| IED ID | IndEnz0002010725 |
| Enzyme Type ID | protease010725 |
| Protein Name |
Ubiquitin carboxyl-terminal hydrolase 1 EC 3.4.19.12 Deubiquitinating enzyme 1 hUBP Ubiquitin thioesterase 1 Ubiquitin-specific-processing protease 1 Cleaved into: Ubiquitin carboxyl-terminal hydrolase 1, N-terminal fragment |
| Gene Name | USP1 |
| 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 | MPGVIPSESNGLSRGSPSKKNRLSLKFFQKKETKRALDFTDSQENEEKASEYRASEIDQVVPAAQSSPINCEKRENLLPFVGLNNLGNTCYLNSILQVLYFCPGFKSGVKHLFNIISRKKEALKDEANQKDKGNCKEDSLASYELICSLQSLIISVEQLQASFLLNPEKYTDELATQPRRLLNTLRELNPMYEGYLQHDAQEVLQCILGNIQETCQLLKKEEVKNVAELPTKVEEIPHPKEEMNGINSIEMDSMRHSEDFKEKLPKGNGKRKSDTEFGNMKKKVKLSKEHQSLEENQRQTRSKRKATSDTLESPPKIIPKYISENESPRPSQKKSRVKINWLKSATKQPSILSKFCSLGKITTNQGVKGQSKENECDPEEDLGKCESDNTTNGCGLESPGNTVTPVNVNEVKPINKGEEQIGFELVEKLFQGQLVLRTRCLECESLTERREDFQDISVPVQEDELSKVEESSEISPEPKTEMKTLRWAISQFASVERIVGEDKYFCENCHHYTEAERSLLFDKMPEVITIHLKCFAASGLEFDCYGGGLSKINTPLLTPLKLSLEEWSTKPTNDSYGLFAVVMHSGITISSGHYTASVKVTDLNSLELDKGNFVVDQMCEIGKPEPLNEEEARGVVENYNDEEVSIRVGGNTQPSKVLNKKNVEAIGLLGGQKSKADYELYNKASNPDKVASTAFAENRNSETSDTTGTHESDRNKESSDQTGINISGFENKISYVVQSLKEYEGKWLLFDDSEVKVTEEKDFLNSLSPSTSPTSTPYLLFYKKL |
| Enzyme Length | 785 |
| Uniprot Accession Number | O94782 |
| Absorption | |
| Active Site | ACT_SITE 90; /note="Nucleophile"; /evidence="ECO:0000269|PubMed:15694335, ECO:0000269|PubMed:16531995, ECO:0000269|PubMed:26388029"; ACT_SITE 593; /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:15694335, ECO:0000269|PubMed:16531995, ECO:0000269|PubMed:18082604, ECO:0000269|PubMed:26388029, ECO:0000269|PubMed:9806842}; |
| DNA Binding | |
| EC Number | 3.4.19.12 |
| Enzyme Function | FUNCTION: Negative regulator of DNA damage repair which specifically deubiquitinates monoubiquitinated FANCD2 (PubMed:15694335). Also involved in PCNA-mediated translesion synthesis (TLS) by deubiquitinating monoubiquitinated PCNA (PubMed:16531995). Has almost no deubiquitinating activity by itself and requires the interaction with WDR48 to have a high activity (PubMed:18082604, PubMed:26388029). {ECO:0000269|PubMed:15694335, ECO:0000269|PubMed:16531995, ECO:0000269|PubMed:18082604, ECO:0000269|PubMed:26388029}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (2); Chain (2); Compositional bias (2); Domain (1); Frameshift (1); Modified residue (6); Mutagenesis (3); Region (4); Sequence caution (2); Sequence conflict (1); Site (1); Turn (1) |
| Keywords | 3D-structure;Autocatalytic cleavage;DNA damage;DNA repair;Hydrolase;Nucleus;Phosphoprotein;Protease;Reference proteome;Thiol protease;Ubl conjugation;Ubl conjugation pathway |
| Interact With | Q8TAF3-1 |
| Induction | INDUCTION: Down-regulated following DNA damage. {ECO:0000269|PubMed:18082604}. |
| Subcellular Location | SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15694335}. |
| Modified Residue | MOD_RES 16; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 42; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:17525332, ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"; MOD_RES 67; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163"; MOD_RES 313; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 475; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"; MOD_RES 768; /note="Phosphoserine"; /evidence="ECO:0000250|UniProtKB:Q8BJQ2" |
| Post Translational Modification | PTM: Autocatalytic cleavage of USP1 following UV irradiation inactivates it leading to an increase in ubiquitinated PCNA, recruitment of POLH and translesion synthesis. {ECO:0000269|PubMed:15694335, ECO:0000269|PubMed:16531995}.; PTM: [Ubiquitin carboxyl-terminal hydrolase 1, N-terminal fragment]: Ubiquitinated by the CRL2(KLHDC2) complex following autocatalytic cleavage, leading to its degradation: the CRL2(KLHDC2) complex recognizes the diglycine (Gly-Gly) at the C-terminus. {ECO:0000269|PubMed:29775578, ECO:0000269|PubMed:30526872}. |
| Signal Peptide | |
| Structure 3D | Electron microscopy (1); X-ray crystallography (3) |
| Cross Reference PDB | 6DO5; 7AY0; 7AY1; 7AY2; |
| Mapped Pubmed ID | 15572677; 19536649; 19596236; 19615732; 19690177; 20385554; 20603015; 20603016; 20603073; 20671156; 21389083; 21464321; 21640107; 21768287; 21925315; 22426999; 22692201; 22701671; 23116119; 23414517; 24076221; 24850727; 25500724; 25744535; 26002196; 26032834; 26117423; 26496610; 26758085; 26825230; 26951930; 27160904; 27463890; 27840911; 28270494; 28302046; 29138248; 30335599; 30456385; 30480413; 30531833; 30576655; 30890612; 31086816; 32133742; 32602291; 32951278; 33390793; 33461373; 33619839; 33795880; 34079090; 34128540; 34154657; |
| Motif | |
| Gene Encoded By | |
| Mass | 88,207 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=0.7 uM for ubiquitin vinyl sulfone (in presence of WDR48) {ECO:0000269|PubMed:18082604}; KM=1.4 uM for ubiquitin vinyl sulfone (in absence of WDR48) {ECO:0000269|PubMed:18082604}; |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |