| IED ID | IndEnz0002000971 |
| Enzyme Type ID | protease000971 |
| Protein Name |
Presequence protease, mitochondrial EC 3.4.24.- Pitrilysin metalloproteinase 1 |
| Gene Name | PITRM1 |
| Organism | Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii) |
| 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) Ponginae Pongo Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii) |
| Enzyme Sequence | MWRCGGRQGLGVLRRLSGGHAHHRAWRWNSNRACERALQYKLGDKIHGFTVNQVTSVPELFLTAVKLIHDDTGARYLHLAREDTNNLFSVQFRTTPMDSTGVPHILEHTVLCGSQKYPCRDPFFRMLNRSLSTFMNAFTASDYTLYPFSTQNPKDFQNLLSVYLDATFFPCLRELDFWQEGWRLEHENPRDPQTALVFKGVVFNEMKGAFTDNERIFSQHLQNRLLPDHTYSVVSGGDPLCILELTWEQLKQFHATHYHPSNARFFTYGNFPLEQHLKQIHEEALSKFQKIEPSTAVPAQTPWDKPREFQITCGPDSFATDPSKQTTVSVSFLLPDITDTFEAFTLSLLSSLLTSGPNSPFYKALIESGLGTDFSPDVGYNGYTREAYFSVGLQGIAEKDIETVRSLVDRTIDEVVEKGFEDDRIEALLHKIEIQMKHQSTSFGLMLTSYIASCWNHDGDPVELLKLGNQLAKFRQCLQENPKFLQEKVKQYFKNNQHKLTLSMRPDDKYHEKQAQVEATKLKQKVEALSPGDRQQIYEKGLELRTQQSKPQDASCLPALKVSDIEPTIPVTELDVVLTAGDIPVQYCAQPTNGMVYFRAFSSLNTLPEELRPYVPLFCSVLTKLGCGLLDYREQAQQIELKTGGMSASPHVLPDDSHMDTYEQGVLFSSLCLDRNLPDMMHLWSEIFNNPCFEEEEHFKVLVKMTAQELTNAIPDSGHLYASIRAGRTLTPAGDLQETFSGMDRVRLMKRIAEMTDIKPILRKLPRIKKHLLNGDNMRCSVNATPQQMSQTEKAVEDFLRSIGRSKKERRPVRPHTVEKPVPSSSGGDAHVPHGSQIIRKLVTEPTFKPWQMKTHFLMPFPVNYVGECIRTVPYMDPDHASLKILARLMTAKFLHTEIREKGGAYGGGAKLSHNGIFSLYSYRDPNTIETLQSFGKAVDWAKSGKFTQQDIDEAKLSVFSTVDAPIAPSNKGMDYFLYGLSDGMKQAHREQLFAVSHDKLLAVSNRYLGTGKSTHSLAILGPENPKIAKDPSWTIR |
| Enzyme Length | 1037 |
| Uniprot Accession Number | Q5RDG3 |
| Absorption | |
| Active Site | ACT_SITE 107; /note=Proton acceptor; /evidence=ECO:0000250|UniProtKB:Q5JRX3 |
| Activity Regulation | ACTIVITY REGULATION: Mainly exists in a closed and catalytically competent conformation but a closed-to-open switch allows substrate entry into the catalytic chamber. Substrate binding induces closure and dimerization. A disulfide bond may lock the enzyme in a closed conformation preventing substrate entry into the catalytic chamber, participating in redox regulation of the enzyme. Inhibited by metal-chelating agents. Inhibited by nickel and zinc excess, and slightly activated by manganese. {ECO:0000250|UniProtKB:Q5JRX3}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | 3.4.24.- |
| Enzyme Function | FUNCTION: Metalloendopeptidase of the mitochondrial matrix that functions in peptide cleavage and degradation rather than in protein processing. Has an ATP-independent activity. Specifically cleaves peptides in the range of 5 to 65 residues. Shows a preference for cleavage after small polar residues and before basic residues, but without any positional preference. Degrades the transit peptides of mitochondrial proteins after their cleavage. Also degrades other unstructured peptides. It is also able to degrade amyloid-beta protein 40, one of the peptides produced by APP processing, when it accumulates in mitochondrion. It is a highly efficient protease, at least toward amyloid-beta protein 40. Cleaves that peptide at a specific position and is probably not processive, releasing digested peptides intermediates that can be further cleaved subsequently. {ECO:0000250|UniProtKB:Q5JRX3}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (1); Chain (1); Compositional bias (1); Disulfide bond (1); Metal binding (3); Modified residue (6); Region (1); Transit peptide (1) |
| Keywords | Acetylation;Disulfide bond;Hydrolase;Metal-binding;Metalloprotease;Mitochondrion;Protease;Reference proteome;Transit peptide;Zinc |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000250|UniProtKB:Q5JRX3}. |
| Modified Residue | MOD_RES 759; /note=N6-acetyllysine; /evidence=ECO:0000250|UniProtKB:Q8K411; MOD_RES 770; /note=N6-acetyllysine; alternate; /evidence=ECO:0000250|UniProtKB:Q8K411; MOD_RES 770; /note=N6-succinyllysine; alternate; /evidence=ECO:0000250|UniProtKB:Q8K411; MOD_RES 849; /note=N6-succinyllysine; /evidence=ECO:0000250|UniProtKB:Q8K411; MOD_RES 884; /note=N6-acetyllysine; /evidence=ECO:0000250|UniProtKB:Q8K411; MOD_RES 946; /note=N6-succinyllysine; /evidence=ECO:0000250|UniProtKB:Q8K411 |
| Post Translational Modification | PTM: A disulfide bond locks the enzyme in the closed conformation preventing substrate entry into the catalytic chamber. {ECO:0000250|UniProtKB:Q5JRX3}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | - |
| Motif | |
| Gene Encoded By | |
| Mass | 117,507 |
| Kinetics | |
| Metal Binding | METAL 104; /note=Zinc; via tele nitrogen; catalytic; /evidence=ECO:0000250|UniProtKB:Q5JRX3; METAL 108; /note=Zinc; via tele nitrogen; catalytic; /evidence=ECO:0000250|UniProtKB:Q5JRX3; METAL 205; /note=Zinc; catalytic; /evidence=ECO:0000250|UniProtKB:Q5JRX3 |
| Rhea ID | |
| Cross Reference Brenda |