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Literature summary for 3.4.21.105 extracted from
- The PARL family of mitochondrial rhomboid proteases (2010), Semin. Cell Dev. Biol., 21, 582-592.
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| A78E | mutant shows rhomboid activity but does not undergo proteolytic modification (beta-cleavage) | Mus musculus |
| DELTA75-79 | mutant Parl, where beta-cleavage is abolished by removing (DELTA75KRSAL79) or mutating the beta-cleavage site (L79E) do not induce fragmentation, indicating that the processing is a gain of function | Mus musculus |
| H313A | mutation of the catalytic residue leads to a complete loss activity | Saccharomyces cerevisiae |
| L262V | in 1031 human subjects a conserved amino acid substitution (L262V) in Parl is associated with increased plasma insulin concentration, a key risk factor for diabetes | Homo sapiens |
| L79E | mutant shows rhomboid activity but does not undergo proteolytic modification (beta-cleavage) | Mus musculus |
| R76E | mutant shows rhomboid activity but does not undergo proteolytic modification (beta-cleavage) | Mus musculus |
| S256A | mutation of the catalytic residue leads to a complete loss activity | Saccharomyces cerevisiae |
| S65D | proteolytic modification (beta-cleavage) is blocked by phosphorylation of residues located in close proximity to the cleavage site. Phosphomimetic substitutions of these amino acids impair the processing without affecting Parl rhomboid activity | Mus musculus |
| S70D | proteolytic modification (beta-cleavage) is blocked by phosphorylation of residues located in close proximity to the cleavage site. Phosphomimetic substitutions of these amino acids impair the processing without affecting Parl rhomboid activity | Mus musculus |
| S77E | mutant shows rhomboid activity but does not undergo proteolytic modification (beta-cleavage) | Mus musculus |
| T69D | proteolytic modification (beta-cleavage) is blocked by phosphorylation of residues located in close proximity to the cleavage site. Phosphomimetic substitutions of these amino acids impair the processing without affecting Parl rhomboid activity | Mus musculus |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| inner membrane | - |
Drosophila melanogaster | - |
- |
| inner membrane | - |
Mus musculus | - |
- |
| inner membrane | - |
Homo sapiens | - |
- |
| inner membrane | - |
Schizosaccharomyces pombe | - |
- |
| inner membrane | - |
Providencia stuartii | - |
- |
| inner membrane | - |
Danio rerio | - |
- |
| inner membrane | - |
Escherichia coli | - |
- |
| inner membrane | protease is inserted in the inner mitochondrial membrane | Saccharomyces cerevisiae | - |
- |
| mitochondrion | - |
Drosophila melanogaster | 5739 | - |
| mitochondrion | - |
Mus musculus | 5739 | - |
| mitochondrion | - |
Saccharomyces cerevisiae | 5739 | - |
| mitochondrion | - |
Schizosaccharomyces pombe | 5739 | - |
| mitochondrion | protease is localised only in the inner mitochondrial membrane, with the N-terminus exposed to the matrix and the C-terminus to the IMS | Homo sapiens | 5739 | - |
Molecular Weight [Da]
| Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
|---|---|---|---|
| 38800 | - |
calculated from cDNA | Saccharomyces cerevisiae |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Danio rerio | - |
- |
- |
| Drosophila melanogaster | - |
- |
- |
| Escherichia coli | P09391 | - |
- |
| Homo sapiens | - |
- |
- |
| Mus musculus | - |
- |
- |
| Providencia stuartii | - |
- |
- |
| Saccharomyces cerevisiae | - |
two rhomboid genes exist Rbd1 and Rbd2 | - |
| Schizosaccharomyces pombe | - |
- |
- |
Posttranslational Modification
| Posttranslational Modification | Comment | Organism |
|---|---|---|
| proteolytic modification | N-terminal domain of Parl undergoes two consecutive processing events, termed alpha- and beta-cleavage. The proximal alpha-cleavage (Gly52/Phe53) is constitutive and linked to the import of the full length Parl protein in the mitochondria. The distal beta-cleavage (Ser77/Ala78) is not constitutive and is subjected to a very complex mechanism of regulation, producing PACT, for Parl C-terminal fragment (spanning amino acid 78-379 of Parl) | Homo sapiens |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| cytochrome c peroxidase Ccp1 + H2O | cleavage of Ccp1 by Pcp1/Rbd1 appears to occur directly after or within its hydrophobic sorting sequence | Saccharomyces cerevisiae | ? | - |
? |  |
| Keren + H2O | Rho-1 recognizes a common region of the transmembrane helix substrate that contains small residues (Gly,Ser,Ala) | Drosophila melanogaster | ? | - |
? | |
| Mgm1p + H2O | inner membrane dynamin-related protein is cleaved by Pcp1/Rbd1. In Mgm1p, substituting GlyGlyMet in the predicted transmembrane helix with bulkier ValValLeu blocks Pcp1/Rbd1-mediated cleavage, suggesting that the GlyGly substrate motif of RHO rhomboids is also important for PARL rhomboids | Saccharomyces cerevisiae | ? | - |
? | |
| Mgm1p + H2O | transmembrane helix Mgm1p (inner membrane dynamin-related protein) of Schizosaccharomyces pombe is cleaved at different place than Mgm1p of Schizosaccharomyces cerevisiae | Schizosaccharomyces pombe | ? | - |
? | |
| Opa-1 + H2O | genetic analysis shows that Opa1 and Parl are part of the same pathway, with Parl positioned upstream of Opa1 in the control of apoptosis | Mus musculus | ? | - |
? | |
| reporter substrate LY2 | using a combinatorial approach it is shown that a negatively charged residue is the primary determinant of cleavage. The amino acid preceding peptide bond hydrolysis (the P1 position) has a preference for the small and polar Ser residue. The amino acid succeeding peptide bond hydrolysis (the P1 position) has a preference for negatively charged Asp | Escherichia coli | ? | - |
? | |
| Spitz + H2O | Rho-1 recognizes a common region of the transmembrane helix substrate that contains small residues (Gly,Ser,Ala) | Drosophila melanogaster | ? | - |
? | |
| thrombomodulin + H2O | human thrombomodulin is cleaved by the human, mouse and zebrafish RHBDL2, but not by the Drosophila Rhomboid-1 and the bacterial Aara rhomboid proteases | Mus musculus | ? | - |
? | |
| thrombomodulin + H2O | human thrombomodulin is cleaved by the human, mouse and zebrafish RHBDL2, but not by the Drosophila Rhomboid-1 and the bacterial Aara rhomboid proteases | Homo sapiens | ? | - |
? | |
| thrombomodulin + H2O | human thrombomodulin is cleaved by the human, mouse and zebrafish RHBDL2, but not by the Drosophila Rhomboid-1 and the bacterial Aara rhomboid proteases | Danio rerio | ? | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| AAR | belongs to the RHO subfamily of rhomboids | Providencia stuartii |
| GlpG | belongs to the RHO subfamily of rhomboids | Escherichia coli |
| PARL | PARL subfamily consists of rhomboid proteins with a domain architecture characterized by an extra transmembrane helix added to the amino terminus of the 6-transmembrane helix rhomboid domain (1 + 6 structure) | Drosophila melanogaster |
| PARL | PARL subfamily consists of rhomboid proteins with a domain architecture characterized by an extra transmembrane helix added to the amino terminus of the 6-transmembrane helix rhomboid domain (1 + 6 structure) | Mus musculus |
| PARL | PARL subfamily consists of rhomboid proteins with a domain architecture characterized by an extra transmembrane helix added to the amino terminus of the 6-transmembrane helix rhomboid domain (1 + 6 structure) | Homo sapiens |
| PARL | PARL subfamily consists of rhomboid proteins with a domain architecture characterized by an extra transmembrane helix added to the amino terminus of the 6-transmembrane helix rhomboid domain (1 + 6 structure) | Saccharomyces cerevisiae |
| PARL | PARL subfamily consists of rhomboid proteins with a domain architecture characterized by an extra transmembrane helix added to the amino terminus of the 6-transmembrane helix rhomboid domain (1 + 6 structure) | Schizosaccharomyces pombe |
| Pcp1/Rbd1 | - |
Saccharomyces cerevisiae |
| Pcp1/Rbd1 | - |
Schizosaccharomyces pombe |
| presenilin-associated rhomboid-like protein | - |
Homo sapiens |
| RHBDL2 | belongs to the RHO subfamily of rhomboids | Mus musculus |
| RHBDL2 | belongs to the RHO subfamily of rhomboids | Homo sapiens |
| RHBDL2 | belongs to the RHO subfamily of rhomboids | Danio rerio |
| RHO-1 | belongs to the RHO subfamily of rhomboids | Drosophila melanogaster |
| Rho-7 | - |
Drosophila melanogaster |
General Information
| General Information | Comment | Organism |
|---|---|---|
| malfunction | ablation of Pcp1/Rbd1 activity has a profound effect on mitochondrial shape. Phenotype observed in Pcp1 knockout cells appears to be due to the selective loss of Mgm1p processing by Pcp1 | Saccharomyces cerevisiae |
| malfunction | functional studies in vivo have shown that approximately 90% of Rho-7 mutant flies that lack the transcriptional start site and the first 18 codons of the protease die before pupariation | Drosophila melanogaster |
| malfunction | mice null for Parl do not show embryonic lethality and synaptic defects are not observed | Homo sapiens |
| malfunction | mice null for Parl do not show embryonic lethality and synaptic defects are not observed. Mice lacking Parl die between weeks 8 and 12 from cachexia sustained by multisystemic atrophy. Mitochondrial morphology and oxidative phosphorylation is not changed as seen in yeast knockout cells. Parl knockout cells are more susceptible to apoptosis | Mus musculus |
| physiological function | Parl is required to regulate the kinetics of cytochrome c release from mitochondria | Mus musculus |
| physiological function | studies in bacteria and Drosophila show that RHO subfamily members Aar from Providencia stuarti and Rho-1 from Drosophila melanogaster can functionally complement each other | Drosophila melanogaster |
| physiological function | studies in bacteria and Drosophila show that RHO subfamily members Aar from Providencia stuarti and Rho-1 from Drosophila melanogaster can functionally complement each other | Escherichia coli |
| physiological function | studies in bacteria and Drosophila show that RHO subfamily members Aar from Providencia stuarti and Rho-1 from Drosophila melanogaster can functionally complement each other. Expression of Aar triggers EGFR signaling when expressed in flies | Mus musculus |
| physiological function | studies in bacteria and Drosophila show that RHO subfamily members Aar from Providencia stuarti and Rho-1 from Drosophila melanogaster can functionally complement each other. Expression of Aar triggers EGFR signaling when expressed in flies | Homo sapiens |
| physiological function | studies in bacteria and Drosophila show that RHO subfamily members Aar from Providencia stuarti and Rho-1 from Drosophila melanogaster can functionally complement each other. Expression of Aar triggers EGFR signaling when expressed in flies | Providencia stuartii |
| physiological function | studies in bacteria and Drosophila show that RHO subfamily members Aar from Providencia stuarti and Rho-1 from Drosophila melanogaster can functionally complement each other. Expression of Aar triggers EGFR signaling when expressed in flies | Danio rerio |
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Release 2023.1 (January 2023)
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