Q99PU7 (BAP1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ubiquitin carboxyl-terminal hydrolase BAP1
EC=3.4.19.12

Alternative name(s):
BRCA1-associated protein 1
Ubiquitin C-terminal hydrolase X4
Short name=UCH-X4

Gene names

Name:	Bap1
Synonyms:	Kiaa0272

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	728 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Acts as a tumor suppressor By similarity.
Catalytic activity	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).
Subunit structure	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 By similarity.
Subcellular location	Cytoplasm By similarity. Nucleus By similarity. Note: Mainly nuclear. Binds to chromatin By similarity.
Tissue specificity	Highly expressed in mammary glands, testis and ovary. Up-regulated in mammary glands during puberty, pregnancy, and as a result of parity. Ref.5
Miscellaneous	Has the ability to ability to suppress tumorigenicity when expressed in NCI-H226 cells (Ref.6).
Sequence similarities	Belongs to the peptidase C12 family. BAP1 subfamily.
Sequence caution	The sequence BAC97918.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Cytoplasm Nucleus
Domain	Coiled coil
Molecular function	Chromatin regulator Hydrolase Protease Thiol protease
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	monoubiquitinated histone H2A deubiquitination Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of cell proliferation Inferred from sequence alignment Ref.5. Source: MGI protein K48-linked deubiquitination Inferred from sequence or structural similarity. Source: UniProtKB regulation of cell cycle Inferred from sequence or structural similarity. Source: UniProtKB regulation of cell growth Inferred from sequence or structural similarity. Source: UniProtKB ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: InterPro
Cellular_component	PR-DUB complex Inferred from sequence or structural similarity. Source: UniProtKB cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB nucleolus Inferred from electronic annotation. Source: Compara
Molecular_function	chromatin binding Inferred from sequence or structural similarity. Source: UniProtKB ubiquitin thiolesterase activity Inferred from sequence or structural similarity. Source: UniProtKB ubiquitin-specific protease activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 728	728	Ubiquitin carboxyl-terminal hydrolase BAP1		PRO_0000211070
Regions
	Region	595 – 720	126	Interaction with BRCA1 By similarity
	Coiled coil	629 – 660	32	Potential
	Motif	363 – 366	4	HBM-like motif By similarity
	Motif	716 – 721	6	Nuclear localization signal By similarity
Sites
	Active site	91	1	Nucleophile Probable
	Active site	169	1	Proton donor By similarity
	Site	184	1	Important for enzyme activity By similarity
Experimental info
	Mutagenesis	91	1	C → A: Abolishes ability to suppress tumorigenicity when expressed in NCI-H226 cells. Ref.6
	Mutagenesis	716 – 721	6	RRKRSR → AAAAAA: Abolishes ability to suppress tumorigenicity when expressed in NCI-H226 cells. Ref.6
	Sequence conflict	725	1	A → V in BAC97918. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q99PU7 [UniParc]. Last modified June 1, 2001. Version 1. Checksum: 2BDEAFB09CD276DB	FASTA	728	80,492
	10 20 30 40 50 60 MNKGWLELES DPGLFTLLVE DFGVKGVQVE EIYDLQSKCQ GPVYGFIFLF KWIEERRSRR 70 80 90 100 110 120 KVSTLVDDTS VIDDDIVNNM FFAHQLIPNS CATHALLSVL LNCSNVDLGP TLSRMKDFTK 130 140 150 160 170 180 GFSPESKGYA IGNAPELAKA HNSHARPEPR HLPEKQNGLS AVRTMEAFHF VSYVPITGRL 190 200 210 220 230 240 FELDGLKVYP IDHGPWGEDE EWTDKARRVI MERIGLATAG EPYHDIRFNL MAVVPDRRIK 250 260 270 280 290 300 YETRLHVLKV NRQTVLEALQ QLIRVTQPEL IQTHKSQESQ LPEESKPASS KSPLGLEAGR 310 320 330 340 350 360 TPVASECTQT DGAEEVAGSC PQTTTHSPPS KCKLVVKPPG SSLNGVPPNP APIVQRLPAF 370 380 390 400 410 420 LDNHNYAKSP MQEEEDLAAG VGRSRVPVRA PQQYSEDEDD YEDEDEDVQN TNPAIRYKRK 430 440 450 460 470 480 GTGKPGSLSN SSDGQLSVLQ PNTINVLTEK LQESQKDLSV PLSIKTSSGA GSPAVAVPTH 490 500 510 520 530 540 SQPSPTPSNE STDTASEIGS AFNSPLRSPI RSANPTRPSS PVTSHISKVL FGEDDSLLRV 550 560 570 580 590 600 DCIRYNRAVR DLGPVISTGL LHLAEDGVLS PLALTEGGKG SSPSTRSSQG SQGSSGLEEK 610 620 630 640 650 660 EVVEVTESRD KPGLNRSSEP LSGEKYSPKE LLALLKCVEA EIANYEACLK EEVEKRKKFK 670 680 690 700 710 720 IDDQRRTHNY DEFICTFISM LAQEGMLANL VEQNISVRRR QGVSIGRLHK QRKPDRRKRS RPYKAKRQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Ubiquitin C-terminal hydrolase." Mizuta R. Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Prediction of the coding sequences of mouse homologues of KIAA gene: III. The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries." Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S., Saga Y., Nagase T., Ohara O., Koga H. DNA Res. 10:167-180(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: NOD.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6. Tissue: Fetal brain.
[5]	"BAP1: a novel ubiquitin hydrolase which binds to the BRCA1 RING finger and enhances BRCA1-mediated cell growth suppression." Jensen D.E., Proctor M., Marquis S.T., Gardner H.P., Ha S.I., Chodosh L.A., Ishov A.M., Tommerup N., Vissing H., Sekido Y., Minna J., Borodovsky A., Schultz D.C., Wilkinson K.D., Maul G.G., Barlev N., Berger S., Prendergast G.C., Rauscher F.J. III Oncogene 16:1097-1112(1998) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[6]	"BRCA1-associated protein-1 is a tumor suppressor that requires deubiquitinating activity and nuclear localization." Ventii K.H., Devi N.S., Friedrich K.L., Chernova T.A., Tighiouart M., Van Meir E.G., Wilkinson K.D. Cancer Res. 68:6953-6962(2008) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF CYS-91 AND 716-ARG--ARG-721.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB047820 mRNA. Translation: BAB32976.1. AK129108 mRNA. Translation: BAC97918.1. Different initiation. AK170576 mRNA. Translation: BAE41889.1. BC050901 mRNA. Translation: AAH50901.1.
IPI	IPI00453853.
RefSeq	NP_081364.1. NM_027088.2.
UniGene	Mm.3779.
3D structure databases
ProteinModelPortal	Q99PU7.
SMR	Q99PU7. Positions 5-284, 629-690.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q99PU7. 5 interactions.
Protein family/group databases
MEROPS	C12.004.
PTM databases
PhosphoSite	Q99PU7.
Proteomic databases
PRIDE	Q99PU7.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000022458; ENSMUSP00000022458; ENSMUSG00000021901.
GeneID	104416.
KEGG	mmu:104416.
UCSC	uc007sxh.1. mouse.
Organism-specific databases
CTD	8314.
MGI	MGI:1206586. Bap1.
Rouge	Search...
Phylogenomic databases
eggNOG	NOG249036.
GeneTree	ENSGT00510000046560.
HOGENOM	HOG000013189.
HOVERGEN	HBG054042.
InParanoid	Q3TCR6.
KO	K08588.
OMA	PQQYSDD.
OrthoDB	EOG4XPQFC.
Gene expression databases
Bgee	Q99PU7.
CleanEx	MM_BAP1.
Genevestigator	Q99PU7.
GermOnline	ENSMUSG00000021901. Mus musculus.
Family and domain databases
Gene3D	3.40.532.10. 1 hit.
InterPro	IPR001578. Peptidase_C12. [Graphical view]
PANTHER	PTHR10589. PTHR10589. 1 hit.
Pfam	PF01088. Peptidase_C12. 1 hit. [Graphical view]
PRINTS	PR00707. UBCTHYDRLASE.
PROSITE	PS00140. UCH_1. False negative. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	BAP1. mouse.
NextBio	357097.
SOURCE	Search...

Entry information

Entry name

BAP1_MOUSE

Accession

Primary (citable) accession number: Q99PU7
Secondary accession number(s): Q3TCR6, Q6ZQE6

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 5, 2005
Last sequence update:	June 1, 2001
Last modified:	May 1, 2013
This is version 89 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program