smg-3 | Cytoplasmic | UPF1, SMG1, UPF3 | Regulates UPF1 helicase activity; stimulates SMG1 kinase activity; establishes a physical link between UPF1 and UPF3 |
| UPF3a (Q9H1J1-1) | 55 | 476 | RENT3A, UPF3 | Nucleocytoplasmic shuttling | UPF2, EJC (eIF4A3, Y14, MAGOH) | Establishes a physical link between UPF1-UPF2 and the EJC; EJC-independent function unknown |
| UPF3b (Q9BZI7-2) | 56 | 470 | RENT3B, UPF3X | Steady state nuclear, nucleocytoplasmic shuttling | UPF2, EJC (eIF4A3, Y14, MAGOH) | Establishes a physical link between UPF1-UPF2 and the EJC; EJC-independent function unknown, functionally dominant over UPF3a |
| SMG1 (Q96Q15-1)b | 410 | 3661 | ATX, LIP | Cytoplasmic and nuclear | UPF1, UPF2, SMG8, SMG9 | Phosphorylates the N- and C-terminus of UPF1 at various SQ and TQ motifs |
| SMG5 (Q9UPR3-1) | 114 | 1016 | EST1B | Steady state cytoplasmic, nucleocytoplasmic shuttling | UPF1, SMG7 | Forms a complex with SMG7; recruits PP2A for UPF1 dephosphorylation; provides additional binding affinity to phosphorylated UPF1 |
| SMG6 (Q86US8-1) | 160 | 1419 | EST1A | Steady state cytoplasmic, nucleocytoplasmic shuttling | UPF1, EJC (via EBM) | Binds phosphorylated, as well as non-phosphorylated UPF1; executes endonucleolytic cleavage of the target mRNA |
| SMG7 (Q92540-2) | 122 | 1091 | EST1C | Steady state cytoplasmic, nucleocytoplasmic shuttling | UPF1, SMG5 | Forms a complex with SMG5; required for SMG5/7 binding to phosphorylated UPF1; recruits POP2 for mRNA deadenylation |
| SMG8 (Q8ND04-1) | 110 | 991 | FLJ10587, FLJ23205 | Cytoplasmic and nuclearc | SMG1, SMG9 | Regulation of SMG1 kinase activity; induces inactivating conformational changes in SMG1 |
| SMG9 (Q9H0W8-1) | 58 | 520 | FLJ12886 | Cytoplasmic and nuclearc | SMG1, SMG8 | Regulation of SMG1 kinase activity; required for SMG1 complex formation |
aAll other information (e.g. length and calculated molecular weight) refer to the isoform indicated here with the Uniprot ID
bSMG1 Q96Q15-1 differs from the mostly used SMG1 clone ENA: BAB70696 by an insertion of 5 glycines at position 14
cImplied by subcellular fractionation and co-immunoprecipitation with SMG1