BAP1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000278 mitotic cell cycle	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Mitotic cell-cycle association is a downstream effect of BAP1-dependent regulation. Reason: BAP1 alters ubiquitination of chromatin and transcriptional regulators, with consequent effects on cell-cycle progression. The mouse ortholog transfer does not identify a separate mitotic apparatus activity of human BAP1.
GO:0001558 regulation of cell growth	IMP PMID:19815555 The deubiquitinating enzyme BAP1 regulates cell growth via i...	KEEP AS NON CORE	Summary: BAP1 regulates cell growth through its interaction with HCFC1. Reason: PMID:19815555 links BAP1 depletion and a catalytically inactive mutant to reduced cell proliferation, with the growth effect dependent on the HCFC1-binding motif. Growth regulation is a downstream consequence of substrate deubiquitination.
GO:0001701 in utero embryonic development	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Embryonic development is a pleiotropic requirement for BAP1. Reason: Mouse Bap1 deficiency causes embryonic lethality. This supports a developmental requirement for the conserved chromatin regulator, while the transferred organismal process does not describe its substrate-specific catalytic function.
GO:0001894 tissue homeostasis	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Tissue homeostasis reflects the consequences of BAP1-dependent gene regulation. Reason: The mouse ortholog annotation captures maintenance of tissue function following Bap1 perturbation. Retain the physiological association separately from the deubiquitinase activity that changes chromatin and regulatory proteins.
GO:0002574 thrombocyte differentiation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Platelet-lineage differentiation is a hematopoietic consequence of BAP1 function. Reason: The ortholog-based annotation is consistent with altered hematopoiesis after Bap1 loss. It does not establish BAP1 as a lineage-specific platelet differentiation factor in human cells.
GO:0003682 chromatin binding	IDA PMID:19815555 The deubiquitinating enzyme BAP1 regulates cell growth via i...	ACCEPT	Summary: BAP1 associates with chromatin as part of its nuclear deubiquitinase function. Reason: PMID:19815555 reports BAP1 enrichment in the chromatin fraction and release by micrococcal nuclease. This supports the original chromatin-binding annotation; that experiment alone does not establish direct DNA contact.
GO:0003682 chromatin binding	IEA GO_REF:0000117	ACCEPT	Summary: The electronic chromatin-binding assignment agrees with direct BAP1 experiments. Reason: The ARBA assertion is corroborated by cellular fractionation and reconstituted nucleosome binding. Chromatin engagement is integral to BAP1 activity and need not be reduced to binding only one chromatin constituent.
GO:0004843 cysteine-type deubiquitinase activity	EXP PMID:30258054 A bidentate Polycomb Repressive-Deubiquitinase complex is re...	ACCEPT	Summary: Human BAP1-ASXL1 has deubiquitinase activity in the cited PR-DUB study. Reason: PMID:30258054 includes direct human BAP1-ASXL1 ubiquitin-AMC and H2AK119-ubiquitinated nucleosome assays despite its Drosophila structure. The cysteine-type activity describes catalytic chemistry across substrates; it complements the existing substrate-specific H2A activity annotation.
GO:0004843 cysteine-type deubiquitinase activity	EXP PMID:9528852 BAP1: a novel ubiquitin hydrolase which binds to the BRCA1 R...	ACCEPT	Summary: The original BAP1 study identifies a ubiquitin carboxyl-terminal hydrolase. Reason: PMID:9528852 explicitly reports ubiquitin hydrolase function. Retain the experimentally curated activity, corroborated by later catalytic-C91 mutant and purified-enzyme experiments. Only the original abstract was available here.
GO:0004843 cysteine-type deubiquitinase activity	IBA GO_REF:0000033	ACCEPT	Summary: The PAINT-inferred cysteine-type deubiquitinase activity is directly supported in human BAP1. Reason: The local PTHR10589 record contains a positive IBD at PTN000063280 for this activity. Human BAP1 experiments independently establish the chemistry. Q92560 appearing among descendant experimental sources is legitimate grounding, not circularity; no evolutionary loss is inferred.
GO:0004843 cysteine-type deubiquitinase activity	IDA PMID:18757409 BRCA1-associated protein-1 is a tumor suppressor that requir...	ACCEPT	Summary: BAP1 catalysis depends on its active-site cysteine. Reason: PMID:18757409 shows recombinant WT BAP1 hydrolyzing ubiquitin-AMC, loss of activity in C91A, and inhibition by ubiquitin vinyl sulfone. These assays directly support the molecular activity without establishing a particular physiological substrate.
GO:0004843 cysteine-type deubiquitinase activity	IDA PMID:19188440 Association of C-terminal ubiquitin hydrolase BRCA1-associat...	ACCEPT	Summary: The HCF-1 study supports catalytically active BAP1. Reason: PMID:19188440 compares WT with catalytic C91A BAP1 in human cells. Retain the curated deubiquitinase activity; the linked K48 process is assessed separately and does not imply unrestricted free-polyubiquitin cleavage.
GO:0004843 cysteine-type deubiquitinase activity	IDA PMID:19815555 The deubiquitinating enzyme BAP1 regulates cell growth via i...	ACCEPT	Summary: BAP1 removes ubiquitin from the transcriptional coregulator HCF-1. Reason: PMID:19815555 reports motif-dependent HCF-1N deubiquitination. This directly supports BAP1 deubiquitinase function on a nonhistone substrate, alongside its established histone activity.
GO:0004843 cysteine-type deubiquitinase activity	IDA PMID:20436459 Histone H2A deubiquitinase activity of the Polycomb repressi...	ACCEPT	Summary: The PR-DUB discovery paper directly assays human BAP1 with ASXL1. Reason: PMID:20436459 separately reconstitutes human BAP1-ASXL1 and fly Calypso-Asx complexes. Human nucleosomal H2A deubiquitination supports the catalytic annotation; fly Hox-repression genetics are not presented as human transcription experiments.
GO:0004843 cysteine-type deubiquitinase activity	IDA PMID:24703950 Autodeubiquitination protects the tumor suppressor BAP1 from...	ACCEPT	Summary: BAP1 autodeubiquitination is an additional manifestation of its catalytic activity. Reason: The complete abstract of PMID:24703950 reports BAP1 removal of UBE2O-installed ubiquitin from itself. Retain the curated activity while limiting detailed mechanistic claims to the accessible abstract.
GO:0004843 cysteine-type deubiquitinase activity	IEA GO_REF:0000120	ACCEPT	Summary: The InterPro/EC inference correctly identifies BAP1 as a cysteine-type deubiquitinase. Reason: Human enzyme assays and catalytic-cysteine mutants support this mechanistically informative activity. The annotation applies to histone and nonhistone substrates, so replacing all copies with the H2A-specific activity would unnecessarily discard broader established substrate coverage.
GO:0004843 cysteine-type deubiquitinase activity	TAS Reactome:R-HSA-5690759	ACCEPT	Summary: Reactome assigns BAP1 the catalytic role in HCF-1 deubiquitination. Reason: R-HSA-5690759 explicitly describes BAP1-mediated HCFC1 deubiquitination. The event supports this activity; neither that event nor the annotation requires a universal increase in HCF-1 stability.
GO:0004843 cysteine-type deubiquitinase activity	TAS Reactome:R-HSA-5690790	ACCEPT	Summary: BAP1 supplies the deubiquitinase chemistry in the Reactome PR-DUB reaction. Reason: R-HSA-5690790 assigns catalytic BAP1 to nucleosomal H2A deubiquitination. Retain cysteine-type chemistry together with the existing H2A-specific activity; they emphasize complementary catalytic and substrate features.
GO:0005515 protein binding	IPI PMID:19117993 BRCA1-associated protein 1 interferes with BRCA1/BARD1 RING ...	MODIFY	Summary: The BRCA1-associated interaction contributes to inhibition of the BRCA1–BARD1 ubiquitin ligase. Reason: PMID:19117993 demonstrates reduced BRCA1 autoubiquitination and NPM1/B23 ubiquitination after BAP1 associates with the BRCA1–BARD1 complex. The more informative activity is ubiquitin ligase inhibition, mediated through the BARD1 RING interaction. Catalytically inactive BAP1 also inhibits the ligase, so this activity is distinct from substrate deubiquitination. The experiments do not establish that BAP1 always dissociates full-length BRCA1 from BARD1 in cells. Proposed replacements: ubiquitin ligase inhibitor activity
GO:0005515 protein binding	IPI PMID:19117993 BRCA1-associated protein 1 interferes with BRCA1/BARD1 RING ...	MODIFY	Summary: BARD1 binding supports the more specific ubiquitin ligase inhibitor activity. Reason: PMID:19117993 identifies a BAP1 region that binds the BARD1 RING domain and interferes with BRCA1–BARD1 ligase activity. Binding accompanied by reduced ubiquitination fits GO:1990948. Inhibition by catalytic-mutant BAP1 distinguishes this regulatory activity from removal of ubiquitin from BRCA1 or BARD1. Proposed replacements: ubiquitin ligase inhibitor activity Supporting Evidence: PMID:19117993 BAP1, C91S, still inhibited the ubiquitination in vitro and in vivo
GO:0005515 protein binding	IPI PMID:19188440 Association of C-terminal ubiquitin hydrolase BRCA1-associat...	KEEP AS NON CORE	Summary: Association with HCFC1 is valid supporting context. Reason: PMID:19188440 identifies an HCFC1-binding motif in BAP1 and associates this interaction with HCFC1 ubiquitination. Retain the established interaction; generic binding alone omits the substrate-regulatory function.
GO:0005515 protein binding	IPI PMID:19615732 Defining the human deubiquitinating enzyme interaction lands...	KEEP AS NON CORE	Summary: Association with HCFC1 is valid supporting context. Reason: PMID:19615732 is an affinity-purification interaction survey. HCFC1 association is independently supported by dedicated BAP1 studies, while this row does not by itself establish a purified binary interaction or define catalytic specificity.
GO:0005515 protein binding	IPI PMID:19615732 Defining the human deubiquitinating enzyme interaction lands...	KEEP AS NON CORE	Summary: Association with ASXL1 is valid supporting context. Reason: PMID:19615732 records a proteomic association with ASXL1. The dedicated PR-DUB biochemical and structural studies corroborate this partner relationship; a generic binding term does not describe ASXL-dependent catalytic activation.
GO:0005515 protein binding	IPI PMID:19815555 The deubiquitinating enzyme BAP1 regulates cell growth via i...	KEEP AS NON CORE	Summary: Association with HCFC1 is valid supporting context. Reason: PMID:19815555 maps the BAP1 motif required for binding the N-terminal HCFC1 Kelch region and links binding to HCFC1 deubiquitination. Preserve the interaction as supporting context for the substrate-specific function.
GO:0005515 protein binding	IPI PMID:20436459 Histone H2A deubiquitinase activity of the Polycomb repressi...	KEEP AS NON CORE	Summary: Association with ASXL1 is valid supporting context. Reason: PMID:20436459 includes recombinant human BAP1–ASXL1 complex experiments as well as Drosophila PR-DUB work. The partner relationship is valid; the more informative function is histone H2A deubiquitination by the complex.
GO:0005515 protein binding	IPI PMID:22897849 ASXL1 mutations promote myeloid transformation through loss ...	KEEP AS NON CORE	Summary: Association with ASXL1 is valid supporting context. Reason: PMID:22897849 reports ASXL1–BAP1 co-immunoprecipitation in human myeloid leukemia cells. This supports association without transferring the distinct ASXL1-dependent PRC2/HOXA phenotype to BAP1.
GO:0005515 protein binding	IPI PMID:24211834 BAP1 is phosphorylated at serine 592 in S-phase following DN...	KEEP AS NON CORE	Summary: Association with HCFC1 is valid supporting context. Reason: PMID:24211834 reports endogenous HeLa co-immunoprecipitation of BAP1 with HCFC1, including phosphorylated BAP1 after UV exposure. The physical association is supported, but generic binding is not a distinct catalytic function.
GO:0005515 protein binding	IPI PMID:25451922 BRCA1-associated protein 1 (BAP1) deubiquitinase antagonizes...	KEEP AS NON CORE	Summary: Association with FOXK1 is valid supporting context. Reason: PMID:25451922 supports association of phosphorylated BAP1 with forkhead factors. FOXK1 is a recruitment partner; the association does not give BAP1 the sequence-specific DNA-binding activity of the transcription factor.
GO:0005515 protein binding	IPI PMID:25451922 BRCA1-associated protein 1 (BAP1) deubiquitinase antagonizes...	KEEP AS NON CORE	Summary: Association with FOXK2 is valid supporting context. Reason: PMID:25451922 links BAP1 Thr493 phosphorylation to FOXK2 association and regulation of FOXK2 target genes. Retain the interaction while distinguishing recruitment from the H2A deubiquitinase activity supplied by BAP1.
GO:0005515 protein binding	IPI PMID:27705803 A High-Density Map for Navigating the Human Polycomb Complex...	KEEP AS NON CORE	Summary: Association with HCFC1 is valid supporting context. Reason: PMID:27705803 uses affinity-purification mass spectrometry to characterize human Polycomb-associated complexes. HCFC1 association is consistent with dedicated BAP1 studies; this proteomic row need not imply isolated binary binding.
GO:0005515 protein binding	IPI PMID:27705803 A High-Density Map for Navigating the Human Polycomb Complex...	KEEP AS NON CORE	Summary: Association with ASXL1 is valid supporting context. Reason: PMID:27705803 maps human PR-DUB-associated protein complexes. ASXL1 is an established BAP1 partner, but the generic interaction term is less informative than the catalytic PR-DUB relationship.
GO:0005515 protein binding	IPI PMID:28614305 BAP1 regulates IP3R3-mediated Ca(2+) flux to mitochondria su...	KEEP AS NON CORE	Summary: Association with ITPR3 is valid supporting context. Reason: PMID:28614305 supports BAP1 association with ITPR3 and removal of ubiquitin that affects receptor stability. The interaction does not make BAP1 a calcium channel; generic binding is retained as non-core context.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	KEEP AS NON CORE	Summary: Association with HCFC1 is valid supporting context. Reason: PMID:33961781 provides cell-line proteomic interaction evidence. The HCFC1 relationship is corroborated by focused BAP1 studies; co-purification does not independently resolve a binary binding mechanism.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	KEEP AS NON CORE	Summary: Association with ASXL1 is valid supporting context. Reason: PMID:33961781 provides proteomic association evidence for a well-established PR-DUB partner. Preserve the association while representing BAP1 function through its substrate-specific catalytic activity.
GO:0005515 protein binding	IPI PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei...	UNDECIDED	Summary: The BAP1–BRAF interaction requires pair-specific experimental context. Reason: PMID:35512704 compares wild-type and mutant cancer-protein interactions. The accessible main-text records do not resolve the BAP1–BRAF construct and variant pair underlying this row. Retain the assertion undecided pending those data; no interaction error is established.
GO:0005515 protein binding	IPI PMID:9528852 BAP1: a novel ubiquitin hydrolase which binds to the BRCA1 R...	MODIFY	Summary: The BRCA1 interaction can be assigned the ligase-inhibitory function established by subsequent work. Reason: PMID:9528852 establishes BRCA1 RING-region binding. The later experiments in PMID:19117993 connect BAP1 association with this same BRCA1–BARD1 complex to inhibition of its ubiquitin-ligase activity. Together they support GO:1990948 rather than generic binding. The functional interpretation comes from the later inhibition experiments; the original binding paper alone did not demonstrate that mechanism. Proposed replacements: ubiquitin ligase inhibitor activity
GO:0005515 protein binding	IPI PMID:9528852 BAP1: a novel ubiquitin hydrolase which binds to the BRCA1 R...	KEEP AS NON CORE	Summary: Association with a BRCA1 isoform is valid supporting context. Reason: The supporting entity is BRCA1 isoform P38398-5, not a BAP1 isoform. The curated interaction is retained as non-core. The later BRCA1–BARD1 inhibition experiments do not establish that this particular BRCA1 isoform was tested, so an isoform-specific ligase-inhibitor interpretation is not assigned to this row.
GO:0005634 nucleus	EXP PMID:24748658 The forkhead transcription factor FOXK2 acts as a chromatin ...	ACCEPT	Summary: The nucleus is a principal site of BAP1 activity. Reason: PMID:24748658 demonstrates nuclear colocalization of endogenous BAP1 and FOXK2 in U2OS cells. This location is appropriate for its established chromatin function.
GO:0005634 nucleus	EXP PMID:30664650 BAP1 complex promotes transcription by opposing PRC1-mediate...	ACCEPT	Summary: The nucleus is a principal site of BAP1 activity. Reason: PMID:30664650 studies nuclear BAP1 complexes and their effects on chromatin-associated histone ubiquitination. This location is appropriate for its established chromatin function.
GO:0005634 nucleus	EXP PMID:35051358 Rare germline heterozygous missense variants in BRCA1-associ...	ACCEPT	Summary: The nucleus is a principal site of BAP1 activity. Reason: PMID:35051358 concerns the nuclear deubiquitinase and functional effects of germline variants; the nuclear location agrees with independent direct localization studies. This location is appropriate for its established chromatin function.
GO:0005634 nucleus	EXP PMID:35446349 Tumor suppressor BAP1 nuclear import is governed by transpor...	ACCEPT	Summary: The nucleus is a principal site of BAP1 activity. Reason: PMID:35446349 demonstrates predominantly nuclear wild-type BAP1 and TNPO1-dependent import in human cells. This location is appropriate for its established chromatin function.
GO:0005634 nucleus	IDA PMID:18757409 BRCA1-associated protein-1 is a tumor suppressor that requir...	ACCEPT	Summary: The nucleus is a principal site of BAP1 activity. Reason: PMID:18757409 visualizes mainly nuclear wild-type BAP1 in HeLa cells and tests localization-signal mutants. This location is appropriate for its established chromatin function.
GO:0005634 nucleus	IDA PMID:19188440 Association of C-terminal ubiquitin hydrolase BRCA1-associat...	ACCEPT	Summary: The nucleus is a principal site of BAP1 activity. Reason: PMID:19188440 supports the nuclear HCFC1-associated BAP1 pool. This location is appropriate for its established chromatin function.
GO:0005634 nucleus	IDA PMID:19815555 The deubiquitinating enzyme BAP1 regulates cell growth via i...	ACCEPT	Summary: The nucleus is a principal site of BAP1 activity. Reason: PMID:19815555 places BAP1 in chromatin-associated regulatory complexes, consistent with nuclear activity. This location is appropriate for its established chromatin function.
GO:0005634 nucleus	IDA PMID:24703950 Autodeubiquitination protects the tumor suppressor BAP1 from...	ACCEPT	Summary: The nucleus is a principal site of BAP1 activity. Reason: PMID:24703950 demonstrates regulation of the nuclear BAP1 pool by autodeubiquitination and UBE2O-dependent cytoplasmic retention. This location is appropriate for its established chromatin function.
GO:0005634 nucleus	IEA GO_REF:0000120	ACCEPT	Summary: The nucleus is a principal site of BAP1 activity. Reason: The electronic subcellular-location mapping agrees with direct human localization experiments and the nuclear histone-substrate mechanism. This location is appropriate for its established chromatin function.
GO:0005634 nucleus	TAS PMID:9528852 BAP1: a novel ubiquitin hydrolase which binds to the BRCA1 R...	ACCEPT	Summary: The nucleus is a principal site of BAP1 activity. Reason: PMID:9528852 describes nuclear BAP1, consistent with later direct localization and chromatin studies. This location is appropriate for its established chromatin function.
GO:0005654 nucleoplasm	IDA GO_REF:0000052	ACCEPT	Summary: BAP1 has a nucleoplasmic pool. Reason: The immunofluorescence-derived source annotation is consistent with independent BAP1 nuclear localization, soluble nuclear complexes and dynamic chromatin association.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-5689630	ACCEPT	Summary: Nucleoplasmic localization is consistent with the curated reaction context. Reason: The Reactome record places BAP1 in the nucleoplasm during association with BAP1-interacting regulatory complexes. This agrees with its experimentally established nuclear localization; the location assertion does not imply that every associated protein is a BAP1 substrate.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-5689649	ACCEPT	Summary: Nucleoplasmic localization is consistent with the curated reaction context. Reason: The Reactome record places BAP1 in the nucleoplasm during association with BRCA1–BARD1. This agrees with its experimentally established nuclear localization; the location assertion does not imply that every associated protein is a BAP1 substrate.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-5690759	ACCEPT	Summary: Nucleoplasmic localization is consistent with the curated reaction context. Reason: The Reactome record places BAP1 in the nucleoplasm during HCFC1 deubiquitination. This agrees with its experimentally established nuclear localization; the location assertion does not imply that every associated protein is a BAP1 substrate.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-5690785	ACCEPT	Summary: Nucleoplasmic localization is consistent with the curated reaction context. Reason: The Reactome record places BAP1 in the nucleoplasm during association with ubiquitinated HCFC1. This agrees with its experimentally established nuclear localization; the location assertion does not imply that every associated protein is a BAP1 substrate.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-5690790	ACCEPT	Summary: Nucleoplasmic localization is consistent with the curated reaction context. Reason: The Reactome record places BAP1 in the nucleoplasm during PR-DUB-mediated H2A deubiquitination. This agrees with its experimentally established nuclear localization; the location assertion does not imply that every associated protein is a BAP1 substrate.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-9700998	ACCEPT	Summary: Nucleoplasmic localization is consistent with the curated reaction context. Reason: The Reactome record places BAP1 in the nucleoplasm during modulation of the BRCA1–BARD1 heterodimer. This agrees with its experimentally established nuclear localization; the location assertion does not imply that every associated protein is a BAP1 substrate.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-9701003	ACCEPT	Summary: Nucleoplasmic localization is consistent with the curated reaction context. Reason: The Reactome record places BAP1 in the nucleoplasm during association with the BRCA1–BARD1 heterodimer. This agrees with its experimentally established nuclear localization; the location assertion does not imply that every associated protein is a BAP1 substrate.
GO:0005694 chromosome	EXP PMID:30664650 BAP1 complex promotes transcription by opposing PRC1-mediate...	ACCEPT	Summary: Chromosome association reflects the chromatin-bound BAP1 pool. Reason: PMID:30664650 links BAP1 complexes to chromatin-associated histone H2A ubiquitination and transcription. Retain chromosome association without implying that BAP1 is a constitutive chromosome scaffold.
GO:0005694 chromosome	IEA GO_REF:0000120	ACCEPT	Summary: The electronic chromosome annotation is consistent with chromatin association. Reason: BAP1 acts on nucleosomal H2A and is experimentally associated with chromatin. This supports the source location mapping without adding sequence-specific DNA recognition or a structural chromosome role.
GO:0005737 cytoplasm	EXP PMID:19815555 The deubiquitinating enzyme BAP1 regulates cell growth via i...	KEEP AS NON CORE	Summary: BAP1 has a regulated cytoplasmic pool. Reason: The experimental source supports a cytoplasmic pool alongside chromatin-associated BAP1. Retain this broader location as context for shuttling and nonhistone functions; the principal histone-substrate activity is nuclear.
GO:0005737 cytoplasm	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: BAP1 has a regulated cytoplasmic pool. Reason: The inherited PAINT annotation is consistent with direct human localization studies and the independently established cytoplasmic BAP1 pool. Retain this broader location as context for shuttling and nonhistone functions; the principal histone-substrate activity is nuclear.
GO:0005737 cytoplasm	IDA PMID:18757409 BRCA1-associated protein-1 is a tumor suppressor that requir...	KEEP AS NON CORE	Summary: BAP1 has a regulated cytoplasmic pool. Reason: PMID:18757409 detects some cytoplasmic wild-type BAP1 in HeLa cells and stronger retention of localization-signal mutants. Retain this broader location as context for shuttling and nonhistone functions; the principal histone-substrate activity is nuclear.
GO:0005737 cytoplasm	IDA PMID:19188440 Association of C-terminal ubiquitin hydrolase BRCA1-associat...	KEEP AS NON CORE	Summary: BAP1 has a regulated cytoplasmic pool. Reason: The HCFC1-associated study supports a cytoplasmic pool in addition to nuclear BAP1. Retain this broader location as context for shuttling and nonhistone functions; the principal histone-substrate activity is nuclear.
GO:0005737 cytoplasm	IDA PMID:24703950 Autodeubiquitination protects the tumor suppressor BAP1 from...	KEEP AS NON CORE	Summary: BAP1 has a regulated cytoplasmic pool. Reason: PMID:24703950 directly links UBE2O-dependent monoubiquitination to cytoplasmic retention of BAP1. Retain this broader location as context for shuttling and nonhistone functions; the principal histone-substrate activity is nuclear.
GO:0005737 cytoplasm	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: BAP1 has a regulated cytoplasmic pool. Reason: The UniProt location mapping is corroborated by experimental detection of cytoplasmic BAP1. Retain this broader location as context for shuttling and nonhistone functions; the principal histone-substrate activity is nuclear.
GO:0005829 cytosol	IDA GO_REF:0000052	KEEP AS NON CORE	Summary: BAP1 has a regulated cytoplasmic pool. Reason: The immunofluorescence-derived cytosol annotation agrees with direct cytoplasmic localization studies. Retain this broader location as context for shuttling and nonhistone functions; the principal histone-substrate activity is nuclear.
GO:0006511 ubiquitin-dependent protein catabolic process	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: Retain a contextual ubiquitin-dependent protein-turnover role outside the principal catalytic summary. Reason: The InterPro UCH-family assignments alone do not demonstrate protein degradation. Independent evidence in the original Results and Discussion of PMID:19188440 reports a modest accumulation of precursor and processed HCFC1 after BAP1 depletion; the authors propose that deubiquitination may facilitate HCFC1 turnover. This supports a contextual, non-core protein-turnover role, with the proteasomal mechanism remaining an interpretation rather than a demonstrated general consequence of BAP1 catalysis. These details come from the separately inspected original article, not solely from its abstract-only local cache.
GO:0008233 peptidase activity	NAS PMID:9528852 BAP1: a novel ubiquitin hydrolase which binds to the BRCA1 R...	MODIFY	Summary: The early peptidase annotation can specify ubiquitin-directed cysteine catalysis. Reason: PMID:9528852 identifies BAP1 as a ubiquitin carboxyl-terminal hydrolase; subsequent C91-mutant experiments establish the catalytic class. GO:0004843 is a verified descendant of peptidase activity and states the supported chemistry. Its presence in other source rows does not make this refinement invalid. Proposed replacements: cysteine-type deubiquitinase activity
GO:0008283 cell population proliferation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Cell proliferation is a context-dependent consequence of BAP1 activity. Reason: BAP1 can support proliferation in some cellular contexts and suppress growth in others. Retain the ortholog-based phenotype without treating proliferation itself as the primary biochemical function.
GO:0008285 negative regulation of cell population proliferation	TAS PMID:9528852 BAP1: a novel ubiquitin hydrolase which binds to the BRCA1 R...	KEEP AS NON CORE	Summary: BAP1 can suppress cell population expansion in a tumor-cell context. Reason: PMID:9528852 reports enhancement of BRCA1-mediated growth suppression. This context-dependent cellular outcome is retained separately from BAP1 catalytic activity; other human cell studies also show growth-supporting effects.
GO:0010467 gene expression	IEA GO_REF:0000107	MODIFY	Summary: BAP1 participates in gene expression through transcriptional regulation. Reason: Reassign this broad orthology-derived process to regulation of DNA-templated transcription, which is supported directly in human cells. This is a change to the regulatory relationship, not a claim that the replacement is an is_a descendant of gene expression. BAP1 modifies chromatin and its transcriptional effects depend on the locus and cellular setting. Proposed replacements: regulation of DNA-templated transcription
GO:0010468 regulation of gene expression	IEA GO_REF:0000117	MODIFY	Summary: The broad electronic gene-expression regulation term can specify transcription. Reason: Human chromatin and transcription experiments support GO:0006355, a verified child of regulation of gene expression. This refinement preserves both activating and repressive contexts without asserting universal directionality. Proposed replacements: regulation of DNA-templated transcription
GO:0016579 protein deubiquitination	IDA PMID:18757409 BRCA1-associated protein-1 is a tumor suppressor that requir...	ACCEPT	Summary: Protein deubiquitination is a central BAP1 process. Reason: The cited paper directly tests ubiquitin-hydrolase catalysis with a model substrate. Retain its curated process assignment, corroborated by independent HCF-1 and nucleosomal H2A substrate experiments; do not describe the model assay itself as identifying a physiological protein substrate.
GO:0016579 protein deubiquitination	IDA PMID:19815555 The deubiquitinating enzyme BAP1 regulates cell growth via i...	ACCEPT	Summary: BAP1 deubiquitinates HCF-1N. Reason: PMID:19815555 directly reports HCF-1N deubiquitination requiring the BAP1 HCF-binding motif. This is catalytic participation in ubiquitin removal, not an inference from a downstream growth phenotype.
GO:0016579 protein deubiquitination	TAS Reactome:R-HSA-5688426	ACCEPT	Summary: BAP1 is a catalytic participant in protein deubiquitination. Reason: The Reactome deubiquitination pathway is consistent with direct BAP1 substrate experiments. Retain the process without applying every generic pathway-summary statement, such as proteasomal ubiquitin recycling, specifically to BAP1.
GO:0030218 erythrocyte differentiation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Erythrocyte differentiation is a downstream hematopoietic phenotype. Reason: The mouse ortholog transfer concerns erythroid differentiation following Bap1 perturbation. BAP1 is a chromatin-associated deubiquitinase rather than an erythrocyte-specific structural or metabolic protein.
GO:0030223 neutrophil differentiation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Neutrophil differentiation is a context-dependent hematopoietic association. Reason: Bap1 loss perturbs myeloid lineage balance in mice. The transferred human annotation is retained as a physiological consequence of altered regulation, not as a distinct core neutrophil differentiation mechanism.
GO:0030851 granulocyte differentiation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Granulocyte differentiation is a downstream lineage phenotype. Reason: This conserved-ortholog inference concerns granulocytic differentiation. It is compatible with the hematopoietic effects of Bap1 deficiency but does not specify a separate granulocyte-directed molecular activity.
GO:0031490 chromatin DNA binding	IEA GO_REF:0000107	ACCEPT	Summary: BAP1 contacts DNA within its nucleosomal substrate. Reason: Human BAP1-ASXL1 structural and biochemical work supports the chromatin-DNA binding inferred from mouse Bap1. The 2023 substrate-bound structure resolves DNA contacts; this is stronger evidence than cellular chromatin fractionation alone and does not imply sequence-specific transcription-factor activity.
GO:0031507 heterochromatin formation	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Retain the PAINT ancestral heterochromatin-formation inference with its evolutionary read limit explicit. Reason: The local family record verifies positive IBD GO:0031507 at PTN000834067, taxon6072, with Calypso experimental grounding. Human and fly BAP1/Calypso membership and conserved PR-DUB biochemistry are consistent with retaining the curator inference. Full topology/MSA was not available, and the human studies read here do not directly reconstruct heterochromatin nucleation and spreading. Keep this contextual process outside the central human catalytic summary; no donor-count, self-donor or target-loss objection is asserted.
GO:0033028 myeloid cell apoptotic process	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Myeloid-cell apoptosis is a downstream survival phenotype. Reason: The mouse ortholog assertion concerns survival of myeloid cells after Bap1 perturbation. Cell death is context dependent and does not define the substrate-specific deubiquitinase function of human BAP1.
GO:0035517 PR-DUB complex	IDA PMID:20436459 Histone H2A deubiquitinase activity of the Polycomb repressi...	ACCEPT	Summary: BAP1 is the catalytic component of human PR-DUB. Reason: PMID:20436459 identifies and reconstitutes human BAP1-ASXL1 as well as the fly complex. Membership is independently supported by later human structural work. Do not impose a single universal oligomeric stoichiometry on all complexes.
GO:0035517 PR-DUB complex	IDA PMID:25451922 BRCA1-associated protein 1 (BAP1) deubiquitinase antagonizes...	ACCEPT	Summary: The curated PR-DUB membership agrees with the established BAP1-ASXL complex. Reason: Retain the source-specific IDA with curator deference. Selected PMID:25451922 sections address recruited BAP1 chromatin complexes; independent reconstitution and structures establish PR-DUB membership. No new purified-complex result is attributed to this paper.
GO:0035517 PR-DUB complex	IPI PMID:20436459 Histone H2A deubiquitinase activity of the Polycomb repressi...	ACCEPT	Summary: Physical association with ASXL supports BAP1 membership in PR-DUB. Reason: The human BAP1-ASXL1 complex in PMID:20436459 supports the IPI membership annotation. Retain both source assertions; sharing the same GO term with another evidence row is not a reason to remove either.
GO:0035520 monoubiquitinated protein deubiquitination	IDA PMID:24703950 Autodeubiquitination protects the tumor suppressor BAP1 from...	ACCEPT	Summary: BAP1 reverses monoubiquitination, including ubiquitin installed on BAP1 itself. Reason: PMID:24703950 explicitly reports reversal of UBE2O-mediated multi-monoubiquitination. This supports the stated process; removal of monoubiquitin from histone H2A independently demonstrates the same process class.
GO:0035726 common myeloid progenitor cell proliferation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Myeloid progenitor proliferation is a context-dependent physiological effect. Reason: Bap1 deficiency alters the abundance and behavior of myeloid progenitors in mice. Retain this ortholog-derived association while distinguishing a progenitor phenotype from BAP1-mediated ubiquitin removal.
GO:0036211 protein modification process	NAS PMID:9528852 BAP1: a novel ubiquitin hydrolase which binds to the BRCA1 R...	MODIFY	Summary: The generic protein-modification process can specify deubiquitination. Reason: The original hydrolase identification and later substrate assays establish removal of ubiquitin. GO:0016579 is a verified descendant of protein modification process and gives the correct specific process rather than retaining an uninformative ancestor. Proposed replacements: protein deubiquitination
GO:0036344 platelet morphogenesis	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Platelet morphogenesis is a downstream hematopoietic association. Reason: The source transfers a mouse platelet phenotype to the human ortholog. BAP1-dependent gene regulation can affect hematopoietic maturation, but this does not establish a platelet-shaping activity of the enzyme itself.
GO:0043249 erythrocyte maturation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Erythrocyte maturation is a non-core lineage outcome. Reason: Retain the source ortholog inference as an erythroid maturation phenotype. It does not demonstrate an erythrocyte-specific biochemical activity beyond the broader regulatory consequences of BAP1 function.
GO:0043363 nucleate erythrocyte differentiation	IEA GO_REF:0000107	MODIFY	Summary: Generalize the erythroid phenotype to erythrocyte differentiation. Reason: The current GO design pattern defines GO:0043363 by differentiation into the mature nucleate-erythrocyte cell type, rather than simply passing through a nucleated precursor. PMID:22878500 reports anemia and erythroid dysplasia with increased nucleated erythroid cells after Bap1 loss in adult mice. Those abnormalities support the broader erythrocyte-differentiation context, but do not demonstrate production of the mature nucleate-erythrocyte cell type. GO:0030218 preserves that contextual lineage role while avoiding the unsupported specialization. The evidence is a mouse knockout phenotype underlying an electronic transfer, not a direct human differentiation assay. Proposed replacements: erythrocyte differentiation
GO:0045892 negative regulation of DNA-templated transcription	IDA PMID:25451922 BRCA1-associated protein 1 (BAP1) deubiquitinase antagonizes...	ACCEPT	Summary: BAP1 can repress FOXK2 target transcription through catalytic chromatin regulation. Reason: PMID:25451922 shows target-expression increases after depletion and repression after WT rescue, requiring catalytic activity. Retain this direct contextual role; activation in human HAP1 cells does not negate it.
GO:0048536 spleen development	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Spleen development is an organismal phenotype rather than BAP1 chemistry. Reason: The transferred annotation records a mouse organ-level role. Disturbed hematopoiesis can alter splenic organization and cellular composition; the human protein remains a deubiquitinase with broader cellular roles.
GO:0051726 regulation of cell cycle	IMP PMID:19188440 Association of C-terminal ubiquitin hydrolase BRCA1-associat...	KEEP AS NON CORE	Summary: HCFC1-associated BAP1 activity affects cell-cycle regulation. Reason: PMID:19188440 links BAP1–HCFC1 association and ubiquitination state to regulation associated with the G1–S transition. This is a cellular consequence of the enzyme–substrate relationship, not a distinct cell-cycle catalytic reaction.
GO:0061484 hematopoietic stem cell homeostasis	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Hematopoietic stem-cell homeostasis is a physiological consequence of BAP1 activity. Reason: Mouse Bap1 perturbation affects stem and progenitor cell maintenance. Retain this conserved regulatory association separately from the catalytic removal of ubiquitin from histone and nonhistone substrates.
GO:0070661 leukocyte proliferation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Leukocyte proliferation is a context-dependent hematopoietic phenotype. Reason: The ortholog-derived annotation is consistent with altered leukocyte production after Bap1 loss. It does not establish an independent leukocyte-specific catalytic or signaling activity.
GO:0071108 protein K48-linked deubiquitination	IMP PMID:19188440 Association of C-terminal ubiquitin hydrolase BRCA1-associat...	ACCEPT	Summary: BAP1 participates in K48-linked HCF-1 deubiquitination in human cells. Reason: The original PMID:19188440 Results and Figure 5B–C compare wild-type BAP1 with C91A in human cells using linkage-restricted ubiquitin and denaturing HCFC1 immunoprecipitation. Inactive BAP1 increases K48-conjugated HCFC1 without the same K63 effect. These separately inspected primary-article experiments support the IMP process in the tested HCFC1 context; they do not establish unrestricted cleavage of every free K48 chain. The local publication cache contains the abstract only.
GO:0140950 histone H2A deubiquitinase activity	IMP PMID:25451922 BRCA1-associated protein 1 (BAP1) deubiquitinase antagonizes...	ACCEPT	Summary: BAP1 supplies histone H2A deubiquitinase activity. Reason: The cited perturbation study supports H2Aub regulation at FOXK2 targets. Human purified-enzyme and substrate-bound structural studies independently establish the molecular activity.
GO:1903749 obsolete positive regulation of protein localization to mitochondrion	HMP PMID:24270810 High-content genome-wide RNAi screens identify regulators of...	KEEP AS NON CORE	Summary: BAP1 perturbation affects parkin recruitment to damaged mitochondria. Reason: PMID:24270810 includes BAP1 among reconfirmed siRNA-screen candidates with knockdown controls. This supports a context-dependent recruitment phenotype, not a mitochondrial import-factor or core mitophagy-enzyme activity. Preserve the source term identifier and label.

Gene Description

Existing Annotations Review

Core Functions

References

Suggested Questions for Experts

Suggested Experiments

📚 Additional Documentation

Notes

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