Table 2.
Human NMD factors
| Protein | Alternative name/name in other species | Characteristics | Direct interaction partners | Cellular localisation | References |
|---|---|---|---|---|---|
| UPF1 | RENT1 (human, mouse) | RNA helicase, nucleic acid-dependent ATPase and RNA-binding protein | UPF2 | Shuttling protein; at steady-state predominantly in the cytoplasm | [48–50, 54, 56, 58–61, 66–71, 73, 74, 80, 83, 92, 96, 102, 103, 188, 225–227] |
| SMG2 (C. elegans) | SMG1 | ||||
| Phosphorylated at serine residues in C-terminal SQ motifs | SMG5a | ||||
| SMG6 | |||||
| SMG7 | |||||
| eRF1 | |||||
| eRF3 | |||||
| PP2Ab | |||||
| BTZe | |||||
| UPF2 | RENT2 (human, mouse) | Phosphoprotein, phosphorylated at serine residues in N-terminal part | UPF1 | Cytoplasmic; mainly perinuclear | [20, 49, 50, 56, 57, 60, 70, 71, 74, 79, 82, 83, 85, 89, 92, 226, 228, 229] |
| Nmd2p (S. cerevisiae) | UPF3A UPF3B | ||||
| SMG3 (C. elegans) | Promotes phosphorylation of UPF1 | eRF3c | |||
| SMG1 | |||||
| UPF3A and UPF3B | UPF3X (= UPF3B) | Associates with the EJC | UPF2 | Shuttling protein; at steady-state primarily in the nucleus (UPF3B) | [39, 49, 56, 60, 79, 83, 85–89, 92, 93, 226, 228] |
| SMG4 (C. elegans) | Promotes phosphorylation of UPF1 | eRF3c | |||
| Y14d | |||||
| MAGOHd | |||||
| BTZe | |||||
| eIF4A3e | |||||
| SMG1 | ATX | Ser/Thr-kinase of PIKK family, phosphorylates UPF1 | UPF1 | Cytoplasm and nucleus | [55, 61, 63, 74, 75, 94, 106, 222, 224] |
| UPF2 | |||||
| SMG8f | |||||
| SMG9f | |||||
| SMG5 | EST1B | Required for UPF1 dephosphorylation, directs PP2A to phosphorylated UPF1 | UPF1a | Cytoplasm; co-localises with SMG7 to P-bodies | [58, 64, 80, 96, 97, 99, 202, 203] |
| SMG7 | |||||
| PP2A | |||||
| SMG6 | EST1A | Ribonuclease with endonucleolytic activity. Required for UPF1 dephosphorylation | UPF1 | Cytoplasm | [64, 81, 96, 99–101, 202, 203] |
| PP2Af | |||||
| SMG7 | EST1C | Required for UPF1 dephosphorylation | UPF1 | Cytoplasm; co-localises with SMG5 to P-bodies | [53, 58, 64, 65, 96, 97, 202, 203] |
| Ebs1p (S. cerevisiae) | SMG5 | ||||
| PP2Af | |||||
| SMG8 | – | Forms a complex with SMG1 | SMG1f | Not analysed | [63] |
| Inhibits SMG1 kinase activity | |||||
| SMG9 | – | Forms a complex with SMG1 | SMG1f | Not analysed | [63] |
| NAG | SMGL1 (C. elegans) | Essential for NMD in humans and C. elegans | Not analysed | Not analysed | [62] |
| DHX34 | SMGL2 (C. elegans) | RNA helicase activity. Essential for NMD in humans and C. elegans | Not analysed | Not analysed | [62] |
aProof for direct interaction missing, shown by immunoprecipitation and mutational analysis (deletion of UPF1’s N-terminal 63 amino acids [58])
bDirect interaction only shown in C. elegans [80]
cDirect interaction only shown in S. cerevisiae [226]
dProof for direct interaction missing; interaction to UPF3B shown by immunoprecipitation and mutational analysis (MAGOH D66A–E68A and Y14 E82A–E83A [92])
eProof for direct interaction missing; detected in complex with UPF3B or UPF1, respectively
fProof for direct interaction missing; detected in complex with indicated factor