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 08-NOV-2023, entry version 68. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 9913-ENSBTAP00000054730; -. DR GeneID; 100124510; -. DR KEGG; bta:100124510; -. DR CTD; 8314; -. DR eggNOG; KOG2778; Eukaryota. DR InParanoid; A2VDM8; -. DR OrthoDB; 276003at2759; -. 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:0035520; P:monoubiquitinated protein deubiquitination; ISS:UniProtKB. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; 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 CDD; cd09617; Peptidase_C12_UCH37_BAP1; 1. DR Gene3D; 1.20.58.860; -; 1. DR Gene3D; 3.40.532.10; Peptidase C12, ubiquitin carboxyl-terminal hydrolase; 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; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE; 1. DR PANTHER; PTHR10589:SF28; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE BAP1; 1. DR Pfam; PF01088; Peptidase_C12; 1. DR Pfam; PF18031; UCH_C; 1. DR PRINTS; PR00707; UBCTHYDRLASE. DR SUPFAM; SSF54001; Cysteine proteinases; 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 //