| IED ID | IndEnz0002011101 |
| Enzyme Type ID | protease011101 |
| Protein Name |
Ubiquitin carboxyl-terminal hydrolase 13 EC 3.4.19.12 Deubiquitinating enzyme 13 Isopeptidase T-3 ISOT-3 Ubiquitin thioesterase 13 Ubiquitin-specific-processing protease 13 |
| Gene Name | USP13 ISOT3 |
| 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 | MQRRGALFGMPGGSGGRKMAAGDIGELLVPHMPTIRVPRSGDRVYKNECAFSYDSPNSEGGLYVCMNTFLAFGREHVERHFRKTGQSVYMHLKRHVREKVRGASGGALPKRRNSKIFLDLDTDDDLNSDDYEYEDEAKLVIFPDHYEIALPNIEELPALVTIACDAVLSSKSPYRKQDPDTWENELPVSKYANNLTQLDNGVRIPPSGWKCARCDLRENLWLNLTDGSVLCGKWFFDSSGGNGHALEHYRDMGYPLAVKLGTITPDGADVYSFQEEEPVLDPHLAKHLAHFGIDMLHMHGTENGLQDNDIKLRVSEWEVIQESGTKLKPMYGPGYTGLKNLGNSCYLSSVMQAIFSIPEFQRAYVGNLPRIFDYSPLDPTQDFNTQMTKLGHGLLSGQYSKPPVKSELIEQVMKEEHKPQQNGISPRMFKAFVSKSHPEFSSNRQQDAQEFFLHLVNLVERNRIGSENPSDVFRFLVEERIQCCQTRKVRYTERVDYLMQLPVAMEAATNKDELIAYELTRREAEANRRPLPELVRAKIPFSACLQAFSEPENVDDFWSSALQAKSAGVKTSRFASFPEYLVVQIKKFTFGLDWVPKKFDVSIDMPDLLDINHLRARGLQPGEEELPDISPPIVIPDDSKDRLMNQLIDPSDIDESSVMQLAEMGFPLEACRKAVYFTGNMGAEVAFNWIIVHMEEPDFAEPLTMPGYGGAASAGASVFGASGLDNQPPEEIVAIITSMGFQRNQAIQALRATNNNLERALDWIFSHPEFEEDSDFVIEMENNANANIISEAKPEGPRVKDGSGTYELFAFISHMGTSTMSGHYICHIKKEGRWVIYNDHKVCASERPPKDLGYMYFYRRIPS |
| Enzyme Length | 863 |
| Uniprot Accession Number | Q92995 |
| Absorption | |
| Active Site | ACT_SITE 345; /note="Nucleophile"; /evidence="ECO:0000305"; ACT_SITE 823; /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 USP13 and inhibits deubiquitinase activity. Regulated by PIK3C3/VPS34-containing complexes. The weak deubiquitinase activity in vitro suggests the existence of some mechanism that activates the enzyme. {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; |
| DNA Binding | |
| EC Number | 3.4.19.12 |
| Enzyme Function | FUNCTION: Deubiquitinase that mediates deubiquitination of target proteins such as BECN1, MITF, SKP2 and USP10 and is involved in various processes such as autophagy and endoplasmic reticulum-associated degradation (ERAD). 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. Also deubiquitinates USP10, an essential regulator of p53/TP53 stability. In turn, PIK3C3/VPS34-containing complexes regulate USP13 stability, suggesting the existence of a regulatory system by which PIK3C3/VPS34-containing complexes regulate p53/TP53 protein levels via USP10 and USP13. Recruited by nuclear UFD1 and mediates deubiquitination of SKP2, thereby regulating endoplasmic reticulum-associated degradation (ERAD). Also regulates ERAD through the deubiquitination of UBL4A a component of the BAG6/BAT3 complex. Mediates stabilization of SIAH2 independently of deubiquitinase activity: binds ubiquitinated SIAH2 and acts by impairing SIAH2 autoubiquitination. Has a weak deubiquitinase activity in vitro and preferentially cleaves 'Lys-63'-linked polyubiquitin chains. In contrast to USP5, it is not able to mediate unanchored polyubiquitin disassembly. Able to cleave ISG15 in vitro; however, additional experiments are required to confirm such data. {ECO:0000269|PubMed:17653289, ECO:0000269|PubMed:21571647, ECO:0000269|PubMed:21659512, ECO:0000269|PubMed:21811243, ECO:0000269|PubMed:21962518, ECO:0000269|PubMed:22216260, ECO:0000269|PubMed:24424410}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (2); Alternative sequence (1); Beta strand (8); Chain (1); Cross-link (2); Domain (3); Helix (10); Metal binding (4); Modified residue (2); Mutagenesis (8); Sequence conflict (5); Turn (3); Zinc finger (1) |
| Keywords | 3D-structure;Alternative splicing;Autophagy;Hydrolase;Isopeptide bond;Metal-binding;Phosphoprotein;Protease;Reference proteome;Repeat;Thiol protease;Ubl conjugation;Ubl conjugation pathway;Zinc;Zinc-finger |
| Interact With | P54252; Q15038; Q13148; Q9BYV6; Q969Q1; P0DTD1 |
| Induction | |
| Subcellular Location | |
| Modified Residue | MOD_RES 114; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:19690332"; MOD_RES 122; /note="Phosphothreonine"; /evidence="ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692" |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | NMR spectroscopy (2) |
| Cross Reference PDB | 2L80; 2LBC; |
| Mapped Pubmed ID | 15231748; 16169070; 19615732; 20379614; 23940278; 24270891; 26280536; 26453058; 26496610; 27869170; 27892457; 27923907; 28498477; 28569838; 29335437; 29396516; 29567855; 30329047; 30986623; 31200745; 31594232; 32101753; 32129945; 32255563; 32453420; 32772043; 33334891; 33592542; 33627786; 33707416; 34001947; 34688658; |
| Motif | |
| Gene Encoded By | |
| Mass | 97,327 |
| Kinetics | |
| Metal Binding | METAL 211; /note=Zinc; /evidence=ECO:0000255|PROSITE-ProRule:PRU00502; METAL 214; /note=Zinc; /evidence=ECO:0000255|PROSITE-ProRule:PRU00502; METAL 231; /note=Zinc; /evidence=ECO:0000255|PROSITE-ProRule:PRU00502; METAL 244; /note=Zinc; /evidence=ECO:0000255|PROSITE-ProRule:PRU00502 |
| Rhea ID | |
| Cross Reference Brenda |