| IED ID | IndEnz0002011794 |
| Enzyme Type ID | protease011794 |
| Protein Name |
Ubiquitin carboxyl-terminal hydrolase 10 EC 3.4.19.12 Deubiquitinating enzyme 10 Ubiquitin thioesterase 10 Ubiquitin-specific-processing protease 10 |
| Gene Name | USP10 KIAA0190 |
| 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 | MALHSPQYIFGDFSPDEFNQFFVTPRSSVELPPYSGTVLCGTQAVDKLPDGQEYQRIEFGVDEVIEPSDTLPRTPSYSISSTLNPQAPEFILGCTASKITPDGITKEASYGSIDCQYPGSALALDGSSNVEAEVLENDGVSGGLGQRERKKKKKRPPGYYSYLKDGGDDSISTEALVNGHANSAVPNSVSAEDAEFMGDMPPSVTPRTCNSPQNSTDSVSDIVPDSPFPGALGSDTRTAGQPEGGPGADFGQSCFPAEAGRDTLSRTAGAQPCVGTDTTENLGVANGQILESSGEGTATNGVELHTTESIDLDPTKPESASPPADGTGSASGTLPVSQPKSWASLFHDSKPSSSSPVAYVETKYSPPAISPLVSEKQVEVKEGLVPVSEDPVAIKIAELLENVTLIHKPVSLQPRGLINKGNWCYINATLQALVACPPMYHLMKFIPLYSKVQRPCTSTPMIDSFVRLMNEFTNMPVPPKPRQALGDKIVRDIRPGAAFEPTYIYRLLTVNKSSLSEKGRQEDAEEYLGFILNGLHEEMLNLKKLLSPSNEKLTISNGPKNHSVNEEEQEEQGEGSEDEWEQVGPRNKTSVTRQADFVQTPITGIFGGHIRSVVYQQSSKESATLQPFFTLQLDIQSDKIRTVQDALESLVARESVQGYTTKTKQEVEISRRVTLEKLPPVLVLHLKRFVYEKTGGCQKLIKNIEYPVDLEISKELLSPGVKNKNFKCHRTYRLFAVVYHHGNSATGGHYTTDVFQIGLNGWLRIDDQTVKVINQYQVVKPTAERTAYLLYYRRVDLL |
| Enzyme Length | 798 |
| Uniprot Accession Number | Q14694 |
| Absorption | |
| Active Site | ACT_SITE 424; /note="Nucleophile"; ACT_SITE 749; /note="Proton acceptor"; /evidence="ECO:0000255|PROSITE-ProRule:PRU10092, ECO:0000255|PROSITE-ProRule:PRU10093" |
| Activity Regulation | ACTIVITY REGULATION: Specifically inhibited by spautin-1 (specific and potent autophagy inhibitor-1), a derivative of MBCQ that binds to USP10 and inhibits deubiquitinase activity. Regulated by PIK3C3/VPS34-containing complexes. {ECO:0000269|PubMed:21962518}. |
| 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; Evidence={ECO:0000269|PubMed:20096447}; |
| DNA Binding | |
| EC Number | 3.4.19.12 |
| Enzyme Function | FUNCTION: Hydrolase that can remove conjugated ubiquitin from target proteins such as p53/TP53, BECN1, SNX3 and CFTR. Acts as an essential regulator of p53/TP53 stability: in unstressed cells, specifically deubiquitinates p53/TP53 in the cytoplasm, leading to counteract MDM2 action and stabilize p53/TP53. Following DNA damage, translocates to the nucleus and deubiquitinates p53/TP53, leading to regulate the p53/TP53-dependent DNA damage response. Component of a regulatory loop that controls autophagy and p53/TP53 levels: mediates deubiquitination of BECN1, a key regulator of autophagy, leading to stabilize the PIK3C3/VPS34-containing complexes. In turn, PIK3C3/VPS34-containing complexes regulate USP10 stability, suggesting the existence of a regulatory system by which PIK3C3/VPS34-containing complexes regulate p53/TP53 protein levels via USP10 and USP13. Does not deubiquitinate MDM2. Deubiquitinates CFTR in early endosomes, enhancing its endocytic recycling. Involved in a TANK-dependent negative feedback response to attenuate NF-kappaB activation via deubiquitinating IKBKG or TRAF6 in response to interleukin-1-beta (IL1B) stimulation or upon DNA damage (PubMed:25861989). Deubiquitinates TBX21 leading to its stabilization (PubMed:24845384). {ECO:0000269|PubMed:11439350, ECO:0000269|PubMed:18632802, ECO:0000269|PubMed:19398555, ECO:0000269|PubMed:20096447, ECO:0000269|PubMed:21962518, ECO:0000269|PubMed:24845384, ECO:0000269|PubMed:25861989}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (2); Alternative sequence (2); Chain (1); Compositional bias (2); Domain (1); Erroneous initiation (1); Initiator methionine (1); Modified residue (13); Mutagenesis (5); Natural variant (3); Region (5); Sequence conflict (2) |
| Keywords | Acetylation;Alternative splicing;Autophagy;Cytoplasm;DNA damage;DNA repair;Endosome;Hydrolase;Nucleus;Phosphoprotein;Protease;Reference proteome;Thiol protease;Ubl conjugation;Ubl conjugation pathway |
| Interact With | Q13283; Q9UN86; Q9UN86-2; P14136; Q8WXH2; P63244; Q5D1E8 |
| Induction | INDUCTION: Following DNA damage. Down-regulated in renal cell carcinomas. {ECO:0000269|PubMed:20096447}. |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:20096447}. Nucleus {ECO:0000269|PubMed:20096447, ECO:0000269|PubMed:24845384}. Early endosome {ECO:0000269|PubMed:19398555}. Note=Cytoplasmic in normal conditions (PubMed:20096447). After DNA damage, translocates to the nucleus following phosphorylation by ATM (PubMed:20096447). {ECO:0000269|PubMed:20096447}. |
| Modified Residue | MOD_RES 2; /note="N-acetylalanine"; /evidence="ECO:0007744|PubMed:20068231"; MOD_RES 24; /note="Phosphothreonine"; /evidence="ECO:0007744|PubMed:20068231"; MOD_RES 42; /note="Phosphothreonine; by ATM"; /evidence="ECO:0000269|PubMed:20096447"; MOD_RES 100; /note="Phosphothreonine"; /evidence="ECO:0007744|PubMed:18669648"; MOD_RES 211; /note="Phosphoserine"; /evidence="ECO:0000250|UniProtKB:P52479"; MOD_RES 226; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648"; MOD_RES 321; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:24275569"; MOD_RES 337; /note="Phosphoserine; by ATM"; /evidence="ECO:0000269|PubMed:20096447"; MOD_RES 365; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:16964243, ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:24275569"; MOD_RES 370; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:16964243, ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"; MOD_RES 547; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 563; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:19690332"; MOD_RES 576; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:17081983, ECO:0007744|PubMed:17487921, ECO:0007744|PubMed:17693683, ECO:0007744|PubMed:18318008, ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" |
| Post Translational Modification | PTM: Phosphorylated by ATM following DNA damage, leading to stablization and translocation it to the nucleus. {ECO:0000269|PubMed:20096447}.; PTM: Ubiquitinated. Deubiquitinated by USP13. {ECO:0000269|PubMed:21962518}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 16368182; 16773218; 18391951; 19615732; 20215869; 20379614; 20467437; 20562859; 21150319; 22085928; 22216260; 23775713; 23902751; 23986595; 24255178; 24270572; 24332849; 24768535; 25168367; 25416956; 25497084; 25578727; 25609649; 25640309; 25665578; 26496610; 26555087; 26876938; 27022092; 27558965; 28851806; 28852924; 29378906; 29698567; 29803676; 30107050; 30281322; 30375264; 30604502; 30894572; 30940456; 30975888; 31332267; 31501480; 31659108; 31721429; 31748695; 32129945; 32217697; 32382008; 33095475; 33197885; 33577797; 33838681; 34416231; 34599966; 34983926; |
| Motif | |
| Gene Encoded By | |
| Mass | 87,134 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |