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Protein

Ubiquitin carboxyl-terminal hydrolase BAP1

Gene

BAP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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)LengthDescriptionGraphical viewFeature identifierActions
Active sitei91 – 911NucleophileCurated
Active sitei169 – 1691Proton donorBy similarity
Sitei184 – 1841Important for enzyme activityBy similarity

GO - Molecular functioni

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

GO - Biological processi

  • cellular protein modification process Source: UniProtKB
  • 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
  • ubiquitin-dependent protein catabolic process Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Ubl conjugation pathway

Enzyme and pathway databases

BRENDAi3.4.19.12. 2681.
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

HGNCiHGNC:950. BAP1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
  • PR-DUB complex Source: UniProtKB
Complete GO annotation...

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)1 Publication
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)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi91 – 911C → A or S: Abolishes enzymatic activity without affecting its ability to interfere with BRCA1 E3 ligase activity. 5 Publications
Mutagenesisi363 – 3664NHNY → AAAA: Abolishes interaction with HCFC1. 2 Publications
Mutagenesisi656 – 6616KRKKFK → AAAAAA: Does not affect nuclear localization. 1 Publication
Mutagenesisi691 – 71121Missing : Abolishes ubiquitination by UBE2O. 1 PublicationAdd
BLAST
Mutagenesisi691 – 6911L → P: Abolishes interaction with BRCA1. 1 Publication
Mutagenesisi717 – 7226RRKRSR → AAAAAA: Abolishes nuclear localization. 1 Publication

Organism-specific databases

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

Chemistry

ChEMBLiCHEMBL1293314.

Polymorphism and mutation databases

BioMutaiBAP1.
DMDMi68565074.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 729729Ubiquitin carboxyl-terminal hydrolase BAP1PRO_0000211069Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei292 – 2921PhosphoserineCombined sources
Modified residuei369 – 3691PhosphoserineCombined sources
Modified residuei395 – 3951PhosphoserineBy similarity
Modified residuei521 – 5211PhosphoserineCombined sources
Modified residuei537 – 5371PhosphoserineCombined sources
Modified residuei585 – 5851PhosphoserineCombined sources
Modified residuei597 – 5971PhosphoserineCombined sources

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.
PhosphoSiteiQ92560.

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.
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

WithEntry#Exp.IntActNotes
ASXL1Q8IXJ94EBI-1791447,EBI-1646500
BRCA1P383983EBI-1791447,EBI-349905
BRCA1P38398-52EBI-1791447,EBI-2015072
HCFC1P516103EBI-1791447,EBI-396176

Protein-protein interaction databases

BioGridi113911. 63 interactions.
DIPiDIP-47004N.
IntActiQ92560. 39 interactions.
STRINGi9606.ENSP00000417132.

Chemistry

BindingDBiQ92560.

Structurei

3D structure databases

ProteinModelPortaliQ92560.
SMRiQ92560. Positions 5-284, 636-694.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni596 – 721126Interaction with BRCA1Add
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili630 – 66132Sequence analysisAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi363 – 3664HBM-like motif
Motifi717 – 7226Nuclear localization signal2 Publications

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.
OMAiYKRKGPG.
OrthoDBiEOG091G08R7.
PhylomeDBiQ92560.
TreeFamiTF313976.

Family and domain databases

Gene3Di3.40.532.10. 1 hit.
InterProiIPR001578. Peptidase_C12_UCH.
[Graphical view]
PANTHERiPTHR10589. PTHR10589. 1 hit.
PfamiPF01088. Peptidase_C12. 1 hit.
[Graphical view]
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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti47 – 471I → F Found in a primary uveal melanoma; somatic mutation; induces cytoplasmic accumulation; loss of deubiquitinase activity; upregulates heat shock response; induces formation of beta-amyloid aggregates. 2 Publications
VAR_075251
Natural varianti63 – 631S → C Found in a malignant pleural mesothelioma sample; somatic mutation. 1 Publication
VAR_065976
Natural varianti81 – 811F → V Found in a malignant pleural mesothelioma sample; somatic mutation; induces cytoplasmic accumulation; loss of deubiquitinase activity; upregulates heat shock response; induces formation of beta-amyloid aggregates. 2 Publications
VAR_065977
Natural varianti91 – 911C → W Found in a malignant pleural mesothelioma sample. 1 Publication
VAR_065978
Natural varianti95 – 951A → 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 beta-amyloid aggregates. 4 Publications
VAR_063498
Natural varianti178 – 1781G → V in a lung cancer sample; induces cytoplasmic accumulation; impairs deubiquitinase activity; upregulates heat shock response; induces formation of beta-amyloid aggregates. 3 Publications
VAR_063499
Natural varianti315 – 3151E → A Found in a malignant pleural mesothelioma sample. 1 Publication
Corresponds to variant rs149974450 [ dbSNP | Ensembl ].
VAR_065979
Natural varianti616 – 6161V → E.
Corresponds to variant rs35353781 [ dbSNP | Ensembl ].
VAR_051517
Natural varianti685 – 6851E → V Found in a malignant pleural mesothelioma cell line. 1 Publication
VAR_065980

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

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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.

3D structure databases

ProteinModelPortaliQ92560.
SMRiQ92560. Positions 5-284, 636-694.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113911. 63 interactions.
DIPiDIP-47004N.
IntActiQ92560. 39 interactions.
STRINGi9606.ENSP00000417132.

Chemistry

BindingDBiQ92560.
ChEMBLiCHEMBL1293314.

Protein family/group databases

MEROPSiC12.004.

PTM databases

iPTMnetiQ92560.
PhosphoSiteiQ92560.

Polymorphism and mutation databases

BioMutaiBAP1.
DMDMi68565074.

Proteomic databases

EPDiQ92560.
MaxQBiQ92560.
PaxDbiQ92560.
PeptideAtlasiQ92560.
PRIDEiQ92560.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi8314.
GeneCardsiBAP1.
HGNCiHGNC:950. BAP1.
HPAiCAB004322.
HPA028814.
HPA055560.
MalaCardsiBAP1.
MIMi156240. phenotype.
603089. gene.
614327. phenotype.
neXtProtiNX_Q92560.
Orphaneti289539. BAP1-related tumor predisposition syndrome.
PharmGKBiPA25254.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BRENDAi3.4.19.12. 2681.
SIGNORiQ92560.

Miscellaneous databases

ChiTaRSiBAP1. human.
GeneWikiiBAP1.
GenomeRNAii8314.
PROiQ92560.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000163930.
CleanExiHS_BAP1.
ExpressionAtlasiQ92560. baseline and differential.
GenevisibleiQ92560. HS.

Family and domain databases

Gene3Di3.40.532.10. 1 hit.
InterProiIPR001578. Peptidase_C12_UCH.
[Graphical view]
PANTHERiPTHR10589. PTHR10589. 1 hit.
PfamiPF01088. Peptidase_C12. 1 hit.
[Graphical view]
PRINTSiPR00707. UBCTHYDRLASE.
ProtoNetiSearch...

Entry informationi

Entry nameiBAP1_HUMAN
AccessioniPrimary (citable) accession number: Q92560
Secondary accession number(s): A8K993, Q6LEM0, Q7Z5E8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 5, 2005
Last sequence update: November 1, 1998
Last modified: September 7, 2016
This is version 139 of the entry and version 2 of the sequence. [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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.