ID BRD3_HUMAN Reviewed; 726 AA.
AC Q15059; B1APD9; Q4G5Y3; Q5T1R7; Q8N5M3; Q92645;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 27-MAR-2024, entry version 205.
DE RecName: Full=Bromodomain-containing protein 3;
DE AltName: Full=RING3-like protein;
GN Name=BRD3 {ECO:0000303|PubMed:18406326, ECO:0000312|HGNC:HGNC:1104};
GN Synonyms=KIAA0043 {ECO:0000303|PubMed:7584044}, RING3L;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Bone marrow;
RX PubMed=7584044; DOI=10.1093/dnares/1.5.223;
RA Nomura N., Nagase T., Miyajima N., Sazuka T., Tanaka A., Sato S., Seki N.,
RA Kawarabayasi Y., Ishikawa K., Tabata S.;
RT "Prediction of the coding sequences of unidentified human genes. II. The
RT coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of
RT cDNA clones from human cell line KG-1.";
RL DNA Res. 1:223-229(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=16008511; DOI=10.1089/dna.2005.24.432;
RA Ishii H., Mimori K., Mori M., Vecchione A.;
RT "Differentially expressed genes in endothelial differentiation.";
RL DNA Cell Biol. 24:432-437(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Colon;
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 [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 363-726, AND TISSUE SPECIFICITY.
RX PubMed=9373153; DOI=10.1016/s0378-1119(97)00415-0;
RA Thorpe K.L., Gorman P., Thomas C., Sheer D., Trowsdale J., Beck S.;
RT "Chromosomal localization, gene structure and transcription pattern of the
RT ORFX gene, a homologue of the MHC-linked RING3 gene.";
RL Gene 200:177-183(1997).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH ACETYLATED CHROMATIN.
RX PubMed=18406326; DOI=10.1016/j.molcel.2008.01.018;
RA LeRoy G., Rickards B., Flint S.J.;
RT "The double bromodomain proteins Brd2 and Brd3 couple histone acetylation
RT to transcription.";
RL Mol. Cell 30:51-60(2008).
RN [8]
RP CHROMOSOMAL TRANSLOCATION WITH NUTM1.
RX PubMed=17934517; DOI=10.1038/sj.onc.1210852;
RA French C.A., Ramirez C.L., Kolmakova J., Hickman T.T., Cameron M.J.,
RA Thyne M.E., Kutok J.L., Toretsky J.A., Tadavarthy A.K., Kees U.R.,
RA Fletcher J.A., Aster J.C.;
RT "BRD-NUT oncoproteins: a family of closely related nuclear proteins that
RT block epithelial differentiation and maintain the growth of carcinoma
RT cells.";
RL Oncogene 27:2237-2242(2008).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-263 AND SER-563, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [12]
RP ACTIVITY REGULATION.
RX PubMed=20871596; DOI=10.1038/nature09504;
RA Filippakopoulos P., Qi J., Picaud S., Shen Y., Smith W.B., Fedorov O.,
RA Morse E.M., Keates T., Hickman T.T., Felletar I., Philpott M., Munro S.,
RA McKeown M.R., Wang Y., Christie A.L., West N., Cameron M.J., Schwartz B.,
RA Heightman T.D., La Thangue N., French C.A., Wiest O., Kung A.L., Knapp S.,
RA Bradner J.E.;
RT "Selective inhibition of BET bromodomains.";
RL Nature 468:1067-1073(2010).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-263, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-263 AND SER-563, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-263, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and 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 [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-281, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [17]
RP SUBCELLULAR LOCATION.
RX PubMed=25593309; DOI=10.1101/gad.252189.114;
RA Gong F., Chiu L.Y., Cox B., Aymard F., Clouaire T., Leung J.W.,
RA Cammarata M., Perez M., Agarwal P., Brodbelt J.S., Legube G., Miller K.M.;
RT "Screen identifies bromodomain protein ZMYND8 in chromatin recognition of
RT transcription-associated DNA damage that promotes homologous
RT recombination.";
RL Genes Dev. 29:197-211(2015).
RN [18]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-414, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [19]
RP ACTIVITY REGULATION.
RX PubMed=31969702; DOI=10.1038/s41586-020-1930-8;
RA Faivre E.J., McDaniel K.F., Albert D.H., Mantena S.R., Plotnik J.P.,
RA Wilcox D., Zhang L., Bui M.H., Sheppard G.S., Wang L., Sehgal V., Lin X.,
RA Huang X., Lu X., Uziel T., Hessler P., Lam L.T., Bellin R.J., Mehta G.,
RA Fidanze S., Pratt J.K., Liu D., Hasvold L.A., Sun C., Panchal S.C.,
RA Nicolette J.J., Fossey S.L., Park C.H., Longenecker K., Bigelow L.,
RA Torrent M., Rosenberg S.H., Kati W.M., Shen Y.;
RT "Selective inhibition of the BD2 bromodomain of BET proteins in prostate
RT cancer.";
RL Nature 578:306-310(2020).
RN [20]
RP FUNCTION.
RX PubMed=32895492; DOI=10.1038/s41556-020-0572-2;
RA Daneshvar K., Ardehali M.B., Klein I.A., Hsieh F.K., Kratkiewicz A.J.,
RA Mahpour A., Cancelliere S.O.L., Zhou C., Cook B.M., Li W., Pondick J.V.,
RA Gupta S.K., Moran S.P., Young R.A., Kingston R.E., Mullen A.C.;
RT "lncRNA DIGIT and BRD3 protein form phase-separated condensates to regulate
RT endoderm differentiation.";
RL Nat. Cell Biol. 22:1211-1222(2020).
RN [21]
RP ACTIVITY REGULATION.
RX PubMed=32193360; DOI=10.1126/science.aaz8455;
RA Gilan O., Rioja I., Knezevic K., Bell M.J., Yeung M.M., Harker N.R.,
RA Lam E.Y.N., Chung C.W., Bamborough P., Petretich M., Urh M., Atkinson S.J.,
RA Bassil A.K., Roberts E.J., Vassiliadis D., Burr M.L., Preston A.G.S.,
RA Wellaway C., Werner T., Gray J.R., Michon A.M., Gobbetti T., Kumar V.,
RA Soden P.E., Haynes A., Vappiani J., Tough D.F., Taylor S., Dawson S.J.,
RA Bantscheff M., Lindon M., Drewes G., Demont E.H., Daniels D.L., Grandi P.,
RA Prinjha R.K., Dawson M.A.;
RT "Selective targeting of BD1 and BD2 of the BET proteins in cancer and
RT immunoinflammation.";
RL Science 368:387-394(2020).
RN [22]
RP STRUCTURE BY NMR OF 25-415.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the first and second bromodomain from human
RT bromodomain containing protein 3.";
RL Submitted (FEB-2009) to the PDB data bank.
RN [23]
RP X-RAY CRYSTALLOGRAPHY (1.36 ANGSTROMS) OF 24-416, FUNCTION, SUBUNIT, AND
RP DOMAIN.
RX PubMed=22464331; DOI=10.1016/j.cell.2012.02.013;
RA Filippakopoulos P., Picaud S., Mangos M., Keates T., Lambert J.P.,
RA Barsyte-Lovejoy D., Felletar I., Volkmer R., Muller S., Pawson T.,
RA Gingras A.C., Arrowsmith C.H., Knapp S.;
RT "Histone recognition and large-scale structural analysis of the human
RT bromodomain family.";
RL Cell 149:214-231(2012).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 307-416 IN COMPLEX WITH
RP ACETYLATED HISTONE H3 PEPTIDE, FUNCTION, AND DOMAIN.
RX PubMed=27105114; DOI=10.1016/j.molcel.2016.03.028;
RA Li Y., Sabari B.R., Panchenko T., Wen H., Zhao D., Guan H., Wan L.,
RA Huang H., Tang Z., Zhao Y., Roeder R.G., Shi X., Allis C.D., Li H.;
RT "Molecular coupling of histone crotonylation and active transcription by
RT AF9 YEATS domain.";
RL Mol. Cell 62:181-193(2016).
RN [25] {ECO:0007744|PDB:6BGG, ECO:0007744|PDB:6BGH}
RP STRUCTURE BY NMR OF 557-644 IN COMPLEX WITH CHD4 AND SMARCA4, FUNCTION,
RP DOMAIN, AND INTERACTION WITH CHD4; NSD3 AND SMARCA4.
RX PubMed=29567837; DOI=10.1074/jbc.ra117.000678;
RA Wai D.C.C., Szyszka T.N., Campbell A.E., Kwong C., Wilkinson-White L.E.,
RA Silva A.P.G., Low J.K.K., Kwan A.H., Gamsjaeger R., Chalmers J.D.,
RA Patrick W.M., Lu B., Vakoc C.R., Blobel G.A., Mackay J.P.;
RT "The BRD3 ET domain recognizes a short peptide motif through a mechanism
RT that is conserved across chromatin remodelers and transcriptional
RT regulators.";
RL J. Biol. Chem. 293:7160-7175(2018).
RN [26] {ECO:0007744|PDB:7JMY, ECO:0007744|PDB:7JQ8, ECO:0007744|PDB:7JYN, ECO:0007744|PDB:7JYZ}
RP STRUCTURE BY NMR OF 554-640 IN COMPLEX WITH NSD3, INTERACTION WITH NSD3,
RP AND INTERACTION WITH INTEGRASE PROTEIN OF MLV VIRUS (MICROBIAL INFECTION).
RX PubMed=33592170; DOI=10.1016/j.str.2021.01.010;
RA Aiyer S., Swapna G.V.T., Ma L.C., Liu G., Hao J., Chalmers G., Jacobs B.C.,
RA Montelione G.T., Roth M.J.;
RT "A common binding motif in the ET domain of BRD3 forms polymorphic
RT structural interfaces with host and viral proteins.";
RL Structure 29:886-898(2021).
RN [27]
RP VARIANTS [LARGE SCALE ANALYSIS] ASN-36; THR-161; VAL-172; GLN-435; HIS-441
RP AND PRO-447.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Chromatin reader that recognizes and binds acetylated
CC histones, thereby controlling gene expression and remodeling chromatin
CC structures (PubMed:18406326, PubMed:32895492, PubMed:22464331,
CC PubMed:27105114). Recruits transcription factors and coactivators to
CC target gene sites, and activates RNA polymerase II machinery for
CC transcriptional elongation (PubMed:32895492, PubMed:29567837). In
CC vitro, binds acetylated lysine residues on the N-terminus of histone
CC H2A, H2B, H3 and H4 (PubMed:18406326). Involved in endoderm
CC differentiation via its association with long non-coding RNA (lncRNA)
CC DIGIT: BRD3 undergoes liquid-liquid phase separation upon binding to
CC lncRNA DIGIT, promoting binding to histone H3 acetylated at 'Lys-18'
CC (H3K18ac) to induce endoderm gene expression (PubMed:32895492). Also
CC binds non-histones acetylated proteins, such as GATA1 and GATA2:
CC regulates transcription by promoting the binding of the transcription
CC factor GATA1 to its targets (By similarity).
CC {ECO:0000250|UniProtKB:Q8K2F0, ECO:0000269|PubMed:18406326,
CC ECO:0000269|PubMed:22464331, ECO:0000269|PubMed:27105114,
CC ECO:0000269|PubMed:29567837, ECO:0000269|PubMed:32895492}.
CC -!- ACTIVITY REGULATION: Inhibited by JQ1, a thieno-triazolo-1,4-diazepine
CC derivative, which specifically inhibits members of the BET family
CC (BRD2, BRD3 and BRD4) (PubMed:20871596). The first bromo domain is
CC inhibited by GSK778 (iBET-BD1), which specifically inhibits the first
CC bromo domain of members of the BET family (BRD2, BRD3 and BRD4)
CC (PubMed:32193360). The second bromo domain is inhibited by ABBV-744,
CC which specifically inhibits the second bromo domain of members of the
CC BET family (BRD2, BRD3 and BRD4) (PubMed:31969702). The second bromo
CC domain is inhibited by GSK046 (iBET-BD2), which specifically inhibits
CC the second bromo domain of members of the BET family (BRD2, BRD3 and
CC BRD4) (PubMed:32193360). {ECO:0000269|PubMed:20871596,
CC ECO:0000269|PubMed:31969702, ECO:0000269|PubMed:32193360}.
CC -!- SUBUNIT: Interacts (via bromo domain 1) with GATA1 acetylated at 'Lys-
CC 312' and 'Lys-315' (By similarity). Interacts (via bromo domain 1) with
CC GATA2 acetylated on lysine residues (By similarity). Interacts (via NET
CC domain) with CHD4 (via KIKL motif) (PubMed:29567837). Interacts (via
CC NET domain) with SMARCA4 (via KIKL motif) (PubMed:29567837). Interacts
CC (via NET domain) with NSD3 (via KIKL motif) (PubMed:29567837,
CC PubMed:33592170). {ECO:0000250|UniProtKB:Q8K2F0,
CC ECO:0000269|PubMed:29567837, ECO:0000269|PubMed:33592170}.
CC -!- SUBUNIT: (Microbial infection) Interacts with the Integrase protein of
CC Moloney murine leukemia virus (MLV). {ECO:0000269|PubMed:33592170}.
CC -!- INTERACTION:
CC Q15059; P01106: MYC; NbExp=3; IntAct=EBI-1383460, EBI-447544;
CC Q15059-2; O00505: KPNA3; NbExp=3; IntAct=EBI-13468085, EBI-358297;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:25593309}. Chromosome
CC {ECO:0000269|PubMed:18406326}. Note=Detected on chromatin.
CC {ECO:0000269|PubMed:18406326}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q15059-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q15059-2; Sequence=VSP_010247, VSP_010248;
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:9373153}.
CC -!- DOMAIN: The Bromo domains specifically recognize and bind acetylated
CC histones. {ECO:0000269|PubMed:27105114}.
CC -!- DOMAIN: The NET domain recognizes and binds the 'KIKL' motif found in
CC chromatin proteins. {ECO:0000269|PubMed:29567837}.
CC -!- DISEASE: Note=A chromosomal aberration involving BRD3 is found in a
CC rare, aggressive, and lethal carcinoma arising in midline organs of
CC young people. Translocation t(15;9)(q14;q34) with NUTM1 which produces
CC a BRD3-NUTM1 fusion protein. {ECO:0000269|PubMed:17934517}.
CC -!- SIMILARITY: Belongs to the BET family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA05393.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; D26362; BAA05393.2; ALT_INIT; mRNA.
DR EMBL; AY513270; AAS82952.1; -; mRNA.
DR EMBL; AL445931; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471090; EAW88113.1; -; Genomic_DNA.
DR EMBL; CH471090; EAW88114.1; -; Genomic_DNA.
DR EMBL; BC032124; AAH32124.1; -; mRNA.
DR EMBL; Z81330; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS6980.1; -. [Q15059-1]
DR RefSeq; NP_031397.1; NM_007371.3. [Q15059-1]
DR RefSeq; XP_006717354.1; XM_006717291.2. [Q15059-1]
DR RefSeq; XP_011517354.1; XM_011519052.2. [Q15059-1]
DR PDB; 2E7N; NMR; -; A=306-415.
DR PDB; 2NXB; X-ray; 1.40 A; A/B=24-144.
DR PDB; 2OO1; X-ray; 1.70 A; A/B/C/D=307-416.
DR PDB; 2YW5; NMR; -; A=25-155.
DR PDB; 3S91; X-ray; 2.06 A; A=24-144.
DR PDB; 3S92; X-ray; 1.36 A; A=306-416.
DR PDB; 5A7C; X-ray; 1.90 A; A/B/C/D=306-416.
DR PDB; 5HFR; X-ray; 1.70 A; A/B/C/D=306-416.
DR PDB; 5HJC; X-ray; 2.60 A; A=307-416.
DR PDB; 6BGG; NMR; -; B=557-644.
DR PDB; 6BGH; NMR; -; A=557-643.
DR PDB; 6I41; X-ray; 1.90 A; B=245-253.
DR PDB; 6I5P; X-ray; 1.81 A; B/D/F/H=245-253.
DR PDB; 6I68; X-ray; 1.85 A; B/D/F/H=245-253.
DR PDB; 6I7A; X-ray; 2.20 A; B/D/F/H=245-253.
DR PDB; 6QJU; X-ray; 1.20 A; A/B=24-144.
DR PDB; 6U4A; X-ray; 1.88 A; A/B=25-147.
DR PDB; 6ULP; X-ray; 2.80 A; A/B=307-419.
DR PDB; 7JMY; NMR; -; A=554-640.
DR PDB; 7JQ8; NMR; -; A=554-640.
DR PDB; 7JYN; NMR; -; A=554-640.
DR PDB; 7JYZ; NMR; -; B=554-640.
DR PDB; 7L72; X-ray; 1.50 A; A=306-416.
DR PDB; 7L9L; X-ray; 1.55 A; A=306-416.
DR PDB; 7LAY; X-ray; 1.45 A; A/B=24-144.
DR PDB; 7LAZ; X-ray; 2.30 A; A/B=24-144.
DR PDB; 7LB4; X-ray; 2.00 A; A/B=306-416.
DR PDB; 7LBT; X-ray; 2.70 A; A/B/C/D=306-416.
DR PDB; 7R8R; X-ray; 1.80 A; A=24-144.
DR PDB; 7RJK; X-ray; 1.85 A; A/B=24-144.
DR PDB; 7RJL; X-ray; 1.50 A; A/B=24-144.
DR PDB; 7RJM; X-ray; 2.10 A; A/B=24-144.
DR PDB; 7RJN; X-ray; 1.95 A; A/B=24-144.
DR PDB; 7S3P; X-ray; 2.89 A; A/B/C/D/E/F/G/H/I/J/K=306-416.
DR PDB; 7TO7; X-ray; 1.93 A; A/B/D/E=25-147.
DR PDB; 7TO8; X-ray; 1.50 A; A/B=25-147.
DR PDB; 7TO9; X-ray; 1.60 A; A/B=25-147.
DR PDB; 7TOA; X-ray; 1.41 A; A/B=32-147.
DR PDB; 7UG5; X-ray; 1.80 A; A/B/C/D=306-416.
DR PDB; 8B5A; X-ray; 1.92 A; A=307-416.
DR PDB; 8CV5; X-ray; 1.47 A; A=307-419.
DR PDBsum; 2E7N; -.
DR PDBsum; 2NXB; -.
DR PDBsum; 2OO1; -.
DR PDBsum; 2YW5; -.
DR PDBsum; 3S91; -.
DR PDBsum; 3S92; -.
DR PDBsum; 5A7C; -.
DR PDBsum; 5HFR; -.
DR PDBsum; 5HJC; -.
DR PDBsum; 6BGG; -.
DR PDBsum; 6BGH; -.
DR PDBsum; 6I41; -.
DR PDBsum; 6I5P; -.
DR PDBsum; 6I68; -.
DR PDBsum; 6I7A; -.
DR PDBsum; 6QJU; -.
DR PDBsum; 6U4A; -.
DR PDBsum; 6ULP; -.
DR PDBsum; 7JMY; -.
DR PDBsum; 7JQ8; -.
DR PDBsum; 7JYN; -.
DR PDBsum; 7JYZ; -.
DR PDBsum; 7L72; -.
DR PDBsum; 7L9L; -.
DR PDBsum; 7LAY; -.
DR PDBsum; 7LAZ; -.
DR PDBsum; 7LB4; -.
DR PDBsum; 7LBT; -.
DR PDBsum; 7R8R; -.
DR PDBsum; 7RJK; -.
DR PDBsum; 7RJL; -.
DR PDBsum; 7RJM; -.
DR PDBsum; 7RJN; -.
DR PDBsum; 7S3P; -.
DR PDBsum; 7TO7; -.
DR PDBsum; 7TO8; -.
DR PDBsum; 7TO9; -.
DR PDBsum; 7TOA; -.
DR PDBsum; 7UG5; -.
DR PDBsum; 8B5A; -.
DR PDBsum; 8CV5; -.
DR AlphaFoldDB; Q15059; -.
DR SASBDB; Q15059; -.
DR SMR; Q15059; -.
DR BioGRID; 113715; 485.
DR DIP; DIP-39755N; -.
DR IntAct; Q15059; 25.
DR MINT; Q15059; -.
DR STRING; 9606.ENSP00000305918; -.
DR BindingDB; Q15059; -.
DR ChEMBL; CHEMBL1795186; -.
DR GuidetoPHARMACOLOGY; 2725; -.
DR GlyCosmos; Q15059; 5 sites, 1 glycan.
DR GlyGen; Q15059; 6 sites, 1 O-linked glycan (6 sites).
DR iPTMnet; Q15059; -.
DR PhosphoSitePlus; Q15059; -.
DR BioMuta; BRD3; -.
DR DMDM; 12643726; -.
DR EPD; Q15059; -.
DR jPOST; Q15059; -.
DR MassIVE; Q15059; -.
DR MaxQB; Q15059; -.
DR PaxDb; 9606-ENSP00000305918; -.
DR PeptideAtlas; Q15059; -.
DR ProteomicsDB; 60414; -. [Q15059-1]
DR ProteomicsDB; 60415; -. [Q15059-2]
DR Pumba; Q15059; -.
DR ABCD; Q15059; 1 sequenced antibody.
DR Antibodypedia; 31966; 440 antibodies from 34 providers.
DR DNASU; 8019; -.
DR Ensembl; ENST00000303407.12; ENSP00000305918.6; ENSG00000169925.17. [Q15059-1]
DR Ensembl; ENST00000371834.6; ENSP00000360900.2; ENSG00000169925.17. [Q15059-2]
DR GeneID; 8019; -.
DR KEGG; hsa:8019; -.
DR MANE-Select; ENST00000303407.12; ENSP00000305918.6; NM_007371.4; NP_031397.1.
DR UCSC; uc004cew.4; human. [Q15059-1]
DR AGR; HGNC:1104; -.
DR CTD; 8019; -.
DR DisGeNET; 8019; -.
DR GeneCards; BRD3; -.
DR HGNC; HGNC:1104; BRD3.
DR HPA; ENSG00000169925; Low tissue specificity.
DR MIM; 601541; gene.
DR neXtProt; NX_Q15059; -.
DR OpenTargets; ENSG00000169925; -.
DR PharmGKB; PA25415; -.
DR VEuPathDB; HostDB:ENSG00000169925; -.
DR eggNOG; KOG1474; Eukaryota.
DR GeneTree; ENSGT00940000153385; -.
DR HOGENOM; CLU_001499_0_4_1; -.
DR InParanoid; Q15059; -.
DR OMA; KMNIPHY; -.
DR OrthoDB; 152619at2759; -.
DR PhylomeDB; Q15059; -.
DR TreeFam; TF317345; -.
DR PathwayCommons; Q15059; -.
DR SignaLink; Q15059; -.
DR SIGNOR; Q15059; -.
DR BioGRID-ORCS; 8019; 18 hits in 1176 CRISPR screens.
DR ChiTaRS; BRD3; human.
DR EvolutionaryTrace; Q15059; -.
DR GeneWiki; BRD3; -.
DR GenomeRNAi; 8019; -.
DR Pharos; Q15059; Tchem.
DR PRO; PR:Q15059; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q15059; Protein.
DR Bgee; ENSG00000169925; Expressed in nipple and 220 other cell types or tissues.
DR ExpressionAtlas; Q15059; baseline and differential.
DR Genevisible; Q15059; HS.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0106222; F:lncRNA binding; IDA:UniProtKB.
DR GO; GO:0070577; F:lysine-acetylated histone binding; IDA:UniProtKB.
DR GO; GO:0140693; F:molecular condensate scaffold activity; IDA:UniProtKB.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0035987; P:endodermal cell differentiation; IDA:UniProtKB.
DR GO; GO:0071168; P:protein localization to chromatin; IDA:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR CDD; cd05497; Bromo_Brdt_I_like; 1.
DR CDD; cd05498; Bromo_Brdt_II_like; 1.
DR DisProt; DP03059; -.
DR Gene3D; 1.20.1270.220; -; 1.
DR Gene3D; 1.20.920.10; Bromodomain-like; 2.
DR InterPro; IPR043508; Bromo_Brdt_I.
DR InterPro; IPR043509; Bromo_Brdt_II.
DR InterPro; IPR001487; Bromodomain.
DR InterPro; IPR036427; Bromodomain-like_sf.
DR InterPro; IPR018359; Bromodomain_CS.
DR InterPro; IPR027353; NET_dom.
DR InterPro; IPR038336; NET_sf.
DR PANTHER; PTHR22880:SF246; BROMODOMAIN-CONTAINING PROTEIN 3; 1.
DR PANTHER; PTHR22880; FALZ-RELATED BROMODOMAIN-CONTAINING PROTEINS; 1.
DR Pfam; PF17035; BET; 1.
DR Pfam; PF00439; Bromodomain; 2.
DR PRINTS; PR00503; BROMODOMAIN.
DR SMART; SM00297; BROMO; 2.
DR SUPFAM; SSF47370; Bromodomain; 2.
DR PROSITE; PS00633; BROMODOMAIN_1; 2.
DR PROSITE; PS50014; BROMODOMAIN_2; 2.
DR PROSITE; PS51525; NET; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Bromodomain;
KW Chromatin regulator; Chromosomal rearrangement; Chromosome; Coiled coil;
KW Isopeptide bond; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Transcription; Transcription regulation; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330"
FT CHAIN 2..726
FT /note="Bromodomain-containing protein 3"
FT /id="PRO_0000211181"
FT DOMAIN 51..123
FT /note="Bromo 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00035"
FT DOMAIN 326..398
FT /note="Bromo 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00035"
FT DOMAIN 562..644
FT /note="NET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00857"
FT REGION 1..35
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 78..80
FT /note="Acetylated histone H3 binding"
FT /evidence="ECO:0000269|PubMed:27105114"
FT REGION 149..169
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 237..305
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 421..462
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 477..575
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 637..726
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 453..524
FT /evidence="ECO:0000255"
FT COILED 645..684
FT /evidence="ECO:0000255"
FT COMPBIAS 14..29
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 247..266
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 273..305
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 498..524
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 535..551
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 652..673
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 697..726
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 647..648
FT /note="Breakpoint for translocation to form BDR3-NUTM1
FT fusion protein"
FT /evidence="ECO:0000269|PubMed:17934517"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT MOD_RES 263
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 281
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 563
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:21406692"
FT CROSSLNK 414
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 549..556
FT /note="QLKKGGKQ -> DHFLTCGV (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_010247"
FT VAR_SEQ 557..726
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_010248"
FT VARIANT 36
FT /note="T -> N (in a renal clear cell carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041913"
FT VARIANT 161
FT /note="A -> T (in a gastric adenocarcinoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041914"
FT VARIANT 172
FT /note="A -> V (in dbSNP:rs34609592)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041915"
FT VARIANT 435
FT /note="K -> Q (in dbSNP:rs36093130)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041916"
FT VARIANT 441
FT /note="R -> H (in dbSNP:rs56017928)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041917"
FT VARIANT 447
FT /note="S -> P (in dbSNP:rs55754444)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041918"
FT STRAND 29..31
FT /evidence="ECO:0007829|PDB:2YW5"
FT HELIX 37..44
FT /evidence="ECO:0007829|PDB:6QJU"
FT HELIX 46..52
FT /evidence="ECO:0007829|PDB:6QJU"
FT HELIX 57..59
FT /evidence="ECO:0007829|PDB:6QJU"
FT TURN 65..69
FT /evidence="ECO:0007829|PDB:6QJU"
FT HELIX 73..76
FT /evidence="ECO:0007829|PDB:6QJU"
FT HELIX 83..91
FT /evidence="ECO:0007829|PDB:6QJU"
FT HELIX 98..115
FT /evidence="ECO:0007829|PDB:6QJU"
FT HELIX 121..137
FT /evidence="ECO:0007829|PDB:6QJU"
FT HELIX 310..323
FT /evidence="ECO:0007829|PDB:3S92"
FT HELIX 325..327
FT /evidence="ECO:0007829|PDB:3S92"
FT HELIX 328..331
FT /evidence="ECO:0007829|PDB:3S92"
FT HELIX 332..334
FT /evidence="ECO:0007829|PDB:3S92"
FT TURN 340..344
FT /evidence="ECO:0007829|PDB:3S92"
FT HELIX 348..351
FT /evidence="ECO:0007829|PDB:3S92"
FT HELIX 358..366
FT /evidence="ECO:0007829|PDB:3S92"
FT HELIX 373..390
FT /evidence="ECO:0007829|PDB:3S92"
FT HELIX 396..413
FT /evidence="ECO:0007829|PDB:3S92"
FT HELIX 558..561
FT /evidence="ECO:0007829|PDB:6BGH"
FT HELIX 567..569
FT /evidence="ECO:0007829|PDB:6BGG"
FT HELIX 574..585
FT /evidence="ECO:0007829|PDB:6BGG"
FT HELIX 589..602
FT /evidence="ECO:0007829|PDB:6BGG"
FT HELIX 604..608
FT /evidence="ECO:0007829|PDB:6BGG"
FT STRAND 611..613
FT /evidence="ECO:0007829|PDB:6BGH"
FT STRAND 615..617
FT /evidence="ECO:0007829|PDB:6BGG"
FT TURN 618..620
FT /evidence="ECO:0007829|PDB:6BGG"
FT HELIX 623..636
FT /evidence="ECO:0007829|PDB:6BGG"
FT TURN 640..642
FT /evidence="ECO:0007829|PDB:6BGG"
SQ SEQUENCE 726 AA; 79542 MW; 64F526FC3C1033AA CRC64;
MSTATTVAPA GIPATPGPVN PPPPEVSNPS KPGRKTNQLQ YMQNVVVKTL WKHQFAWPFY
QPVDAIKLNL PDYHKIIKNP MDMGTIKKRL ENNYYWSASE CMQDFNTMFT NCYIYNKPTD
DIVLMAQALE KIFLQKVAQM PQEEVELLPP APKGKGRKPA AGAQSAGTQQ VAAVSSVSPA
TPFQSVPPTV SQTPVIAATP VPTITANVTS VPVPPAAAPP PPATPIVPVV PPTPPVVKKK
GVKRKADTTT PTTSAITASR SESPPPLSDP KQAKVVARRE SGGRPIKPPK KDLEDGEVPQ
HAGKKGKLSE HLRYCDSILR EMLSKKHAAY AWPFYKPVDA EALELHDYHD IIKHPMDLST
VKRKMDGREY PDAQGFAADV RLMFSNCYKY NPPDHEVVAM ARKLQDVFEM RFAKMPDEPV
EAPALPAPAA PMVSKGAESS RSSEESSSDS GSSDSEEERA TRLAELQEQL KAVHEQLAAL
SQAPVNKPKK KKEKKEKEKK KKDKEKEKEK HKVKAEEEKK AKVAPPAKQA QQKKAPAKKA
NSTTTAGRQL KKGGKQASAS YDSEEEEEGL PMSYDEKRQL SLDINRLPGE KLGRVVHIIQ
SREPSLRDSN PDEIEIDFET LKPTTLRELE RYVKSCLQKK QRKPFSASGK KQAAKSKEEL
AQEKKKELEK RLQDVSGQLS SSKKPARKEK PGSAPSGGPS RLSSSSSSES GSSSSSGSSS
DSSDSE
//
