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 27-MAR-2024, entry version 210. 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 (PubMed:19214193, PubMed:20656690, CC PubMed:24075985, PubMed:26344097). 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) (PubMed:14636569, PubMed:19202061, PubMed:16707425, CC PubMed:17525341, PubMed:19261748, PubMed:19261749, PubMed:19261746). 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) (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:26195665, PubMed:26344097). 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). Acts as CC a regulator of the NLRP3 inflammasome by mediating deubiquitination of CC NLRP3, leading to NLRP3 inflammasome assembly (By similarity). 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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. 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 EMDB; EMD-0132; -. DR EMDB; EMD-4759; -. DR EMDB; EMD-4760; -. DR SMR; P46736; -. DR BioGRID; 122599; 130. DR ComplexPortal; CPX-4425; BRCA1-A complex. DR ComplexPortal; CPX-955; BRCC E3 ubiquitin ligase complex. DR CORUM; P46736; -. DR DIP; DIP-48719N; -. DR IntAct; P46736; 42. 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; 9606-ENSP00000358474; -. DR PeptideAtlas; 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 Pumba; P46736; -. DR Antibodypedia; 31407; 395 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 AGR; HGNC:24185; -. 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; 1083821at2759; -. 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; 33 hits in 819 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 209 other cell types or tissues. DR ExpressionAtlas; P46736; baseline and differential. 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:0061578; F:K63-linked deubiquitinase activity; IDA:UniProtKB. 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:0140861; P:DNA repair-dependent chromatin remodeling; IMP:UniProtKB. DR GO; GO:0006302; P:double-strand break repair; IMP:UniProtKB. DR GO; GO:0007095; P:mitotic G2 DNA damage checkpoint signaling; IMP:UniProtKB. DR GO; GO:0044818; P:mitotic G2/M transition checkpoint; NAS:ComplexPortal. DR GO; GO:0045739; P:positive regulation of DNA repair; IMP:UniProtKB. DR GO; GO:1900227; P:positive regulation of NLRP3 inflammasome complex assembly; IDA:UniProt. DR GO; GO:0070536; P:protein K63-linked deubiquitination; IDA:UniProtKB. DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW. DR GO; GO:2000001; P:regulation of DNA damage checkpoint; NAS:ComplexPortal. DR GO; GO:0006282; P:regulation of DNA repair; NAS: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 Gene3D; 3.40.140.10; Cytidine Deaminase, domain 2; 1. DR InterPro; IPR040749; BRCC36_C. DR InterPro; IPR000555; JAMM/MPN+_dom. DR InterPro; IPR037518; MPN. DR InterPro; IPR033860; MPN_BRCC36. DR PANTHER; PTHR10410; EUKARYOTIC TRANSLATION INITIATION FACTOR 3 -RELATED; 1. DR PANTHER; PTHR10410:SF2; LYS-63-SPECIFIC DEUBIQUITINASE; 1. DR Pfam; PF18110; BRCC36_C; 1. DR Pfam; PF01398; JAB; 1. DR SMART; SM00232; JAB_MPN; 1. DR SUPFAM; SSF102712; JAB1/MPN domain; 1. DR PROSITE; PS50249; MPN; 1. DR Genevisible; P46736; HS. 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 //