| IED ID | IndEnz0002009145 |
| Enzyme Type ID | protease009145 |
| Protein Name |
Ubiquitin carboxyl-terminal hydrolase 37 EC 3.4.19.12 Deubiquitinating enzyme 37 Ubiquitin thioesterase 37 Ubiquitin-specific-processing protease 37 |
| Gene Name | USP37 KIAA1594 |
| 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 | MSPLKIHGPIRIRSMQTGITKWKEGSFEIVEKENKVSLVVHYNTGGIPRIFQLSHNIKNVVLRPSGAKQSRLMLTLQDNSFLSIDKVPSKDAEEMRLFLDAVHQNRLPAAMKPSQGSGSFGAILGSRTSQKETSRQLSYSDNQASAKRGSLETKDDIPFRKVLGNPGRGSIKTVAGSGIARTIPSLTSTSTPLRSGLLENRTEKRKRMISTGSELNEDYPKENDSSSNNKAMTDPSRKYLTSSREKQLSLKQSEENRTSGLLPLQSSSFYGSRAGSKEHSSGGTNLDRTNVSSQTPSAKRSLGFLPQPVPLSVKKLRCNQDYTGWNKPRVPLSSHQQQQLQGFSNLGNTCYMNAILQSLFSLQSFANDLLKQGIPWKKIPLNALIRRFAHLLVKKDICNSETKKDLLKKVKNAISATAERFSGYMQNDAHEFLSQCLDQLKEDMEKLNKTWKTEPVSGEENSPDISATRAYTCPVITNLEFEVQHSIICKACGEIIPKREQFNDLSIDLPRRKKPLPPRSIQDSLDLFFRAEELEYSCEKCGGKCALVRHKFNRLPRVLILHLKRYSFNVALSLNNKIGQQVIIPRYLTLSSHCTENTKPPFTLGWSAHMAISRPLKASQMVNSCITSPSTPSKKFTFKSKSSLALCLDSDSEDELKRSVALSQRLCEMLGNEQQQEDLEKDSKLCPIEPDKSELENSGFDRMSEEELLAAVLEISKRDASPSLSHEDDDKPTSSPDTGFAEDDIQEMPENPDTMETEKPKTITELDPASFTEITKDCDENKENKTPEGSQGEVDWLQQYDMEREREEQELQQALAQSLQEQEAWEQKEDDDLKRATELSLQEFNNSFVDALGSDEDSGNEDVFDMEYTEAEAEELKRNAETGNLPHSYRLISVVSHIGSTSSSGHYISDVYDIKKQAWFTYNDLEVSKIQEAAVQSDRDRSGYIFFYMHKEIFDELLETEKNSQSLSTEVGKTTRQAL |
| Enzyme Length | 979 |
| Uniprot Accession Number | Q86T82 |
| Absorption | |
| Active Site | ACT_SITE 350; /note="Nucleophile"; /evidence="ECO:0000269|PubMed:27296872"; ACT_SITE 906; /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, ECO:0000269|PubMed:27296872}; |
| DNA Binding | |
| EC Number | 3.4.19.12 |
| Enzyme Function | FUNCTION: Deubiquitinase that antagonizes the anaphase-promoting complex (APC/C) during G1/S transition by mediating deubiquitination of cyclin-A (CCNA1 and CCNA2), thereby promoting S phase entry. Specifically mediates deubiquitination of 'Lys-11'-linked polyubiquitin chains, a specific ubiquitin-linkage type mediated by the APC/C complex. Also mediates deubiquitination of 'Lys-48'-linked polyubiquitin chains in vitro. Phosphorylation at Ser-628 during G1/S phase maximizes the deubiquitinase activity, leading to prevent degradation of cyclin-A (CCNA1 and CCNA2) (PubMed:21596315). Plays an important role in the regulation of DNA replication by stabilizing the licensing factor CDT1 (PubMed:27296872). {ECO:0000269|PubMed:21596315, ECO:0000269|PubMed:27296872}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (2); Alternative sequence (2); Beta strand (7); Chain (1); Compositional bias (7); Domain (4); Erroneous gene model prediction (1); Helix (1); Modified residue (6); Motif (6); Mutagenesis (8); Natural variant (1); Region (4); Sequence conflict (8); Turn (2) |
| Keywords | 3D-structure;Alternative splicing;Cell cycle;Cell division;Hydrolase;Mitosis;Phosphoprotein;Protease;Reference proteome;Repeat;Thiol protease;Ubl conjugation;Ubl conjugation pathway |
| Interact With | |
| Induction | INDUCTION: Induced by E2F transcription factors in G1. {ECO:0000269|PubMed:21596315}. |
| Subcellular Location | |
| Modified Residue | MOD_RES 170; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 210; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 628; /note="Phosphoserine; by CDK2"; /evidence="ECO:0000269|PubMed:21596315, ECO:0000269|PubMed:27296872"; MOD_RES 650; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648"; MOD_RES 652; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648"; MOD_RES 770; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163" |
| Post Translational Modification | PTM: Polyubiquitinated via 'Lys-11'-linked ubiquitin by the APC(CDH1) complex during late mitosis, leading to its degradation. Able to mediate auto-deubiquitination. {ECO:0000269|PubMed:21596315}.; PTM: Phosphorylated at Ser-628 by CDK2 during G1/S phase but not during mitosis; phosphorylation at Ser-628 is required for deubiquitinase activity. Also polyubiquitinated during early G1 phase, without leading to degradation. {ECO:0000269|PubMed:21596315}. |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (1) |
| Cross Reference PDB | 3U12; |
| Mapped Pubmed ID | 19615732; 19851296; 20198315; 22665064; 23027877; 23208507; 24324262; 25284584; 25609649; 26299517; 28483947; 30482232; 30858488; 32461361; 33390801; 34606619; |
| Motif | MOTIF 32..34; /note=KEN box 1; MOTIF 71..79; /note=D-box 1; MOTIF 96..105; /note=D-box 2; MOTIF 160..168; /note=D-box 3; MOTIF 221..223; /note=KEN box 2; MOTIF 782..784; /note=KEN box 3 |
| Gene Encoded By | |
| Mass | 110,170 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |