Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT57LALQ)

• DOT Name: Cysteine-rich protein 2-binding protein (KAT14)
• Synonyms: CSRP2-binding protein; ADA2A-containing complex subunit 2; ATAC2; CRP2-binding partner; CRP2BP; Lysine acetyltransferase 14
• Gene Name: KAT14
• Related Disease: Posterior polymorphous corneal dystrophy
• UniProt ID: CSR2B_HUMAN
• Pfam ID: PF00583
• Sequence:
  MDSSIHLSSLISRHDDEATRTSTSEGLEEGEVEGETLLIVESEDQASVDLSHDQSGDSLN
  SDEGDVSWMEEQLSYFCDKCQKWIPASQLREQLSYLKGDNFFRFTCSDCSADGKEQYERL
  KLTWQQVVMLAMYNLSLEGSGRQGYFRWKEDICAFIEKHWTFLLGNRKKTSTWWSTVAGC
  LSVGSPMYFRSGAQEFGEPGWWKLVHNKPPTMKPEGEKLSASTLKIKAASKPTLDPIITV
  EGLRKRASRNPVESAMELKEKRSRTQEAKDIRRAQKEAAGFLDRSTSSTPVKFISRGRRP
  DVILEKGEVIDFSSLSSSDRTPLTSPSPSPSLDFSAPGTPASHSATPSLLSEADLIPDVM
  PPQALFHDDDEMEGDGVIDPGMEYVPPPAGSVASGPVVGVRKKVRGPEQIKQEVESEEEK
  PDRMDIDSEDTDSNTSLQTRAREKRKPQLEKDTKPKEPRYTPVSIYEEKLLLKRLEACPG
  AVAMTPEARRLKRKLIVRQAKRDRGLPLFDLDQVVNAALLLVDGIYGAKEGGISRLPAGQ
  ATYRTTCQDFRILDRYQTSLPSRKGFRHQTTKFLYRLVGSEDMAVDQSIVSPYTSRILKP
  YIRRDYETKPPKLQLLSQIRSHLHRSDPHWTPEPDAPLDYCYVRPNHIPTINSMCQEFFW
  PGIDLSECLQYPDFSVVVLYKKVIIAFGFMVPDVKYNEAYISFLFVHPEWRRAGIATFMI
  YHLIQTCMGKDVTLHVSASNPAMLLYQKFGFKTEEYVLDFYDKYYPLESTECKHAFFLRL
  RR
• Function: Component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4. May function as a scaffold for the ATAC complex to promote ATAC complex stability. Has also weak histone acetyltransferase activity toward histone H4. Required for the normal progression through G1 and G2/M phases of the cell cycle.
• Tissue Specificity: Expressed in skeletal muscle, heart, lung, placenta, brain, liver, pancreas and kidney. High expression in skeletal muscle and heart. Lower expression in lung.
• Reactome Pathway:
  Formation of WDR5-containing histone-modifying complexes (R-HSA-9772755)
  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
Posterior polymorphous corneal dystrophy	DISHAYH6	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Cysteine-rich protein 2-binding protein (KAT14).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cysteine-rich protein 2-binding protein (KAT14).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Cysteine-rich protein 2-binding protein (KAT14).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Cysteine-rich protein 2-binding protein (KAT14).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Cysteine-rich protein 2-binding protein (KAT14).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Cysteine-rich protein 2-binding protein (KAT14).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Cysteine-rich protein 2-binding protein (KAT14).	[8]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Cysteine-rich protein 2-binding protein (KAT14).	[9]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Cysteine-rich protein 2-binding protein (KAT14).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Cysteine-rich protein 2-binding protein (KAT14).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Cysteine-rich protein 2-binding protein (KAT14).	[6]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Cysteine-rich protein 2-binding protein (KAT14).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Cysteine-rich protein 2-binding protein (KAT14).	[12]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Cysteine-rich protein 2-binding protein (KAT14).	[13]

References

• [1] Association of a Chromosomal Rearrangement Event with Mouse Posterior Polymorphous Corneal Dystrophy and Alterations in Csrp2bp, Dzank1, and Ovol2 Gene Expression.PLoS One. 2016 Jun 16;11(6):e0157577. doi: 10.1371/journal.pone.0157577. eCollection 2016.
• [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] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Convergent transcriptional profiles induced by endogenous estrogen and distinct xenoestrogens in breast cancer cells. Carcinogenesis. 2006 Aug;27(8):1567-78.
• [7] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [8] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [9] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [10] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [11] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [13] Transcriptomic alterations induced by Ochratoxin A in rat and human renal proximal tubular in vitro models and comparison to a rat in vivo model. Arch Toxicol. 2012 Apr;86(4):571-89.