BRCC3_CAMFO
ID BRCC3_CAMFO Reviewed; 253 AA.
AC E2AXC7;
DT 17-FEB-2016, integrated into UniProtKB/Swiss-Prot.
DT 30-NOV-2010, sequence version 1.
DT 03-AUG-2022, entry version 43.
DE RecName: Full=Lys-63-specific deubiquitinase BRCC36 {ECO:0000305};
DE EC=3.4.19.- {ECO:0000269|PubMed:26344097};
GN Name=BRCC3 {ECO:0000305}; Synonyms=BRCC36 {ECO:0000303|PubMed:26344097};
GN ORFNames=EAG_15736 {ECO:0000312|EMBL:EFN61907.1};
OS Camponotus floridanus (Florida carpenter ant).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Hymenoptera; Apocrita; Aculeata; Formicoidea;
OC Formicidae; Formicinae; Camponotus.
OX NCBI_TaxID=104421;
RN [1] {ECO:0000312|EMBL:EFN61907.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=20798317; DOI=10.1126/science.1192428;
RA Bonasio R., Zhang G., Ye C., Mutti N.S., Fang X., Qin N., Donahue G.,
RA Yang P., Li Q., Li C., Zhang P., Huang Z., Berger S.L., Reinberg D.,
RA Wang J., Liebig J.;
RT "Genomic comparison of the ants Camponotus floridanus and Harpegnathos
RT saltator.";
RL Science 329:1068-1071(2010).
RN [2] {ECO:0007744|PDB:5CW3, ECO:0007744|PDB:5CW4, ECO:0007744|PDB:5CW5}
RP X-RAY CRYSTALLOGRAPHY (2.54 ANGSTROMS) IN COMPLEX WITH ZINC AND ABRAXAS2,
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, IDENTIFICATION IN THE BRISC
RP COMPLEX, INTERACTION WITH ABRAXAS2, SUBUNIT, AND MUTAGENESIS OF GLU-30;
RP 94-HIS--HIS-96; ILE-99; MET-117; GLU-183; ASP-186; ALA-205 AND ILE-212.
RX PubMed=26344097; DOI=10.1016/j.molcel.2015.07.028;
RA Zeqiraj E., Tian L., Piggott C.A., Pillon M.C., Duffy N.M.,
RA Ceccarelli D.F., Keszei A.F., Lorenzen K., Kurinov I., Orlicky S.,
RA Gish G.D., Heck A.J., Guarne A., Greenberg R.A., Sicheri F.;
RT "Higher-order assembly of BRCC36-KIAA0157 is required for DUB activity and
RT biological function.";
RL Mol. Cell 59:970-983(2015).
CC -!- FUNCTION: Metalloprotease that specifically cleaves 'Lys-63'-linked
CC polyubiquitin chains, leaving the last ubiquitin chain attached to its
CC substrates. Catalytic subunit of the BRISC complex; does not have
CC activity by itself, but needs to be associated into a heterotetramer
CC with ABRAXAS2 for minimal in vitro activity (PubMed:26344097). Plays a
CC role in regulating the onset of apoptosis via its role in modulating
CC 'Lys-63'-linked ubiquitination of target proteins (By similarity).
CC Required for normal mitotic spindle assembly and microtubule attachment
CC to kinetochores via its role in deubiquitinating spindle assembly
CC factors (By similarity). {ECO:0000250|UniProtKB:Q15018,
CC ECO:0000250|UniProtKB:Q3TCJ1, ECO:0000269|PubMed:26344097}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:26344097};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:26344097};
CC -!- SUBUNIT: 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. The heterodimer with ABRAXAS2 assembles into a
CC heterotetramer. The BRISC complex binds polyubiquitin.
CC {ECO:0000269|PubMed:26344097}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P46736}. Nucleus
CC {ECO:0000250|UniProtKB:P46736}. Cytoplasm, cytoskeleton, spindle pole
CC {ECO:0000250|UniProtKB:Q15018}. Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:Q15018}. Note=A minor proportion is detected in
CC the nucleus. Translocates into the nucleus in response to DNA damage.
CC Directly binds to microtubules and is detected at the minus end of K-
CC fibers. {ECO:0000250|UniProtKB:Q15018}.
CC -!- SIMILARITY: Belongs to the peptidase M67A family. BRCC36 subfamily.
CC {ECO:0000305}.
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DR EMBL; GL443548; EFN61907.1; -; Genomic_DNA.
DR RefSeq; XP_011265678.1; XM_011267376.2.
DR PDB; 5CW3; X-ray; 2.55 A; A/C=1-253.
DR PDB; 5CW4; X-ray; 2.54 A; A/C=1-253.
DR PDB; 5CW5; X-ray; 2.74 A; A/C=1-253.
DR PDBsum; 5CW3; -.
DR PDBsum; 5CW4; -.
DR PDBsum; 5CW5; -.
DR AlphaFoldDB; E2AXC7; -.
DR SMR; E2AXC7; -.
DR STRING; 104421.E2AXC7; -.
DR MEROPS; M67.004; -.
DR GeneID; 105257032; -.
DR KEGG; cfo:105257032; -.
DR InParanoid; E2AXC7; -.
DR OMA; QLPKILC; -.
DR OrthoDB; 968461at2759; -.
DR Proteomes; UP000000311; Unassembled WGS sequence.
DR GO; GO:0070531; C:BRCA1-A complex; IEA:InterPro.
DR GO; GO:0070552; C:BRISC complex; IEA:InterPro.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
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; IEA:InterPro.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0006281; P:DNA repair; IEA:InterPro.
DR GO; GO:0070536; P:protein K63-linked deubiquitination; IEA:InterPro.
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; Cell cycle; Cell division; Coiled coil; Cytoplasm;
KW Cytoskeleton; Hydrolase; Metal-binding; Metalloprotease; Mitosis; Nucleus;
KW Protease; Reference proteome; Ubl conjugation pathway; Zinc.
FT CHAIN 1..253
FT /note="Lys-63-specific deubiquitinase BRCC36"
FT /id="PRO_0000435530"
FT DOMAIN 9..145
FT /note="MPN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01182"
FT COILED 227..249
FT /evidence="ECO:0000255"
FT MOTIF 94..107
FT /note="JAMM motif"
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 96
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01182"
FT BINDING 107
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01182"
FT MUTAGEN 30
FT /note="E->A: Abolishes metalloprotease activity."
FT /evidence="ECO:0000269|PubMed:26344097"
FT MUTAGEN 94..96
FT /note="HSH->QSQ: Abolishes zinc binding and disrupts the
FT structure of the active site region."
FT /evidence="ECO:0000269|PubMed:26344097"
FT MUTAGEN 99
FT /note="I->R: Nearly abolishes metalloprotease activity."
FT /evidence="ECO:0000269|PubMed:26344097"
FT MUTAGEN 117
FT /note="M->A: Nearly abolishes metalloprotease activity."
FT /evidence="ECO:0000269|PubMed:26344097"
FT MUTAGEN 183
FT /note="E->A: Abolishes metalloprotease activity; when
FT associated with A-186."
FT /evidence="ECO:0000269|PubMed:26344097"
FT MUTAGEN 186
FT /note="D->A: Abolishes metalloprotease activity; when
FT associated with A-183."
FT /evidence="ECO:0000269|PubMed:26344097"
FT MUTAGEN 205
FT /note="A->D: Abolishes tetramerization and metalloprotease
FT activity; when associated with D-212."
FT /evidence="ECO:0000269|PubMed:26344097"
FT MUTAGEN 212
FT /note="I->D: Abolishes tetramerization and metalloprotease
FT activity; when associated with D-205."
FT /evidence="ECO:0000269|PubMed:26344097"
FT STRAND 8..12
FT /evidence="ECO:0007829|PDB:5CW4"
FT HELIX 13..23
FT /evidence="ECO:0007829|PDB:5CW4"
FT STRAND 27..29
FT /evidence="ECO:0007829|PDB:5CW4"
FT STRAND 32..39
FT /evidence="ECO:0007829|PDB:5CW4"
FT STRAND 41..51
FT /evidence="ECO:0007829|PDB:5CW4"
FT HELIX 66..82
FT /evidence="ECO:0007829|PDB:5CW4"
FT STRAND 88..97
FT /evidence="ECO:0007829|PDB:5CW4"
FT HELIX 105..117
FT /evidence="ECO:0007829|PDB:5CW4"
FT STRAND 122..131
FT /evidence="ECO:0007829|PDB:5CW4"
FT TURN 133..135
FT /evidence="ECO:0007829|PDB:5CW4"
FT STRAND 138..147
FT /evidence="ECO:0007829|PDB:5CW4"
FT STRAND 149..154
FT /evidence="ECO:0007829|PDB:5CW4"
FT STRAND 157..160
FT /evidence="ECO:0007829|PDB:5CW4"
FT HELIX 167..189
FT /evidence="ECO:0007829|PDB:5CW4"
FT HELIX 197..217
FT /evidence="ECO:0007829|PDB:5CW4"
FT HELIX 219..249
FT /evidence="ECO:0007829|PDB:5CW4"
SQ SEQUENCE 253 AA; 28745 MW; CD6A4911B66BABFB CRC64;
MDDSSLQKVE LQTDVYMVCL QHALSTENFE VMGLLIGNFA CGIAKISAVI ILRRLDKKKD
RVEISSEQLL KAAAEAERLT VELNRPMRVL GWYHSHPHIT VCPSHVDVRT QATYQTMDHS
FVGLIFSVFS EGKESKEHEI FLNCFQSDNG EATEIPLEIV HTPDISDRCL RTMTDLSKIL
VQEEEDMAEA CKDHPDVLAS IHNNAVRTRA LIHITDIITK PLVQTFEKRI ALNKLRATHL
QRQLQELQKM CNG
