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 | 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 Maximum [Da] | Comment | Organism |
---|---|---|---|
38800 | - |
calculated from cDNA | Saccharomyces cerevisiae |
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 | 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 | 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 | 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 | 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 |