| IED ID | IndEnz0002013006 |
| Enzyme Type ID | protease013006 |
| Protein Name |
Ubiquitin carboxyl-terminal hydrolase 28 EC 3.4.19.12 Deubiquitinating enzyme 28 Ubiquitin thioesterase 28 Ubiquitin-specific-processing protease 28 |
| Gene Name | USP28 KIAA1515 |
| 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 | MTAELQQDDAAGAADGHGSSCQMLLNQLREITGIQDPSFLHEALKASNGDITQAVSLLTDERVKEPSQDTVATEPSEVEGSAANKEVLAKVIDLTHDNKDDLQAAIALSLLESPKIQADGRDLNRMHEATSAETKRSKRKRCEVWGENPNPNDWRRVDGWPVGLKNVGNTCWFSAVIQSLFQLPEFRRLVLSYSLPQNVLENCRSHTEKRNIMFMQELQYLFALMMGSNRKFVDPSAALDLLKGAFRSSEEQQQDVSEFTHKLLDWLEDAFQLAVNVNSPRNKSENPMVQLFYGTFLTEGVREGKPFCNNETFGQYPLQVNGYRNLDECLEGAMVEGDVELLPSDHSVKYGQERWFTKLPPVLTFELSRFEFNQSLGQPEKIHNKLEFPQIIYMDRYMYRSKELIRNKRECIRKLKEEIKILQQKLERYVKYGSGPARFPLPDMLKYVIEFASTKPASESCPPESDTHMTLPLSSVHCSVSDQTSKESTSTESSSQDVESTFSSPEDSLPKSKPLTSSRSSMEMPSQPAPRTVTDEEINFVKTCLQRWRSEIEQDIQDLKTCIASTTQTIEQMYCDPLLRQVPYRLHAVLVHEGQANAGHYWAYIYNQPRQSWLKYNDISVTESSWEEVERDSYGGLRNVSAYCLMYINDKLPYFNAEAAPTESDQMSEVEALSVELKHYIQEDNWRFEQEVEEWEEEQSCKIPQMESSTNSSSQDYSTSQEPSVASSHGVRCLSSEHAVIVKEQTAQAIANTARAYEKSGVEAALSEVMLSPAMQGVILAIAKARQTFDRDGSEAGLIKAFHEEYSRLYQLAKETPTSHSDPRLQHVLVYFFQNEAPKRVVERTLLEQFADKNLSYDERSISIMKVAQAKLKEIGPDDMNMEEYKKWHEDYSLFRKVSVYLLTGLELYQKGKYQEALSYLVYAYQSNAALLMKGPRRGVKESVIALYRRKCLLELNAKAASLFETNDDHSVTEGINVMNELIIPCIHLIINNDISKDDLDAIEVMRNHWCSYLGQDIAENLQLCLGEFLPRLLDPSAEIIVLKEPPTIRPNSPYDLCSRFAAVMESIQGVSTVTVK |
| Enzyme Length | 1077 |
| Uniprot Accession Number | Q96RU2 |
| Absorption | |
| Active Site | ACT_SITE 171; /note="Nucleophile"; ACT_SITE 600; /note="Proton acceptor"; /evidence="ECO:0000255|PROSITE-ProRule:PRU10092, ECO:0000255|PROSITE-ProRule:PRU10093" |
| 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: Deubiquitinase involved in DNA damage response checkpoint and MYC proto-oncogene stability. Involved in DNA damage induced apoptosis by specifically deubiquitinating proteins of the DNA damage pathway such as CLSPN. Also involved in G2 DNA damage checkpoint, by deubiquitinating CLSPN, and preventing its degradation by the anaphase promoting complex/cyclosome (APC/C). In contrast, it does not deubiquitinate PLK1. Specifically deubiquitinates MYC in the nucleoplasm, leading to prevent MYC degradation by the proteasome: acts by specifically interacting with isoform 1 of FBXW7 (FBW7alpha) in the nucleoplasm and counteracting ubiquitination of MYC by the SCF(FBW7) complex. In contrast, it does not interact with isoform 4 of FBXW7 (FBW7gamma) in the nucleolus, allowing MYC degradation and explaining the selective MYC degradation in the nucleolus. Deubiquitinates ZNF304, hence preventing ZNF304 degradation by the proteasome and leading to the activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) in a subset of colorectal cancers (CRC) cells (PubMed:24623306). {ECO:0000269|PubMed:16901786, ECO:0000269|PubMed:17558397, ECO:0000269|PubMed:17873522, ECO:0000269|PubMed:18662541, ECO:0000269|PubMed:24623306}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (2); Alternative sequence (3); Beta strand (17); Chain (1); Compositional bias (2); Cross-link (2); Domain (2); Helix (27); Modified residue (5); Mutagenesis (2); Region (3); Sequence conflict (1); Turn (5) |
| Keywords | 3D-structure;Alternative splicing;DNA damage;DNA repair;Hydrolase;Isopeptide bond;Nucleus;Phosphoprotein;Protease;Reference proteome;Thiol protease;Ubl conjugation;Ubl conjugation pathway |
| Interact With | |
| Induction | INDUCTION: Down-regulated upon hypoxia (PubMed:20046830). Up-regulated by the transcription factor c-Jun/JUN in a KRAS-dependent manner in colorectal cancer (CRC) cells (PubMed:24623306). {ECO:0000269|PubMed:20046830, ECO:0000269|PubMed:24623306}. |
| Subcellular Location | SUBCELLULAR LOCATION: Nucleus, nucleoplasm {ECO:0000269|PubMed:17558397}. |
| Modified Residue | MOD_RES 67; /note=Phosphoserine; /evidence=ECO:0000269|PubMed:16901786; MOD_RES 375; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:23186163; MOD_RES 550; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q5I043; MOD_RES 714; /note=Phosphoserine; /evidence=ECO:0000269|PubMed:16901786; MOD_RES 1048; /note=Phosphothreonine; /evidence=ECO:0007744|PubMed:24275569 |
| Post Translational Modification | PTM: Degraded upon nickel ion level or hypoxia exposure.; PTM: Phosphorylated upon DNA damage at Ser-67 and Ser-714, by ATM or ATR (PubMed:16901786). Phosphorylated by PRKD1 (PubMed:24623306). {ECO:0000269|PubMed:16901786, ECO:0000269|PubMed:24623306}. |
| Signal Peptide | |
| Structure 3D | NMR spectroscopy (2); X-ray crystallography (6) |
| Cross Reference PDB | 2LVA; 2MUU; 6H4H; 6H4I; 6HEH; 6HEI; 6HEJ; 6HEK; |
| Mapped Pubmed ID | 17478428; 19615732; 20711500; 22144179; 22653443; 23832602; 24075993; 24347490; 24687851; 24960159; 25260751; 25359778; 25437563; 25609649; 25656529; 26209720; 26268556; 26514267; 27371829; 27432896; 27432897; 27546791; 29089421; 29545478; 29880484; 30206969; 30910399; 30926242; 30926243; 31604991; 31938050; 31982308; 32053284; 32128997; 32578360; 33664871; |
| Motif | |
| Gene Encoded By | |
| Mass | 122,491 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |