BAP1
entrez
8314
canonical
uniprot
Q92560
canonical
ensembl
ENSG00000163930
resolver
ensp
ENSP00000296288
resolver
ensp
ENSP00000417132
resolver
enst
ENST00000296288
resolver
enst
ENST00000460680
resolver
genesymbol
BAP1
resolver
genesymbol_syn
KIAA0272
resolver
hgnc
HGNC:950
resolver
uniprot
A8K993
resolver
uniprot
F8W6N3
resolver
uniprot
Q6LEM0
resolver
uniprot
Q7Z5E8
resolver
uniprot_entry
BAP1_HUMAN
resolver
uniprot_entry
F8W6N3_HUMAN
resolver
uniprot_sec
A8K993
resolver
uniprot_sec
Q6LEM0
resolver
uniprot_sec
Q7Z5E8
resolver
amino_acid_sequence
MNKGWLELESDPGLFTLLVEDFGVKGVQVEEIYDLQSKCQGPVYGFIFLFKWIEERRSRRKVSTLVDDTSVIDDDIVNNMFFAHQLIPNSCATHALLSVLLNCSSVDLGPTLSRMKDFTKGFSPESKGYAIGNAPELAKAHNSHARPEPRHLPEKQNGLSAVRTMEAFHFVSYVPITGRLFELDGLKVYPIDHGPWGEDEEWTDKARRVIMERIGLATAGEPYHDIRFNLMAVVPDRRIKYEARLHVLKVNRQTVLEALQQLIRVTQPELIQTHKSQESQLPEESKSASNKSPLVLEANRAPAASEGNHTDGAEEAAGSCAQAPSHSPPNKPKLVVKPPGSSLNGVHPNPTPIVQRLPAFLDNHNYAKSPMQEEEDLAAGVGRSRVPVRPPQQYSDDEDDYEDDEEDDVQNTNSALRYKGKGTGKPGALSGSADGQLSVLQPNTINVLAEKLKESQKDLSIPLSIKTSSGAGSPAVAVPTHSQPSPTPSNESTDTASEIGSAFNSPLRSPIRSANPTRPSSPVTSHISKVLFGEDDSLLRVDCIRYNRAVRDLGPVISTGLLHLAEDGVLSPLALTEGGKGSSPSIRPIQGSQGSSSPVEKEVVEATDSREKTGMVRPGEPLSGEKYSPKELLALLKCVEAEIANYEACLKEEVEKRKKFKIDDQRRTHNYDEFICTFISMLAQEGMLANLVEQNISVRRRQGVSIGRLHKQRKPDRRKRSRPYKAKRQ
uniprot
proteins
disease_involvement
DISEASE: Mesothelioma, malignant (MESOM) [MIM:156240]: An aggressive neoplasm of the serosal lining of the chest. It appears as broad sheets of cells, with some regions containing spindle-shaped, sarcoma-like cells and other regions showing adenomatous patterns. Pleural mesotheliomas have been linked to exposure to asbestos. {ECO:0000269|PubMed:21642991, ECO:0000269|PubMed:21874000}. Note=The gene represented in this entry is involved in disease pathogenesis.; DISEASE: Tumor predisposition syndrome 1 (TPDS1) [MIM:614327]: An autosomal dominant condition characterized by predisposition to develop a variety of tumors, including benign melanocytic tumors as well as several malignant tumors, including uveal melanoma, cutaneous melanoma, malignant mesothelioma on exposure to asbestos, lung adenocarcinoma and meningioma. {ECO:0000269|PubMed:21874000, ECO:0000269|PubMed:21874003, ECO:0000269|PubMed:21941004, ECO:0000269|PubMed:23684012}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Melanoma, uveal, 2 (UVM2) [MIM:606661]: Most common intraocular malignancy, arising from melanocytes in the iris, ciliary body, or choroid. Metastases develop in more than 30% of case patients, almost invariably in the liver, with poor prognosis. {ECO:0000269|PubMed:25687217, ECO:0000269|PubMed:32002398}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Kury-Isidor syndrome (KURIS) [MIM:619762]: An autosomal dominant neurodevelopmental disorder characterized mainly by mild global developmental delay apparent from infancy or early childhood, and behavioral problems, including autism in most patients. Intellectual development may be mildly delayed, borderline, or even normal. Additional variable systemic features may include poor overall growth, hypotonia, distal skeletal anomalies, seizures, and non-specific dysmorphic facial features. {ECO:0000269|PubMed:19117993, ECO:0000269|PubMed:19815555, ECO:0000269|PubMed:20805357, ECO:0000269|PubMed:25451922, ECO:0000269|PubMed:35051358}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
3.4.19.12
uniprot
proteins
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, PubMed:35051358). Catalytic component of the polycomb repressive deubiquitinase (PR-DUB) complex, a complex that specifically mediates deubiquitination of histone H2A monoubiquitinated at 'Lys-120' (H2AK119ub1) (PubMed:20436459, PubMed:25451922, PubMed:30664650, PubMed:35051358). Does not deubiquitinate monoubiquitinated histone H2B (PubMed:20436459, PubMed:30664650). The PR-DUB complex is an epigenetic regulator of gene expression and acts as a transcriptional coactivator, affecting genes involved in development, cell communication, signaling, cell proliferation and cell viability (PubMed:20805357, PubMed:30664650, PubMed:36180891). Antagonizes PRC1 mediated H2AK119ub1 monoubiquitination (PubMed:30664650). As part of the PR-DUB complex, associates with chromatin enriched in histone marks H3K4me1, H3K4me3, and H3K27Ac, but not in H3K27me3 (PubMed:36180891). Recruited to specific gene-regulatory regions by YY1 (PubMed:20805357). 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 counteract monoubiquitination at the nuclear localization signal (NLS), thereby protecting it from cytoplasmic sequestration (PubMed:24703950). Negatively regulates epithelial-mesenchymal transition (EMT) of trophoblast stem cells during placental development by regulating genes involved in epithelial cell integrity, cell adhesion and cytoskeletal organization (PubMed:34170818). {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:20805357, ECO:0000269|PubMed:24703950, ECO:0000269|PubMed:25451922, ECO:0000269|PubMed:30664650, ECO:0000269|PubMed:34170818, ECO:0000269|PubMed:35051358, ECO:0000269|PubMed:36180891}.
uniprot
proteins
mass_dalton
80362
uniprot
proteins
mutagenesis
MUTAGEN 56..60; /note="RRSRR->AASAA: Probably disrupts interaction with the histone H2A-H2B acidic patch. Severely attenuates deubiquitination of histone H2AK119ub1 substrates in the context of the nucleosome but does not disrupt nucleosome interaction."; /evidence="ECO:0000269|PubMed:36991118, ECO:0000269|PubMed:37556531"; MUTAGEN 56; /note="R->C: Reduces deubiquitination activity towards H2AK119ub1 substrates in the context of the nucleosome."; /evidence="ECO:0000269|PubMed:37556531"; MUTAGEN 59; /note="R->W: Reduces deubiquitination activity towards H2AK119ub1 substrates in the context of the nucleosome."; /evidence="ECO:0000269|PubMed:37556531"; MUTAGEN 91; /note="C->A: Abolishes deubiquitinase activity. Has no effect on interaction with HCFC1."; /evidence="ECO:0000269|PubMed:18757409, ECO:0000269|PubMed:19188440, ECO:0000269|PubMed:9528852"; MUTAGEN 251; /note="N->R: Severely attenuates deubiquitination of histone H2AK119ub1 substrates, possibly due to disruption of homodimerization."; /evidence="ECO:0000269|PubMed:30258054"; MUTAGEN 363..366; /note="NHNY->AAAA: Abolishes interaction with HCFC1 without affecting interaction with FOXK1 and FOXK2."; /evidence="ECO:0000269|PubMed:19188440, ECO:0000269|PubMed:19815555, ECO:0000269|PubMed:25451922"; MUTAGEN 489; /note="S->A: Does not affect interaction with FOXK1 and FOXK2."; /evidence="ECO:0000269|PubMed:25451922"; MUTAGEN 492; /note="S->A: Does not affect interaction with FOXK1 and FOXK2."; /evidence="ECO:0000269|PubMed:25451922"; MUTAGEN 493; /note="T->A,L: Abolished interaction with FOXK1 and FOXK2."; /evidence="ECO:0000269|PubMed:25451922"; MUTAGEN 495; /note="T->A: Does not affect interaction with FOXK1 and FOXK2."; /evidence="ECO:0000269|PubMed:25451922"; MUTAGEN 635; /note="L->A: Severely attenuated deubiquitination of histone H2AK119ub1 substrates, possibly due to disruption of homodimerization. No effect on intrinsic catalytic activity."; /evidence="ECO:0000269|PubMed:30258054"; MUTAGEN 656..661; /note="KRKKFK->AAAAAA: Does not affect nuclear localization."; /evidence="ECO:0000269|PubMed:18757409"; MUTAGEN 684..729; /note="Missing: Predominantly localizes to the cytosol."; /evidence="ECO:0000269|PubMed:35446349"; MUTAGEN 691..711; /note="Missing: Abolishes ubiquitination by UBE2O."; /evidence="ECO:0000269|PubMed:24703950"; MUTAGEN 691; /note="L->P: Abolishes interaction with BRCA1."; /evidence="ECO:0000269|PubMed:9528852"; MUTAGEN 697..729; /note="Missing: Abolishes deubiquitination activity towards H2AK119ub1 substrates in the context of the nucleosome, probably due to disruption of nucleosome interaction. Does not affect deubiquitination of H2AK119ub1 on free histones."; /evidence="ECO:0000269|PubMed:36991118"; MUTAGEN 699..702; /note="Missing: Severely reduces deubiquitination activity towards H2AK119ub1 substrates in the context of the nucleosome but only mildly disrupts nucleosome interaction."; /evidence="ECO:0000269|PubMed:36991118"; MUTAGEN 699..701; /note="RRR->AAA: Reduced nucleosomal binding."; /evidence="ECO:0000269|PubMed:37556531"; MUTAGEN 699..700; /note="RR->DD: Reduced nucleosomal binding."; /evidence="ECO:0000269|PubMed:37556531"; MUTAGEN 699; /note="R->W: Slight or no reduction of deubiquitination efficiency towards H2AK119ub1 substrates in the context of the nucleosome."; /evidence="ECO:0000269|PubMed:36991118, ECO:0000269|PubMed:37556531"; MUTAGEN 700; /note="R->Q: Slightly reduces deubiquitination activity towards H2AK119ub1 substrates in the context of the nucleosome."; /evidence="ECO:0000269|PubMed:36991118"; MUTAGEN 701; /note="R->C: Reduces deubiquitination activity towards H2AK119ub1 substrates in the context of the nucleosome."; /evidence="ECO:0000269|PubMed:36991118, ECO:0000269|PubMed:37556531"; MUTAGEN 702; /note="Missing: Slightly reduces deubiquitination activity towards H2AK119ub1 substrates in the context of the nucleosome."; /evidence="ECO:0000269|PubMed:36991118"; MUTAGEN 703; /note="G->P,R: Reduces deubiquitination activity towards H2AK119ub1 substrates in the context of the nucleosome."; /evidence="ECO:0000269|PubMed:36991118"; MUTAGEN 708; /note="R->A: Reduces deubiquitination activity towards H2AK119ub1 substrates in the context of the nucleosome."; /evidence="ECO:0000269|PubMed:36991118"; MUTAGEN 711..729; /note="Missing: Disrupts nucleosome interaction and abolishes deubiquitination activity towards H2AK119ub1 substrates in the context of the nucleosome. Does not affect deubiquitination of H2AK119ub1 on free histones."; /evidence="ECO:0000269|PubMed:36991118"; MUTAGEN 711..718; /note="Missing: Reduces deubiquitination activity towards H2AK119ub1 substrates in the context of the nucleosome, probably due to disruption of nucleosome interaction. Does not affect deubiquitination of H2AK119ub1 on free histones."; /evidence="ECO:0000269|PubMed:36991118"; MUTAGEN 713..729; /note="Missing: Impairs deubiquitination activity of histone H2AK118ub1 substrates, probably due to disruption of nucleosome association."; /evidence="ECO:0000269|PubMed:30258054"; MUTAGEN 713; /note="R->A: Reduces deubiquitination activity towards H2AK119ub1 substrates in the context of the nucleosome."; /evidence="ECO:0000269|PubMed:36991118"; MUTAGEN 717..722; /note="RRKRSR->AAAAAA: Abolishes nuclear localization."; /evidence="ECO:0000269|PubMed:18757409"; MUTAGEN 718..729; /note="Missing: Disrupts nucleosome interaction and reduces deubiquitination activity towards H2AK119ub1 substrates in the context of the nucleosome."; /evidence="ECO:0000269|PubMed:36991118
uniprot
proteins
post_translational_modification
PTM: Ubiquitinated: monoubiquitinated at multiple sites within its nuclear localization signal (NLS) BY UBE2O, leading to cytoplasmic retention (PubMed:24703950). Able to mediate autodeubiquitination via intramolecular interactions to counteract cytoplasmic retention (PubMed:24703950). Monoubiquitinated on at least 4 sites near or within its PY-NLS (PubMed:35446349). {ECO:0000269|PubMed:24703950, ECO:0000269|PubMed:35446349}.
uniprot
proteins
protein_family
BAP1 subfamily
uniprot
proteins
protein_family
Peptidase C12 family
uniprot
proteins
pubmed
10546591
uniprot
proteins
pubmed
12168954
uniprot
proteins
pubmed
12485996
uniprot
proteins
pubmed
12800201
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
18220336
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18757409
uniprot
proteins
pubmed
19117993
uniprot
proteins
pubmed
19188440
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
19815555
uniprot
proteins
pubmed
20436459
uniprot
proteins
pubmed
20805357
uniprot
proteins
pubmed
21642991
uniprot
proteins
pubmed
21874000
uniprot
proteins
pubmed
21874003
uniprot
proteins
pubmed
21941004
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23684012
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24634419
uniprot
proteins
pubmed
24703950
uniprot
proteins
pubmed
24748658
uniprot
proteins
pubmed
25080371
uniprot
proteins
pubmed
25451922
uniprot
proteins
pubmed
25687217
uniprot
proteins
pubmed
26680512
uniprot
proteins
pubmed
30258054
uniprot
proteins
pubmed
30664650
uniprot
proteins
pubmed
32002398
uniprot
proteins
pubmed
34170818
uniprot
proteins
pubmed
35051358
uniprot
proteins
pubmed
35446349
uniprot
proteins
pubmed
36180891
uniprot
proteins
pubmed
36991118
uniprot
proteins
pubmed
37556531
uniprot
proteins
pubmed
9039502
uniprot
proteins
pubmed
9528852
uniprot
proteins
sequence_length
729
uniprot
proteins
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:30664650, ECO:0000269|PubMed:35051358, ECO:0000269|PubMed:35446349, ECO:0000269|PubMed:9528852}. Chromosome {ECO:0000269|PubMed:30664650}. Note=Mainly nuclear (PubMed:24703950, PubMed:30664650). Binds to chromatin (PubMed:30664650). Localizes to the cytoplasm when monoubiquitinated by the E2/E3 hybrid ubiquitin-protein ligase UBE2O (PubMed:24703950). Recruitment to chromatin is dependent on ASXL1/2/3 and recruitment to specific genes on FOXK1/2 (By similarity). Nuclear localization is redundantly mediated by the importin and transportin systems; TNPO1/transportin-1 is the major mediator of nuclear localization (PubMed:35446349). {ECO:0000250|UniProtKB:Q99PU7, ECO:0000269|PubMed:24703950, ECO:0000269|PubMed:30664650, ECO:0000269|PubMed:35446349}.
uniprot
proteins