| IED ID | IndEnz0002011734 |
| Enzyme Type ID | protease011734 |
| 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 | Mus musculus (Mouse) |
| 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 Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Mus Mus Mus musculus (Mouse) |
| Enzyme Sequence | MTAELQQDDSAGAADGHGSSCQMLLNQLREITGIQDPSFLHEALKASNGDITQAVSLLTDQRVKEPSHDTTAAEPSEVEESATSKDLLAKVIDLTHDNKDDLQAAIALSLLESPNIQADNRDLNRAHEANSAETKRSKRKRCEVWGENHNPNNWRRVDGWPVGLKNVGNTCWFSAVIQSLFQLPEFRRLVLSYNLPQNILENCRSHTEKRNIMFMQELQYLFALLLGSNRKFVDPSAALDLLKGAFRSSEEQQQDVSEFTHKLLDWLEDAFQLAVNVNSHLRNKSENPMVQLFYGTFLTEGVREGKPFCNNETFGQYPLQVNGYHNLDECLEGAMVEGDIALLPSDRSVKYGQERWFTKLPPVLTFELSRFEFNQSLGQPEKIHNKLEFPQIIYMDRYMYKSKELIRSKRESVRKLKEEIQVLQQKLERYVKYGSGPSRFPLPDMLKYVIEFASTKPASESCLSGSAEHVTLPLPSVHCPISDLTPKESSSPESCSQNAGSTFSSPEDALPSSEGMNGPFTSPHSSLETPAPPAPRTVTDEEMNFVKTCLQRWRSEIEQDIQDLKNCISSSTKAIEQMYCDPLLRQVPYRLHAVLVHEGQASAGHYWAYIYNQPRQTWLKYNDISVTESSWEELERDSYGGLRNVSAYCLMYINDNLPHFSAEASSNESDETAGEVEALSVELRQYIQEDNWRFQQEVEEWEEEQSCKIPQMESSPNSSSQDFSTSQESPAVSSHEVRCLSSEHAVIAKEQTAQAIANTAHAYEKSGVEAALSEAFHEEYSRLYQLAKETPTSHSDPRLQHVLVYFFQNEAPKRVVERTLLEQFADRNLSYDERSISIMKVAQAKLMEIGPDDMNMEEYKRWHEDYSLFRKVSVYLLTGLELFQKGKYQEALSYLVYAYQSNAGLLVKGPRRGVKESVIALYRRKCLLELNAKAASLFETNDDHSVTEGINVMNELIIPCIHLIINNDISKDDLDAIEVMRNHWCSYLGKDIAENLQLCLGEFLPRLLDPSAEIIVLKEPPTIRPNSPYDLCNRFAAVMESIQGVSTVTVK |
| Enzyme Length | 1051 |
| Uniprot Accession Number | Q5I043 |
| Absorption | |
| Active Site | ACT_SITE 171; /note="Nucleophile"; /evidence="ECO:0000255|PROSITE-ProRule:PRU10092, ECO:0000255|PROSITE-ProRule:PRU10093"; ACT_SITE 605; /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 FBXW7 (FBW7alpha) in the nucleoplasm and counteracting ubiquitination of MYC by the SCF(FBXW7) complex. 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. {ECO:0000250|UniProtKB:Q96RU2}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (2); Alternative sequence (1); Chain (1); Compositional bias (3); Cross-link (1); Domain (2); Modified residue (5); Region (4); Sequence conflict (2) |
| Keywords | Alternative splicing;DNA damage;DNA repair;Hydrolase;Isopeptide bond;Nucleus;Phosphoprotein;Protease;Reference proteome;Thiol protease;Ubl conjugation;Ubl conjugation pathway |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Nucleus, nucleoplasm {ECO:0000250}. |
| Modified Residue | MOD_RES 67; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q96RU2; MOD_RES 376; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q96RU2; MOD_RES 555; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:21183079; MOD_RES 720; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q96RU2; MOD_RES 1022; /note=Phosphothreonine; /evidence=ECO:0000250|UniProtKB:Q96RU2 |
| Post Translational Modification | PTM: Degraded upon nickel ion level or hypoxia exposure. {ECO:0000250}.; PTM: Phosphorylated upon DNA damage at Ser-67 and Ser-720, by ATM or ATR. Phosphorylated by PRKD1. {ECO:0000250|UniProtKB:Q96RU2}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 10725249; 12466851; 12904583; 14610273; 17967808; 18799693; 21267068; 21731673; 24687851; 24960159; 25313962; 25437563; 25716680; 28077597; 29545478; 33226141; 33410253; 34050161; |
| Motif | |
| Gene Encoded By | |
| Mass | 119,318 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |