| IED ID | IndEnz0002009228 |
| Enzyme Type ID | protease009228 |
| Protein Name |
Ubiquitin thioesterase OTU1 EC 3.4.19.12 DUBA-8 HIV-1-induced protease 7 HIN-7 HsHIN7 OTU domain-containing protein 2 |
| Gene Name | YOD1 DUBA8 HIN7 OTUD2 PRO0907 |
| 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 | MFGPAKGRHFGVHPAPGFPGGVSQQAAGTKAGPAGAWPVGSRTDTMWRLRCKAKDGTHVLQGLSSRTRVRELQGQIAAITGIAPGGQRILVGYPPECLDLSNGDTILEDLPIQSGDMLIIEEDQTRPRSSPAFTKRGASSYVRETLPVLTRTVVPADNSCLFTSVYYVVEGGVLNPACAPEMRRLIAQIVASDPDFYSEAILGKTNQEYCDWIKRDDTWGGAIEISILSKFYQCEICVVDTQTVRIDRFGEDAGYTKRVLLIYDGIHYDPLQRNFPDPDTPPLTIFSSNDDIVLVQALELADEARRRRQFTDVNRFTLRCMVCQKGLTGQAEAREHAKETGHTNFGEV |
| Enzyme Length | 348 |
| Uniprot Accession Number | Q5VVQ6 |
| Absorption | |
| Active Site | ACT_SITE 157; /evidence=ECO:0000250|UniProtKB:Q96FW1; ACT_SITE 160; /note=Nucleophile; /evidence=ECO:0000305|PubMed:23827681; ACT_SITE 267; /evidence=ECO:0000305|PubMed:23827681; ACT_SITE 342; /evidence=ECO:0000250|UniProtKB:Q96FW1 |
| Activity Regulation | |
| Binding Site | BINDING 266; /note="Substrate; via carbonyl oxygen"; /evidence="ECO:0000269|PubMed:23827681, ECO:0007744|PDB:4BOS" |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).; EC=3.4.19.12; Evidence={ECO:0000269|PubMed:19818707, ECO:0000269|PubMed:23827681}; |
| DNA Binding | |
| EC Number | 3.4.19.12 |
| Enzyme Function | FUNCTION: Hydrolase that can remove conjugated ubiquitin from proteins and participates in endoplasmic reticulum-associated degradation (ERAD) for misfolded lumenal proteins. May act by triming the ubiquitin chain on the associated substrate to facilitate their threading through the VCP/p97 pore. Ubiquitin moieties on substrates may present a steric impediment to the threading process when the substrate is transferred to the VCP pore and threaded through VCP's axial channel. Mediates deubiquitination of 'Lys-27'-, 'Lys-29'- and 'Lys-33'-linked polyubiquitin chains. Also able to hydrolyze 'Lys-11'-linked ubiquitin chains. Cleaves both polyubiquitin and di-ubiquitin. May play a role in macroautophagy, regulating for instance the clearance of damaged lysosomes. May recruit PLAA, UBXN6 and VCP to damaged lysosome membranes decorated with K48-linked ubiquitin chains and remove these chains allowing autophagosome formation (PubMed:27753622). {ECO:0000269|PubMed:19818707, ECO:0000269|PubMed:23827681, ECO:0000269|PubMed:27753622}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (4); Alternative sequence (1); Beta strand (8); Binding site (1); Chain (1); Domain (1); Erroneous gene model prediction (1); Erroneous translation (1); Helix (8); Mutagenesis (5); Region (6); Sequence conflict (2); Turn (3); Zinc finger (1) |
| Keywords | 3D-structure;Alternative splicing;Cytoplasm;Hydrolase;Metal-binding;Protease;Reference proteome;Thiol protease;Ubl conjugation pathway;Unfolded protein response;Zinc;Zinc-finger |
| Interact With | Q15038; Q96D03; Q92567-2; Q0VD86; P25791-3; Q9UHC7; Q9NPE2; Q96CS7; Q9NRQ2; O14818; P35250-2; Q9NWF9; Q99942; Q8N0X7; Q9Y458; Q05BL1; Q9Y4K3; Q9BZR9; P0CG48; Q9BZV1; P55072; Q9NU63-3 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:27753622}. Note=Recruited to damaged lysosomes decorated with K48-linked ubiquitin chains. {ECO:0000269|PubMed:27753622}. |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (3) |
| Cross Reference PDB | 4BOQ; 4BOS; 4BOZ; |
| Mapped Pubmed ID | 19615732; 24610782; 25747718; 26463207; 28244869; 28416659; 28502290; 30145984; 30345304; 30952814; 34527075; |
| Motif | |
| Gene Encoded By | |
| Mass | 38,322 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda | 3.4.19.12; |