| IED ID | IndEnz0002013279 |
| Enzyme Type ID | protease013279 |
| Protein Name |
Ubiquitin carboxyl-terminal hydrolase isozyme L3 UCH-L3 EC 3.4.19.12 Ubiquitin thioesterase L3 |
| Gene Name | UCHL3 |
| 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 | MEGQRWLPLEANPEVTNQFLKQLGLHPNWQFVDVYGMDPELLSMVPRPVCAVLLLFPITEKYEVFRTEEEEKIKSQGQDVTSSVYFMKQTISNACGTIGLIHAIANNKDKMHFESGSTLKKFLEESVSMSPEERARYLENYDAIRVTHETSAHEGQTEAPSIDEKVDLHFIALVHVDGHLYELDGRKPFPINHGETSDETLLEDAIEVCKKFMERDPDELRFNAIALSAA |
| Enzyme Length | 230 |
| Uniprot Accession Number | P15374 |
| Absorption | |
| Active Site | ACT_SITE 95; /note="Nucleophile"; /evidence="ECO:0000269|PubMed:19154770, ECO:0000269|PubMed:20380862, ECO:0000269|PubMed:9790970"; ACT_SITE 169; /note="Proton donor"; /evidence="ECO:0000250|UniProtKB:P09936" |
| Activity Regulation | ACTIVITY REGULATION: Inhibited by monoubiquitin and diubiquitin. {ECO:0000269|PubMed:19154770}. |
| 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:15157086, ECO:0000269|PubMed:15531586, ECO:0000269|PubMed:19047059, ECO:0000269|PubMed:20380862, ECO:0000269|PubMed:2530630, ECO:0000269|PubMed:9790970}; |
| DNA Binding | |
| EC Number | 3.4.19.12 |
| Enzyme Function | FUNCTION: Deubiquitinating enzyme (DUB) that controls levels of cellular ubiquitin through processing of ubiquitin precursors and ubiquitinated proteins. Thiol protease that recognizes and hydrolyzes a peptide bond at the C-terminal glycine of either ubiquitin or NEDD8. Has a 10-fold preference for Arg and Lys at position P3'', and exhibits a preference towards 'Lys-48'-linked ubiquitin chains. Deubiquitinates ENAC in apical compartments, thereby regulating apical membrane recycling. Indirectly increases the phosphorylation of IGFIR, AKT and FOXO1 and promotes insulin-signaling and insulin-induced adipogenesis. Required for stress-response retinal, skeletal muscle and germ cell maintenance. May be involved in working memory. Can hydrolyze UBB(+1), a mutated form of ubiquitin which is not effectively degraded by the proteasome and is associated with neurogenerative disorders. {ECO:0000269|PubMed:19154770, ECO:0000269|PubMed:21762696, ECO:0000269|PubMed:22689415, ECO:0000269|PubMed:2530630, ECO:0000269|PubMed:9790970}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (2); Beta strand (8); Chain (1); Helix (10); Modified residue (1); Mutagenesis (3); Region (3); Site (1); Turn (1) |
| Keywords | 3D-structure;Cytoplasm;Hydrolase;Phosphoprotein;Protease;Reference proteome;Thiol protease;Ubl conjugation pathway |
| Interact With | G5E9A7; Q15797; Q7Z699 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm. |
| Modified Residue | MOD_RES 130; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (4) |
| Cross Reference PDB | 1UCH; 1XD3; 6ISU; 6QML; |
| Mapped Pubmed ID | 10406793; 11566882; 12401499; 12759363; 16402389; 16713569; 19343046; 19476499; 19615732; 19636824; 21453705; 21900206; 22679485; 23416715; 25194810; 25369561; 26235645; 26752685; 27780264; 28583475; 29898404; 30559450; 30589182; 31477831; 31642235; 32180254; 32486284; 32546741; 32738097; 33238157; 33616859; 34016790; 9521656; |
| Motif | |
| Gene Encoded By | |
| Mass | 26,183 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda | 3.4.19.12; |