Full text data of BRCC3
BRCC3
(BRCC36, C6.1A, CXorf53)
[Confidence: low (only semi-automatic identification from reviews)]
Lys-63-specific deubiquitinase BRCC36; 3.4.19.- (BRCA1-A complex subunit BRCC36; BRCA1/BRCA2-containing complex subunit 3; BRCA1/BRCA2-containing complex subunit 36; BRISC complex subunit BRCC36)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Lys-63-specific deubiquitinase BRCC36; 3.4.19.- (BRCA1-A complex subunit BRCC36; BRCA1/BRCA2-containing complex subunit 3; BRCA1/BRCA2-containing complex subunit 36; BRISC complex subunit BRCC36)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P46736
ID BRCC3_HUMAN Reviewed; 316 AA.
AC P46736; A6QRF8; A6QRF9; A8MUX5; A8MWH0; A9Z1Y0; A9Z1Y5; B1B062;
read moreAC B4DQN7; Q16107; Q53YX5; Q9BTZ6;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2002, sequence version 2.
DT 22-JAN-2014, entry version 129.
DE RecName: Full=Lys-63-specific deubiquitinase BRCC36;
DE EC=3.4.19.-;
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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'
RT of the 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-
RT lymphocytic 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
RP BRCC 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.,
RA Godwin A.K., Shiekhattar R.;
RT "Regulation of BRCC, a holoenzyme complex containing BRCA1 and BRCA2,
RT by a 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G.,
RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S.,
RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R.,
RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L.,
RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A.,
RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S.,
RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R.,
RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M.,
RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N.,
RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D.,
RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W.,
RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C.,
RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C.,
RA 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.,
RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S.,
RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I.,
RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L.,
RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P.,
RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S.,
RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A.,
RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J.,
RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J.,
RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S.,
RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z.,
RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C.,
RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W.,
RA 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.,
RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I.,
RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N.,
RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J.,
RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E.,
RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S.,
RA 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.,
RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S.,
RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L.,
RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A.,
RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L.,
RA Williams G., Williams L., Williamson A., Williamson H., Wilming L.,
RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H.,
RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A.,
RA 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.,
RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T.,
RA Gibbs R.A., Beck S., 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
RT project: 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 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
RT phosphorylation 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 FAM175A.
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, IDENTIFICATION IN THE BRCA1-A COMPLEX, AND MUTAGENESIS OF
RP 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 FAM175A.
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.,
RA Wang Y., 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 BRE AND
RP FAM175A.
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-
RT associated 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.,
RA Morrissey D.E., Greenberg R.A.;
RT "The Rap80-BRCC36 de-ubiquitinating enzyme complex antagonizes RNF8-
RT Ubc13-dependent ubiquitination events at DNA double strand breaks.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:3166-3171(2009).
RN [16]
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.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Metalloprotease that specifically cleaves 'Lys-63'-
CC linked polyubiquitin chains. Does not have activity toward 'Lys-
CC 48'-linked polyubiquitin chains. Component of the BRCA1-A complex,
CC a complex that specifically recognizes 'Lys-63'-linked
CC ubiquitinated histones H2A and H2AX at DNA lesions sites, leading
CC to target the BRCA1-BARD1 heterodimer to sites of DNA damage at
CC double-strand breaks (DSBs). In the BRCA1-A complex, it
CC specifically removes 'Lys-63'-linked ubiquitin on histones H2A and
CC H2AX, antagonizing the RNF8-dependent ubiquitination at double-
CC strand breaks (DSBs). Catalytic subunit of the BRISC complex, a
CC multiprotein complex that specifically cleaves 'Lys-63'-linked
CC ubiquitin in various substrates. Mediates the specific 'Lys-63'-
CC specific deubiquitination associated with the COP9 signalosome
CC complex (CSN), via the interaction of the BRISC complex with the
CC CSN complex.
CC -!- SUBUNIT: Component of the BRCA1-A complex, at least composed of
CC the BRCA1, BARD1, UIMC1/RAP80, FAM175A/Abraxas, BRCC3/BRCC36,
CC BRE/BRCC45 and BABAM1/NBA1. In the BRCA1-A complex, interacts
CC directly with FAM175A/Abraxas and BRE/BRCC45. Component of the
CC BRISC complex, at least composed of the FAM175B/ABRO1,
CC BRCC3/BRCC36, BRE/BRCC45 and BABAM1/NBA1. The BRISC complex
CC interacts with the CSN complex. Component of the BRCA1/BRCA2
CC containing complex (BRCC), which also contains BRCA1, BRCA2,
CC BARD1, BRE and RAD51. BRCC is a ubiquitin E3 ligase complex that
CC enhances cellular survival following DNA damage. Interacts with
CC BRCA1. Binds polyubiquitin.
CC -!- SUBCELLULAR LOCATION: Nucleus. Note=Localizes at sites of DNA
CC damage at double-strand breaks (DSBs).
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 Note=No experimental confirmation available;
CC Name=5;
CC IsoId=P46736-5; Sequence=VSP_037259;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Heart, brain, placenta, lung, liver, skeletal
CC muscle, kidney and pancreas. Aberrantly expressed in the vast
CC majority of breast tumors.
CC -!- DISEASE: Note=A chromosomal aberration involving BRCC3 is a cause
CC of pro-lymphocytic T-cell leukemia (T-PLL). Translocation
CC t(X;14)(q28;q11) with TCRA.
CC -!- SIMILARITY: Belongs to the peptidase M67A family. BRCC36
CC subfamily.
CC -!- SIMILARITY: Contains 1 MPN (JAB/Mov34) domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB29005.2; Type=Erroneous initiation;
CC Sequence=CAO03573.1; Type=Erroneous gene model prediction;
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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; CAH70537.1; -; Genomic_DNA.
DR EMBL; BX470111; CAH70537.1; JOINED; Genomic_DNA.
DR EMBL; BX293995; CAH70538.1; -; Genomic_DNA.
DR EMBL; BX470111; CAH70538.1; JOINED; Genomic_DNA.
DR EMBL; BX470111; CAI41654.1; -; Genomic_DNA.
DR EMBL; BX293995; CAI41654.1; JOINED; Genomic_DNA.
DR EMBL; BX470111; CAI41655.1; -; Genomic_DNA.
DR EMBL; BX293995; CAI41655.1; JOINED; Genomic_DNA.
DR EMBL; BX470111; CAO03573.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BX470111; CAO03574.1; -; Genomic_DNA.
DR EMBL; BX470111; CAO03575.1; -; Genomic_DNA.
DR EMBL; BX293995; CAO03575.1; JOINED; Genomic_DNA.
DR EMBL; BX470111; CAO03576.1; -; Genomic_DNA.
DR EMBL; BX293995; CAO03576.1; JOINED; Genomic_DNA.
DR EMBL; BX293995; CAO03601.1; -; Genomic_DNA.
DR EMBL; BX470111; CAO03601.1; JOINED; Genomic_DNA.
DR EMBL; BX293995; CAO03602.1; -; Genomic_DNA.
DR EMBL; BX470111; CAO03602.1; JOINED; Genomic_DNA.
DR EMBL; BC002999; AAH02999.1; -; mRNA.
DR EMBL; BC006540; AAH06540.1; -; mRNA.
DR PIR; I38167; I38167.
DR RefSeq; NP_001018065.1; NM_001018055.2.
DR RefSeq; NP_001229569.1; NM_001242640.1.
DR RefSeq; NP_077308.1; NM_024332.3.
DR RefSeq; XP_005274806.1; XM_005274749.1.
DR RefSeq; XP_005274807.1; XM_005274750.1.
DR RefSeq; XP_005277965.1; XM_005277908.1.
DR RefSeq; XP_005277966.1; XM_005277909.1.
DR UniGene; Hs.558537; -.
DR ProteinModelPortal; P46736; -.
DR SMR; P46736; 10-193.
DR DIP; DIP-48719N; -.
DR IntAct; P46736; 21.
DR MINT; MINT-1475401; -.
DR MEROPS; M67.004; -.
DR PhosphoSite; P46736; -.
DR DMDM; 20532383; -.
DR PaxDb; P46736; -.
DR PRIDE; P46736; -.
DR DNASU; 79184; -.
DR Ensembl; ENST00000330045; ENSP00000328641; ENSG00000185515.
DR Ensembl; ENST00000340647; ENSP00000344103; ENSG00000185515.
DR Ensembl; ENST00000369459; ENSP00000358471; ENSG00000185515.
DR Ensembl; ENST00000369462; ENSP00000358474; ENSG00000185515.
DR Ensembl; ENST00000594541; ENSP00000470674; ENSG00000269884.
DR Ensembl; ENST00000597217; ENSP00000469831; ENSG00000269884.
DR Ensembl; ENST00000597826; ENSP00000473083; ENSG00000269884.
DR Ensembl; ENST00000601378; ENSP00000469902; ENSG00000269884.
DR GeneID; 79184; -.
DR KEGG; hsa:79184; -.
DR UCSC; uc004fna.3; human.
DR CTD; 79184; -.
DR GeneCards; GC0XP154299; -.
DR HGNC; HGNC:24185; BRCC3.
DR MIM; 300617; gene.
DR neXtProt; NX_P46736; -.
DR Orphanet; 280679; Moyamoya disease - short stature - facial dysmorphism - hypergonadotropic hypogonadism.
DR PharmGKB; PA134922847; -.
DR eggNOG; NOG322509; -.
DR HOVERGEN; HBG002142; -.
DR KO; K11864; -.
DR GeneWiki; BRCC3; -.
DR GenomeRNAi; 79184; -.
DR NextBio; 68176; -.
DR PRO; PR:P46736; -.
DR ArrayExpress; P46736; -.
DR Bgee; P46736; -.
DR CleanEx; HS_BRCC3; -.
DR Genevestigator; P46736; -.
DR GO; GO:0070531; C:BRCA1-A complex; IDA:UniProtKB.
DR GO; GO:0070552; C:BRISC complex; IDA:UniProtKB.
DR GO; GO:0000152; C:nuclear ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0004843; F:deubiquitinase activity; IMP:UniProtKB.
DR GO; GO:0030234; F:enzyme regulator activity; IDA:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008237; F:metallopeptidase activity; IMP:UniProtKB.
DR GO; GO:0031593; F:polyubiquitin binding; IDA:UniProtKB.
DR GO; GO:0004221; F:ubiquitin thiolesterase activity; IMP:UniProtKB.
DR GO; GO:0006302; P:double-strand break repair; IMP:UniProtKB.
DR GO; GO:0031572; P:G2 DNA damage checkpoint; IMP:UniProtKB.
DR GO; GO:0070537; P:histone H2A K63-linked deubiquitination; IDA:UniProtKB.
DR GO; GO:0045739; P:positive regulation of DNA repair; IMP:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0010165; P:response to X-ray; IDA:MGI.
DR InterPro; IPR000555; JAB_MPN_dom.
DR Pfam; PF01398; JAB; 1.
DR SMART; SM00232; JAB_MPN; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Chromatin regulator;
KW Chromosomal rearrangement; Complete proteome;
KW Direct protein sequencing; DNA damage; DNA repair; Hydrolase;
KW Metal-binding; Metalloprotease; Nucleus; Polymorphism; Protease;
KW Proto-oncogene; Reference proteome; Ubl conjugation pathway; Zinc.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 316 Lys-63-specific deubiquitinase BRCC36.
FT /FTId=PRO_0000213967.
FT DOMAIN 7 148 MPN.
FT MOTIF 122 135 JAMM motif.
FT METAL 122 122 Zinc; catalytic (Probable).
FT METAL 124 124 Zinc; catalytic (Probable).
FT METAL 135 135 Zinc; catalytic (By similarity).
FT MOD_RES 2 2 N-acetylalanine.
FT VAR_SEQ 1 114 Missing (in isoform 4).
FT /FTId=VSP_037257.
FT VAR_SEQ 46 46 T -> TS (in isoform 3).
FT /FTId=VSP_037258.
FT VAR_SEQ 183 252 ESLHGPRDFWSSSQHISIEGQKEEERYERIEIPIHIVPHVT
FT IGKVCLESAVELPKILCQEEQDAYRRIHS -> D (in
FT isoform 5).
FT /FTId=VSP_037259.
FT VAR_SEQ 184 208 Missing (in isoform 1 and isoform 3).
FT /FTId=VSP_003261.
FT VARIANT 74 74 I -> V (in dbSNP:rs28997578).
FT /FTId=VAR_050097.
FT MUTAGEN 122 124 HSH->QSQ: Abolishes metalloprotease
FT activity and function in DNA repair.
FT MUTAGEN 122 122 H->Q: Loss of deubiquitinase activity.
FT CONFLICT 225 225 G -> W (in Ref. 2; AAB29005).
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
//
ID BRCC3_HUMAN Reviewed; 316 AA.
AC P46736; A6QRF8; A6QRF9; A8MUX5; A8MWH0; A9Z1Y0; A9Z1Y5; B1B062;
read moreAC B4DQN7; Q16107; Q53YX5; Q9BTZ6;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2002, sequence version 2.
DT 22-JAN-2014, entry version 129.
DE RecName: Full=Lys-63-specific deubiquitinase BRCC36;
DE EC=3.4.19.-;
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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'
RT of the 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-
RT lymphocytic 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
RP BRCC 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.,
RA Godwin A.K., Shiekhattar R.;
RT "Regulation of BRCC, a holoenzyme complex containing BRCA1 and BRCA2,
RT by a 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G.,
RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S.,
RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R.,
RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L.,
RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A.,
RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S.,
RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R.,
RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M.,
RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N.,
RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D.,
RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W.,
RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C.,
RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C.,
RA 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.,
RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S.,
RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I.,
RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L.,
RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P.,
RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S.,
RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A.,
RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J.,
RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J.,
RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S.,
RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z.,
RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C.,
RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W.,
RA 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.,
RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I.,
RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N.,
RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J.,
RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E.,
RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S.,
RA 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.,
RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S.,
RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L.,
RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A.,
RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L.,
RA Williams G., Williams L., Williamson A., Williamson H., Wilming L.,
RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H.,
RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A.,
RA 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.,
RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T.,
RA Gibbs R.A., Beck S., 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
RT project: 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 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
RT phosphorylation 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 FAM175A.
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, IDENTIFICATION IN THE BRCA1-A COMPLEX, AND MUTAGENESIS OF
RP 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 FAM175A.
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.,
RA Wang Y., 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 BRE AND
RP FAM175A.
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-
RT associated 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.,
RA Morrissey D.E., Greenberg R.A.;
RT "The Rap80-BRCC36 de-ubiquitinating enzyme complex antagonizes RNF8-
RT Ubc13-dependent ubiquitination events at DNA double strand breaks.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:3166-3171(2009).
RN [16]
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.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Metalloprotease that specifically cleaves 'Lys-63'-
CC linked polyubiquitin chains. Does not have activity toward 'Lys-
CC 48'-linked polyubiquitin chains. Component of the BRCA1-A complex,
CC a complex that specifically recognizes 'Lys-63'-linked
CC ubiquitinated histones H2A and H2AX at DNA lesions sites, leading
CC to target the BRCA1-BARD1 heterodimer to sites of DNA damage at
CC double-strand breaks (DSBs). In the BRCA1-A complex, it
CC specifically removes 'Lys-63'-linked ubiquitin on histones H2A and
CC H2AX, antagonizing the RNF8-dependent ubiquitination at double-
CC strand breaks (DSBs). Catalytic subunit of the BRISC complex, a
CC multiprotein complex that specifically cleaves 'Lys-63'-linked
CC ubiquitin in various substrates. Mediates the specific 'Lys-63'-
CC specific deubiquitination associated with the COP9 signalosome
CC complex (CSN), via the interaction of the BRISC complex with the
CC CSN complex.
CC -!- SUBUNIT: Component of the BRCA1-A complex, at least composed of
CC the BRCA1, BARD1, UIMC1/RAP80, FAM175A/Abraxas, BRCC3/BRCC36,
CC BRE/BRCC45 and BABAM1/NBA1. In the BRCA1-A complex, interacts
CC directly with FAM175A/Abraxas and BRE/BRCC45. Component of the
CC BRISC complex, at least composed of the FAM175B/ABRO1,
CC BRCC3/BRCC36, BRE/BRCC45 and BABAM1/NBA1. The BRISC complex
CC interacts with the CSN complex. Component of the BRCA1/BRCA2
CC containing complex (BRCC), which also contains BRCA1, BRCA2,
CC BARD1, BRE and RAD51. BRCC is a ubiquitin E3 ligase complex that
CC enhances cellular survival following DNA damage. Interacts with
CC BRCA1. Binds polyubiquitin.
CC -!- SUBCELLULAR LOCATION: Nucleus. Note=Localizes at sites of DNA
CC damage at double-strand breaks (DSBs).
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 Note=No experimental confirmation available;
CC Name=5;
CC IsoId=P46736-5; Sequence=VSP_037259;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Heart, brain, placenta, lung, liver, skeletal
CC muscle, kidney and pancreas. Aberrantly expressed in the vast
CC majority of breast tumors.
CC -!- DISEASE: Note=A chromosomal aberration involving BRCC3 is a cause
CC of pro-lymphocytic T-cell leukemia (T-PLL). Translocation
CC t(X;14)(q28;q11) with TCRA.
CC -!- SIMILARITY: Belongs to the peptidase M67A family. BRCC36
CC subfamily.
CC -!- SIMILARITY: Contains 1 MPN (JAB/Mov34) domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB29005.2; Type=Erroneous initiation;
CC Sequence=CAO03573.1; Type=Erroneous gene model prediction;
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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; CAH70537.1; -; Genomic_DNA.
DR EMBL; BX470111; CAH70537.1; JOINED; Genomic_DNA.
DR EMBL; BX293995; CAH70538.1; -; Genomic_DNA.
DR EMBL; BX470111; CAH70538.1; JOINED; Genomic_DNA.
DR EMBL; BX470111; CAI41654.1; -; Genomic_DNA.
DR EMBL; BX293995; CAI41654.1; JOINED; Genomic_DNA.
DR EMBL; BX470111; CAI41655.1; -; Genomic_DNA.
DR EMBL; BX293995; CAI41655.1; JOINED; Genomic_DNA.
DR EMBL; BX470111; CAO03573.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BX470111; CAO03574.1; -; Genomic_DNA.
DR EMBL; BX470111; CAO03575.1; -; Genomic_DNA.
DR EMBL; BX293995; CAO03575.1; JOINED; Genomic_DNA.
DR EMBL; BX470111; CAO03576.1; -; Genomic_DNA.
DR EMBL; BX293995; CAO03576.1; JOINED; Genomic_DNA.
DR EMBL; BX293995; CAO03601.1; -; Genomic_DNA.
DR EMBL; BX470111; CAO03601.1; JOINED; Genomic_DNA.
DR EMBL; BX293995; CAO03602.1; -; Genomic_DNA.
DR EMBL; BX470111; CAO03602.1; JOINED; Genomic_DNA.
DR EMBL; BC002999; AAH02999.1; -; mRNA.
DR EMBL; BC006540; AAH06540.1; -; mRNA.
DR PIR; I38167; I38167.
DR RefSeq; NP_001018065.1; NM_001018055.2.
DR RefSeq; NP_001229569.1; NM_001242640.1.
DR RefSeq; NP_077308.1; NM_024332.3.
DR RefSeq; XP_005274806.1; XM_005274749.1.
DR RefSeq; XP_005274807.1; XM_005274750.1.
DR RefSeq; XP_005277965.1; XM_005277908.1.
DR RefSeq; XP_005277966.1; XM_005277909.1.
DR UniGene; Hs.558537; -.
DR ProteinModelPortal; P46736; -.
DR SMR; P46736; 10-193.
DR DIP; DIP-48719N; -.
DR IntAct; P46736; 21.
DR MINT; MINT-1475401; -.
DR MEROPS; M67.004; -.
DR PhosphoSite; P46736; -.
DR DMDM; 20532383; -.
DR PaxDb; P46736; -.
DR PRIDE; P46736; -.
DR DNASU; 79184; -.
DR Ensembl; ENST00000330045; ENSP00000328641; ENSG00000185515.
DR Ensembl; ENST00000340647; ENSP00000344103; ENSG00000185515.
DR Ensembl; ENST00000369459; ENSP00000358471; ENSG00000185515.
DR Ensembl; ENST00000369462; ENSP00000358474; ENSG00000185515.
DR Ensembl; ENST00000594541; ENSP00000470674; ENSG00000269884.
DR Ensembl; ENST00000597217; ENSP00000469831; ENSG00000269884.
DR Ensembl; ENST00000597826; ENSP00000473083; ENSG00000269884.
DR Ensembl; ENST00000601378; ENSP00000469902; ENSG00000269884.
DR GeneID; 79184; -.
DR KEGG; hsa:79184; -.
DR UCSC; uc004fna.3; human.
DR CTD; 79184; -.
DR GeneCards; GC0XP154299; -.
DR HGNC; HGNC:24185; BRCC3.
DR MIM; 300617; gene.
DR neXtProt; NX_P46736; -.
DR Orphanet; 280679; Moyamoya disease - short stature - facial dysmorphism - hypergonadotropic hypogonadism.
DR PharmGKB; PA134922847; -.
DR eggNOG; NOG322509; -.
DR HOVERGEN; HBG002142; -.
DR KO; K11864; -.
DR GeneWiki; BRCC3; -.
DR GenomeRNAi; 79184; -.
DR NextBio; 68176; -.
DR PRO; PR:P46736; -.
DR ArrayExpress; P46736; -.
DR Bgee; P46736; -.
DR CleanEx; HS_BRCC3; -.
DR Genevestigator; P46736; -.
DR GO; GO:0070531; C:BRCA1-A complex; IDA:UniProtKB.
DR GO; GO:0070552; C:BRISC complex; IDA:UniProtKB.
DR GO; GO:0000152; C:nuclear ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0004843; F:deubiquitinase activity; IMP:UniProtKB.
DR GO; GO:0030234; F:enzyme regulator activity; IDA:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008237; F:metallopeptidase activity; IMP:UniProtKB.
DR GO; GO:0031593; F:polyubiquitin binding; IDA:UniProtKB.
DR GO; GO:0004221; F:ubiquitin thiolesterase activity; IMP:UniProtKB.
DR GO; GO:0006302; P:double-strand break repair; IMP:UniProtKB.
DR GO; GO:0031572; P:G2 DNA damage checkpoint; IMP:UniProtKB.
DR GO; GO:0070537; P:histone H2A K63-linked deubiquitination; IDA:UniProtKB.
DR GO; GO:0045739; P:positive regulation of DNA repair; IMP:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0010165; P:response to X-ray; IDA:MGI.
DR InterPro; IPR000555; JAB_MPN_dom.
DR Pfam; PF01398; JAB; 1.
DR SMART; SM00232; JAB_MPN; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Chromatin regulator;
KW Chromosomal rearrangement; Complete proteome;
KW Direct protein sequencing; DNA damage; DNA repair; Hydrolase;
KW Metal-binding; Metalloprotease; Nucleus; Polymorphism; Protease;
KW Proto-oncogene; Reference proteome; Ubl conjugation pathway; Zinc.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 316 Lys-63-specific deubiquitinase BRCC36.
FT /FTId=PRO_0000213967.
FT DOMAIN 7 148 MPN.
FT MOTIF 122 135 JAMM motif.
FT METAL 122 122 Zinc; catalytic (Probable).
FT METAL 124 124 Zinc; catalytic (Probable).
FT METAL 135 135 Zinc; catalytic (By similarity).
FT MOD_RES 2 2 N-acetylalanine.
FT VAR_SEQ 1 114 Missing (in isoform 4).
FT /FTId=VSP_037257.
FT VAR_SEQ 46 46 T -> TS (in isoform 3).
FT /FTId=VSP_037258.
FT VAR_SEQ 183 252 ESLHGPRDFWSSSQHISIEGQKEEERYERIEIPIHIVPHVT
FT IGKVCLESAVELPKILCQEEQDAYRRIHS -> D (in
FT isoform 5).
FT /FTId=VSP_037259.
FT VAR_SEQ 184 208 Missing (in isoform 1 and isoform 3).
FT /FTId=VSP_003261.
FT VARIANT 74 74 I -> V (in dbSNP:rs28997578).
FT /FTId=VAR_050097.
FT MUTAGEN 122 124 HSH->QSQ: Abolishes metalloprotease
FT activity and function in DNA repair.
FT MUTAGEN 122 122 H->Q: Loss of deubiquitinase activity.
FT CONFLICT 225 225 G -> W (in Ref. 2; AAB29005).
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
//
MIM
300617
*RECORD*
*FIELD* NO
300617
*FIELD* TI
*300617 BRCA1/BRCA2-CONTAINING COMPLEX, SUBUNIT 3; BRCC3
;;C6.1A;;
BRCC36
*FIELD* TX
read more
CLONING
Kenwrick et al., 1992 identified cDNA clones corresponding to the BRCC3
and MTCP1 (300116) genes, which they called C6.1A and C6.1B,
respectively. The C6.1A gene was highly conserved between species and
expressed abundantly in many human and mouse tissues.
Dong et al. (2003) determined that the BRCC3 gene encodes a 316-amino
acid protein with a molecular mass of 36 kD. BRCC3 shares sequence
homology with the JAMM domain of POH1 (PSMD14; 607173) and COPS5
(604850).
GENE FUNCTION
Dong et al. (2003) demonstrated that in human cell lines BRCC3 and BRE
(610497) are components of a holoenzyme complex containing BRCA1
(113705), BRCA2 (600185), BARD1 (601593), and RAD51 (179617), which they
called the BRCA1- and BRCA2-containing complex (BRCC). The complex
showed UBC5 (see UBE2D1; 602961)-dependent ubiquitin E3 ligase activity.
Inclusion of BRE and BRCC3 enhanced ubiquitination by the complex, and
cancer-associated truncations in BRCA1 reduced the association of BRE
and BRCC3 with the complex. RNA interference of BRE and BRCC3 in HeLa
cells increased cell sensitivity to ionizing radiation and resulted in a
defect in G2/M checkpoint arrest. Dong et al. (2003) concluded that BRCC
is a ubiquitin E3 ligase that enhances cellular survival following DNA
damage.
Okamoto et al. (2013) addressed the molecular properties of TRF2
(602027) that are both necessary and sufficient to protect chromosome
ends in mouse embryonic fibroblasts, and stated that their data
supported a 2-step mechanism for TRF2-mediated end protection. First,
the dimerization domain of TRF2 is required to inhibit ATM (607585)
activation, the key initial step involved in the activation of a DNA
damage response (DDR). Next, TRF2 independently suppresses the
propagation of DNA damage signaling downstream of ATM activation. This
novel modulation of the DDR at telomeres occurs at the level of the E3
ubiquitin ligase RNF168 (612688). Inhibition of RNF168 at telomeres
involves the deubiquitinating enzyme BRCC3 and the ubiquitin ligase UBR5
(608413), and is sufficient to suppress chromosome end-to-end fusions.
Okamoto et al. (2013) concluded that this 2-step mechanism for
TRF2-mediated end protection helped to explain the apparent paradox of
frequent localization of DDR proteins at functional telomeres without
concurrent induction of detrimental DNA repair activities.
MAPPING
By somatic cell hybrid analysis, Kenwrick et al. (1992) mapped the BRCC3
gene to chromosome Xq28.
MOLECULAR GENETICS
In affected members of 3 unrelated families with an X-linked recessive
syndromic form of moyamoya disease (MYMY4; 300845), Miskinyte et al.
(2011) identified 3 different deletions on chromosome Xq28. The critical
region of overlap was a 3.4-kb region including exon 1 of the
MTCP1/MTCP1NB gene (300116) and the first 3 exons of the BRCC3 gene,
resulting in loss of BRCC3 and MTCP1NB expression in patient
lymphoblastoid cell lines. Morpholino knockdown of Brcc3 in zebrafish
resulted in defective angiogenesis that could be rescued by endothelial
expression of Brcc3, suggesting that loss of BRCC3 function was
responsible for the human disorder. The phenotype is a multisystem
disorder characterized by moyamoya disease, short stature,
hypergonadotropic hypogonadism, and facial dysmorphism. Other variable
features include dilated cardiomyopathy and premature graying of the
hair. Miskinyte et al. (2011) noted that some of the features of the
disorder were reminiscent of chromosome breakage syndromes.
*FIELD* RF
1. Dong, Y.; Hakimi, M.-A.; Chen, X.; Kumaraswamy, E.; Cooch, N. S.;
Godwin, A. K.; Shiekhattar, R.: Regulation of BRCC, a holoenzyme
complex containing BRCA1 and BRCA2, by a signalosome-like subunit
and its role in DNA repair. Molec. Cell 12: 1087-1099, 2003.
2. Kenwrick, S.; Levinson, B.; Taylor, S.; Shapiro, A.; Gitschier,
J.: Isolation and sequence of two genes associated with a CpG island
5-prime of the factor VIII gene. Hum. Molec. Genet. 1: 179-186,
1992.
3. Miskinyte, S.; Butler, M. G.; Herve, D.; Sarret, C.; Nicolino,
M.; Petralia, J. D.; Bergametti, F.; Arnould, M.; Pham, V. N.; Gore,
A. V.; Spengos, K.; Gazal, S.; Woimant, F.; Steinberg, G. K.; Weinstein,
B. M.; Tournier-Lasserve, E.: Loss of BRCC3 deubiquitinating enzyme
leads to abnormal angiogenesis and is associated with syndromic moyamoya. Am.
J. Hum. Genet. 88: 718-728, 2011.
4. Okamoto, K.; Bartocci, C.; Ouzounov, I.; Diedrich, J. K.; Yates,
J. R, III; Denchi, E. L.: A two-step mechanism for TRF2-mediated
chromosome-end protection. Nature 494: 502-505, 2013.
*FIELD* CN
Ada Hamosh - updated: 3/7/2013
Cassandra L. Kniffin - updated: 6/6/2011
*FIELD* CD
Patricia A. Hartz: 10/16/2006
*FIELD* ED
alopez: 03/08/2013
alopez: 3/8/2013
terry: 3/7/2013
carol: 8/11/2011
carol: 6/7/2011
ckniffin: 6/6/2011
carol: 6/29/2010
wwang: 10/16/2006
*RECORD*
*FIELD* NO
300617
*FIELD* TI
*300617 BRCA1/BRCA2-CONTAINING COMPLEX, SUBUNIT 3; BRCC3
;;C6.1A;;
BRCC36
*FIELD* TX
read more
CLONING
Kenwrick et al., 1992 identified cDNA clones corresponding to the BRCC3
and MTCP1 (300116) genes, which they called C6.1A and C6.1B,
respectively. The C6.1A gene was highly conserved between species and
expressed abundantly in many human and mouse tissues.
Dong et al. (2003) determined that the BRCC3 gene encodes a 316-amino
acid protein with a molecular mass of 36 kD. BRCC3 shares sequence
homology with the JAMM domain of POH1 (PSMD14; 607173) and COPS5
(604850).
GENE FUNCTION
Dong et al. (2003) demonstrated that in human cell lines BRCC3 and BRE
(610497) are components of a holoenzyme complex containing BRCA1
(113705), BRCA2 (600185), BARD1 (601593), and RAD51 (179617), which they
called the BRCA1- and BRCA2-containing complex (BRCC). The complex
showed UBC5 (see UBE2D1; 602961)-dependent ubiquitin E3 ligase activity.
Inclusion of BRE and BRCC3 enhanced ubiquitination by the complex, and
cancer-associated truncations in BRCA1 reduced the association of BRE
and BRCC3 with the complex. RNA interference of BRE and BRCC3 in HeLa
cells increased cell sensitivity to ionizing radiation and resulted in a
defect in G2/M checkpoint arrest. Dong et al. (2003) concluded that BRCC
is a ubiquitin E3 ligase that enhances cellular survival following DNA
damage.
Okamoto et al. (2013) addressed the molecular properties of TRF2
(602027) that are both necessary and sufficient to protect chromosome
ends in mouse embryonic fibroblasts, and stated that their data
supported a 2-step mechanism for TRF2-mediated end protection. First,
the dimerization domain of TRF2 is required to inhibit ATM (607585)
activation, the key initial step involved in the activation of a DNA
damage response (DDR). Next, TRF2 independently suppresses the
propagation of DNA damage signaling downstream of ATM activation. This
novel modulation of the DDR at telomeres occurs at the level of the E3
ubiquitin ligase RNF168 (612688). Inhibition of RNF168 at telomeres
involves the deubiquitinating enzyme BRCC3 and the ubiquitin ligase UBR5
(608413), and is sufficient to suppress chromosome end-to-end fusions.
Okamoto et al. (2013) concluded that this 2-step mechanism for
TRF2-mediated end protection helped to explain the apparent paradox of
frequent localization of DDR proteins at functional telomeres without
concurrent induction of detrimental DNA repair activities.
MAPPING
By somatic cell hybrid analysis, Kenwrick et al. (1992) mapped the BRCC3
gene to chromosome Xq28.
MOLECULAR GENETICS
In affected members of 3 unrelated families with an X-linked recessive
syndromic form of moyamoya disease (MYMY4; 300845), Miskinyte et al.
(2011) identified 3 different deletions on chromosome Xq28. The critical
region of overlap was a 3.4-kb region including exon 1 of the
MTCP1/MTCP1NB gene (300116) and the first 3 exons of the BRCC3 gene,
resulting in loss of BRCC3 and MTCP1NB expression in patient
lymphoblastoid cell lines. Morpholino knockdown of Brcc3 in zebrafish
resulted in defective angiogenesis that could be rescued by endothelial
expression of Brcc3, suggesting that loss of BRCC3 function was
responsible for the human disorder. The phenotype is a multisystem
disorder characterized by moyamoya disease, short stature,
hypergonadotropic hypogonadism, and facial dysmorphism. Other variable
features include dilated cardiomyopathy and premature graying of the
hair. Miskinyte et al. (2011) noted that some of the features of the
disorder were reminiscent of chromosome breakage syndromes.
*FIELD* RF
1. Dong, Y.; Hakimi, M.-A.; Chen, X.; Kumaraswamy, E.; Cooch, N. S.;
Godwin, A. K.; Shiekhattar, R.: Regulation of BRCC, a holoenzyme
complex containing BRCA1 and BRCA2, by a signalosome-like subunit
and its role in DNA repair. Molec. Cell 12: 1087-1099, 2003.
2. Kenwrick, S.; Levinson, B.; Taylor, S.; Shapiro, A.; Gitschier,
J.: Isolation and sequence of two genes associated with a CpG island
5-prime of the factor VIII gene. Hum. Molec. Genet. 1: 179-186,
1992.
3. Miskinyte, S.; Butler, M. G.; Herve, D.; Sarret, C.; Nicolino,
M.; Petralia, J. D.; Bergametti, F.; Arnould, M.; Pham, V. N.; Gore,
A. V.; Spengos, K.; Gazal, S.; Woimant, F.; Steinberg, G. K.; Weinstein,
B. M.; Tournier-Lasserve, E.: Loss of BRCC3 deubiquitinating enzyme
leads to abnormal angiogenesis and is associated with syndromic moyamoya. Am.
J. Hum. Genet. 88: 718-728, 2011.
4. Okamoto, K.; Bartocci, C.; Ouzounov, I.; Diedrich, J. K.; Yates,
J. R, III; Denchi, E. L.: A two-step mechanism for TRF2-mediated
chromosome-end protection. Nature 494: 502-505, 2013.
*FIELD* CN
Ada Hamosh - updated: 3/7/2013
Cassandra L. Kniffin - updated: 6/6/2011
*FIELD* CD
Patricia A. Hartz: 10/16/2006
*FIELD* ED
alopez: 03/08/2013
alopez: 3/8/2013
terry: 3/7/2013
carol: 8/11/2011
carol: 6/7/2011
ckniffin: 6/6/2011
carol: 6/29/2010
wwang: 10/16/2006