Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXDXYFZ)

• DOT Name: Bromodomain-containing protein 1 (BRD1)
• Synonyms: BR140-like protein; Bromodomain and PHD finger-containing protein 2
• Gene Name: BRD1
• UniProt ID: BRD1_HUMAN
• PDB ID: 2KU3 ; 2L43 ; 2LQ6 ; 3LYI ; 3RCW ; 4Z02 ; 5AME ; 5AMF ; 5FG6 ; 5GK9 ; 5N49 ; 5PNX ; 5PNY ; 5PNZ ; 5PO0 ; 5PO1 ; 5PO2 ; 5PO3 ; 5PO4 ; 5PO5 ; 5PO6 ; 5PO7 ; 5PO8 ; 5PO9 ; 5POA ; 5POB ; 5POC ; 5POD ; 5POE ; 5POF ; 5POG ; 5POH ; 5POI ; 5POJ ; 5POK ; 5POL ; 5POM ; 5PON ; 5POO ; 5POP ; 5POQ ; 5POR ; 5POS ; 5POT ; 5POU ; 5POV ; 5POW ; 5POX ; 5POY ; 5POZ ; 5PP0 ; 5PP1 ; 5PP2 ; 5PP3 ; 5PP4 ; 5PP5 ; 5PP6 ; 5PP7 ; 5PP8 ; 5PP9 ; 5PPA ; 5PPB ; 5PPC ; 5PPD ; 5PPE ; 5PPF ; 5PPG ; 5PPH ; 5PPI ; 5PPJ ; 5PPK ; 5PPL ; 5PPM ; 5PPN ; 5PPO ; 5PPP ; 5PPQ ; 5PPR ; 5PPS ; 5PPT ; 5PPU ; 5PPV ; 5PPW ; 5PPX ; 5PPY ; 5PPZ ; 5PQ0 ; 5PQ1 ; 5PQ2 ; 5PQ3 ; 5PQ4 ; 5PQ5 ; 5PQ6 ; 5PQ7 ; 5PQ8 ; 5PQ9 ; 5PQA ; 5PQB ; 5PQC ; 5PQD ; 5PQE ; 5PQF ; 5PQG ; 5PQH ; 5PQI ; 5PQJ ; 5PQK ; 5PQL ; 5PQM ; 5PQN ; 5PQO ; 5PQP ; 5PQQ ; 5PQR ; 5PQS ; 5PQT ; 5PQU ; 5PQV ; 5PQW ; 5PQX ; 5PQY ; 5PQZ ; 5PR0 ; 5PR1 ; 5PR2 ; 5PR4 ; 5PR5 ; 5PR6 ; 5PR7 ; 5PR8 ; 5PR9 ; 5PRA ; 5PRB ; 5PRD ; 5PRE ; 5PRF ; 5PRG ; 5PRH ; 5PRI ; 5PRJ ; 5PRK ; 5PRL ; 5PRM ; 5PRO ; 5PRP ; 5PRQ ; 5PRR ; 5PRS ; 5PRT ; 5PRU ; 5PRV ; 5PRW ; 5PRX ; 5PRY ; 5PRZ ; 5PS0 ; 5PS1 ; 5PS2 ; 5PS3 ; 5PS4 ; 5PS5 ; 5PS6 ; 5PS7 ; 5PS8 ; 5PS9 ; 5PSA ; 5PSB ; 5PSC ; 5PSD ; 5PSE ; 5PSF ; 5PSG ; 5PSH ; 5PSI ; 5PSJ ; 5PSK ; 5PSL ; 5PSM ; 5PSN ; 5PSO ; 5PSP ; 5PSQ ; 5PSR ; 5PSS ; 5PST ; 5PSU ; 5PSV ; 5PSW ; 5PSX ; 5PSY ; 5PSZ ; 5PT0 ; 5PT1 ; 5PT2 ; 5PT3 ; 5PT4 ; 5PT5 ; 5PT6 ; 5PT7 ; 5PT8 ; 5PT9 ; 5PTA ; 5PTB ; 5PTC ; 5PTE ; 5PTF ; 5PTG ; 5PTH ; 5PTJ ; 5PTK ; 5PTL ; 5PTM ; 5PTN ; 5PTO ; 5PTQ ; 5PTR ; 5PTS ; 5PTT ; 5PTU ; 5PTV ; 5PTW ; 5PTX ; 5PTY ; 5PTZ ; 5PU0 ; 5PU1 ; 5PU2 ; 5PU3 ; 5PU4 ; 5PU5 ; 5PU6 ; 5PU7 ; 5PU8 ; 5PU9 ; 5PUA ; 5PUB ; 5PUC ; 5PUD ; 5PUE ; 5PUF ; 5PUG ; 5PUH ; 5PUI ; 5PUJ ; 5PUK ; 5PUL ; 5PUM ; 5PUN ; 5PUO ; 5PUP ; 5PUQ ; 5PUR ; 5PUS ; 5PUT ; 5PUU ; 5PUV ; 5PUW ; 5PUX ; 5PUY ; 5PUZ ; 5PV0 ; 5PV1 ; 5PV2 ; 5PV3 ; 5PV4 ; 5PV5 ; 5PV6 ; 5PV7 ; 5PV8 ; 5PV9 ; 5PVA ; 5PVB ; 5PVC ; 5PVD ; 5PVE ; 5PVF ; 5PVG ; 5PVH ; 5PVI ; 5PVJ ; 5PVK ; 5PVL ; 5PVM ; 5PVN ; 5PVO ; 5PVP ; 5PVQ ; 5PVR ; 5PVS ; 5PVT ; 5PVU ; 5PVV ; 5PVW ; 5PVX ; 5PVY ; 5PVZ ; 5PW0 ; 5PW1 ; 5PW2 ; 5PW3 ; 5PW4 ; 5PW5 ; 5PW6 ; 5PW7 ; 5PW8 ; 5PW9 ; 5PWA ; 5PWB ; 6IN2 ; 6MAJ ; 6MAK ; 7D0O ; 7D0P ; 7D0Q ; 7D0R ; 7D0S ; 7LH9
• Pfam ID: PF00439 ; PF10513 ; PF13831 ; PF00855 ; PF13832
• Sequence:
  MRRKGRCHRGSAARHPSSPCSVKHSPTRETLTYAQAQRMVEIEIEGRLHRISIFDPLEII
  LEDDLTAQEMSECNSNKENSERPPVCLRTKRHKNNRVKKKNEALPSAHGTPASASALPEP
  KVRIVEYSPPSAPRRPPVYYKFIEKSAEELDNEVEYDMDEEDYAWLEIVNEKRKGDCVPA
  VSQSMFEFLMDRFEKESHCENQKQGEQQSLIDEDAVCCICMDGECQNSNVILFCDMCNLA
  VHQECYGVPYIPEGQWLCRHCLQSRARPADCVLCPNKGGAFKKTDDDRWGHVVCALWIPE
  VGFANTVFIEPIDGVRNIPPARWKLTCYLCKQKGVGACIQCHKANCYTAFHVTCAQKAGL
  YMKMEPVKELTGGGTTFSVRKTAYCDVHTPPGCTRRPLNIYGDVEMKNGVCRKESSVKTV
  RSTSKVRKKAKKAKKALAEPCAVLPTVCAPYIPPQRLNRIANQVAIQRKKQFVERAHSYW
  LLKRLSRNGAPLLRRLQSSLQSQRSSQQRENDEEMKAAKEKLKYWQRLRHDLERARLLIE
  LLRKREKLKREQVKVEQVAMELRLTPLTVLLRSVLDQLQDKDPARIFAQPVSLKEVPDYL
  DHIKHPMDFATMRKRLEAQGYKNLHEFEEDFDLIIDNCMKYNARDTVFYRAAVRLRDQGG
  VVLRQARREVDSIGLEEASGMHLPERPAAAPRRPFSWEDVDRLLDPANRAHLGLEEQLRE
  LLDMLDLTCAMKSSGSRSKRAKLLKKEIALLRNKLSQQHSQPLPTGPGLEGFEEDGAALG
  PEAGEEVLPRLETLLQPRKRSRSTCGDSEVEEESPGKRLDAGLTNGFGGARSEQEPGGGL
  GRKATPRRRCASESSISSSNSPLCDSSFNAPKCGRGKPALVRRHTLEDRSELISCIENGN
  YAKAARIAAEVGQSSMWISTDAAASVLEPLKVVWAKCSGYPSYPALIIDPKMPRVPGHHN
  GVTIPAPPLDVLKIGEHMQTKSDEKLFLVLFFDNKRSWQWLPKSKMVPLGIDETIDKLKM
  MEGRNSSIRKAVRIAFDRAMNHLSRVHGEPTSDLSDID
• Function: Scaffold subunit of various histone acetyltransferase (HAT) complexes, such as the MOZ/MORF and HBO1 complexes, that acts as a regulator of hematopoiesis. Plays a key role in HBO1 complex by directing KAT7/HBO1 specificity towards histone H3 'Lys-14' acetylation (H3K14ac), thereby promoting erythroid differentiation.
• Tissue Specificity: Highly expressed in testis.
• Reactome Pathway:
  Regulation of TP53 Activity through Acetylation (R-HSA-6804758)
  HATs acetylate histones (R-HSA-3214847)

Molecular Interaction Atlas (MIA) of This DOT

6 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Bromodomain-containing protein 1 (BRD1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Bromodomain-containing protein 1 (BRD1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Bromodomain-containing protein 1 (BRD1).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Bromodomain-containing protein 1 (BRD1).	[4]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Bromodomain-containing protein 1 (BRD1).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Bromodomain-containing protein 1 (BRD1).	[11]

5 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Bromodomain-containing protein 1 (BRD1).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Bromodomain-containing protein 1 (BRD1).	[6]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Bromodomain-containing protein 1 (BRD1).	[8]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Bromodomain-containing protein 1 (BRD1).	[10]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Bromodomain-containing protein 1 (BRD1).	[10]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 affects the binding of Bromodomain-containing protein 1 (BRD1).	[7]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [6] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [7] Selective inhibition of BET bromodomains. Nature. 2010 Dec 23;468(7327):1067-73.
• [8] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [9] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [10] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [11] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.