| IED ID | IndEnz0002013005 |
| Enzyme Type ID | protease013005 |
| Protein Name |
Ubiquitin carboxyl-terminal hydrolase 36 EC 3.4.19.12 Deubiquitinating enzyme 36 Ubiquitin thioesterase 36 Ubiquitin-specific-processing protease 36 |
| Gene Name | USP36 KIAA1453 |
| 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 | MPIVDKLKEALKPGRKDSADDGELGKLLASSAKKVLLQKIEFEPASKSFSYQLEALKSKYVLLNPKTEGASRHKSGDDPPARRQGSEHTYESCGDGVPAPQKVLFPTERLSLRWERVFRVGAGLHNLGNTCFLNATIQCLTYTPPLANYLLSKEHARSCHQGSFCMLCVMQNHIVQAFANSGNAIKPVSFIRDLKKIARHFRFGNQEDAHEFLRYTIDAMQKACLNGCAKLDRQTQATTLVHQIFGGYLRSRVKCSVCKSVSDTYDPYLDVALEIRQAANIVRALELFVKADVLSGENAYMCAKCKKKVPASKRFTIHRTSNVLTLSLKRFANFSGGKITKDVGYPEFLNIRPYMSQNNGDPVMYGLYAVLVHSGYSCHAGHYYCYVKASNGQWYQMNDSLVHSSNVKVVLNQQAYVLFYLRIPGSKKSPEGLISRTGSSSLPGRPSVIPDHSKKNIGNGIISSPLTGKRQDSGTMKKPHTTEEIGVPISRNGSTLGLKSQNGCIPPKLPSGSPSPKLSQTPTHMPTILDDPGKKVKKPAPPQHFSPRTAQGLPGTSNSNSSRSGSQRQGSWDSRDVVLSTSPKLLATATANGHGLKGNDESAGLDRRGSSSSSPEHSASSDSTKAPQTPRSGAAHLCDSQETNCSTAGHSKTPPSGADSKTVKLKSPVLSNTTTEPASTMSPPPAKKLALSAKKASTLWRATGNDLRPPPPSPSSDLTHPMKTSHPVVASTWPVHRARAVSPAPQSSSRLQPPFSPHPTLLSSTPKPPGTSEPRSCSSISTALPQVNEDLVSLPHQLPEASEPPQSPSEKRKKTFVGEPQRLGSETRLPQHIREATAAPHGKRKRKKKKRPEDTAASALQEGQTQRQPGSPMYRREGQAQLPAVRRQEDGTQPQVNGQQVGCVTDGHHASSRKRRRKGAEGLGEEGGLHQDPLRHSCSPMGDGDPEAMEESPRKKKKKKRKQETQRAVEEDGHLKCPRSAKPQDAVVPESSSCAPSANGWCPGDRMGLSQAPPVSWNGERESDVVQELLKYSSDKAYGRKVLTWDGKMSAVSQDAIEDSRQARTETVVDDWDEEFDRGKEKKIKKFKREKRRNFNAFQKLQTRRNFWSVTHPAKAASLSYRR |
| Enzyme Length | 1123 |
| Uniprot Accession Number | Q9P275 |
| Absorption | |
| Active Site | ACT_SITE 131; /note="Nucleophile"; /evidence="ECO:0000255|PROSITE-ProRule:PRU10092, ECO:0000255|PROSITE-ProRule:PRU10093, ECO:0000269|PubMed:19208757, ECO:0000269|PubMed:21268071, ECO:0000269|PubMed:25775507, ECO:0000269|PubMed:27445338, ECO:0000269|PubMed:29274341"; ACT_SITE 382; /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; Evidence={ECO:0000269|PubMed:14715245}; |
| DNA Binding | |
| EC Number | 3.4.19.12 |
| Enzyme Function | FUNCTION: Deubiquitinase essential for the regulation of nucleolar structure and function. Required for cell and organism viability. Plays an important role in ribosomal RNA processing and protein synthesis, which is mediated, at least in part, through deubiquitination of DHX33, NPM1 and FBL, regulating their protein stability (PubMed:29273634, PubMed:19208757, PubMed:22902402). Functions as a transcriptional repressor by deubiquiting histone H2B at the promoters of genes critical for cellular differentiation, such as CDKN1A, thereby preventing histone H3 'Lys-4' trimethylation (H3K4) (PubMed:29274341). Specifically deubiquitinates MYC in the nucleolus, leading to prevent MYC degradation by the proteasome: acts by specifically interacting with isoform 3 of FBXW7 (FBW7gamma) in the nucleolus and counteracting ubiquitination of MYC by the SCF(FBW7) complex. In contrast, it does not interact with isoform 1 of FBXW7 (FBW7alpha) in the nucleoplasm (PubMed:25775507). Interacts to and regulates the actions of E3 ubiquitin-protein ligase NEDD4L over substrates such as NTRK1, KCNQ2 and KCNQ3, affecting their expression an functions (PubMed:27445338). Deubiquitinates SOD2, regulates SOD2 protein stability (PubMed:21268071). Deubiquitinase activity is required to control selective autophagy activation by ubiquitinated proteins (PubMed:22622177). {ECO:0000269|PubMed:19208757, ECO:0000269|PubMed:21268071, ECO:0000269|PubMed:22622177, ECO:0000269|PubMed:22902402, ECO:0000269|PubMed:25775507, ECO:0000269|PubMed:27445338, ECO:0000269|PubMed:29273634, ECO:0000269|PubMed:29274341}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (2); Chain (1); Compositional bias (12); Domain (1); Erroneous initiation (1); Modified residue (9); Mutagenesis (1); Natural variant (8); Region (4); Sequence caution (1); Sequence conflict (2) |
| Keywords | Cytoplasm;Hydrolase;Nucleus;Phosphoprotein;Protease;Reference proteome;Thiol protease;Ubl conjugation;Ubl conjugation pathway |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Nucleus, nucleolus {ECO:0000269|PubMed:12429849, ECO:0000269|PubMed:19208757, ECO:0000269|PubMed:25775507, ECO:0000269|PubMed:27445338}. Cytoplasm {ECO:0000269|PubMed:27445338}. |
| Modified Residue | MOD_RES 429; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 464; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163"; MOD_RES 546; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 582; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"; MOD_RES 667; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"; MOD_RES 682; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"; MOD_RES 713; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"; MOD_RES 742; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692"; MOD_RES 952; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:17081983, ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" |
| Post Translational Modification | PTM: Polyubiquitinated by NEDD4L, no effect on USP36 protein levels. Both proteins interact with and regulate each other's ubiquitination levels. {ECO:0000269|PubMed:27445338}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 19615732; 21150319; 25665578; 26496610; 26638075; |
| Motif | |
| Gene Encoded By | |
| Mass | 122,908 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |