| TCID | Name | Domain | Kingdom/Phylum | Protein(s) |
|---|---|---|---|---|
|
3.A.29.1.1 | The mitochondrial i-AAA protease complex involved in inner membrane insertion and turnover. It consists of Yta10, Yta11 and Yta12 (Lee et al. 2017). | Eukaryota |
Fungi, Ascomycota | Protease complex of Saccharomyces cerevisiae Yta10, Afg3 of 761 aas with 2 TMSs Yta11, Yme1, Osd1, of 747 aas and 2 TMSs Yta12, RCA1, of 825 aas |
|
3.A.29.1.2 | Mitochondrial AAA protease complex of two enzymes, Yta10/12 (Afg3-like or Spg-7) and Yta11 (Ymel-1). It is a mitochondrial ATP-dependent metalloprotease complex mediating degradation of non-assembled mitochondrial inner membrane proteins and necessary for the assembly of the mitochondrial respiratory chain and ATPase complexes. It functions both in post-translational assembly and in the turnover of mistranslated or misfolded polypeptides (Nargund et al. 2012, Pellegrino et al. 2014, Nargund et al. 2015). | Eukaryota |
Metazoa, Nematoda | Protease complex of Caenorhabditis elegans Spg-7 (Ata10/12), 782 aas and 2 TMSs Yme1 (Ata11; Ymel-1), 723 aas and 1 TMS |
|
3.A.29.1.3 | Uncharacterized protein of 960 aas and 6 - 9 TMSs in a 2 + 4 + 3 TMS arrangement. The last 3 peaks of hydrophobicity are small and may not be TMSs. The large hydrophiic C-terminal domain is homologous to the proteases of this family. The first six strongly hydrophobic TMSs are not part of this protease domain. This region is homologous to a part (residues 2220 - 2380) of the Orf1a polyprotein (YP_009725295) of the SARS coronavirus. | Bacteria |
Candidatus Spechtbacteria | UP of Candidatus Spechtbacteria bacterium |
|
3.A.29.1.4 | FtsH zinc metaloprotease of 634 aas and 2 TMSs. 3-d structures have been determined (Uthoff and Baumann 2018). The active FtsH is a dodecamer, which consists of two FtsH hexamers. A tilted conformation of the cytosolic domain in the FtsH dodecamer, visualized by negative stain TEM suggests a lateral substrate entrance between the membrane and cytosolic domains. Such a substrate path was resolved in the cryo-EM structure of the FtsH hexamer (Carvalho et al. 2020). | Bacteria |
Aquificota | FtsH of Aquifex aeolicus |
|
3.A.29.1.5 | ATP-dependent zinc metaloprotease, FtsH of 644 aas and 2 TMSs. Acts as a processive, ATP-dependent zinc metallopeptidase for both cytoplasmic and membrane proteins. It plays a role in the quality control of integral membrane proteins and degrades a few membrane proteins that have not been assembled into complexes such as SecY, F0 ATPase subunit a and YccA. It also degrades cytoplasmic proteins, sigma-32, LpxC, KdtA and the phage lambda cII protein among others. Membrane proteins are digested in a processive manner starting at either the N- or C-terminus; recognition requires a cytoplasmic tail of about 20 residues with no apparent sequence requirements. It presumably dislocates membrane-spanning and periplasmic segments of the protein into the cytoplasm to degrade them, in a process that probably requires ATP (Bittner et al. 2017). | Bacteria |
Pseudomonadota | FtsH of E. coli |
|
3.A.29.1.6 | FtsH cell division protease of 637 aas and 2 N-terminal TMSs. | Bacteria |
Candidatus Peregrinibacteria | FtsH of Candidatus Peribacter riflensis |
|
3.A.29.1.7 | ATP-dependent zinc metalloprotease, FtsH, of 610 aas and 2 TMSs. It acts as a processive, ATP-dependent zinc metallopeptidase for both cytoplasmic and membrane proteins, and it plays a role in the quality control of integral membrane proteins.The cryo-EM structure in a fully ADP-bound symmetric state has been solved (Liu et al. 2022). Comparisons of the ADP-state structure with its apo-state and a substrate-engaged yeast YME1 structure show conformational changes in the ATPase domains, rather than the protease domains. A reconstruction of the full-length TmFtsH provides structural insights for the dynamic transmembrane and the periplasmic domains. The structural analyses expand the understanding of conformational switches between different nucleotide states in ATP hydrolysis by FtsH (Liu et al. 2022). | Bacteria |
Thermotogota | FtsH of Thermotoga maritima |
|
3.A.29.1.8 | ATP-dependent zinc metalloprotease, FtsH, of 639 aas and 2 TMSs (N-terminal at residues 30 and 130. The structure of this ATP-dependent metalloprotease in its functionally relevant hexameric form has been determined (Brangulis et al. 2023). ATP-dependent FtsH proteases are conserved in bacteria, mitochondria, and chloroplasts, where they play essential roles in the degradation of misfolded/unneeded membrane and cytosolic proteins. It is crucial for mouse and tick infectivity and in vitro growth of the Lyme disease-causing agent Borrelia burgdorferi. It is functionally active, possessing both protease and ATPase activities (Brangulis et al. 2023). | Eukaryota |
Spirochaetota | FtsH of Borrelia burgdorferi |