BAP1_BOVIN
ID BAP1_BOVIN Reviewed; 711 AA.
AC A2VDM8;
DT 13-JUL-2010, integrated into UniProtKB/Swiss-Prot.
DT 20-MAR-2007, sequence version 1.
DT 03-AUG-2022, entry version 63.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase BAP1;
DE EC=3.4.19.12 {ECO:0000250|UniProtKB:Q92560};
DE AltName: Full=BRCA1-associated protein 1;
GN Name=BAP1;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Basal ganglia;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Deubiquitinating enzyme that plays a key role in chromatin by
CC mediating deubiquitination of histone H2A and HCFC1. Catalytic
CC component of the PR-DUB complex, a complex that specifically mediates
CC deubiquitination of histone H2A monoubiquitinated at 'Lys-119'
CC (H2AK119ub1). Does not deubiquitinate monoubiquitinated histone H2B.
CC Acts as a regulator of cell growth by mediating deubiquitination of
CC HCFC1 N-terminal and C-terminal chains, with some specificity toward
CC 'Lys-48'-linked polyubiquitin chains compared to 'Lys-63'-linked
CC polyubiquitin chains. Deubiquitination of HCFC1 does not lead to
CC increase stability of HCFC1. Interferes with the BRCA1 and BARD1
CC heterodimer activity by inhibiting their ability to mediate
CC ubiquitination and autoubiquitination. It however does not mediate
CC deubiquitination of BRCA1 and BARD1. Able to mediate
CC autodeubiquitination via intramolecular interactions to couteract
CC monoubiquitination at the nuclear localization signal (NLS), thereby
CC protecting it from cytoplasmic sequestration. Acts as a tumor
CC suppressor. {ECO:0000250|UniProtKB:Q92560}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide
CC and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-
CC residue protein attached to proteins as an intracellular targeting
CC signal).; EC=3.4.19.12; Evidence={ECO:0000250|UniProtKB:Q92560};
CC -!- SUBUNIT: Component of the PR-DUB complex, at least composed of BAP1 and
CC ASXL1. Interacts with BRCA1 (via the RING finger). Interacts (via HBM-
CC like motif) with HCFC1. Interacts (when phosphorylated at Thr-475) with
CC FOXK1. Interacts (when phosphorylated at Thr-475) with FOXK2; leading
CC to recruit the PR-DUB complex and repress FOXK2 target genes.
CC {ECO:0000250|UniProtKB:Q92560}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q92560}. Nucleus
CC {ECO:0000250|UniProtKB:Q92560}. Note=Mainly nuclear. Binds to
CC chromatin. Localizes to the cytoplasm when monoubiquitinated by the
CC E2/E3 hybrid ubiquitin-protein ligase UBE2O.
CC {ECO:0000250|UniProtKB:Q92560}.
CC -!- PTM: Ubiquitinated: monoubiquitinated at multiple site of its nuclear
CC localization signal (NLS) BY UBE2O, leading to cytoplasmic retention.
CC Able to mediate autodeubiquitination via intramolecular interactions to
CC couteract cytoplasmic retention. {ECO:0000250|UniProtKB:Q92560}.
CC -!- SIMILARITY: Belongs to the peptidase C12 family. BAP1 subfamily.
CC {ECO:0000305}.
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DR EMBL; BC133317; AAI33318.1; -; mRNA.
DR RefSeq; NP_001096019.1; NM_001102549.1.
DR AlphaFoldDB; A2VDM8; -.
DR SMR; A2VDM8; -.
DR STRING; 9913.ENSBTAP00000054730; -.
DR MEROPS; C12.004; -.
DR PaxDb; A2VDM8; -.
DR PRIDE; A2VDM8; -.
DR GeneID; 100124510; -.
DR KEGG; bta:100124510; -.
DR CTD; 8314; -.
DR eggNOG; KOG2778; Eukaryota.
DR InParanoid; A2VDM8; -.
DR OrthoDB; 1363547at2759; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0035517; C:PR-DUB complex; ISS:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISS:UniProtKB.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0035522; P:monoubiquitinated histone H2A deubiquitination; ISS:UniProtKB.
DR GO; GO:0035520; P:monoubiquitinated protein deubiquitination; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0016579; P:protein deubiquitination; ISS:UniProtKB.
DR GO; GO:0071108; P:protein K48-linked deubiquitination; ISS:UniProtKB.
DR GO; GO:0051726; P:regulation of cell cycle; ISS:UniProtKB.
DR GO; GO:0001558; P:regulation of cell growth; ISS:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR Gene3D; 3.40.532.10; -; 1.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR001578; Peptidase_C12_UCH.
DR InterPro; IPR036959; Peptidase_C12_UCH_sf.
DR InterPro; IPR041507; UCH_C.
DR PANTHER; PTHR10589; PTHR10589; 1.
DR Pfam; PF01088; Peptidase_C12; 1.
DR Pfam; PF18031; UCH_C; 1.
DR PRINTS; PR00707; UBCTHYDRLASE.
DR SUPFAM; SSF54001; SSF54001; 1.
PE 2: Evidence at transcript level;
KW Chromatin regulator; Coiled coil; Cytoplasm; Hydrolase; Nucleus;
KW Phosphoprotein; Protease; Reference proteome; Thiol protease;
KW Ubl conjugation; Ubl conjugation pathway.
FT CHAIN 1..711
FT /note="Ubiquitin carboxyl-terminal hydrolase BAP1"
FT /id="PRO_0000395816"
FT REGION 255..337
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 354..420
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 446..506
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 557..605
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 578..703
FT /note="Interaction with BRCA1"
FT /evidence="ECO:0000250"
FT REGION 685..711
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 612..643
FT /evidence="ECO:0000255"
FT MOTIF 345..348
FT /note="HBM-like motif"
FT /evidence="ECO:0000250|UniProtKB:Q92560"
FT MOTIF 699..704
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:Q92560"
FT COMPBIAS 255..288
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 558..579
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 583..597
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 686..711
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 91
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q92560"
FT ACT_SITE 169
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P09936"
FT SITE 184
FT /note="Important for enzyme activity"
FT /evidence="ECO:0000250|UniProtKB:P09936"
FT MOD_RES 274
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92560"
FT MOD_RES 351
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92560"
FT MOD_RES 377
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99PU7"
FT MOD_RES 475
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q92560"
FT MOD_RES 503
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92560"
FT MOD_RES 519
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92560"
FT MOD_RES 567
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92560"
FT MOD_RES 579
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92560"
SQ SEQUENCE 711 AA; 78333 MW; 31D9E5B4AF11C286 CRC64;
MNKGWLELES DPGLFTLLVE DFGVKGVQVE EIYDLQSKCQ GPVYGFIFLF KWIEERRSRR
KVSTLVDDTS VIDDDIVNNM FFAHQLIPNS CATHALLSVL LNCSNVDLGP TLSRMKDFTK
GFSPESKGYA IGNAPELAKA HNSHARPEPR HLPEKQNGLS AVRTMEAFHF VSYVPITGRL
FELDGLKVYP IDHGPWGEDE EWTDKARRVI MERIGLATAG IKYEARLHVL KVNRQTVLEA
LQQLIRVTQP ELIQTHKSQE SQLPEESKPA SSKSPLALET SRAPVASEST HTDGVEEVAG
SCPQAPTHSP PSKPKLVVKP PGSNINGVPP NPTPIVQRLP AFLDNHNYAK SPMQEEEDLA
AGVGRSRVPV RPPQQYSDDE DDYEDEEEDD AQSTSSAIRY KRKGPGKPGP LSSSGDGQLS
VLQPNTINVL AEKLKESQKD LSIPLSIKTS SGAGSPAVAV PTHSQPSPTP SNESTDTASE
IGSAFNSPLR SPIRSANPTR PSSPVTSHIS KVLFGEDDSL LRVDCIRYNR AVRDLGPVIS
TGLLHLAEDG VLSPLALTES GKGSSPSIRP SQGSQGSGSP EEKEVVEAVD SREKPGLVRP
SESLNGEKYS PKELLALLKC VEAEIANYEA CLKEEVEKRK KFKIDDQRRT HNYDEFICTF
ISMLAQEGML ANLVEQNISV RRRQGVSIGR LHKQRKPDRR KRSRPYKAKR Q
