BRCC3_XENLA
ID BRCC3_XENLA Reviewed; 261 AA.
AC Q66GV6;
DT 05-MAY-2009, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 81.
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;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases.
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.
CC {ECO:0000250|UniProtKB:P46736}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:E2AXC7};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:E2AXC7};
CC -!- SUBUNIT: Component of the BRCA1-A complex, at least composed of brca1,
CC bard1, uimc1/rap80, abraxas1, brcc3/brcc36, babam2 and babam1/nba1. In
CC the BRCA1-A complex, interacts directly with ABRAXAS1 and babam2.
CC Component of the BRISC complex, at least composed of ABRAXAS2,
CC brcc3/brcc36, babam2 and babam1/nba1. Within the complex, interacts
CC directly with abraxas2. Both the BRCA1-A complex and the BRISC complex
CC bind polyubiquitin (By similarity). {ECO:0000250|UniProtKB:P46736}.
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 -!- SIMILARITY: Belongs to the peptidase M67A family. BRCC36 subfamily.
CC {ECO:0000305}.
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DR EMBL; BC082208; AAH82208.1; -; mRNA.
DR RefSeq; NP_001087827.1; NM_001094358.1.
DR AlphaFoldDB; Q66GV6; -.
DR SMR; Q66GV6; -.
DR BioGRID; 104548; 1.
DR IntAct; Q66GV6; 1.
DR MEROPS; M67.004; -.
DR MaxQB; Q66GV6; -.
DR DNASU; 447688; -.
DR GeneID; 447688; -.
DR KEGG; xla:447688; -.
DR CTD; 447688; -.
DR Xenbase; XB-GENE-5812935; brcc3.L.
DR OMA; CIGEIDT; -.
DR OrthoDB; 968461at2759; -.
DR Proteomes; UP000186698; Chromosome 8L.
DR Bgee; 447688; Expressed in testis and 20 other tissues.
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; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0000922; C:spindle pole; IEA:UniProtKB-SubCell.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IEA:InterPro.
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: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:0007095; P:mitotic G2 DNA damage checkpoint signaling; ISS:UniProtKB.
DR GO; GO:0045739; P:positive regulation of DNA repair; ISS:UniProtKB.
DR GO; GO:0070536; P:protein K63-linked deubiquitination; ISS:UniProtKB.
DR GO; GO:0010212; P:response to ionizing radiation; ISS:UniProtKB.
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 2: Evidence at transcript level;
KW Cell cycle; Cell division; Chromatin regulator; Cytoplasm; Cytoskeleton;
KW DNA damage; DNA repair; Hydrolase; Metal-binding; Metalloprotease; Mitosis;
KW Nucleus; Protease; Reference proteome; Ubl conjugation pathway; Zinc.
FT CHAIN 1..261
FT /note="Lys-63-specific deubiquitinase BRCC36"
FT /id="PRO_0000373949"
FT DOMAIN 6..149
FT /note="MPN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01182"
FT MOTIF 92..105
FT /note="JAMM motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01182"
FT BINDING 92
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01182"
FT BINDING 94
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01182"
FT BINDING 105
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01182"
SQ SEQUENCE 261 AA; 29789 MW; 38909EDACD36C5A5 CRC64;
MAVQAVHIQG DAFLVCVTHS LSTEREEVMG LCIGEVDTQK LVHIHSVIIL RRSDKRKDRV
EISPEQLSAA TIEADRLADI TGRPMRVVGW YHSHPHITVW PSHVDVRTQA MYQMMDVGFV
GLIFSCFIED KNTKTGRILY TCFQSVQAQK SSEYERIEVP LHVVPHNTIR KVCLESAVEL
PRILCQEEQD AYRRIHSLGH LDSITKIHNG SVFTKNLCGQ MSAISGPLLQ WLEDRLEQNR
QRAQELQSEK EQLLQELKTL G
