| IED ID | IndEnz0002016517 |
| Enzyme Type ID | protease016517 |
| Protein Name |
Ubiquitin carboxyl-terminal hydrolase BAP1 EC 3.4.19.12 BRCA1-associated protein 1 Cerebral protein 6 |
| Gene Name | BAP1 KIAA0272 hucep-6 |
| 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 | MNKGWLELESDPGLFTLLVEDFGVKGVQVEEIYDLQSKCQGPVYGFIFLFKWIEERRSRRKVSTLVDDTSVIDDDIVNNMFFAHQLIPNSCATHALLSVLLNCSSVDLGPTLSRMKDFTKGFSPESKGYAIGNAPELAKAHNSHARPEPRHLPEKQNGLSAVRTMEAFHFVSYVPITGRLFELDGLKVYPIDHGPWGEDEEWTDKARRVIMERIGLATAGEPYHDIRFNLMAVVPDRRIKYEARLHVLKVNRQTVLEALQQLIRVTQPELIQTHKSQESQLPEESKSASNKSPLVLEANRAPAASEGNHTDGAEEAAGSCAQAPSHSPPNKPKLVVKPPGSSLNGVHPNPTPIVQRLPAFLDNHNYAKSPMQEEEDLAAGVGRSRVPVRPPQQYSDDEDDYEDDEEDDVQNTNSALRYKGKGTGKPGALSGSADGQLSVLQPNTINVLAEKLKESQKDLSIPLSIKTSSGAGSPAVAVPTHSQPSPTPSNESTDTASEIGSAFNSPLRSPIRSANPTRPSSPVTSHISKVLFGEDDSLLRVDCIRYNRAVRDLGPVISTGLLHLAEDGVLSPLALTEGGKGSSPSIRPIQGSQGSSSPVEKEVVEATDSREKTGMVRPGEPLSGEKYSPKELLALLKCVEAEIANYEACLKEEVEKRKKFKIDDQRRTHNYDEFICTFISMLAQEGMLANLVEQNISVRRRQGVSIGRLHKQRKPDRRKRSRPYKAKRQ |
| Enzyme Length | 729 |
| Uniprot Accession Number | Q92560 |
| Absorption | |
| Active Site | ACT_SITE 91; /note="Nucleophile"; /evidence="ECO:0000269|PubMed:18757409, ECO:0000269|PubMed:19117993, ECO:0000269|PubMed:19188440, ECO:0000269|PubMed:19815555, ECO:0000269|PubMed:25451922, ECO:0000269|PubMed:9528852"; ACT_SITE 169; /note="Proton donor"; /evidence="ECO:0000250|UniProtKB:P09936" |
| 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:20436459, ECO:0000269|PubMed:9528852}; |
| DNA Binding | |
| EC Number | 3.4.19.12 |
| Enzyme Function | FUNCTION: Deubiquitinating enzyme that plays a key role in chromatin by mediating deubiquitination of histone H2A and HCFC1 (PubMed:12485996, PubMed:18757409, PubMed:20436459, PubMed:25451922). Catalytic component of the PR-DUB complex, a complex that specifically mediates deubiquitination of histone H2A monoubiquitinated at 'Lys-119' (H2AK119ub1) (PubMed:20436459, PubMed:25451922). Does not deubiquitinate monoubiquitinated histone H2B (PubMed:20436459). Acts as a regulator of cell growth by mediating deubiquitination of HCFC1 N-terminal and C-terminal chains, with some specificity toward 'Lys-48'-linked polyubiquitin chains compared to 'Lys-63'-linked polyubiquitin chains (PubMed:19188440, PubMed:19815555). Deubiquitination of HCFC1 does not lead to increase stability of HCFC1 (PubMed:19188440, PubMed:19815555). Interferes with the BRCA1 and BARD1 heterodimer activity by inhibiting their ability to mediate ubiquitination and autoubiquitination (PubMed:19117993). It however does not mediate deubiquitination of BRCA1 and BARD1 (PubMed:19117993). Able to mediate autodeubiquitination via intramolecular interactions to couteract monoubiquitination at the nuclear localization signal (NLS), thereby protecting it from cytoplasmic sequestration (PubMed:24703950). Acts as a tumor suppressor (PubMed:9528852). {ECO:0000269|PubMed:12485996, ECO:0000269|PubMed:18757409, ECO:0000269|PubMed:19117993, ECO:0000269|PubMed:19188440, ECO:0000269|PubMed:19815555, ECO:0000269|PubMed:20436459, ECO:0000269|PubMed:24703950, ECO:0000269|PubMed:25451922, ECO:0000269|PubMed:9528852}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (2); Chain (1); Coiled coil (1); Compositional bias (2); Erroneous initiation (1); Modified residue (8); Motif (2); Mutagenesis (10); Natural variant (9); Region (6); Site (1) |
| Keywords | Chromatin regulator;Coiled coil;Cytoplasm;Hydrolase;Nucleus;Phosphoprotein;Protease;Reference proteome;Thiol protease;Ubl conjugation;Ubl conjugation pathway |
| Interact With | Q8IXJ9; P38398; P38398-5; P51610; Q14573 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18757409, ECO:0000269|PubMed:19188440, ECO:0000269|PubMed:19815555, ECO:0000269|PubMed:24703950}. Nucleus {ECO:0000269|PubMed:18757409, ECO:0000269|PubMed:19188440, ECO:0000269|PubMed:19815555, ECO:0000269|PubMed:24703950, ECO:0000269|PubMed:24748658, ECO:0000269|PubMed:9528852}. Note=Mainly nuclear. Binds to chromatin. Localizes to the cytoplasm when monoubiquitinated by the E2/E3 hybrid ubiquitin-protein ligase UBE2O (PubMed:24703950). {ECO:0000269|PubMed:24703950}. |
| Modified Residue | MOD_RES 292; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:23186163; MOD_RES 369; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:23186163; MOD_RES 395; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q99PU7; MOD_RES 493; /note=Phosphothreonine; /evidence=ECO:0000269|PubMed:25451922; MOD_RES 521; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:23186163; MOD_RES 537; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:23186163; MOD_RES 585; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:23186163; MOD_RES 597; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:23186163 |
| Post Translational Modification | PTM: Ubiquitinated: monoubiquitinated at multiple site of its nuclear localization signal (NLS) BY UBE2O, leading to cytoplasmic retention. Able to mediate autodeubiquitination via intramolecular interactions to couteract cytoplasmic retention. {ECO:0000269|PubMed:24703950}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 11927591; 12890688; 18950845; 19197335; 19367581; 19615732; 19950226; 20360068; 20711500; 20805357; 21051595; 21484256; 21941004; 22321046; 22367297; 22545102; 22683710; 22863556; 22878500; 22889334; 22897849; 22935333; 22958294; 23026932; 23171164; 23277170; 23333114; 23341325; 23495950; 23620406; 23644518; 23684012; 23709298; 23849051; 23867514; 23915344; 23963927; 23977234; 24018818; 24029645; 24076305; 24128712; 24166983; 24185509; 24187051; 24211834; 24243779; 24247622; 24373783; 24382589; 24511587; 24697775; 24705312; 24894717; 24938780; 24970262; 25058347; 25147369; 25225064; 25225168; 25228651; 25231345; 25260751; 25283999; 25380601; 25465300; 25468148; 25479927; 25488749; 25506912; 25609649; 25636086; 25640309; 25658628; 25687217; 25787093; 25796603; 25830670; 25889843; 25938359; 25952750; 25970771; 25972334; 25974357; 25976137; 26011428; 26022455; 26028330; 26096145; 26118501; 26191197; 26226841; 26246155; 26300218; 26300492; 26376834; 26409435; 26416890; 26437366; 26448191; 26452128; 26463840; 26496992; 26611647; 26645730; 26683624; 26701415; 26719535; 26739236; 26744134; 26765459; 26774355; 26876698; 26885612; 26891804; 26896281; 26900815; 26923342; 26982343; 27015033; 27072194; 27114369; 27116551; 27123562; 27181379; 27223342; 27553041; 27718540; 27749792; 27771374; 27813512; 27859460; 27864835; 27916271; 27984124; 28034829; 28038708; 28062663; 28098597; 28122578; 28256910; 28284891; 28339037; 28342657; 28362705; 28389374; 28404968; 28408295; 28409567; 28444874; 28482042; 28488170; 28551647; 28560743; 28597019; 28614305; 28618948; 28661472; 28665402; 28746778; 28753773; 28935764; 29061454; 29076876; 29113987; 29122566; 29159179; 29266978; 29284740; 29317634; 29345617; 29426696; 29530782; 29623743; 29686263; 29689622; 29761599; 29763720; 29778232; 29802871; 29994997; 30013160; 30073324; 30076753; 30202049; 30305612; 30338612; 30377796; 30395583; 30429020; 30446457; 30463901; 30477459; 30553477; 30640754; 30660076; 30664650; 30669483; 30686559; 30716094; 30777124; 30801340; 30907299; 31000662; 31058349; 31058963; 31130514; 31165505; 31323388; 31425584; 31555735; 31570769; 31580399; 31619462; 31635476; 31657441; 31706282; 31734934; 31735283; 31780633; 31862487; 31864162; 31960425; 32096236; 32097618; 32131485; 32486284; 32669118; 32678499; 32819560; 32829890; 32932212; 32944962; 32945606; 33155366; 33208912; 33210135; 33316260; 33341088; 33397551; 33462414; 33516665; 33529461; 33658435; 33866194; 33903674; 34170818; 34186160; 34257556; 34591877; |
| Motif | MOTIF 363..366; /note="HBM-like motif"; /evidence="ECO:0000269|PubMed:19188440, ECO:0000269|PubMed:19815555, ECO:0000269|PubMed:25451922"; MOTIF 717..722; /note="Nuclear localization signal"; /evidence="ECO:0000269|PubMed:18757409, ECO:0000269|PubMed:24703950" |
| Gene Encoded By | |
| Mass | 80,362 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda | 3.4.19.12; |