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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; 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 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. DR Genevisible; Q15059; HS. 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 //