| IED ID | IndEnz0002006715 |
| Enzyme Type ID | protease006715 |
| Protein Name |
Presenilins-associated rhomboid-like protein, mitochondrial EC 3.4.21.105 Mitochondrial intramembrane cleaving protease PARL Cleaved into: P-beta Pbeta |
| Gene Name | PARL PSARL PRO2207 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MAWRGWAQRGWGCGQAWGASVGGRSCEELTAVLTPPQLLGRRFNFFIQQKCGFRKAPRKVEPRRSDPGTSGEAYKRSALIPPVEETVFYPSPYPIRSLIKPLFFTVGFTGCAFGSAAIWQYESLKSRVQSYFDGIKADWLDSIRPQKEGDFRKEINKWWNNLSDGQRTVTGIIAANVLVFCLWRVPSLQRTMIRYFTSNPASKVLCSPMLLSTFSHFSLFHMAANMYVLWSFSSSIVNILGQEQFMAVYLSAGVISNFVSYVGKVATGRYGPSLGASGAIMTVLAAVCTKIPEGRLAIIFLPMFTFTAGNALKAIIAMDTAGMILGWKFFDHAAHLGGALFGIWYVTYGHELIWKNREPLVKIWHEIRTNGPKKGGGSK |
| Enzyme Length | 379 |
| Uniprot Accession Number | Q9H300 |
| Absorption | |
| Active Site | ACT_SITE 277; /note=Nucleophile; /evidence=ECO:0000250; ACT_SITE 335; /evidence=ECO:0000250 |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=Cleaves type-1 transmembrane domains using a catalytic dyad composed of serine and histidine that are contributed by different transmembrane domains.; EC=3.4.21.105; Evidence={ECO:0000269|PubMed:22354088}; |
| DNA Binding | |
| EC Number | 3.4.21.105 |
| Enzyme Function | FUNCTION: Required for the control of apoptosis during postnatal growth. Essential for proteolytic processing of an antiapoptotic form of OPA1 which prevents the release of mitochondrial cytochrome c in response to intrinsic apoptotic signals (By similarity). Required for the maturation of PINK1 into its 52kDa mature form after its cleavage by mitochondrial-processing peptidase (MPP) (PubMed:22354088). Promotes changes in mitochondria morphology regulated by phosphorylation of P-beta domain (PubMed:14732705, PubMed:17116872). {ECO:0000250|UniProtKB:Q5XJY4, ECO:0000269|PubMed:14732705, ECO:0000269|PubMed:17116872, ECO:0000269|PubMed:22354088}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (2); Alternative sequence (1); Chain (1); Modified residue (3); Mutagenesis (8); Natural variant (2); Peptide (1); Topological domain (8); Transit peptide (1); Transmembrane (7) |
| Keywords | Alternative splicing;Direct protein sequencing;Hydrolase;Membrane;Mitochondrion;Mitochondrion inner membrane;Nucleus;Phosphoprotein;Protease;Reference proteome;Serine protease;Transit peptide;Transmembrane;Transmembrane helix |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000269|PubMed:17116872, ECO:0000269|PubMed:22354088}; Multi-pass membrane protein {ECO:0000269|PubMed:17116872}.; SUBCELLULAR LOCATION: [P-beta]: Nucleus {ECO:0000269|PubMed:17116872}. Note=Translocated into the nucleus by an unknown mechanism (PubMed:17116872). {ECO:0000269|PubMed:17116872}. |
| Modified Residue | MOD_RES 65; /note=Phosphoserine; /evidence=ECO:0000269|PubMed:17116872; MOD_RES 69; /note=Phosphothreonine; /evidence=ECO:0000269|PubMed:17116872; MOD_RES 70; /note=Phosphoserine; /evidence=ECO:0000269|PubMed:17116872 |
| Post Translational Modification | PTM: P-beta is proteolytically processed (beta-cleavage) in a PARL-dependent manner. The cleavage is inhibited when residues Ser-65, Thr-69 and Ser-70 are all phosphorylated. {ECO:0000269|PubMed:17116872}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 17019603; 19185381; 21138942; 27642048; 27737933; |
| Motif | |
| Gene Encoded By | |
| Mass | 42,190 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda | 3.4.21.105; |