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Literature summary extracted from

  • Hill, R.B.; Pellegrini, L.
    The PARL family of mitochondrial rhomboid proteases (2010), Semin. Cell Dev. Biol., 21, 582-592.
    View publication on PubMedView publication on EuropePMC

Protein Variants

EC Number Protein Variants Comment Organism
3.4.21.105 A78E mutant shows rhomboid activity but does not undergo proteolytic modification (beta-cleavage) Mus musculus
3.4.21.105 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
3.4.21.105 H313A mutation of the catalytic residue leads to a complete loss activity Saccharomyces cerevisiae
3.4.21.105 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
3.4.21.105 L79E mutant shows rhomboid activity but does not undergo proteolytic modification (beta-cleavage) Mus musculus
3.4.21.105 R76E mutant shows rhomboid activity but does not undergo proteolytic modification (beta-cleavage) Mus musculus
3.4.21.105 S256A mutation of the catalytic residue leads to a complete loss activity Saccharomyces cerevisiae
3.4.21.105 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
3.4.21.105 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
3.4.21.105 S77E mutant shows rhomboid activity but does not undergo proteolytic modification (beta-cleavage) Mus musculus
3.4.21.105 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

EC Number Localization Comment Organism GeneOntology No. Textmining
3.4.21.105 inner membrane
-
 Drosophila melanogaster
-
-
3.4.21.105 inner membrane
-
 Mus musculus
-
-
3.4.21.105 inner membrane
-
 Homo sapiens
-
-
3.4.21.105 inner membrane
-
 Schizosaccharomyces pombe
-
-
3.4.21.105 inner membrane
-
 Providencia stuartii
-
-
3.4.21.105 inner membrane
-
 Danio rerio
-
-
3.4.21.105 inner membrane
-
 Escherichia coli
-
-
3.4.21.105 inner membrane protease is inserted in the inner mitochondrial membrane Saccharomyces cerevisiae
-
-
3.4.21.105 mitochondrion
-
 Drosophila melanogaster 5739
-
3.4.21.105 mitochondrion
-
 Mus musculus 5739
-
3.4.21.105 mitochondrion
-
 Saccharomyces cerevisiae 5739
-
3.4.21.105 mitochondrion
-
 Schizosaccharomyces pombe 5739
-
3.4.21.105 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]

EC Number Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
3.4.21.105 38800
-
 calculated from cDNA Saccharomyces cerevisiae

Organism

EC Number Organism UniProt Comment Textmining
3.4.21.105 Danio rerio
-
-
-
3.4.21.105 Drosophila melanogaster
-
-
-
3.4.21.105 Escherichia coli P09391
-
-
3.4.21.105 Homo sapiens
-
-
-
3.4.21.105 Mus musculus
-
-
-
3.4.21.105 Providencia stuartii
-
-
-
3.4.21.105 Saccharomyces cerevisiae
-
 two rhomboid genes exist Rbd1 and Rbd2
-
3.4.21.105 Schizosaccharomyces pombe
-
-
-

Posttranslational Modification

EC Number Posttranslational Modification Comment Organism
3.4.21.105 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)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
3.4.21.105 cytochrome c peroxidase Ccp1 + H2O cleavage of Ccp1 by Pcp1/Rbd1 appears to occur directly after or within its hydrophobic sorting sequence Saccharomyces cerevisiae ?
-
 ?
3.4.21.105 Keren + H2O Rho-1 recognizes a common region of the transmembrane helix substrate that contains small residues (Gly,Ser,Ala) Drosophila melanogaster ?
-
 ?
3.4.21.105 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 ?
-
 ?
3.4.21.105 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 ?
-
 ?
3.4.21.105 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 ?
-
 ?
3.4.21.105 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 ?
-
 ?
3.4.21.105 Spitz + H2O Rho-1 recognizes a common region of the transmembrane helix substrate that contains small residues (Gly,Ser,Ala) Drosophila melanogaster ?
-
 ?
3.4.21.105 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 ?
-
 ?
3.4.21.105 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 ?
-
 ?
3.4.21.105 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

EC Number Synonyms Comment Organism
3.4.21.105 AAR belongs to the RHO subfamily of rhomboids Providencia stuartii
3.4.21.105 GlpG belongs to the RHO subfamily of rhomboids Escherichia coli
3.4.21.105 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
3.4.21.105 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
3.4.21.105 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
3.4.21.105 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
3.4.21.105 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
3.4.21.105 Pcp1/Rbd1
-
 Saccharomyces cerevisiae
3.4.21.105 Pcp1/Rbd1
-
 Schizosaccharomyces pombe
3.4.21.105 presenilin-associated rhomboid-like protein
-
 Homo sapiens
3.4.21.105 RHBDL2 belongs to the RHO subfamily of rhomboids Mus musculus
3.4.21.105 RHBDL2 belongs to the RHO subfamily of rhomboids Homo sapiens
3.4.21.105 RHBDL2 belongs to the RHO subfamily of rhomboids Danio rerio
3.4.21.105 RHO-1 belongs to the RHO subfamily of rhomboids Drosophila melanogaster
3.4.21.105 Rho-7
-
 Drosophila melanogaster

General Information

EC Number General Information Comment Organism
3.4.21.105 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
3.4.21.105 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
3.4.21.105 malfunction mice null for Parl do not show embryonic lethality and synaptic defects are not observed Homo sapiens
3.4.21.105 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
3.4.21.105 physiological function Parl is required to regulate the kinetics of cytochrome c release from mitochondria Mus musculus
3.4.21.105 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
3.4.21.105 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
3.4.21.105 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
3.4.21.105 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
3.4.21.105 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
3.4.21.105 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