Hmdb loader
You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.
Identification
HMDB Protein ID HMDBP13773
Secondary Accession Numbers None
Name Lys-63-specific deubiquitinase BRCC36
Synonyms
  1. BRCA1-A complex subunit BRCC36
  2. BRCA1/BRCA2-containing complex subunit 3
  3. BRCA1/BRCA2-containing complex subunit 36
  4. BRISC complex subunit BRCC36
Gene Name BRCC3
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function Metalloprotease that specifically cleaves 'Lys-63'-linked polyubiquitin chains (PubMed:19214193, PubMed:20656690, PubMed:24075985, PubMed:26344097). Does not have activity toward 'Lys-48'-linked polyubiquitin chains. Component of the BRCA1-A complex, a complex that specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). In the BRCA1-A complex, it specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX, antagonizing the RNF8-dependent ubiquitination at double-strand breaks (DSBs) (PubMed:20656690). Catalytic subunit of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked ubiquitin in various substrates (PubMed:20656690, PubMed:24075985, PubMed:26344097, PubMed:26195665). Mediates the specific 'Lys-63'-specific deubiquitination associated with the COP9 signalosome complex (CSN), via the interaction of the BRISC complex with the CSN complex (PubMed:19214193). The BRISC complex is required for normal mitotic spindle assembly and microtubule attachment to kinetochores via its role in deubiquitinating NUMA1 (PubMed:26195665). Plays a role in interferon signaling via its role in the deubiquitination of the interferon receptor IFNAR1; deubiquitination increases IFNAR1 activity by enhancing its stability and cell surface expression (PubMed:24075985, PubMed:26344097). Down-regulates the response to bacterial lipopolysaccharide (LPS) via its role in IFNAR1 deubiquitination (PubMed:24075985).
Pathways
  • Homologous recombination
  • NOD-like receptor signaling pathway
Reactions Not Available
GO Classification
Biological Process
cell cycle
protein deubiquitination
cell division
double-strand break repair via nonhomologous end joining
response to ionizing radiation
double-strand break repair
response to X-ray
protein K63-linked deubiquitination
histone H2A K63-linked deubiquitination
signal transduction involved in G2 DNA damage checkpoint
positive regulation of DNA repair
Cellular Component
cytosol
cytoplasm
nucleus
nucleoplasm
ubiquitin ligase complex
BRISC complex
BRCA1-A complex
nuclear ubiquitin ligase complex
spindle pole
Molecular Function
thiol-dependent deubiquitinase
metal ion binding
isopeptidase activity
metallopeptidase activity
polyubiquitin binding
enzyme regulator activity
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 316
Molecular Weight 36071.695
Theoretical pI 5.919
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P46736
UniProtKB/Swiss-Prot Entry Name BRCC3_HUMAN
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
  1. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039 ]
  2. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  3. Ross MT, Grafham DV, Coffey AJ, Scherer S, McLay K, Muzny D, Platzer M, Howell GR, Burrows C, Bird CP, Frankish A, Lovell FL, Howe KL, Ashurst JL, Fulton RS, Sudbrak R, Wen G, Jones MC, Hurles ME, Andrews TD, Scott CE, Searle S, Ramser J, Whittaker A, Deadman R, Carter NP, Hunt SE, Chen R, Cree A, Gunaratne P, Havlak P, Hodgson A, Metzker ML, Richards S, Scott G, Steffen D, Sodergren E, Wheeler DA, Worley KC, Ainscough R, Ambrose KD, Ansari-Lari MA, Aradhya S, Ashwell RI, Babbage AK, Bagguley CL, Ballabio A, Banerjee R, Barker GE, Barlow KF, Barrett IP, Bates KN, Beare DM, Beasley H, Beasley O, Beck A, Bethel G, Blechschmidt K, Brady N, Bray-Allen S, Bridgeman AM, Brown AJ, Brown MJ, Bonnin D, Bruford EA, Buhay C, Burch P, Burford D, Burgess J, Burrill W, Burton J, Bye JM, Carder C, Carrel L, Chako J, Chapman JC, Chavez D, Chen E, Chen G, Chen Y, Chen Z, Chinault C, Ciccodicola A, Clark SY, Clarke G, Clee CM, Clegg S, Clerc-Blankenburg K, Clifford K, Cobley V, Cole CG, Conquer JS, Corby N, Connor RE, David R, Davies J, Davis C, Davis J, Delgado O, Deshazo D, Dhami P, Ding Y, Dinh H, Dodsworth S, Draper H, Dugan-Rocha S, Dunham A, Dunn M, Durbin KJ, Dutta I, Eades T, Ellwood M, Emery-Cohen A, Errington H, Evans KL, Faulkner L, Francis F, Frankland J, Fraser AE, Galgoczy P, Gilbert J, Gill R, Glockner G, Gregory SG, Gribble S, Griffiths C, Grocock R, Gu Y, Gwilliam R, Hamilton C, Hart EA, Hawes A, Heath PD, Heitmann K, Hennig S, Hernandez J, Hinzmann B, Ho S, Hoffs M, Howden PJ, Huckle EJ, Hume J, Hunt PJ, Hunt AR, Isherwood J, Jacob L, Johnson D, Jones S, de Jong PJ, Joseph SS, Keenan S, Kelly S, Kershaw JK, Khan Z, Kioschis P, Klages S, Knights AJ, Kosiura A, Kovar-Smith C, Laird GK, Langford C, Lawlor S, Leversha M, Lewis L, Liu W, Lloyd C, Lloyd DM, Loulseged H, Loveland JE, Lovell JD, Lozado R, Lu J, Lyne R, Ma J, Maheshwari M, Matthews LH, McDowall J, McLaren S, McMurray A, Meidl P, Meitinger T, Milne S, Miner G, Mistry SL, Morgan M, Morris S, Muller I, Mullikin JC, Nguyen N, Nordsiek G, Nyakatura G, O'Dell CN, Okwuonu G, Palmer S, Pandian R, Parker D, Parrish J, Pasternak S, Patel D, Pearce AV, Pearson DM, Pelan SE, Perez L, Porter KM, Ramsey Y, Reichwald K, Rhodes S, Ridler KA, Schlessinger D, Schueler MG, Sehra HK, Shaw-Smith C, Shen H, Sheridan EM, Shownkeen R, Skuce CD, Smith ML, Sotheran EC, Steingruber HE, Steward CA, Storey R, Swann RM, Swarbreck D, Tabor PE, Taudien S, Taylor T, Teague B, Thomas K, Thorpe A, Timms K, Tracey A, Trevanion S, Tromans AC, d'Urso M, Verduzco D, Villasana D, Waldron L, Wall M, Wang Q, Warren J, Warry GL, Wei X, West A, Whitehead SL, Whiteley MN, Wilkinson JE, Willey DL, Williams G, Williams L, Williamson A, Williamson H, Wilming L, Woodmansey RL, Wray PW, Yen J, Zhang J, Zhou J, Zoghbi H, Zorilla S, Buck D, Reinhardt R, Poustka A, Rosenthal A, Lehrach H, Meindl A, Minx PJ, Hillier LW, Willard HF, Wilson RK, Waterston RH, Rice CM, Vaudin M, Coulson A, Nelson DL, Weinstock G, Sulston JE, Durbin R, Hubbard T, Gibbs RA, Beck S, Rogers J, Bentley DR: The DNA sequence of the human X chromosome. Nature. 2005 Mar 17;434(7031):325-37. [PubMed:15772651 ]
  4. Dong Y, Hakimi MA, Chen X, Kumaraswamy E, Cooch NS, Godwin AK, Shiekhattar R: Regulation of BRCC, a holoenzyme complex containing BRCA1 and BRCA2, by a signalosome-like subunit and its role in DNA repair. Mol Cell. 2003 Nov;12(5):1087-99. [PubMed:14636569 ]
  5. Wang B, Elledge SJ: Ubc13/Rnf8 ubiquitin ligases control foci formation of the Rap80/Abraxas/Brca1/Brcc36 complex in response to DNA damage. Proc Natl Acad Sci U S A. 2007 Dec 26;104(52):20759-63. Epub 2007 Dec 5. [PubMed:18077395 ]
  6. Shao G, Lilli DR, Patterson-Fortin J, Coleman KA, Morrissey DE, Greenberg RA: The Rap80-BRCC36 de-ubiquitinating enzyme complex antagonizes RNF8-Ubc13-dependent ubiquitination events at DNA double strand breaks. Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3166-71. doi: 10.1073/pnas.0807485106. Epub 2009 Feb 6. [PubMed:19202061 ]
  7. Zhou H, Di Palma S, Preisinger C, Peng M, Polat AN, Heck AJ, Mohammed S: Toward a comprehensive characterization of a human cancer cell phosphoproteome. J Proteome Res. 2013 Jan 4;12(1):260-71. doi: 10.1021/pr300630k. Epub 2012 Dec 18. [PubMed:23186163 ]
  8. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [PubMed:21269460 ]
  9. Zheng H, Gupta V, Patterson-Fortin J, Bhattacharya S, Katlinski K, Wu J, Varghese B, Carbone CJ, Aressy B, Fuchs SY, Greenberg RA: A BRISC-SHMT complex deubiquitinates IFNAR1 and regulates interferon responses. Cell Rep. 2013 Oct 17;5(1):180-93. doi: 10.1016/j.celrep.2013.08.025. Epub 2013 Sep 26. [PubMed:24075985 ]
  10. Zeqiraj E, Tian L, Piggott CA, Pillon MC, Duffy NM, Ceccarelli DF, Keszei AF, Lorenzen K, Kurinov I, Orlicky S, Gish GD, Heck AJ, Guarne A, Greenberg RA, Sicheri F: Higher-Order Assembly of BRCC36-KIAA0157 Is Required for DUB Activity and Biological Function. Mol Cell. 2015 Sep 17;59(6):970-83. doi: 10.1016/j.molcel.2015.07.028. Epub 2015 Sep 3. [PubMed:26344097 ]
  11. Kenwrick S, Levinson B, Taylor S, Shapiro A, Gitschier J: Isolation and sequence of two genes associated with a CpG island 5' of the factor VIII gene. Hum Mol Genet. 1992 Jun;1(3):179-86. doi: 10.1093/hmg/1.3.179. [PubMed:1303175 ]
  12. Fisch P, Forster A, Sherrington PD, Dyer MJ, Rabbitts TH: The chromosomal translocation t(X;14)(q28;q11) in T-cell pro-lymphocytic leukaemia breaks within one gene and activates another. Oncogene. 1993 Dec;8(12):3271-6. [PubMed:8247530 ]
  13. Chen X, Arciero CA, Wang C, Broccoli D, Godwin AK: BRCC36 is essential for ionizing radiation-induced BRCA1 phosphorylation and nuclear foci formation. Cancer Res. 2006 May 15;66(10):5039-46. doi: 10.1158/0008-5472.CAN-05-4194. [PubMed:16707425 ]
  14. Wang B, Hurov K, Hofmann K, Elledge SJ: NBA1, a new player in the Brca1 A complex, is required for DNA damage resistance and checkpoint control. Genes Dev. 2009 Mar 15;23(6):729-39. doi: 10.1101/gad.1770309. Epub 2009 Mar 4. [PubMed:19261749 ]
  15. Shao G, Patterson-Fortin J, Messick TE, Feng D, Shanbhag N, Wang Y, Greenberg RA: MERIT40 controls BRCA1-Rap80 complex integrity and recruitment to DNA double-strand breaks. Genes Dev. 2009 Mar 15;23(6):740-54. doi: 10.1101/gad.1739609. Epub 2009 Mar 4. [PubMed:19261746 ]
  16. Feng L, Huang J, Chen J: MERIT40 facilitates BRCA1 localization and DNA damage repair. Genes Dev. 2009 Mar 15;23(6):719-28. doi: 10.1101/gad.1770609. Epub 2009 Mar 4. [PubMed:19261748 ]
  17. Feng L, Wang J, Chen J: The Lys63-specific deubiquitinating enzyme BRCC36 is regulated by two scaffold proteins localizing in different subcellular compartments. J Biol Chem. 2010 Oct 1;285(40):30982-8. doi: 10.1074/jbc.M110.135392. Epub 2010 Jul 22. [PubMed:20656690 ]
  18. Zhang J, Cao M, Dong J, Li C, Xu W, Zhan Y, Wang X, Yu M, Ge C, Ge Z, Yang X: ABRO1 suppresses tumourigenesis and regulates the DNA damage response by stabilizing p53. Nat Commun. 2014 Oct 6;5:5059. doi: 10.1038/ncomms6059. [PubMed:25283148 ]
  19. Yan K, Li L, Wang X, Hong R, Zhang Y, Yang H, Lin M, Zhang S, He Q, Zheng D, Tang J, Yin Y, Shao G: The deubiquitinating enzyme complex BRISC is required for proper mitotic spindle assembly in mammalian cells. J Cell Biol. 2015 Jul 20;210(2):209-24. doi: 10.1083/jcb.201503039. [PubMed:26195665 ]