BAP1_RAT
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 03-AUG-2022, entry version 64.
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; D3ZHS6; -.
DR PeptideAtlas; D3ZHS6; -.
DR PRIDE; D3ZHS6; -.
DR GeneID; 306257; -.
DR KEGG; rno:306257; -.
DR UCSC; RGD:1311938; rat.
DR CTD; 8314; -.
DR RGD; 1311938; Bap1.
DR eggNOG; KOG2778; Eukaryota.
DR InParanoid; D3ZHS6; -.
DR OrthoDB; 1363547at2759; -.
DR PhylomeDB; D3ZHS6; -.
DR TreeFam; TF313976; -.
DR Reactome; R-RNO-5689603; UCH proteinases.
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:0008283; P:cell population proliferation; ISO:RGD.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
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:0035522; P:monoubiquitinated histone H2A deubiquitination; ISS:UniProtKB.
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 transcription, DNA-templated; 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 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 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
