BRCC3_HUMAN
ID BRCC3_HUMAN Reviewed; 316 AA.
AC P46736; A6QRF8; A6QRF9; A8MUX5; A8MWH0; A9Z1Y0; A9Z1Y5; B1B062; B4DQN7;
AC Q16107; Q53YX5; Q9BTZ6;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2002, sequence version 2.
DT 03-AUG-2022, entry version 201.
DE RecName: Full=Lys-63-specific deubiquitinase BRCC36;
DE EC=3.4.19.- {ECO:0000269|PubMed:17525341, ECO:0000269|PubMed:19214193, ECO:0000269|PubMed:20656690, ECO:0000269|PubMed:26344097};
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, CXorf53;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
RX PubMed=1303175; DOI=10.1093/hmg/1.3.179;
RA Kenwrick S., Levinson B., Taylor S., Shapiro A., Gitschier J.;
RT "Isolation and sequence of two genes associated with a CpG island 5' of the
RT factor VIII gene.";
RL Hum. Mol. Genet. 1:179-186(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND CHROMOSOMAL TRANSLOCATION.
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, IDENTIFICATION IN BRCC
RP COMPLEX, AND INTERACTION WITH BRCA1.
RX PubMed=14636569; DOI=10.1016/s1097-2765(03)00424-6;
RA Dong Y., Hakimi M.-A., Chen X., Kumaraswamy E., Cooch N.S., Godwin A.K.,
RA Shiekhattar R.;
RT "Regulation of BRCC, a holoenzyme complex containing BRCA1 and BRCA2, by a
RT signalosome-like subunit and its role in DNA repair.";
RL Mol. Cell 12:1087-1099(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 3 AND 4).
RC TISSUE=Brain, and Teratocarcinoma;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Lung;
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 [7]
RP PROTEIN SEQUENCE OF 2-31; 90-106 AND 227-237, CLEAVAGE OF INITIATOR
RP METHIONINE, ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Embryonic kidney;
RA Bienvenut W.V., Waridel P., Quadroni M.;
RL Submitted (MAR-2009) to UniProtKB.
RN [8]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=16707425; DOI=10.1158/0008-5472.can-05-4194;
RA Chen X., Arciero C.A., Wang C., Broccoli D., Godwin A.K.;
RT "BRCC36 is essential for ionizing radiation-induced BRCA1 phosphorylation
RT and nuclear foci formation.";
RL Cancer Res. 66:5039-5046(2006).
RN [9]
RP IDENTIFICATION IN THE BRCA1-A COMPLEX, SUBCELLULAR LOCATION, AND
RP INTERACTION WITH ABRAXAS1.
RX PubMed=18077395; DOI=10.1073/pnas.0710061104;
RA Wang B., Elledge S.J.;
RT "Ubc13/Rnf8 ubiquitin ligases control foci formation of the
RT Rap80/Abraxas/Brca1/Brcc36 complex in response to DNA damage.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:20759-20763(2007).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, IDENTIFICATION IN THE BRCA1-A COMPLEX, AND
RP MUTAGENESIS OF 122-HIS--HIS-124.
RX PubMed=17525341; DOI=10.1126/science.1139516;
RA Sobhian B., Shao G., Lilli D.R., Culhane A.C., Moreau L.A., Xia B.,
RA Livingston D.M., Greenberg R.A.;
RT "RAP80 targets BRCA1 to specific ubiquitin structures at DNA damage
RT sites.";
RL Science 316:1198-1202(2007).
RN [11]
RP FUNCTION, IDENTIFICATION IN THE BRCA1-A COMPLEX, SUBCELLULAR LOCATION,
RP UBIQUITIN-BINDING, AND INTERACTION WITH ABRAXAS1.
RX PubMed=19261749; DOI=10.1101/gad.1770309;
RA Wang B., Hurov K., Hofmann K., Elledge S.J.;
RT "NBA1, a new player in the Brca1 A complex, is required for DNA damage
RT resistance and checkpoint control.";
RL Genes Dev. 23:729-739(2009).
RN [12]
RP FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE
RP BRCA1-A COMPLEX, AND MUTAGENESIS OF 122-HIS--HIS-124.
RX PubMed=19261746; DOI=10.1101/gad.1739609;
RA Shao G., Patterson-Fortin J., Messick T.E., Feng D., Shanbhag N., Wang Y.,
RA Greenberg R.A.;
RT "MERIT40 controls BRCA1-Rap80 complex integrity and recruitment to DNA
RT double-strand breaks.";
RL Genes Dev. 23:740-754(2009).
RN [13]
RP FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE
RP BRCA1-A COMPLEX, SUBCELLULAR LOCATION, AND INTERACTION WITH BABAM2
RP ANDABRAXAS1.
RX PubMed=19261748; DOI=10.1101/gad.1770609;
RA Feng L., Huang J., Chen J.;
RT "MERIT40 facilitates BRCA1 localization and DNA damage repair.";
RL Genes Dev. 23:719-728(2009).
RN [14]
RP FUNCTION, CATALYTIC ACTIVITY, IDENTIFICATION IN THE BRISC COMPLEX,
RP INTERACTION WITH THE CSN COMPLEX, AND MUTAGENESIS OF HIS-122.
RX PubMed=19214193; DOI=10.1038/emboj.2009.27;
RA Cooper E.M., Cutcliffe C., Kristiansen T.Z., Pandey A., Pickart C.M.,
RA Cohen R.E.;
RT "K63-specific deubiquitination by two JAMM/MPN+ complexes: BRISC-associated
RT Brcc36 and proteasomal Poh1.";
RL EMBO J. 28:621-631(2009).
RN [15]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF 122-HIS--HIS-124.
RX PubMed=19202061; DOI=10.1073/pnas.0807485106;
RA Shao G., Lilli D.R., Patterson-Fortin J., Coleman K.A., Morrissey D.E.,
RA Greenberg R.A.;
RT "The Rap80-BRCC36 de-ubiquitinating enzyme complex antagonizes RNF8-Ubc13-
RT dependent ubiquitination events at DNA double strand breaks.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:3166-3171(2009).
RN [16]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH ABRAXAS2, IDENTIFICATION IN
RP THE ARISC COMPLEX, AND SUBCELLULAR LOCATION.
RX PubMed=20656690; DOI=10.1074/jbc.m110.135392;
RA Feng L., Wang J., Chen J.;
RT "The Lys63-specific deubiquitinating enzyme BRCC36 is regulated by two
RT scaffold proteins localizing in different subcellular compartments.";
RL J. Biol. Chem. 285:30982-30988(2010).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [18]
RP FUNCTION, CATALYTIC ACTIVITY, IDENTIFICATION IN THE BRISC COMPLEX,
RP IDENTIFICATION IN THE ARISC COMPLEX, SUBCELLULAR LOCATION, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=24075985; DOI=10.1016/j.celrep.2013.08.025;
RA Zheng H., Gupta V., Patterson-Fortin J., Bhattacharya S., Katlinski K.,
RA Wu J., Varghese B., Carbone C.J., Aressy B., Fuchs S.Y., Greenberg R.A.;
RT "A BRISC-SHMT complex deubiquitinates IFNAR1 and regulates interferon
RT responses.";
RL Cell Rep. 5:180-193(2013).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-258, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [20]
RP IDENTIFICATION IN THE BRISC COMPLEX.
RX PubMed=25283148; DOI=10.1038/ncomms6059;
RA Zhang J., Cao M., Dong J., Li C., Xu W., Zhan Y., Wang X., Yu M., Ge C.,
RA Ge Z., Yang X.;
RT "ABRO1 suppresses tumourigenesis and regulates the DNA damage response by
RT stabilizing p53.";
RL Nat. Commun. 5:5059-5059(2014).
RN [21]
RP FUNCTION, SUBUNIT, IDENTIFICATION IN A COMPLEX WITH NUMA1 AND ABRAXAS2, AND
RP MUTAGENESIS OF 122-HIS--HIS-124.
RX PubMed=26195665; DOI=10.1083/jcb.201503039;
RA Yan K., Li L., Wang X., Hong R., Zhang Y., Yang H., Lin M., Zhang S.,
RA He Q., Zheng D., Tang J., Yin Y., Shao G.;
RT "The deubiquitinating enzyme complex BRISC is required for proper mitotic
RT spindle assembly in mammalian cells.";
RL J. Cell Biol. 210:209-224(2015).
RN [22]
RP FUNCTION, INTERACTION WITH ABRAXAS2; UIMC1; SHMT2; BABAM2 AND BABAM1,
RP SUBUNIT, MUTAGENESIS OF LEU-23; LEU-27 AND ALA-278, SUBCELLULAR LOCATION,
RP AND CATALYTIC ACTIVITY.
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 (PubMed:19214193, PubMed:20656690,
CC PubMed:24075985, PubMed:26344097). Does not have activity toward 'Lys-
CC 48'-linked polyubiquitin chains. Component of the BRCA1-A complex, a
CC complex that specifically recognizes 'Lys-63'-linked ubiquitinated
CC histones H2A and H2AX at DNA lesions sites, leading to target the
CC BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks
CC (DSBs). In the BRCA1-A complex, it specifically removes 'Lys-63'-linked
CC ubiquitin on histones H2A and H2AX, antagonizing the RNF8-dependent
CC ubiquitination at double-strand breaks (DSBs) (PubMed:20656690).
CC Catalytic subunit of the BRISC complex, a multiprotein complex that
CC specifically cleaves 'Lys-63'-linked ubiquitin in various substrates
CC (PubMed:20656690, PubMed:24075985, PubMed:26344097, PubMed:26195665).
CC Mediates the specific 'Lys-63'-specific deubiquitination associated
CC with the COP9 signalosome complex (CSN), via the interaction of the
CC BRISC complex with the CSN complex (PubMed:19214193). The BRISC complex
CC is required for normal mitotic spindle assembly and microtubule
CC attachment to kinetochores via its role in deubiquitinating NUMA1
CC (PubMed:26195665). Plays a role in interferon signaling via its role in
CC the deubiquitination of the interferon receptor IFNAR1;
CC deubiquitination increases IFNAR1 activity by enhancing its stability
CC and cell surface expression (PubMed:24075985, PubMed:26344097). Down-
CC regulates the response to bacterial lipopolysaccharide (LPS) via its
CC role in IFNAR1 deubiquitination (PubMed:24075985). Deubiquitinates
CC HDAC1 and PWWP2B leading to their stabilization (By similarity).
CC {ECO:0000250|UniProtKB:P46737, ECO:0000269|PubMed:14636569,
CC ECO:0000269|PubMed:16707425, ECO:0000269|PubMed:17525341,
CC ECO:0000269|PubMed:19202061, ECO:0000269|PubMed:19214193,
CC ECO:0000269|PubMed:19261746, ECO:0000269|PubMed:19261748,
CC ECO:0000269|PubMed:19261749, ECO:0000269|PubMed:20656690,
CC ECO:0000269|PubMed:24075985, ECO:0000269|PubMed:26195665,
CC ECO:0000269|PubMed:26344097}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:E2AXC7, ECO:0000305};
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
CC (PubMed:20656690, PubMed:24075985). Component of the BRCA1-A complex,
CC at least composed of BRCA1, BARD1, UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36,
CC babam2 and BABAM1/NBA1. In the BRCA1-A complex, interacts directly with
CC ABRAXAS1 and babam2 (PubMed:18077395, PubMed:19261748). Component of
CC the BRISC complex, at least composed of ABRAXAS2, BRCC3/BRCC36, BABAM2
CC and BABAM1/NBA1 (PubMed:24075985, PubMed:25283148, PubMed:26344097).
CC Identified in a complex with SHMT2 and the other subunits of the BRISC
CC complex (PubMed:24075985). In the BRISC complex, interacts directly
CC with ABRAXAS2 (PubMed:20656690, PubMed:26344097). Identified in a
CC complex with ABRAXAS2 and NUMA1 (PubMed:26195665). The BRISC complex
CC interacts with the CSN complex. Component of the BRCA1/BRCA2 containing
CC complex (BRCC), which also contains BRCA1, BRCA2, BARD1, BABAM2 and
CC RAD51. BRCC is a ubiquitin E3 ligase complex that enhances cellular
CC survival following DNA damage. Interacts with BRCA1. Binds
CC polyubiquitin. Interacts with PWWP2B (By similarity). Interacts with
CC HDAC1; this interaction is enhanced in the presence of PWWP2B (By
CC similarity). {ECO:0000250|UniProtKB:P46737,
CC ECO:0000269|PubMed:14636569, ECO:0000269|PubMed:17525341,
CC ECO:0000269|PubMed:18077395, ECO:0000269|PubMed:19214193,
CC ECO:0000269|PubMed:19261746, ECO:0000269|PubMed:19261748,
CC ECO:0000269|PubMed:19261749, ECO:0000269|PubMed:20656690,
CC ECO:0000269|PubMed:26195665, ECO:0000269|PubMed:26344097}.
CC -!- INTERACTION:
CC P46736; Q6UWZ7: ABRAXAS1; NbExp=4; IntAct=EBI-750352, EBI-1263451;
CC P46736; X5D778: ANKRD11; NbExp=3; IntAct=EBI-750352, EBI-17183751;
CC P46736; Q96RL1-1: UIMC1; NbExp=4; IntAct=EBI-750352, EBI-9640371;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:18077395,
CC ECO:0000269|PubMed:19202061, ECO:0000269|PubMed:19261748,
CC ECO:0000269|PubMed:19261749, ECO:0000269|PubMed:20656690,
CC ECO:0000269|PubMed:24075985, ECO:0000269|PubMed:26344097}. Cytoplasm
CC {ECO:0000269|PubMed:20656690, ECO:0000269|PubMed:24075985}. Cytoplasm,
CC cytoskeleton, spindle pole {ECO:0000305|PubMed:26195665}.
CC Note=Localizes at sites of DNA damage at double-strand breaks (DSBs)
CC (PubMed:20656690, PubMed:26344097). Interaction with ABRAXAS2 retains
CC BRCC3 in the cytoplasm (PubMed:20656690). {ECO:0000269|PubMed:20656690,
CC ECO:0000269|PubMed:26344097}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=2;
CC IsoId=P46736-1; Sequence=Displayed;
CC Name=1;
CC IsoId=P46736-2; Sequence=VSP_003261;
CC Name=3;
CC IsoId=P46736-3; Sequence=VSP_037258, VSP_003261;
CC Name=4;
CC IsoId=P46736-4; Sequence=VSP_037257;
CC Name=5;
CC IsoId=P46736-5; Sequence=VSP_037259;
CC -!- TISSUE SPECIFICITY: Heart, brain, placenta, lung, liver, skeletal
CC muscle, kidney and pancreas. Aberrantly expressed in the vast majority
CC of breast tumors. {ECO:0000269|PubMed:16707425}.
CC -!- DISEASE: Note=A chromosomal aberration involving BRCC3 is a cause of
CC pro-lymphocytic T-cell leukemia (T-PLL). Translocation t(X;14)(q28;q11)
CC with TCRA. {ECO:0000269|PubMed:8247530}.
CC -!- SIMILARITY: Belongs to the peptidase M67A family. BRCC36 subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB29005.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; X64643; CAA45917.1; -; mRNA.
DR EMBL; S68015; AAB29005.2; ALT_INIT; mRNA.
DR EMBL; AY438030; AAR30498.1; -; mRNA.
DR EMBL; AK298886; BAG60999.1; -; mRNA.
DR EMBL; AK299194; BAG61237.1; -; mRNA.
DR EMBL; AK313544; BAG36320.1; -; mRNA.
DR EMBL; BX293995; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX470111; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC002999; AAH02999.1; -; mRNA.
DR EMBL; BC006540; AAH06540.1; -; mRNA.
DR CCDS; CCDS56610.1; -. [P46736-3]
DR CCDS; CCDS56611.1; -. [P46736-1]
DR CCDS; CCDS56612.1; -. [P46736-2]
DR PIR; I38167; I38167.
DR RefSeq; NP_001018065.1; NM_001018055.2. [P46736-2]
DR RefSeq; NP_001229569.1; NM_001242640.1. [P46736-3]
DR RefSeq; NP_077308.1; NM_024332.3. [P46736-1]
DR RefSeq; XP_016885327.1; XM_017029838.1. [P46736-2]
DR PDB; 6H3C; EM; 3.90 A; B/G=1-316.
DR PDB; 6R8F; EM; 3.80 A; A/C=1-316.
DR PDBsum; 6H3C; -.
DR PDBsum; 6R8F; -.
DR AlphaFoldDB; P46736; -.
DR SMR; P46736; -.
DR BioGRID; 122599; 99.
DR ComplexPortal; CPX-4425; BRCA1-A complex.
DR ComplexPortal; CPX-955; BRCC ubiquitin ligase complex.
DR CORUM; P46736; -.
DR DIP; DIP-48719N; -.
DR IntAct; P46736; 36.
DR MINT; P46736; -.
DR STRING; 9606.ENSP00000358474; -.
DR BindingDB; P46736; -.
DR ChEMBL; CHEMBL4105965; -.
DR DrugBank; DB01593; Zinc.
DR DrugBank; DB14487; Zinc acetate.
DR DrugBank; DB14533; Zinc chloride.
DR DrugBank; DB14548; Zinc sulfate, unspecified form.
DR MEROPS; M67.004; -.
DR GlyGen; P46736; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P46736; -.
DR PhosphoSitePlus; P46736; -.
DR BioMuta; BRCC3; -.
DR DMDM; 20532383; -.
DR EPD; P46736; -.
DR jPOST; P46736; -.
DR MassIVE; P46736; -.
DR MaxQB; P46736; -.
DR PaxDb; P46736; -.
DR PeptideAtlas; P46736; -.
DR PRIDE; P46736; -.
DR ProteomicsDB; 55753; -. [P46736-1]
DR ProteomicsDB; 55754; -. [P46736-2]
DR ProteomicsDB; 55755; -. [P46736-3]
DR ProteomicsDB; 55756; -. [P46736-4]
DR ProteomicsDB; 55757; -. [P46736-5]
DR Antibodypedia; 31407; 363 antibodies from 36 providers.
DR DNASU; 79184; -.
DR Ensembl; ENST00000330045.12; ENSP00000328641.7; ENSG00000185515.16. [P46736-2]
DR Ensembl; ENST00000340647.8; ENSP00000344103.4; ENSG00000185515.16. [P46736-3]
DR Ensembl; ENST00000369459.6; ENSP00000358471.2; ENSG00000185515.16. [P46736-5]
DR Ensembl; ENST00000369462.5; ENSP00000358474.1; ENSG00000185515.16. [P46736-1]
DR GeneID; 79184; -.
DR KEGG; hsa:79184; -.
DR MANE-Select; ENST00000330045.12; ENSP00000328641.7; NM_001018055.3; NP_001018065.1. [P46736-2]
DR UCSC; uc004fna.4; human. [P46736-1]
DR CTD; 79184; -.
DR DisGeNET; 79184; -.
DR GeneCards; BRCC3; -.
DR HGNC; HGNC:24185; BRCC3.
DR HPA; ENSG00000185515; Low tissue specificity.
DR MalaCards; BRCC3; -.
DR MIM; 300617; gene.
DR neXtProt; NX_P46736; -.
DR OpenTargets; ENSG00000185515; -.
DR Orphanet; 280679; Moyamoya angiopathy-short stature-facial dysmorphism-hypergonadotropic hypogonadism syndrome.
DR PharmGKB; PA134922847; -.
DR VEuPathDB; HostDB:ENSG00000185515; -.
DR eggNOG; KOG1555; Eukaryota.
DR GeneTree; ENSGT00390000000360; -.
DR HOGENOM; CLU_053351_0_0_1; -.
DR InParanoid; P46736; -.
DR OMA; CIGEIDT; -.
DR OrthoDB; 968461at2759; -.
DR PhylomeDB; P46736; -.
DR TreeFam; TF328524; -.
DR PathwayCommons; P46736; -.
DR Reactome; R-HSA-5689901; Metalloprotease DUBs.
DR Reactome; R-HSA-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
DR Reactome; R-HSA-5693571; Nonhomologous End-Joining (NHEJ).
DR Reactome; R-HSA-5693607; Processing of DNA double-strand break ends.
DR Reactome; R-HSA-69473; G2/M DNA damage checkpoint.
DR SignaLink; P46736; -.
DR SIGNOR; P46736; -.
DR BioGRID-ORCS; 79184; 26 hits in 745 CRISPR screens.
DR ChiTaRS; BRCC3; human.
DR GeneWiki; BRCC3; -.
DR GenomeRNAi; 79184; -.
DR Pharos; P46736; Tbio.
DR PRO; PR:P46736; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; P46736; protein.
DR Bgee; ENSG00000185515; Expressed in parotid gland and 207 other tissues.
DR ExpressionAtlas; P46736; baseline and differential.
DR Genevisible; P46736; HS.
DR GO; GO:0070531; C:BRCA1-A complex; IDA:UniProtKB.
DR GO; GO:0070552; C:BRISC complex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0000152; C:nuclear ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000922; C:spindle pole; IEA:UniProtKB-SubCell.
DR GO; GO:0000151; C:ubiquitin ligase complex; IDA:MGI.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IEA:InterPro.
DR GO; GO:0030234; F:enzyme regulator activity; IDA:MGI.
DR GO; GO:0070122; F:isopeptidase activity; IEA:InterPro.
DR GO; GO:0061578; F:Lys63-specific deubiquitinase activity; TAS:Reactome.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0140492; F:metal-dependent deubiquitinase activity; IMP:UniProtKB.
DR GO; GO:0008237; F:metallopeptidase activity; IMP:UniProtKB.
DR GO; GO:0031593; F:polyubiquitin modification-dependent protein binding; IDA:UniProtKB.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0071479; P:cellular response to ionizing radiation; IMP:ComplexPortal.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0006302; P:double-strand break repair; IMP:UniProtKB.
DR GO; GO:0070537; P:histone H2A K63-linked deubiquitination; IDA:UniProtKB.
DR GO; GO:0035518; P:histone H2A monoubiquitination; IC:ComplexPortal.
DR GO; GO:0007095; P:mitotic G2 DNA damage checkpoint signaling; IMP:UniProtKB.
DR GO; GO:0044818; P:mitotic G2/M transition checkpoint; IC:ComplexPortal.
DR GO; GO:0045739; P:positive regulation of DNA repair; IMP:UniProtKB.
DR GO; GO:0051865; P:protein autoubiquitination; IC:ComplexPortal.
DR GO; GO:0016579; P:protein deubiquitination; TAS:Reactome.
DR GO; GO:0070536; P:protein K63-linked deubiquitination; IDA: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; IMP:UniProtKB.
DR GO; GO:0010165; P:response to X-ray; IDA: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; Chromosomal rearrangement; Cytoplasm; Cytoskeleton;
KW Direct protein sequencing; DNA damage; DNA repair; Hydrolase;
KW Metal-binding; Metalloprotease; Mitosis; Nucleus; Phosphoprotein; Protease;
KW Proto-oncogene; Reference proteome; Ubl conjugation pathway; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.7"
FT CHAIN 2..316
FT /note="Lys-63-specific deubiquitinase BRCC36"
FT /id="PRO_0000213967"
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:0000269|Ref.7"
FT MOD_RES 258
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..114
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_037257"
FT VAR_SEQ 46
FT /note="T -> TS (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_037258"
FT VAR_SEQ 183..252
FT /note="ESLHGPRDFWSSSQHISIEGQKEEERYERIEIPIHIVPHVTIGKVCLESAVE
FT LPKILCQEEQDAYRRIHS -> D (in isoform 5)"
FT /evidence="ECO:0000305"
FT /id="VSP_037259"
FT VAR_SEQ 184..208
FT /note="Missing (in isoform 1 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:1303175,
FT ECO:0000303|PubMed:14702039"
FT /id="VSP_003261"
FT VARIANT 74
FT /note="I -> V (in dbSNP:rs28997578)"
FT /id="VAR_050097"
FT MUTAGEN 23
FT /note="L->R: Abolishes localization to sites of DNA damage
FT and interaction with ABRAXAS2; UIMC1; SHMT2; BARAM2 and
FT BABAM1; when associated with R-27."
FT /evidence="ECO:0000269|PubMed:26344097"
FT MUTAGEN 27
FT /note="L->R: Abolishes localization to sites of DNA damage
FT and interaction with ABRAXAS2; UIMC1; SHMT2; BABAM2 and
FT BABAM1; when associated with R-23."
FT /evidence="ECO:0000269|PubMed:26344097"
FT MUTAGEN 122..124
FT /note="HSH->QSQ: Abolishes metalloprotease activity and
FT function in DNA repair."
FT /evidence="ECO:0000269|PubMed:17525341,
FT ECO:0000269|PubMed:19202061, ECO:0000269|PubMed:19261746,
FT ECO:0000269|PubMed:26195665"
FT MUTAGEN 122
FT /note="H->Q: Loss of deubiquitinase activity."
FT /evidence="ECO:0000269|PubMed:19214193"
FT MUTAGEN 278
FT /note="A->R: Abolishes interaction with UIMC1 and SHMT2."
FT /evidence="ECO:0000269|PubMed:26344097"
FT CONFLICT 225
FT /note="G -> W (in Ref. 2; AAB29005)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 316 AA; 36072 MW; 5720358C1A2F7421 CRC64;
MAVQVVQAVQ AVHLESDAFL VCLNHALSTE KEEVMGLCIG ELNDDTRSDS KFAYTGTEMR
TVAEKVDAVR IVHIHSVIIL RRSDKRKDRV EISPEQLSAA STEAERLAEL TGRPMRVVGW
YHSHPHITVW PSHVDVRTQA MYQMMDQGFV GLIFSCFIED KNTKTGRVLY TCFQSIQAQK
SSESLHGPRD FWSSSQHISI EGQKEEERYE RIEIPIHIVP HVTIGKVCLE SAVELPKILC
QEEQDAYRRI HSLTHLDSVT KIHNGSVFTK NLCSQMSAVS GPLLQWLEDR LEQNQQHLQE
LQQEKEELMQ ELSSLE
