| IED ID | IndEnz0002011419 |
| Enzyme Type ID | protease011419 |
| Protein Name |
Ubiquitin carboxyl-terminal hydrolase 5 EC 3.4.19.12 Deubiquitinating enzyme 5 Isopeptidase T Ubiquitin thioesterase 5 Ubiquitin-specific-processing protease 5 |
| Gene Name | USP5 ISOT |
| 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 | MAELSEEALLSVLPTIRVPKAGDRVHKDECAFSFDTPESEGGLYICMNTFLGFGKQYVERHFNKTGQRVYLHLRRTRRPKEEDPATGTGDPPRKKPTRLAIGVEGGFDLSEEKFELDEDVKIVILPDYLEIARDGLGGLPDIVRDRVTSAVEALLSADSASRKQEVQAWDGEVRQVSKHAFSLKQLDNPARIPPCGWKCSKCDMRENLWLNLTDGSILCGRRYFDGSGGNNHAVEHYRETGYPLAVKLGTITPDGADVYSYDEDDMVLDPSLAEHLSHFGIDMLKMQKTDKTMTELEIDMNQRIGEWELIQESGVPLKPLFGPGYTGIRNLGNSCYLNSVVQVLFSIPDFQRKYVDKLEKIFQNAPTDPTQDFSTQVAKLGHGLLSGEYSKPVPESGDGERVPEQKEVQDGIAPRMFKALIGKGHPEFSTNRQQDAQEFFLHLINMVERNCRSSENPNEVFRFLVEEKIKCLATEKVKYTQRVDYIMQLPVPMDAALNKEELLEYEEKKRQAEEEKMALPELVRAQVPFSSCLEAYGAPEQVDDFWSTALQAKSVAVKTTRFASFPDYLVIQIKKFTFGLDWVPKKLDVSIEMPEELDISQLRGTGLQPGEEELPDIAPPLVTPDEPKGSLGFYGNEDEDSFCSPHFSSPTSPMLDESVIIQLVEMGFPMDACRKAVYYTGNSGAEAAMNWVMSHMDDPDFANPLILPGSSGPGSTSAAADPPPEDCVTTIVSMGFSRDQALKALRATNNSLERAVDWIFSHIDDLDAEAAMDISEGRSAADSISESVPVGPKVRDGPGKYQLFAFISHMGTSTMCGHYVCHIKKEGRWVIYNDQKVCASEKPPKDLGYIYFYQRVAS |
| Enzyme Length | 858 |
| Uniprot Accession Number | P45974 |
| Absorption | |
| Active Site | ACT_SITE 335; /note="Nucleophile"; ACT_SITE 818; /note="Proton acceptor"; /evidence="ECO:0000255|PROSITE-ProRule:PRU10092, ECO:0000255|PROSITE-ProRule:PRU10093" |
| Activity Regulation | |
| Binding Site | BINDING 209; /note=Substrate; BINDING 259; /note=Substrate; BINDING 261; /note=Substrate; via carbonyl oxygen; BINDING 264; /note=Substrate |
| 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; |
| DNA Binding | |
| EC Number | 3.4.19.12 |
| Enzyme Function | FUNCTION: Cleaves linear and branched multiubiquitin polymers with a marked preference for branched polymers. Involved in unanchored 'Lys-48'-linked polyubiquitin disassembly. Binds linear and 'Lys-63'-linked polyubiquitin with a lower affinity. Knock-down of USP5 causes the accumulation of p53/TP53 and an increase in p53/TP53 transcriptional activity because the unanchored polyubiquitin that accumulates is able to compete with ubiquitinated p53/TP53 but not with MDM2 for proteasomal recognition. {ECO:0000269|PubMed:19098288}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (2); Alternative sequence (1); Beta strand (25); Binding site (4); Chain (1); Compositional bias (1); Disulfide bond (1); Domain (3); Helix (26); Initiator methionine (1); Metal binding (4); Modified residue (7); Mutagenesis (11); Region (2); Sequence conflict (4); Turn (15); Zinc finger (1) |
| Keywords | 3D-structure;Acetylation;Alternative splicing;Direct protein sequencing;Disulfide bond;Hydrolase;Metal-binding;Phosphoprotein;Protease;Reference proteome;Repeat;Thiol protease;Ubl conjugation pathway;Zinc;Zinc-finger |
| Interact With | Q15038; P54727; O75528; Q8WW34; Q9NWF9; Q8N0X7; Q8WW34-2; O14773; Q9BZR9; P0CG47 |
| Induction | |
| Subcellular Location | |
| Modified Residue | MOD_RES 2; /note="N-acetylalanine"; /evidence="ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378"; MOD_RES 156; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:24275569"; MOD_RES 292; /note="Phosphothreonine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 623; /note="Phosphothreonine"; /evidence="ECO:0000250|UniProtKB:P56399"; MOD_RES 779; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 783; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"; MOD_RES 785; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163" |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | NMR spectroscopy (2); X-ray crystallography (10) |
| Cross Reference PDB | 2DAG; 2DAK; 2G43; 2G45; 3IHP; 6DXH; 6DXT; 6NFT; 6P9G; 7MS5; 7MS6; 7MS7; |
| Mapped Pubmed ID | 11771738; 12435595; 15231748; 16189514; 16712842; 17353931; 19373254; 19615732; 21976412; 22283393; 23375434; 23720098; 24454762; 25207809; 25416956; 25641936; 25970461; 26235645; 26638075; 27133717; 28807830; 28933784; 29567855; 30809294; 31300459; 31371702; 31455361; 31663737; 31727867; 32683298; 33977498; 34648286; 7578059; |
| Motif | |
| Gene Encoded By | |
| Mass | 95,786 |
| Kinetics | |
| Metal Binding | METAL 199; /note=Zinc; /evidence=ECO:0000255|PROSITE-ProRule:PRU00502; METAL 202; /note=Zinc; /evidence=ECO:0000255|PROSITE-ProRule:PRU00502; METAL 219; /note=Zinc; /evidence=ECO:0000255|PROSITE-ProRule:PRU00502; METAL 232; /note=Zinc; /evidence=ECO:0000255|PROSITE-ProRule:PRU00502 |
| Rhea ID | |
| Cross Reference Brenda | 3.4.19.12; |