Detail Information for IndEnz0002011165
IED ID IndEnz0002011165
Enzyme Type ID protease011165
Protein Name Ubiquitin carboxyl-terminal hydrolase 46
EC 3.4.19.12
Deubiquitinating enzyme 46
Ubiquitin thioesterase 46
Ubiquitin-specific-processing protease 46
Gene Name USP46
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 MTVRNIASICNMGTNASALEKDIGPEQFPINEHYFGLVNFGNTCYCNSVLQALYFCRPFRENVLAYKAQQKKKENLLTCLADLFHSIATQKKKVGVIPPKKFISRLRKENDLFDNYMQQDAHEFLNYLLNTIADILQEEKKQEKQNGKLKNGNMNEPAENNKPELTWVHEIFQGTLTNETRCLNCETVSSKDEDFLDLSVDVEQNTSITHCLRDFSNTETLCSEQKYYCETCCSKQEAQKRMRVKKLPMILALHLKRFKYMEQLHRYTKLSYRVVFPLELRLFNTSSDAVNLDRMYDLVAVVVHCGSGPNRGHYITIVKSHGFWLLFDDDIVEKIDAQAIEEFYGLTSDISKNSESGYILFYQSRE
Enzyme Length 366
Uniprot Accession Number P62068
Absorption
Active Site ACT_SITE 44; /note="Nucleophile"; /evidence="ECO:0000255|PROSITE-ProRule:PRU10092, ECO:0000255|PROSITE-ProRule:PRU10093, ECO:0000269|PubMed:26388029, ECO:0000305|PubMed:22043315"; ACT_SITE 313; /note="Proton acceptor"; /evidence="ECO:0000255|PROSITE-ProRule:PRU10092, ECO:0000255|PROSITE-ProRule:PRU10093"
Activity Regulation ACTIVITY REGULATION: Activated by interaction with WDR48. {ECO:0000269|PubMed:26388029}.
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:14715245, ECO:0000269|PubMed:19075014, ECO:0000269|PubMed:26388029};
DNA Binding
EC Number 3.4.19.12
Enzyme Function FUNCTION: Deubiquitinating enzyme that plays a role in behavior, possibly by regulating GABA action. May act by mediating the deubiquitination of GAD1/GAD67 (By similarity). Has almost no deubiquitinating activity by itself and requires the interaction with WDR48 to have a high activity (PubMed:19075014, PubMed:26388029). Not involved in deubiquitination of monoubiquitinated FANCD2 (PubMed:19075014). {ECO:0000250|UniProtKB:P62069, ECO:0000269|PubMed:19075014, ECO:0000269|PubMed:26388029}.
Temperature Dependency
PH Dependency
Pathway
nucleotide Binding
Features Active site (2); Alternative sequence (4); Beta strand (22); Chain (1); Domain (1); Helix (10); Metal binding (4); Mutagenesis (1); Natural variant (1); Sequence conflict (3); Turn (3)
Keywords 3D-structure;Alternative splicing;Behavior;Hydrolase;Metal-binding;Protease;Reference proteome;Thiol protease;Ubl conjugation pathway;Zinc
Interact With P54253; Q8TBZ3
Induction
Subcellular Location
Modified Residue
Post Translational Modification
Signal Peptide
Structure 3D X-ray crystallography (5)
Cross Reference PDB 5CVM; 5CVN; 5CVO; 5L8H; 6JLQ;
Mapped Pubmed ID 19260141; 19615732; 20111060; 21663972; 22391563; 25814554; 25855980; 30415951; 31542232; 31632687; 33029497; 33576437; 34029571;
Motif
Gene Encoded By
Mass 42,442
Kinetics
Metal Binding METAL 182; /note="Zinc"; /evidence="ECO:0007744|PDB:5CVM, ECO:0007744|PDB:5CVN, ECO:0007744|PDB:5CVO, ECO:0007744|PDB:5L8H"; METAL 185; /note="Zinc"; /evidence="ECO:0007744|PDB:5CVM, ECO:0007744|PDB:5CVN, ECO:0007744|PDB:5CVO, ECO:0007744|PDB:5L8H"; METAL 229; /note="Zinc"; /evidence="ECO:0007744|PDB:5CVM, ECO:0007744|PDB:5CVN, ECO:0007744|PDB:5CVO, ECO:0007744|PDB:5L8H"; METAL 232; /note="Zinc"; /evidence="ECO:0007744|PDB:5CVM, ECO:0007744|PDB:5CVN, ECO:0007744|PDB:5CVO, ECO:0007744|PDB:5L8H"
Rhea ID
Cross Reference Brenda