| IED ID | IndEnz0002010570 |
| Enzyme Type ID | protease010570 |
| Protein Name |
Ubiquitin carboxyl-terminal hydrolase 25 EC 3.4.19.12 Deubiquitinating enzyme 25 USP on chromosome 21 Ubiquitin thioesterase 25 Ubiquitin-specific-processing protease 25 |
| Gene Name | USP25 USP21 |
| 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 | MTVEQNVLQQSAAQKHQQTFLNQLREITGINDTQILQQALKDSNGNLELAVAFLTAKNAKTPQQEETTYYQTALPGNDRYISVGSQADTNVIDLTGDDKDDLQRAIALSLAESNRAFRETGITDEEQAISRVLEASIAENKACLKRTPTEVWRDSRNPYDRKRQDKAPVGLKNVGNTCWFSAVIQSLFNLLEFRRLVLNYKPPSNAQDLPRNQKEHRNLPFMRELRYLFALLVGTKRKYVDPSRAVEILKDAFKSNDSQQQDVSEFTHKLLDWLEDAFQMKAEEETDEEKPKNPMVELFYGRFLAVGVLEGKKFENTEMFGQYPLQVNGFKDLHECLEAAMIEGEIESLHSENSGKSGQEHWFTELPPVLTFELSRFEFNQALGRPEKIHNKLEFPQVLYLDRYMHRNREITRIKREEIKRLKDYLTVLQQRLERYLSYGSGPKRFPLVDVLQYALEFASSKPVCTSPVDDIDASSPPSGSIPSQTLPSTTEQQGALSSELPSTSPSSVAAISSRSVIHKPFTQSRIPPDLPMHPAPRHITEEELSVLESCLHRWRTEIENDTRDLQESISRIHRTIELMYSDKSMIQVPYRLHAVLVHEGQANAGHYWAYIFDHRESRWMKYNDIAVTKSSWEELVRDSFGGYRNASAYCLMYINDKAQFLIQEEFNKETGQPLVGIETLPPDLRDFVEEDNQRFEKELEEWDAQLAQKALQEKLLASQKLRESETSVTTAQAAGDPEYLEQPSRSDFSKHLKEETIQIITKASHEHEDKSPETVLQSAIKLEYARLVKLAQEDTPPETDYRLHHVVVYFIQNQAPKKIIEKTLLEQFGDRNLSFDERCHNIMKVAQAKLEMIKPEEVNLEEYEEWHQDYRKFRETTMYLIIGLENFQRESYIDSLLFLICAYQNNKELLSKGLYRGHDEELISHYRRECLLKLNEQAAELFESGEDREVNNGLIIMNEFIVPFLPLLLVDEMEEKDILAVEDMRNRWCSYLGQEMEPHLQEKLTDFLPKLLDCSMEIKSFHEPPKLPSYSTHELCERFARIMLSLSRTPADGR |
| Enzyme Length | 1055 |
| Uniprot Accession Number | Q9UHP3 |
| Absorption | |
| Active Site | ACT_SITE 178; /evidence=ECO:0000269|PubMed:19440361; ACT_SITE 599; /evidence=ECO:0000250; ACT_SITE 607; /evidence=ECO:0000250 |
| Activity Regulation | |
| Binding Site | |
| 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: Deubiquitinating enzyme that hydrolyzes ubiquitin moieties conjugated to substrates and thus, functions to process newly synthesized Ubiquitin, to recycle ubiquitin molecules or to edit polyubiquitin chains and prevents proteasomal degradation of substrates. Hydrolyzes both 'Lys-48'- and 'Lys-63'-linked tetraubiquitin chains.; FUNCTION: The muscle-specific isoform (USP25m) may have a role in the regulation of muscular differentiation and function. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (3); Alternative sequence (2); Beta strand (22); Chain (1); Coiled coil (2); Compositional bias (1); Cross-link (2); Domain (4); Helix (39); Modified residue (2); Motif (1); Mutagenesis (8); Region (3); Sequence conflict (2); Turn (9) |
| Keywords | 3D-structure;Alternative splicing;Coiled coil;Cytoplasm;Hydrolase;Isopeptide bond;Nucleus;Phosphoprotein;Protease;Reference proteome;Repeat;Thiol protease;Ubl conjugation;Ubl conjugation pathway |
| Interact With | O15481; Q9UJV3-2; P17612; Q3MIT2; P54725; P54727; P61956; P43405; P37173; Q9BTV4; Q9BUY5; P0DTD1 |
| Induction | INDUCTION: The muscle-specific isoform (USP25m) is up-regulated during myocyte differentiation. Levels increase up to 100-fold towards completion of differentiation. {ECO:0000269|PubMed:16501887}. |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16501887, ECO:0000269|PubMed:19440361}.; SUBCELLULAR LOCATION: [Isoform USP25m]: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}. Note=Some transient punctuate nuclear location in myotubes during myocyte development. {ECO:0000250}. |
| Modified Residue | MOD_RES 85; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:23186163; MOD_RES 740; /note=Phosphotyrosine; /evidence=ECO:0000269|PubMed:19909739 |
| Post Translational Modification | PTM: Acetylated. {ECO:0000269|PubMed:19440361}.; PTM: Sumoylation impairs binding to and hydrolysis of ubiquitin chains. Sumoylated preferentially with SUMO2 or SUMO3. Desumoylated by SENP1. Regulated by ubiquitination on the same residue. {ECO:0000269|PubMed:19440361}.; PTM: Preferentially monoubiquitinated but can also be polyubiquitinated. Autodeubiquitinated. Ubiquitination activates the enzymatic activity either by preventing sumoylation or by allowing novel interactions. {ECO:0000269|PubMed:19440361}.; PTM: Phosphorylation in the C-terminal by SYK regulates USP25 cellular levels. {ECO:0000269|PubMed:19440361, ECO:0000269|PubMed:19909739}. |
| Signal Peptide | |
| Structure 3D | NMR spectroscopy (1); X-ray crystallography (6) |
| Cross Reference PDB | 2MUX; 5GP7; 5O71; 6H4J; 6H4K; 6HEL; 6HEM; |
| Mapped Pubmed ID | 15231748; 18523997; 19165232; 19615732; 19760754; 20379614; 21480003; 21516116; 22153077; 22590560; 23042150; 24260525; 24997798; 25416956; 25755282; 25929833; 27693347; 28538147; 28619731; 29518389; 30231795; 30478318; 30745998; 30926242; 30926243; 30953360; 32578360; 33202887; |
| Motif | MOTIF 89..95; /note=Required for SUMO paralog-specific binding |
| Gene Encoded By | |
| Mass | 122,218 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |