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Protein

Ubiquitin carboxyl-terminal hydrolase BAP1

Gene

BAP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Deubiquitinating enzyme that plays a key role in chromatin by mediating deubiquitination of histone H2A and HCFC1. Catalytic component of the PR-DUB complex, a complex that specifically mediates deubiquitination of histone H2A monoubiquitinated at 'Lys-119' (H2AK119ub1). Does not deubiquitinate monoubiquitinated histone H2B. 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. Deubiquitination of HCFC1 does not lead to increase stability of HCFC1. Interferes with the BRCA1 and BARD1 heterodimer activity by inhibiting their ability to mediate ubiquitination and autoubiquitination. It however does not mediate deubiquitination of BRCA1 and BARD1. 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.8 Publications

Catalytic activityi

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).1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei91NucleophileCurated1
Active sitei169Proton donorBy similarity1
Sitei184Important for enzyme activityBy similarity1

GO - Molecular functioni

  • chromatin binding Source: UniProtKB
  • peptidase activity Source: UniProtKB
  • thiol-dependent ubiquitin-specific protease activity Source: UniProtKB
  • thiol-dependent ubiquitinyl hydrolase activity Source: UniProtKB

GO - Biological processi

  • cellular protein modification process Source: UniProtKB
  • macrophage homeostasis Source: Ensembl
  • monoubiquitinated histone H2A deubiquitination Source: UniProtKB
  • monoubiquitinated protein deubiquitination Source: UniProtKB
  • negative regulation of cell proliferation Source: ProtInc
  • positive regulation of protein targeting to mitochondrion Source: ParkinsonsUK-UCL
  • protein deubiquitination Source: UniProtKB
  • protein K48-linked deubiquitination Source: UniProtKB
  • regulation of cell cycle Source: UniProtKB
  • regulation of cell growth Source: UniProtKB
  • regulation of cytokine production involved in inflammatory response Source: Ensembl
  • response to inorganic substance Source: Ensembl
  • ubiquitin-dependent protein catabolic process Source: InterPro

Keywordsi

Molecular functionChromatin regulator, Hydrolase, Protease, Thiol protease
Biological processUbl conjugation pathway

Enzyme and pathway databases

BRENDAi3.4.19.12 2681
ReactomeiR-HSA-5689603 UCH proteinases
R-HSA-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
SIGNORiQ92560

Protein family/group databases

MEROPSiC12.004

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin carboxyl-terminal hydrolase BAP1 (EC:3.4.19.12)
Alternative name(s):
BRCA1-associated protein 1
Cerebral protein 6
Gene namesi
Name:BAP1
Synonyms:KIAA0272
ORF Names:hucep-6
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000163930.9
HGNCiHGNC:950 BAP1
MIMi603089 gene
neXtProtiNX_Q92560

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Mesothelioma, malignant (MESOM)2 Publications
The gene represented in this entry is involved in disease pathogenesis.
Disease descriptionAn 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.
See also OMIM:156240
Tumor predisposition syndrome (TPDS)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:614327

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi91C → A or S: Abolishes enzymatic activity without affecting its ability to interfere with BRCA1 E3 ligase activity. 5 Publications1
Mutagenesisi363 – 366NHNY → AAAA: Abolishes interaction with HCFC1. 2 Publications4
Mutagenesisi656 – 661KRKKFK → AAAAAA: Does not affect nuclear localization. 1 Publication6
Mutagenesisi691 – 711Missing : Abolishes ubiquitination by UBE2O. 1 PublicationAdd BLAST21
Mutagenesisi691L → P: Abolishes interaction with BRCA1. 1 Publication1
Mutagenesisi717 – 722RRKRSR → AAAAAA: Abolishes nuclear localization. 1 Publication6

Organism-specific databases

DisGeNETi8314
MalaCardsiBAP1
MIMi156240 phenotype
614327 phenotype
OpenTargetsiENSG00000163930
Orphaneti289539 BAP1-related tumor predisposition syndrome
PharmGKBiPA25254

Chemistry databases

ChEMBLiCHEMBL1293314

Polymorphism and mutation databases

BioMutaiBAP1
DMDMi68565074

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002110691 – 729Ubiquitin carboxyl-terminal hydrolase BAP1Add BLAST729

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei292PhosphoserineCombined sources1
Modified residuei369PhosphoserineCombined sources1
Modified residuei395PhosphoserineBy similarity1
Modified residuei521PhosphoserineCombined sources1
Modified residuei537PhosphoserineCombined sources1
Modified residuei585PhosphoserineCombined sources1
Modified residuei597PhosphoserineCombined sources1

Post-translational modificationi

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.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ92560
MaxQBiQ92560
PaxDbiQ92560
PeptideAtlasiQ92560
PRIDEiQ92560

PTM databases

iPTMnetiQ92560
PhosphoSitePlusiQ92560

Expressioni

Tissue specificityi

Highly expressed in testis, placenta and ovary. Expressed in breast.1 Publication

Gene expression databases

BgeeiENSG00000163930
CleanExiHS_BAP1
ExpressionAtlasiQ92560 baseline and differential
GenevisibleiQ92560 HS

Organism-specific databases

HPAiCAB004322
HPA028814
HPA028815
HPA055560

Interactioni

Subunit structurei

Component of the PR-DUB complex, at least composed of BAP1 and ASXL1. Interacts with BRCA1 (via the RING finger). Interacts (via HBM-like motif) with HCFC1.5 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi113911, 71 interactors
DIPiDIP-47004N
IntActiQ92560, 55 interactors
MINTiQ92560
STRINGi9606.ENSP00000417132

Chemistry databases

BindingDBiQ92560

Structurei

3D structure databases

ProteinModelPortaliQ92560
SMRiQ92560
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni596 – 721Interaction with BRCA1Add BLAST126

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili630 – 661Sequence analysisAdd BLAST32

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi363 – 366HBM-like motif4
Motifi717 – 722Nuclear localization signal2 Publications6

Sequence similaritiesi

Belongs to the peptidase C12 family. BAP1 subfamily.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG2778 Eukaryota
ENOG410XP0P LUCA
GeneTreeiENSGT00510000046560
HOGENOMiHOG000013189
HOVERGENiHBG054042
InParanoidiQ92560
KOiK08588
OMAiCIRYNRA
OrthoDBiEOG091G08R7
PhylomeDBiQ92560
TreeFamiTF313976

Family and domain databases

Gene3Di3.40.532.10, 1 hit
InterProiView protein in InterPro
IPR001578 Peptidase_C12_UCH
IPR036959 Peptidase_C12_UCH_sf
PANTHERiPTHR10589 PTHR10589, 1 hit
PfamiView protein in Pfam
PF01088 Peptidase_C12, 1 hit
PRINTSiPR00707 UBCTHYDRLASE

Sequencei

Sequence statusi: Complete.

Q92560-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNKGWLELES DPGLFTLLVE DFGVKGVQVE EIYDLQSKCQ GPVYGFIFLF
60 70 80 90 100
KWIEERRSRR KVSTLVDDTS VIDDDIVNNM FFAHQLIPNS CATHALLSVL
110 120 130 140 150
LNCSSVDLGP TLSRMKDFTK GFSPESKGYA IGNAPELAKA HNSHARPEPR
160 170 180 190 200
HLPEKQNGLS AVRTMEAFHF VSYVPITGRL FELDGLKVYP IDHGPWGEDE
210 220 230 240 250
EWTDKARRVI MERIGLATAG EPYHDIRFNL MAVVPDRRIK YEARLHVLKV
260 270 280 290 300
NRQTVLEALQ QLIRVTQPEL IQTHKSQESQ LPEESKSASN KSPLVLEANR
310 320 330 340 350
APAASEGNHT DGAEEAAGSC AQAPSHSPPN KPKLVVKPPG SSLNGVHPNP
360 370 380 390 400
TPIVQRLPAF LDNHNYAKSP MQEEEDLAAG VGRSRVPVRP PQQYSDDEDD
410 420 430 440 450
YEDDEEDDVQ NTNSALRYKG KGTGKPGALS GSADGQLSVL QPNTINVLAE
460 470 480 490 500
KLKESQKDLS IPLSIKTSSG AGSPAVAVPT HSQPSPTPSN ESTDTASEIG
510 520 530 540 550
SAFNSPLRSP IRSANPTRPS SPVTSHISKV LFGEDDSLLR VDCIRYNRAV
560 570 580 590 600
RDLGPVISTG LLHLAEDGVL SPLALTEGGK GSSPSIRPIQ GSQGSSSPVE
610 620 630 640 650
KEVVEATDSR EKTGMVRPGE PLSGEKYSPK ELLALLKCVE AEIANYEACL
660 670 680 690 700
KEEVEKRKKF KIDDQRRTHN YDEFICTFIS MLAQEGMLAN LVEQNISVRR
710 720
RQGVSIGRLH KQRKPDRRKR SRPYKAKRQ
Length:729
Mass (Da):80,362
Last modified:November 1, 1998 - v2
Checksum:i031DA03AE1841D85
GO

Sequence cautioni

The sequence BAA13401 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07525147I → F Found in a primary uveal melanoma; somatic mutation; induces cytoplasmic accumulation; loss of deubiquitinase activity; upregulates heat shock response; induces formation of amyloid-beta aggregates. 2 Publications1
Natural variantiVAR_06597663S → C Found in a malignant pleural mesothelioma sample; somatic mutation. 1 Publication1
Natural variantiVAR_06597781F → V Found in a malignant pleural mesothelioma sample; somatic mutation; induces cytoplasmic accumulation; loss of deubiquitinase activity; upregulates heat shock response; induces formation of amyloid-beta aggregates. 2 Publications1
Natural variantiVAR_06597891C → W Found in a malignant pleural mesothelioma sample. 1 Publication1
Natural variantiVAR_06349895A → D in a lung cancer sample; also found in a malignant pleural mesothelioma cell line; induces cytoplasmic accumulation; loss of deubiquitinase activity; upregulates heat shock response; induces formation of amyloid-beta aggregates. 4 Publications1
Natural variantiVAR_063499178G → V in a lung cancer sample; induces cytoplasmic accumulation; impairs deubiquitinase activity; upregulates heat shock response; induces formation of beta-amyloid aggregates. 3 Publications1
Natural variantiVAR_065979315E → A Found in a malignant pleural mesothelioma sample. 1 PublicationCorresponds to variant dbSNP:rs149974450EnsemblClinVar.1
Natural variantiVAR_051517616V → E. Corresponds to variant dbSNP:rs35353781Ensembl.1
Natural variantiVAR_065980685E → V Found in a malignant pleural mesothelioma cell line. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF045581 mRNA Translation: AAC15970.1
D88812 mRNA Translation: BAB46921.1
D87462 mRNA Translation: BAA13401.2 Different initiation.
AK292608 mRNA Translation: BAF85297.1
CH471055 Genomic DNA Translation: EAW65220.1
BC001596 mRNA Translation: AAH01596.1
AY130008 mRNA Translation: AAN05092.1
CCDSiCCDS2853.1
RefSeqiNP_004647.1, NM_004656.3
UniGeneiHs.106674

Genome annotation databases

EnsembliENST00000460680; ENSP00000417132; ENSG00000163930
GeneIDi8314
KEGGihsa:8314
UCSCiuc003ddx.5 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiBAP1_HUMAN
AccessioniPrimary (citable) accession number: Q92560
Secondary accession number(s): A8K993, Q6LEM0, Q7Z5E8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 5, 2005
Last sequence update: November 1, 1998
Last modified: May 23, 2018
This is version 151 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Peptidase families
    Classification of peptidase families and list of entries
  6. SIMILARITY comments
    Index of protein domains and families

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