Reviewed, UniProtKB/Swiss-Prot P46737 (BRCC3_MOUSE)

Names and origin

Protein names

Recommended name:
    Lys-63-specific deubiquitinase BRCC36
    EC=3.1.2.15
Alternative name(s):
    BRCA1-A complex subunit BRCC36
    BRISC complex subunit BRCC36
    BRCA1/BRCA2-containing complex subunit 3
    BRCA1/BRCA2-containing complex subunit 36

Gene names

Name:	Brcc3
Synonyms:	Brcc36, C6.1a

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	291 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript level.

General annotation (Comments)

Function	Metalloprotease that specifically cleaves 'Lys-63'-linked polyubiquitin chains. Does not have activity toward 'Lys-48'-linked polyubiquitin chains. Component of the BRCA1-A complex, a complex that specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). In the BRCA1-A complex, it specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX, antagonizing the RNF8-dependent ubiquitination at double-strand breaks (DSBs). Catalytic subunit of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked ubiquitin in various substrates. Mediates the specific 'Lys-63'-specific deubiquitination associated with the COP9 signalosome complex (CSN), via the interaction of the BRISC complex with the CSN complex By similarity.
Catalytic activity	Ubiquitin C-terminal thioester + H2O = ubiquitin + a thiol.
Subunit structure	Component of the BRCA1-A complex, at least composed of the BRCA1, BARD1, UIMC1/RAP80, FAM175A/Abraxas, BRCC3/BRCC36, BRE/BRCC45 and MERIT40/NBA1. In the BRCA1-A complex, interacts directly with FAM175A/Abraxas and BRE/BRCC45. Component of the BRISC complex, at least composed of the FAM175B/ABRO1, BRCC3/BRCC36, BRE/BRCC45 and MERIT40/NBA1. The BRISC complex interacts with the CSN complex. Component of the BRCA1/BRCA2 containing complex (BRCC), which also contains BRCA1, BRCA2, BARD1, BRE and RAD51. BRCC is a ubiquitin E3 ligase complex that enhances cellular survival following DNA damage. Interacts with BRCA1. Binds polyubiquitin By similarity.
Subcellular location	Nucleus By similarity. Note: Localizes at sites of DNA damage at double-strand breaks (DSBs) By similarity.
Sequence similarities	Belongs to the peptidase M67A family. BRCC36 subfamily. Contains 1 MPN (JAB/Mov34) domain.

Ontologies

Keywords
Biological process	DNA damage DNA repair Ubl conjugation pathway
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Ligand	Metal-binding Zinc
Molecular function	Chromatin regulator Hydrolase Metalloprotease Protease
PTM	Acetylation
Gene Ontology (GO)
Biological process	G2/M transition DNA damage checkpoint Inferred from sequence or structural similarity. Source: UniProtKB double-strand break repair Inferred from sequence or structural similarity. Source: UniProtKB histone H2A K63-linked deubiquitination Inferred from sequence or structural similarity. Source: UniProtKB modification-dependent protein catabolic process Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of DNA repair Inferred from sequence or structural similarity. Source: UniProtKB response to ionizing radiation Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	BRCA1-A complex Inferred from sequence or structural similarity. Source: UniProtKB BRISC complex Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	metallopeptidase activity Inferred from sequence or structural similarity. Source: UniProtKB polyubiquitin 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 zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P46737-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P46737-2)

The sequence of this isoform differs from the canonical sequence as follows:
     183-227: EYERIEIPIHIVPHITIGKVCLESAVELPKILCQEEQDAYRRIHS → D

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 291	290	Lys-63-specific deubiquitinase BRCC36		PRO_0000213968
Regions
	Motif	122 – 135	14	JAMM motif
Sites
	Metal binding	122	1	Zinc; catalytic By similarity
	Metal binding	124	1	Zinc; catalytic By similarity
	Metal binding	135	1	Zinc; catalytic By similarity
Amino acid modifications
	Modified residue	2	1	N-acetylalanine By similarity
Natural variations
	Alternative sequence	183 – 227	45	EYERI…RRIHS → D in isoform 2.		VSP_037260
Experimental info
	Sequence conflict	108	1	A → S in BAE29117. Ref.2
	Sequence conflict	201	1	K → E in BAE29117. Ref.2
	Sequence conflict	280	1	K → R in BAB27894. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1995. Version 1. Checksum: 82D18B79D8EC5F72	FASTA	291	33,340
	10 20 30 40 50 60 MAVQVVQAVQ AVHLESDAFL VCLNHALSTE KEEVMGLCIG ELNDDIRSDS KFTYTGTEMR 70 80 90 100 110 120 TVQEKMDTIR IVHIHSVIIL RRSDKRKDRV EISPEQLSAA STEAERLAEL TGRPMRVVGW 130 140 150 160 170 180 YHSHPHITVW PSHVDVRTQA MYQMMDQGFV GLIFSCFIED KNTKTGRVLY TCFQSIQAQK 190 200 210 220 230 240 SSEYERIEIP IHIVPHITIG KVCLESAVEL PKILCQEEQD AYRRIHSLTH LDSVTKIHNG 250 260 270 280 290 SVFTKNLCSQ MSAVSGPLLQ WLEDRLEQNQ QHLQELQQEK EELMEELSSL E
	Isoform 2. Checksum: 6FEF9E1B6BC8DA73	FASTA	247	28,203
	10 20 30 40 50 60 MAVQVVQAVQ AVHLESDAFL VCLNHALSTE KEEVMGLCIG ELNDDIRSDS KFTYTGTEMR 70 80 90 100 110 120 TVQEKMDTIR IVHIHSVIIL RRSDKRKDRV EISPEQLSAA STEAERLAEL TGRPMRVVGW 130 140 150 160 170 180 YHSHPHITVW PSHVDVRTQA MYQMMDQGFV GLIFSCFIED KNTKTGRVLY TCFQSIQAQK 190 200 210 220 230 240 SSDLTHLDSV TKIHNGSVFT KNLCSQMSAV SGPLLQWLED RLEQNQQHLQ ELQQEKEELM EELSSLE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The chromosomal translocation t(X;14)(q28;q11) in T-cell pro-lymphocytic leukaemia breaks within one gene and activates another." Fisch P., Forster A., Sherrington P.D., Dyer M.J.S., Rabbitts T.H. Oncogene 8:3271-3276(1993) [PubMed: 8247530] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Embryo.
[2]	"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: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Strain: C57BL/6J. Tissue: Bone marrow and Embryo.
[3]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed: 19468303] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORMS 1 AND 2). Strain: C57BL/6J.
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Strain: C57BL/6. Tissue: Brain and Mammary tumor.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	S68022 mRNA. Translation: AAB29006.2. AK011876 mRNA. Translation: BAB27894.1. AK149844 mRNA. Translation: BAE29117.1. AL671860 Genomic DNA. Translation: CAM46071.1. AL671860 Genomic DNA. Translation: CAP19082.1. BC021313 mRNA. Translation: AAH21313.1. BC048179 mRNA. Translation: AAH48179.1.
IPI	IPI00137103. IPI00880818.
RefSeq	NP_666068.1.
UniGene	Mm.226957
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	P46737.
PTM databases
PhosphoSite	P46737.
Proteomic databases
PRIDE	P46737.
Genome annotation databases
Ensembl	ENSMUST00000033544; ENSMUSP00000033544; ENSMUSG00000031201; Mus musculus. [Genome view] ENSMUST00000114074; ENSMUSP00000109708; ENSMUSG00000031201; Mus musculus. [Genome view] ENSMUST00000114075; ENSMUSP00000109709; ENSMUSG00000031201; Mus musculus. [Genome view] ENSMUST00000116565; ENSMUSP00000112264; ENSMUSG00000031201; Mus musculus. [Genome view]
GeneID	210766.
KEGG	mmu:210766.
UCSC	uc009tpy.1. mouse.
Organism-specific databases
CTD	210766.
MGI	MGI:2389572. Brcc3.
Phylogenomic databases
HOGENOM	P46737.
HOVERGEN	P46737.
OMA	GTEMRTV.
Gene expression databases
ArrayExpress	P46737.
Bgee	P46737.
CleanEx	MM_BRCC3.
Genevestigator	P46737.
GermOnline	ENSMUSG00000031201. Mus musculus.
Family and domain databases
InterPro	IPR000555. Mov34_MPN_PAD1. [Graphical view]
Pfam	PF01398. Mov34. 1 hit. [Graphical view]
SMART	SM00232. JAB_MPN. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	373053.
SOURCE	Search...

Entry information

Entry name

BRCC3_MOUSE

Accession

Primary (citable) accession number: P46737
Secondary accession number(s): A3KGA9 , A8Y5K0, Q3UDZ4, Q9D025

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1995
Last modified:	November 3, 2009
This is version 72 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)