BRCC3_MOUSE
ID BRCC3_MOUSE Reviewed; 291 AA.
AC P46737; A3KGA9; A8Y5K0; Q3UDZ4; Q9D025;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Lys-63-specific deubiquitinase BRCC36;
DE EC=3.4.19.- {ECO:0000250|UniProtKB:P46736};
DE AltName: Full=BRCA1-A complex subunit BRCC36;
DE AltName: Full=BRCA1/BRCA2-containing complex subunit 3;
DE AltName: Full=BRCA1/BRCA2-containing complex subunit 36;
DE AltName: Full=BRISC complex subunit BRCC36;
GN Name=Brcc3; Synonyms=Brcc36, C6.1a;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Embryo;
RX PubMed=8247530;
RA Fisch P., Forster A., Sherrington P.D., Dyer M.J.S., Rabbitts T.H.;
RT "The chromosomal translocation t(X;14)(q28;q11) in T-cell pro-lymphocytic
RT leukaemia breaks within one gene and activates another.";
RL Oncogene 8:3271-3276(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Bone marrow, and Embryo;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND ALTERNATIVE SPLICING
RP (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Brain, and Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP FUNCTION, AND INTERACTION WITH PWWP2B AND HDAC1.
RX PubMed=34180153; DOI=10.1002/advs.202102060;
RA Yan L., Jin W., Zhao Q., Cui X., Shi T., Xu Y., Li F., Jin W., Zhang Z.,
RA Zhang Z., Tang Q.Q., Pan D.;
RT "PWWP2B Fine-Tunes Adipose Thermogenesis by Stabilizing HDACs in a NuRD
RT Subcomplex.";
RL Adv. Sci. 8:e2102060-e2102060(2021).
CC -!- FUNCTION: Metalloprotease that specifically cleaves 'Lys-63'-linked
CC polyubiquitin chains. Does not have activity toward 'Lys-48'-linked
CC polyubiquitin chains. Component of the BRCA1-A complex, a complex that
CC specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and
CC H2AX at DNA lesions sites, leading to target the BRCA1-BARD1
CC heterodimer to sites of DNA damage at double-strand breaks (DSBs). In
CC the BRCA1-A complex, it specifically removes 'Lys-63'-linked ubiquitin
CC on histones H2A and H2AX, antagonizing the RNF8-dependent
CC ubiquitination at double-strand breaks (DSBs). Catalytic subunit of the
CC BRISC complex, a multiprotein complex that specifically cleaves 'Lys-
CC 63'-linked ubiquitin in various substrates. Mediates the specific 'Lys-
CC 63'-specific deubiquitination associated with the COP9 signalosome
CC complex (CSN), via the interaction of the BRISC complex with the CSN
CC complex. The BRISC complex is required for normal mitotic spindle
CC assembly and microtubule attachment to kinetochores via its role in
CC deubiquitinating NUMA1. Plays a role in interferon signaling via its
CC role in the deubiquitination of the interferon receptor IFNAR1;
CC deubiquitination increases IFNAR1 activity by enhancing its stability
CC and cell surface expression. Down-regulates the response to bacterial
CC lipopolysaccharide (LPS) via its role in IFNAR1 deubiquitination (By
CC similarity). Deubiquitinates HDAC1 and PWWP2B leading to their
CC stabilization (PubMed:34180153). {ECO:0000250|UniProtKB:P46736,
CC ECO:0000269|PubMed:34180153}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:E2AXC7,
CC ECO:0000250|UniProtKB:P46736};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:E2AXC7};
CC -!- SUBUNIT: Component of the ARISC complex, at least composed of
CC UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1. Component
CC of the BRCA1-A complex, at least composed of BRCA1, BARD1, UIMC1/RAP80,
CC ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1. In the BRCA1-A complex,
CC interacts directly with ABRAXAS1 and BABAM2. Component of the BRISC
CC complex, at least composed of ABRAXAS2, BRCC3/BRCC36, BABAM2 and
CC BABAM1/NBA1. Identified in a complex with SHMT2 and the other subunits
CC of the BRISC complex. In the BRISC complex, interacts directly with
CC ABRAXAS2. Identified in a complex with ABRAXAS2 and NUMA1. The BRISC
CC complex interacts with the CSN complex. Component of the BRCA1/BRCA2
CC containing complex (BRCC), which also contains BRCA1, BRCA2, BARD1,
CC BABAM2 and RAD51. BRCC is a ubiquitin E3 ligase complex that enhances
CC cellular survival following DNA damage. Interacts with BRCA1. Binds
CC polyubiquitin (By similarity). Interacts with PWWP2B (PubMed:34180153).
CC Interacts with HDAC1; this interaction is enhanced in the presence of
CC PWWP2B (PubMed:34180153). {ECO:0000250|UniProtKB:P46736,
CC ECO:0000269|PubMed:34180153}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P46736}. Cytoplasm
CC {ECO:0000250|UniProtKB:P46736}. Cytoplasm, cytoskeleton, spindle pole
CC {ECO:0000250|UniProtKB:P46736}. Note=Localizes at sites of DNA damage
CC at double-strand breaks (DSBs). Interaction with ABRAXAS2 retains BRCC3
CC in the cytoplasm. {ECO:0000250|UniProtKB:P46736}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P46737-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P46737-2; Sequence=VSP_037260;
CC -!- SIMILARITY: Belongs to the peptidase M67A family. BRCC36 subfamily.
CC {ECO:0000305}.
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DR EMBL; S68022; AAB29006.2; -; mRNA.
DR EMBL; AK011876; BAB27894.1; -; mRNA.
DR EMBL; AK149844; BAE29117.1; -; mRNA.
DR EMBL; AL671860; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC021313; AAH21313.1; -; mRNA.
DR EMBL; BC048179; AAH48179.1; -; mRNA.
DR CCDS; CCDS41031.1; -. [P46737-1]
DR RefSeq; NP_001159929.1; NM_001166457.1. [P46737-1]
DR RefSeq; NP_001159931.1; NM_001166459.1. [P46737-1]
DR RefSeq; NP_666068.1; NM_145956.4. [P46737-1]
DR RefSeq; XP_011245856.1; XM_011247554.2.
DR PDB; 6GVW; X-ray; 3.75 A; B/G=1-291.
DR PDBsum; 6GVW; -.
DR AlphaFoldDB; P46737; -.
DR SMR; P46737; -.
DR BioGRID; 229180; 24.
DR ComplexPortal; CPX-4702; BRCA1-A complex.
DR ComplexPortal; CPX-972; BRCC ubiquitin ligase complex.
DR IntAct; P46737; 2.
DR MINT; P46737; -.
DR STRING; 10090.ENSMUSP00000033544; -.
DR MEROPS; M67.004; -.
DR iPTMnet; P46737; -.
DR PhosphoSitePlus; P46737; -.
DR EPD; P46737; -.
DR jPOST; P46737; -.
DR MaxQB; P46737; -.
DR PaxDb; P46737; -.
DR PeptideAtlas; P46737; -.
DR PRIDE; P46737; -.
DR ProteomicsDB; 273700; -. [P46737-1]
DR ProteomicsDB; 273701; -. [P46737-2]
DR DNASU; 210766; -.
DR Ensembl; ENSMUST00000033544; ENSMUSP00000033544; ENSMUSG00000031201. [P46737-1]
DR Ensembl; ENSMUST00000114074; ENSMUSP00000109708; ENSMUSG00000031201. [P46737-1]
DR Ensembl; ENSMUST00000118428; ENSMUSP00000114057; ENSMUSG00000031201. [P46737-2]
DR GeneID; 210766; -.
DR KEGG; mmu:210766; -.
DR UCSC; uc009tpy.2; mouse. [P46737-1]
DR CTD; 79184; -.
DR MGI; MGI:2389572; Brcc3.
DR VEuPathDB; HostDB:ENSMUSG00000031201; -.
DR eggNOG; KOG1555; Eukaryota.
DR GeneTree; ENSGT00390000000360; -.
DR HOGENOM; CLU_053351_0_0_1; -.
DR InParanoid; P46737; -.
DR OMA; CIGEIDT; -.
DR OrthoDB; 968461at2759; -.
DR PhylomeDB; P46737; -.
DR TreeFam; TF328524; -.
DR Reactome; R-MMU-5689901; Metalloprotease DUBs.
DR Reactome; R-MMU-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
DR Reactome; R-MMU-5693607; Processing of DNA double-strand break ends.
DR Reactome; R-MMU-69473; G2/M DNA damage checkpoint.
DR BioGRID-ORCS; 210766; 19 hits in 109 CRISPR screens.
DR ChiTaRS; Brcc3; mouse.
DR PRO; PR:P46737; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; P46737; protein.
DR Bgee; ENSMUSG00000031201; Expressed in embryonic post-anal tail and 249 other tissues.
DR ExpressionAtlas; P46737; baseline and differential.
DR Genevisible; P46737; MM.
DR GO; GO:0070531; C:BRCA1-A complex; ISS:UniProtKB.
DR GO; GO:0070552; C:BRISC complex; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0000152; C:nuclear ubiquitin ligase complex; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0000922; C:spindle pole; IEA:UniProtKB-SubCell.
DR GO; GO:0000151; C:ubiquitin ligase complex; ISO:MGI.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IEA:InterPro.
DR GO; GO:0030234; F:enzyme regulator activity; ISO:MGI.
DR GO; GO:0070122; F:isopeptidase activity; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0140492; F:metal-dependent deubiquitinase activity; ISS:UniProtKB.
DR GO; GO:0008237; F:metallopeptidase activity; ISS:UniProtKB.
DR GO; GO:0031593; F:polyubiquitin modification-dependent protein binding; ISS:UniProtKB.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0071479; P:cellular response to ionizing radiation; ISO:MGI.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0006302; P:double-strand break repair; ISS:UniProtKB.
DR GO; GO:0070537; P:histone H2A K63-linked deubiquitination; ISS:UniProtKB.
DR GO; GO:0035518; P:histone H2A monoubiquitination; IC:ComplexPortal.
DR GO; GO:0007095; P:mitotic G2 DNA damage checkpoint signaling; ISS:UniProtKB.
DR GO; GO:0044818; P:mitotic G2/M transition checkpoint; IC:ComplexPortal.
DR GO; GO:0045739; P:positive regulation of DNA repair; ISS:UniProtKB.
DR GO; GO:0051865; P:protein autoubiquitination; IC:ComplexPortal.
DR GO; GO:0016579; P:protein deubiquitination; IDA:UniProtKB.
DR GO; GO:0070536; P:protein K63-linked deubiquitination; ISS:UniProtKB.
DR GO; GO:2000001; P:regulation of DNA damage checkpoint; IC:ComplexPortal.
DR GO; GO:0006282; P:regulation of DNA repair; IC:ComplexPortal.
DR GO; GO:0010212; P:response to ionizing radiation; ISS:UniProtKB.
DR GO; GO:0010165; P:response to X-ray; ISO:MGI.
DR CDD; cd08068; MPN_BRCC36; 1.
DR InterPro; IPR040749; BRCC36_C.
DR InterPro; IPR000555; JAMM/MPN+_dom.
DR InterPro; IPR037518; MPN.
DR InterPro; IPR033860; MPN_BRCC36.
DR Pfam; PF18110; BRCC36_C; 1.
DR Pfam; PF01398; JAB; 1.
DR SMART; SM00232; JAB_MPN; 1.
DR PROSITE; PS50249; MPN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cell cycle; Cell division;
KW Chromatin regulator; Cytoplasm; Cytoskeleton; DNA damage; DNA repair;
KW Hydrolase; Metal-binding; Metalloprotease; Mitosis; Nucleus;
KW Phosphoprotein; Protease; Reference proteome; Ubl conjugation pathway;
KW Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P46736"
FT CHAIN 2..291
FT /note="Lys-63-specific deubiquitinase BRCC36"
FT /id="PRO_0000213968"
FT DOMAIN 12..179
FT /note="MPN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01182"
FT MOTIF 122..135
FT /note="JAMM motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01182"
FT BINDING 122
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01182"
FT BINDING 124
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01182"
FT BINDING 135
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01182"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:P46736"
FT MOD_RES 233
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P46736"
FT VAR_SEQ 183..227
FT /note="EYERIEIPIHIVPHITIGKVCLESAVELPKILCQEEQDAYRRIHS -> D
FT (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_037260"
FT CONFLICT 108
FT /note="A -> S (in Ref. 2; BAE29117)"
FT /evidence="ECO:0000305"
FT CONFLICT 201
FT /note="K -> E (in Ref. 2; BAE29117)"
FT /evidence="ECO:0000305"
FT CONFLICT 280
FT /note="K -> R (in Ref. 2; BAB27894)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 291 AA; 33340 MW; 82D18B79D8EC5F72 CRC64;
MAVQVVQAVQ AVHLESDAFL VCLNHALSTE KEEVMGLCIG ELNDDIRSDS KFTYTGTEMR
TVQEKMDTIR IVHIHSVIIL RRSDKRKDRV EISPEQLSAA STEAERLAEL TGRPMRVVGW
YHSHPHITVW PSHVDVRTQA MYQMMDQGFV GLIFSCFIED KNTKTGRVLY TCFQSIQAQK
SSEYERIEIP IHIVPHITIG KVCLESAVEL PKILCQEEQD AYRRIHSLTH LDSVTKIHNG
SVFTKNLCSQ MSAVSGPLLQ WLEDRLEQNQ QHLQELQQEK EELMEELSSL E
