Reviewed, UniProtKB/Swiss-Prot Q92560 (BAP1_HUMAN)

Names and origin

Protein names

Recommended name:
    Ubiquitin carboxyl-terminal hydrolase BAP1
    EC=3.4.19.12
Alternative name(s):
    BRCA1-associated protein 1
    Cerebral protein 6

Gene names

Name:	BAP1
Synonyms:	KIAA0272
ORF Names:	hucep-6

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	729 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Deubiquitinating enzyme which may be involved in BRCA1 signal transduction pathway. Ref.1
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). Ref.1
Subunit structure	Interacts with the RING finger domain of BRCA1. Ref.1
Subcellular location	Nucleus. Ref.1
Tissue specificity	Highly expressed in testis, placenta and ovary. Expressed in breast. Ref.1
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.7 Ref.8 Ref.9
Involvement in disease	Defects in BAP1 are found in non-small cell lung cancer (NSCLC) cell lines. Ref.1 Ref.6 Tumor-associated antigen found in several childhood medulloblastoma. Ref.1 Ref.6
Sequence similarities	Belongs to the peptidase C12 family.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Domain	Coiled coil
Molecular function	Hydrolase Protease Thiol protease
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	negative regulation of cell proliferation Ref.1 Traceable author statement. Source: ProtInc protein modification process Ref.1 Non-traceable author statement. Source: UniProtKB ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: InterPro
Cellular component	nucleus Ref.1 Traceable author statement. Source: ProtInc
Molecular function	cysteine-type peptidase activity Inferred from electronic annotation. Source: UniProtKB-KW protein binding Ref.1 Inferred from physical interaction. Source: IntAct ubiquitin thiolesterase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BRCA1	P38398	1	EBI-1791447,EBI-349905
BRCA1	P38398-5	1	EBI-1791447,EBI-2015072

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 729	729	Ubiquitin carboxyl-terminal hydrolase BAP1		PRO_0000211069
Regions
	Region	596 – 721	126	Interaction with BRCA1
	Coiled coil	630 – 661	32	Potential
Sites
	Active site	91	1
	Active site	169	1	By similarity
	Active site	184	1	By similarity
Amino acid modifications
	Modified residue	395	1	Phosphoserine Ref.9
	Modified residue	487	1	Phosphothreonine Ref.7
	Modified residue	489	1	Phosphoserine Ref.7
	Modified residue	583	1	Phosphoserine Ref.8
	Modified residue	592	1	Phosphoserine Ref.8
	Modified residue	597	1	Phosphoserine Ref.8
Natural variations
	Natural variant	616	1	V → E: dbSNP rs35353781.		VAR_051517
Experimental info
	Mutagenesis	91	1	C → S: Abolishes enzymatic activity. Ref.1
	Mutagenesis	691	1	L → P: Abolishes interaction with BRCA1. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q92560-1 [UniParc]. Last modified November 1, 1998. Version 2. Checksum: 031DA03AE1841D85	FASTA	729	80,362
	10 20 30 40 50 60 MNKGWLELES DPGLFTLLVE DFGVKGVQVE EIYDLQSKCQ GPVYGFIFLF KWIEERRSRR 70 80 90 100 110 120 KVSTLVDDTS VIDDDIVNNM FFAHQLIPNS CATHALLSVL LNCSSVDLGP 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 YEARLHVLKV NRQTVLEALQ QLIRVTQPEL IQTHKSQESQ LPEESKSASN KSPLVLEANR 310 320 330 340 350 360 APAASEGNHT DGAEEAAGSC AQAPSHSPPN KPKLVVKPPG SSLNGVHPNP TPIVQRLPAF 370 380 390 400 410 420 LDNHNYAKSP MQEEEDLAAG VGRSRVPVRP PQQYSDDEDD YEDDEEDDVQ NTNSALRYKG 430 440 450 460 470 480 KGTGKPGALS GSADGQLSVL QPNTINVLAE KLKESQKDLS IPLSIKTSSG AGSPAVAVPT 490 500 510 520 530 540 HSQPSPTPSN ESTDTASEIG SAFNSPLRSP IRSANPTRPS SPVTSHISKV LFGEDDSLLR 550 560 570 580 590 600 VDCIRYNRAV RDLGPVISTG LLHLAEDGVL SPLALTEGGK GSSPSIRPIQ GSQGSSSPVE 610 620 630 640 650 660 KEVVEATDSR EKTGMVRPGE PLSGEKYSPK ELLALLKCVE AEIANYEACL KEEVEKRKKF 670 680 690 700 710 720 KIDDQRRTHN YDEFICTFIS MLAQEGMLAN LVEQNISVRR RQGVSIGRLH KQRKPDRRKR SRPYKAKRQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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: 9528852] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], ENZYME ACTIVITY, FUNCTION, MUTAGENESIS OF CYS-91 AND LEU-691, INTERACTION WITH BRCA1, TISSUE SPECIFICITY, DISEASE, SUBCELLULAR LOCATION. Tissue: B-cell.
[2]	"Biological functions of a novel human gene, hucep-6, which is specifically expressed in the central nervous system." Yoshimoto M., Yazaki M., Takayama K., Matsumoto K. Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[3]	"Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain." Nagase T., Seki N., Ishikawa K., Ohira M., Kawarabayasi Y., Ohara O., Tanaka A., Kotani H., Miyajima N., Nomura N. DNA Res. 3:321-329(1996) [PubMed: 9039502] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[4]	"Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones." Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T. DNA Res. 9:99-106(2002) [PubMed: 12168954] [Abstract] Cited for: SEQUENCE REVISION.
[5]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Skin.
[6]	"Novel tumor antigens identified by autologous antibody screening of childhood medulloblastoma cDNA libraries." Behrends U., Schneider I., Roessler S., Frauenknecht H., Golbeck A., Lechner B., Eigenstetter G., Zobywalski C., Mueller-Weihrich S., Graubner U., Schmid I., Sackerer D., Spaeth M., Goetz C., Prantl F., Asmuss H.-P., Bise K., Mautner J. Int. J. Cancer 106:244-251(2003) [PubMed: 12800201] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 164-729, DISEASE. Tissue: Medulloblastoma.
[7]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-487 AND SER-489, MASS SPECTROMETRY. Tissue: Epithelium.
[8]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-583; SER-592 AND SER-597, MASS SPECTROMETRY.
[9]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-395, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF045581 mRNA. Translation: AAC15970.1. D88812 mRNA. Translation: BAB46921.1. D87462 mRNA. Translation: BAA13401.2. Different initiation. BC001596 mRNA. Translation: AAH01596.1. AY130008 mRNA. Translation: AAN05092.1.
IPI	IPI00465087.
RefSeq	NP_004647.1.
UniGene	Hs.106674
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q92560. 2 interactions.
Protein family/group databases
MEROPS	C12.004.
PTM databases
PhosphoSite	Q92560.
Proteomic databases
PRIDE	Q92560.
Genome annotation databases
Ensembl	ENSG00000163930. Homo sapiens. [Contig view]
GeneID	8314.
KEGG	hsa:8314.
Organism-specific databases
GeneCards	GC03M052410.
H-InvDB	HIX0003355.
HGNC	HGNC:950. BAP1.
HPA	CAB004322.
MIM	603089. gene.
PharmGKB	PA25254.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q92560.
HOVERGEN	Q92560.
OMA	Q92560. PTPSNES.
Enzyme and pathway databases
BRENDA	3.4.19.12. 247.
Gene expression databases
ArrayExpress	Q92560.
Bgee	Q92560.
CleanEx	HS_BAP1.
GermOnline	ENSG00000163930. Homo sapiens.
Family and domain databases
InterPro	IPR001578. Peptidase_C12. [Graphical view]
Gene3D	G3DSA:3.40.532.10. Peptidase_C12. 1 hit.
PANTHER	PTHR10589. Peptidase_C12. 1 hit.
Pfam	PF01088. Peptidase_C12. 1 hit. [Graphical view]
PRINTS	PR00707. UBCTHYDRLASE.
ProDom	PD350662. Peptidase_C12. 1 hit. [Graphical view] [Entries sharing at least one domain]
PROSITE	PS00140. UCH_1. False negative. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	31137.
SOURCE	Search...

Entry information

Entry name

BAP1_HUMAN

Accession

Primary (citable) accession number: Q92560
Secondary accession number(s): Q6LEM0, Q7Z5E8

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 5, 2005
Last sequence update:	November 1, 1998
Last modified:	June 16, 2009
This is version 69 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)