| IED ID | IndEnz0002013800 |
| Enzyme Type ID | protease013800 |
| Protein Name |
Cysteine protease RavZ EC 3.4.22.- Region allowing vacuole colocalization protein Z |
| Gene Name | ravZ lpg1683 |
| Organism | Legionella pneumophila subsp. pneumophila (strain Philadelphia 1 / ATCC 33152 / DSM 7513) |
| Taxonomic Lineage | cellular organisms Bacteria Proteobacteria Gammaproteobacteria Legionellales Legionellaceae Legionella Legionella pneumophila Legionella pneumophila subsp. pneumophila Legionella pneumophila subsp. pneumophila (strain Philadelphia 1 / ATCC 33152 / DSM 7513) |
| Enzyme Sequence | MKGKLTGKDKLIVDEFEELGEQESDIDEFDLLEGDEKLPGDSELDKTTSIYPPETSWEVNKGMNSSRLHKLYSLFFDKSSAFYLGDDVSVLEDKPLTGAYGFQSKKNDQQIFLFRPDSDYVAGYHVDAKSDAGWVNDKLDRRLSEISEFCSKATQPATFILPFVEMPTDITKGVQHQVLLTISYDPKSKQLTPTVYDSIGRDTYSESLSSYFKGKYRTTCDEILTQSIEKAIKSTDFTLGKFTRAAYNHQNRLTEGNCGSYTFRTIKEVISSSAQGTEVKIPGSGYITSNSYLTSQHVQDIESCIKYRNLGVVDIESALTEGKTLPVQLSEFIVALEDYGKLRSQQSEKSMLNFIGYSKTAKLTAVELLIGILNDIKGKNEISESQYDKLVKEVDCLMDSSLGKLVQFHLKNLGAESLQKLVLPCVKFDDTIDDFVTIEKDELFDVPDITGEELASKKGIEQGALDKEALLKQKQIKTDLLDLREEDKTGLKKPLHGGIKVK |
| Enzyme Length | 502 |
| Uniprot Accession Number | Q5ZUV9 |
| Absorption | |
| Active Site | ACT_SITE 176; /evidence="ECO:0000269|PubMed:26343456"; ACT_SITE 197; /evidence="ECO:0000269|PubMed:26343456"; ACT_SITE 258; /evidence="ECO:0000269|PubMed:23112293, ECO:0000269|PubMed:26343456, ECO:0000269|PubMed:28395732" |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=[protein]-C-terminal L-amino acid-glycyl-phosphatidylethanolamide + H2O = 1,2-diacyl-sn-glycero-3-phosphoethanolamine-N-glycine + [protein]-C-terminal <stereo>L-</stereo>-amino acid; Xref=Rhea:RHEA:67664, Rhea:RHEA-COMP:17323, Rhea:RHEA-COMP:17349, ChEBI:CHEBI:15377, ChEBI:CHEBI:90782, ChEBI:CHEBI:172870, ChEBI:CHEBI:172941; Evidence={ECO:0000269|PubMed:23112293, ECO:0000269|PubMed:26343456, ECO:0000269|PubMed:28395732, ECO:0000269|PubMed:32686895, ECO:0000269|PubMed:33298241}; CATALYTIC ACTIVITY: Reaction=[protein]-C-terminal L-amino acid-glycyl-phosphatidylserine + H2O = 1,2-diacyl-sn-glycero-3-phospho-L-serine-N-glycine + [protein]-C-terminal <stereo>L-</stereo>-amino acid; Xref=Rhea:RHEA:67912, Rhea:RHEA-COMP:17326, Rhea:RHEA-COMP:17349, ChEBI:CHEBI:15377, ChEBI:CHEBI:90782, ChEBI:CHEBI:172942, ChEBI:CHEBI:176543; Evidence={ECO:0000269|PubMed:33909989}; |
| DNA Binding | |
| EC Number | 3.4.22.- |
| Enzyme Function | FUNCTION: Cysteine protease effector that inhibits host cell autophagy by targeting lipid-conjugated ATG8 family proteins on pre-autophagosomal structures (PubMed:23112293, PubMed:29458288, PubMed:32686895, PubMed:31722778, PubMed:31719622, PubMed:33298241, PubMed:26343456, PubMed:28395732). Specifically hydrolyzes the amide bond between the C-terminal glycine residue and an adjacent aromatic residue in ATG8 proteins conjugated to phosphatidylethanolamine (PE), producing an ATG8 protein that cannot be reconjugated by host ATG7 and ATG3 (PubMed:23112293, PubMed:29458288, PubMed:32686895, PubMed:26343456, PubMed:28395732). Mechanistically, Ravz interacts with ATG8 proteins conjugated to PE via its LIR motifs, extracts them from the membrane of autophagosomes and integrates the PE part into its own lipid-binding site (PubMed:28395732). It then removes the lipid component of the ATG8 protein (PubMed:28395732). Also able to mediate delipidation of ATG8 proteins conjugated to phosphatidylserine (PS) during non-canonical autophagy (PubMed:33909989). Inhibits host ubiquitin recruitment to bacteria-containing vacuoles, suggesting that it is able to mediate delipidation of other proteins in addition to ATG8 proteins (PubMed:28971069). It is however not involved in the exclusion of autophagy adapters from bacteria-containing vacuoles decorated with ubiquitin (PubMed:32482642). {ECO:0000269|PubMed:23112293, ECO:0000269|PubMed:26343456, ECO:0000269|PubMed:28395732, ECO:0000269|PubMed:28971069, ECO:0000269|PubMed:29458288, ECO:0000269|PubMed:31719622, ECO:0000269|PubMed:31722778, ECO:0000269|PubMed:32482642, ECO:0000269|PubMed:32686895, ECO:0000269|PubMed:33298241, ECO:0000269|PubMed:33909989}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (3); Chain (1); Motif (3); Mutagenesis (23); Region (3) |
| Keywords | 3D-structure;Host cytoplasmic vesicle;Host membrane;Hydrolase;Membrane;Protease;Reference proteome;Secreted;Thiol protease;Virulence |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:20880356}. Host cytoplasmic vesicle membrane {ECO:0000269|PubMed:23112293, ECO:0000269|PubMed:26343456, ECO:0000269|PubMed:31719622, ECO:0000269|PubMed:31722778, ECO:0000269|PubMed:33298241}. Note=Translocated into the host cell via the type IV secretion system (T4SS) (Probable). In host cells, localizes to mature autophagosome membranes (PubMed:23112293, PubMed:31722778, PubMed:31719622, PubMed:33298241, PubMed:26343456). {ECO:0000269|PubMed:23112293, ECO:0000269|PubMed:26343456, ECO:0000269|PubMed:31719622, ECO:0000269|PubMed:31722778, ECO:0000269|PubMed:33298241, ECO:0000305|PubMed:23112293}. |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (9) |
| Cross Reference PDB | 5CQC; 5HZY; 5IO3; 5IZV; 5MS2; 5MS5; 5MS7; 5MS8; 5XAD; |
| Mapped Pubmed ID | - |
| Motif | MOTIF 9..23; /note=LIR 1; /evidence=ECO:0000269|PubMed:27791457; MOTIF 23..37; /note=LIR 2; /evidence=ECO:0000269|PubMed:27791457; MOTIF 429..443; /note=LIR 3; /evidence=ECO:0000269|PubMed:27791457 |
| Gene Encoded By | |
| Mass | 56,242 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | RHEA:67664; RHEA:67912 |
| Cross Reference Brenda |