Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPC9GXB)

• DOT Name: Peregrin (BRPF1)
• Synonyms: Bromodomain and PHD finger-containing protein 1; Protein Br140
• Gene Name: BRPF1
• Related Disease: Intellectual developmental disorder with dysmorphic facies and ptosis
• UniProt ID: BRPF1_HUMAN
• PDB ID: 2D9E ; 2RS9 ; 2X35 ; 2X4W ; 2X4X ; 2X4Y ; 3L42 ; 3MO8 ; 4LC2 ; 4QYD ; 4QYL ; 4UYE ; 5C6S ; 5C7N ; 5C85 ; 5C87 ; 5C89 ; 5D7X ; 5DY7 ; 5DYA ; 5DYC ; 5E3D ; 5E3G ; 5EM3 ; 5EPR ; 5EPS ; 5EQ1 ; 5ERC ; 5ETB ; 5ETD ; 5EV9 ; 5EVA ; 5EWC ; 5EWD ; 5EWH ; 5EWV ; 5EWW ; 5FFV ; 5FFW ; 5FFY ; 5FG4 ; 5FG5 ; 5G4R ; 5G4S ; 5MWG ; 5MWH ; 5MWZ ; 5MYG ; 5O4S ; 5O4T ; 5O55 ; 5O5A ; 5O5F ; 5O5H ; 5OV8 ; 5OWA ; 5OWB ; 5OWE ; 5T4U ; 5T4V ; 6EKQ ; 6U04 ; 7C4I
• Pfam ID: PF00439 ; PF10513 ; PF13831 ; PF00855 ; PF13832
• Sequence:
  MGVDFDVKTFCHNLRATKPPYECPVETCRKVYKSYSGIEYHLYHYDHDNPPPPQQTPLRK
  HKKKGRQSRPANKQSPSPSEVSQSPGREVMSYAQAQRMVEVDLHGRVHRISIFDNLDVVS
  EDEEAPEEAPENGSNKENTETPAATPKSGKHKNKEKRKDSNHHHHHNVSASTTPKLPEVV
  YRELEQDTPDAPPRPTSYYRYIEKSAEELDEEVEYDMDEEDYIWLDIMNERRKTEGVSPI
  PQEIFEYLMDRLEKESYFESHNKGDPNALVDEDAVCCICNDGECQNSNVILFCDMCNLAV
  HQECYGVPYIPEGQWLCRRCLQSPSRAVDCALCPNKGGAFKQTDDGRWAHVVCALWIPEV
  CFANTVFLEPIDSIEHIPPARWKLTCYICKQRGSGACIQCHKANCYTAFHVTCAQQAGLY
  MKMEPVRETGANGTSFSVRKTAYCDIHTPPGSARRLPALSHSEGEEDEDEEEDEGKGWSS
  EKVKKAKAKSRIKMKKARKILAEKRAAAPVVSVPCIPPHRLSKITNRLTIQRKSQFMQRL
  HSYWTLKRQSRNGVPLLRRLQTHLQSQRNCDQVGRDSEDKNWALKEQLKSWQRLRHDLER
  ARLLVELIRKREKLKRETIKVQQIAMEMQLTPFLILLRKTLEQLQEKDTGNIFSEPVPLS
  EVPDYLDHIKKPMDFFTMKQNLEAYRYLNFDDFEEDFNLIVSNCLKYNAKDTIFYRAAVR
  LREQGGAVLRQARRQAEKMGIDFETGMHIPHSLAGDEATHHTEDAAEEERLVLLENQKHL
  PVEEQLKLLLERLDEVNASKQSVGRSRRAKMIKKEMTALRRKLAHQRETGRDGPERHGPS
  SRGSLTPHPAACDKDGQTDSAAEESSSQETSKGLGPNMSSTPAHEVGRRTSVLFSKKNPK
  TAGPPKRPGRPPKNRESQMTPSHGGSPVGPPQLPIMSSLRQRKRGRSPRPSSSSDSDSDK
  STEDPPMDLPANGFSGGNQPVKKSFLVYRNDCSLPRSSSDSESSSSSSSSAASDRTSTTP
  SKQGRGKPSFSRGTFPEDSSEDTSGTENEAYSVGTGRGVGHSMVRKSLGRGAGWLSEDED
  SPLDALDLVWAKCRGYPSYPALIIDPKMPREGMFHHGVPIPVPPLEVLKLGEQMTQEARE
  HLYLVLFFDNKRTWQWLPRTKLVPLGVNQDLDKEKMLEGRKSNIRKSVQIAYHRALQHRS
  KVQGEQSSETSDSD
• Function: Scaffold subunit of various histone acetyltransferase (HAT) complexes, such as the MOZ/MORF and HBO1 complexes, which have a histone H3 acetyltransferase activity. Plays a key role in HBO1 complex by directing KAT7/HBO1 specificity towards histone H3 'Lys-14' acetylation (H3K14ac). Some HAT complexes preferentially mediate histone H3 'Lys-23' (H3K23ac) acetylation. Positively regulates the transcription of RUNX1 and RUNX2.
• Tissue Specificity: High levels 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

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Intellectual developmental disorder with dysmorphic facies and ptosis	DISQ95E8	Strong	Autosomal dominant	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Peregrin (BRPF1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Peregrin (BRPF1).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Peregrin (BRPF1).	[4]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Peregrin (BRPF1).	[5]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Peregrin (BRPF1).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Peregrin (BRPF1).	[7]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Peregrin (BRPF1).	[8]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Peregrin (BRPF1).	[8]

References

• [1] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [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] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] A comprehensive analysis of Wnt/beta-catenin signaling pathway-related genes and crosstalk pathways in the treatment of As2O3 in renal cancer. Ren Fail. 2018 Nov;40(1):331-339.
• [6] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [7] 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.
• [8] 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.