| IED ID | IndEnz0002003847 |
| Enzyme Type ID | protease003847 |
| Protein Name |
Serine protease HTRA2, mitochondrial EC 3.4.21.108 High temperature requirement protein A2 HtrA2 Omi stress-regulated endoprotease Serine protease 25 Serine proteinase OMI |
| Gene Name | HTRA2 OMI PRSS25 |
| 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 | MAAPRAGRGAGWSLRAWRALGGIRWGRRPRLTPDLRALLTSGTSDPRARVTYGTPSLWARLSVGVTEPRACLTSGTPGPRAQLTAVTPDTRTREASENSGTRSRAWLAVALGAGGAVLLLLWGGGRGPPAVLAAVPSPPPASPRSQYNFIADVVEKTAPAVVYIEILDRHPFLGREVPISNGSGFVVAADGLIVTNAHVVADRRRVRVRLLSGDTYEAVVTAVDPVADIATLRIQTKEPLPTLPLGRSADVRQGEFVVAMGSPFALQNTITSGIVSSAQRPARDLGLPQTNVEYIQTDAAIDFGNSGGPLVNLDGEVIGVNTMKVTAGISFAIPSDRLREFLHRGEKKNSSSGISGSQRRYIGVMMLTLSPSILAELQLREPSFPDVQHGVLIHKVILGSPAHRAGLRPGDVILAIGEQMVQNAEDVYEAVRTQSQLAVQIRRGRETLTLYVTPEVTE |
| Enzyme Length | 458 |
| Uniprot Accession Number | O43464 |
| Absorption | |
| Active Site | ACT_SITE 198; /note=Charge relay system; /evidence=ECO:0000269|PubMed:11967569; ACT_SITE 228; /note=Charge relay system; /evidence=ECO:0000269|PubMed:11967569; ACT_SITE 306; /note=Charge relay system; /evidence=ECO:0000269|PubMed:11967569 |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=Cleavage of non-polar aliphatic amino-acids at the P1 position, with a preference for Val, Ile and Met. At the P2 and P3 positions, Arg is selected most strongly with a secondary preference for other hydrophilic residues.; EC=3.4.21.108; |
| DNA Binding | |
| EC Number | 3.4.21.108 |
| Enzyme Function | FUNCTION: Serine protease that shows proteolytic activity against a non-specific substrate beta-casein. Promotes or induces cell death either by direct binding to and inhibition of BIRC proteins (also called inhibitor of apoptosis proteins, IAPs), leading to an increase in caspase activity, or by a BIRC inhibition-independent, caspase-independent and serine protease activity-dependent mechanism. Cleaves THAP5 and promotes its degradation during apoptosis. Isoform 2 seems to be proteolytically inactive. {ECO:0000269|PubMed:15200957, ECO:0000269|PubMed:19502560}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (3); Alternative sequence (4); Beta strand (22); Chain (1); Domain (1); Helix (9); Motif (1); Mutagenesis (2); Natural variant (9); Propeptide (1); Region (1); Transit peptide (1); Transmembrane (1); Turn (4) |
| Keywords | 3D-structure;Alternative splicing;Apoptosis;Autocatalytic cleavage;Direct protein sequencing;Disease variant;Endoplasmic reticulum;Epilepsy;Hydrolase;Membrane;Mitochondrion;Neurodegeneration;Parkinson disease;Parkinsonism;Protease;Reference proteome;Serine protease;Transit peptide;Transmembrane;Transmembrane helix;Zymogen |
| Interact With | Q6ZTN6-2; Q86TN1; Q9Y575-3; Q96DX5-3; Q96FT7-4; Q96CA5; Q7Z7K6; A0A140G945; Q5TAQ9-2; O00303; Q8TC29; Q13216-2; Q99871; Q02363; Q8IY31-2; Q8N5Z5; Q6P597; P57682; Q9Y2M5; P08727; Q14525; Q1L5Z9; Q99683; Q8NA82; Q8N594; Q8WY64; Q9P0J0; Q13562; O15381-5; Q96FW1; Q6GQQ9-2; Q9NUU6; Q9HBE1-4; Q9NV79; O14813; O75925; Q8WWB5; Q96T49; Q6ZMI0-5; P17980; P57052; Q8WVD3; Q96D59; Q96GQ5; Q8N488; Q8N6K7-2; Q9NR46; Q96GM5; Q16637-3; Q8WXH5; Q5VWN6; Q86WV5; O95150; Q6DKK2; Q495M9; O75604-3; Q8NEZ2; Q15007-2; O00308; P98170; P24278; Q9UNY5; Q8N0Y2-2; O60304; O15535; Q86V28; P02666; Q60855; P02666 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Mitochondrion intermembrane space. Mitochondrion membrane {ECO:0000305}; Single-pass membrane protein {ECO:0000305}. Note=Predominantly present in the intermembrane space. Released into the cytosol following apoptotic stimuli, such as UV treatment, and stimulation of mitochondria with caspase-8 truncated BID/tBID.; SUBCELLULAR LOCATION: [Isoform 1]: Endoplasmic reticulum {ECO:0000269|PubMed:10644717}. |
| Modified Residue | |
| Post Translational Modification | PTM: Autoproteolytically activated. {ECO:0000269|PubMed:10873535}. |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (10) |
| Cross Reference PDB | 1LCY; 2PZD; 5FHT; 5M3N; 5M3O; 5TNY; 5TNZ; 5TO0; 5TO1; 5WYN; |
| Mapped Pubmed ID | 11602612; 11604410; 11801603; 12815069; 12835328; 14605674; 14645012; 15036614; 15201285; 15236609; 15294909; 15328349; 16713569; 16968707; 17130845; 17266347; 17297443; 17311912; 17353931; 17656586; 17684015; 17718385; 17906618; 17922292; 18060880; 18241672; 18259191; 18362145; 18662332; 18769594; 18790661; 18800009; 18979398; 19076428; 19224617; 19355862; 19424634; 19570340; 19656851; 19680265; 19763263; 20012177; 20036034; 20122399; 20125124; 20202124; 20469960; 20562859; 20651226; 20711500; 20877624; 20938363; 21163861; 21198825; 21338583; 21486948; 21701498; 21701785; 21732781; 21883444; 21908615; 22001920; 22246992; 22265821; 22391154; 22490291; 22503729; 22923201; 22976834; 23123883; 23159167; 23242108; 23306356; 23457469; 23542127; 23581228; 23608143; 23682386; 24090154; 24337630; 24606398; 24698088; 24798695; 25086674; 25288153; 25484138; 25628093; 25791756; 26340347; 26702898; 26965693; 27571206; 27825081; 28602551; 29022916; 29168038; 29266444; 30068699; 30114719; 30361890; 31547195; 31609081; 31683713; 32353215; 32486357; 33239198; |
| Motif | MOTIF 134..137; /note=IAP-binding motif |
| Gene Encoded By | |
| Mass | 48,841 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda | 3.4.21.108; |