ID   BAP1_RAT                Reviewed;         727 AA.
AC   D3ZHS6;
DT   13-JUL-2010, integrated into UniProtKB/Swiss-Prot.
DT   13-JUL-2010, sequence version 2.
DT   08-NOV-2023, entry version 70.
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   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Brown Norway;
RA   Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-292 AND SER-394, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22673903; DOI=10.1038/ncomms1871;
RA   Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA   Olsen J.V.;
RT   "Quantitative maps of protein phosphorylation sites across 14 different rat
RT   organs and tissues.";
RL   Nat. Commun. 3:876-876(2012).
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-491) with
CC       FOXK1. Interacts (when phosphorylated at Thr-491) 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   -!- SEQUENCE CAUTION:
CC       Sequence=EDL88955.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR   EMBL; CH474046; EDL88955.1; ALT_SEQ; Genomic_DNA.
DR   RefSeq; NP_001100762.1; NM_001107292.1.
DR   RefSeq; XP_006252668.1; XM_006252606.3.
DR   AlphaFoldDB; D3ZHS6; -.
DR   SMR; D3ZHS6; -.
DR   STRING; 10116.ENSRNOP00000025853; -.
DR   MEROPS; C12.004; -.
DR   iPTMnet; D3ZHS6; -.
DR   PhosphoSitePlus; D3ZHS6; -.
DR   jPOST; D3ZHS6; -.
DR   PaxDb; 10116-ENSRNOP00000025853; -.
DR   PeptideAtlas; D3ZHS6; -.
DR   GeneID; 306257; -.
DR   KEGG; rno:306257; -.
DR   UCSC; RGD:1311938; rat.
DR   AGR; RGD:1311938; -.
DR   CTD; 8314; -.
DR   RGD; 1311938; Bap1.
DR   eggNOG; KOG2778; Eukaryota.
DR   InParanoid; D3ZHS6; -.
DR   OrthoDB; 276003at2759; -.
DR   PhylomeDB; D3ZHS6; -.
DR   TreeFam; TF313976; -.
DR   Reactome; R-RNO-5689603; UCH proteinases.
DR   Reactome; R-RNO-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
DR   PRO; PR:D3ZHS6; -.
DR   Proteomes; UP000002494; Unplaced.
DR   Proteomes; UP000234681; Chromosome 16.
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:0031490; F:chromatin DNA binding; ISO:RGD.
DR   GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISS:UniProtKB.
DR   GO; GO:0140950; F:histone H2A deubiquitinase activity; ISO:RGD.
DR   GO; GO:0008283; P:cell population proliferation; ISO:RGD.
DR   GO; GO:0035726; P:common myeloid progenitor cell proliferation; ISO:RGD.
DR   GO; GO:0030218; P:erythrocyte differentiation; ISO:RGD.
DR   GO; GO:0043249; P:erythrocyte maturation; ISO:RGD.
DR   GO; GO:0010467; P:gene expression; ISO:RGD.
DR   GO; GO:0030851; P:granulocyte differentiation; ISO:RGD.
DR   GO; GO:0061484; P:hematopoietic stem cell homeostasis; ISO:RGD.
DR   GO; GO:0001701; P:in utero embryonic development; ISO:RGD.
DR   GO; GO:0070661; P:leukocyte proliferation; ISO:RGD.
DR   GO; GO:0061519; P:macrophage homeostasis; ISO:RGD.
DR   GO; GO:0000278; P:mitotic cell cycle; ISO:RGD.
DR   GO; GO:0035520; P:monoubiquitinated protein deubiquitination; ISS:UniProtKB.
DR   GO; GO:0033028; P:myeloid cell apoptotic process; ISO:RGD.
DR   GO; GO:0045892; P:negative regulation of DNA-templated transcription; ISS:UniProtKB.
DR   GO; GO:0070050; P:neuron cellular homeostasis; ISO:RGD.
DR   GO; GO:0030223; P:neutrophil differentiation; ISO:RGD.
DR   GO; GO:0043363; P:nucleate erythrocyte differentiation; ISO:RGD.
DR   GO; GO:0036344; P:platelet morphogenesis; ISO:RGD.
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:1900015; P:regulation of cytokine production involved in inflammatory response; ISO:RGD.
DR   GO; GO:0050727; P:regulation of inflammatory response; ISO:RGD.
DR   GO; GO:0010035; P:response to inorganic substance; ISO:RGD.
DR   GO; GO:0002574; P:thrombocyte differentiation; ISO:RGD.
DR   GO; GO:0001894; P:tissue homeostasis; ISO:RGD.
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   1: Evidence at protein 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..727
FT                   /note="Ubiquitin carboxyl-terminal hydrolase BAP1"
FT                   /id="PRO_0000395817"
FT   REGION          273..351
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          372..435
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          462..522
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          573..622
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          594..719
FT                   /note="Interaction with BRCA1"
FT                   /evidence="ECO:0000250"
FT   REGION          702..727
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          628..659
FT                   /evidence="ECO:0000255"
FT   MOTIF           363..366
FT                   /note="HBM-like motif"
FT                   /evidence="ECO:0000250|UniProtKB:Q92560"
FT   MOTIF           715..720
FT                   /note="Nuclear localization signal"
FT                   /evidence="ECO:0000250|UniProtKB:Q92560"
FT   COMPBIAS        273..287
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        317..349
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        576..598
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        599..613
FT                   /note="Basic and acidic 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         292
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         369
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q92560"
FT   MOD_RES         394
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         491
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q92560"
FT   MOD_RES         519
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q92560"
FT   MOD_RES         535
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q92560"
FT   MOD_RES         583
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q92560"
FT   MOD_RES         595
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q92560"
SQ   SEQUENCE   727 AA;  80310 MW;  CEC525B181CDC02A CRC64;
     MNKGWLELES DPGLFTLLVE DFGVKGVQVE EIYDLQSKCQ GPVYGFIFLF KWIEERRSRR
     KVSTLVDDTS VIDDDIVNSM FFAHQLIPNS CATHALLSVL LNCSNVDLGP TLSRMKDFTK
     GFSPESKGYA IGNAPELAKA HNSHARPEPR HLPEKQNGLS AVRTMEAFHF VSYVPITGRL
     FELDGLKVYP IDHGPWGEDE EWTDKARRVI MERIGLATAG EPYHDIRFNL MAVVPDRRVK
     YEARLHVLKG NRQTVLEALQ QLIRVTQPEL IQTHKSQESQ LPEESKPASS KSPFGLEAGR
     TPAASECTHT DGAEEVAGSC PQTTTHSPPS KSKLVVKPSG SSLNGVPPTP TPIVQRLPAF
     LDNHNYAKSP MQEEEDLAAG VGRSRVPVRP QQYSDDEEDY EDEEEDVQNT SSAIRYKRKG
     TGKPGSLSNS SDGQLSVLQP NTINVLTEKL QESQKDLSIP LSIKTSSGAG SPAVAVPTHS
     QPSPTPSNES TDTASEIGSA FNSPLRSPIR SANPTRPSSP VTSHISKVLF GEDDSLLRVD
     CIRYNRAVRD LGPVISTGLL HLAEDGVLSP LALTEGGKGS SPSTRSSQGS QGSSSLEEKE
     VVEVTDSRDK SGLNRSSEPL SGEKYSPKEL LALLKCVEAE IANYEACLKE EVEKRKKFKI
     DDQRRTHNYD EFICTFISML AQEGMLANLV EQNISVRRRQ GVSIGRLHKQ RKPDRRKRSR
     PYKAKRQ
//