Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTPFG2M)

• DOT Name: Beta/gamma crystallin domain-containing protein 2 (CRYBG2)
• Synonyms: Absent in melanoma 1-like protein
• Gene Name: CRYBG2
• UniProt ID: CRBG2_HUMAN
• Pfam ID: PF00030 ; PF00652
• Sequence:
  MEEAGGPMARAKARVVSATLTWRQRPPTQEEIKHGFHKVSLVSGAQMEAPQKEMFEFSRR
  EEVEVNGFATQEEETVNCQGPRDTAGSKNFQSHGPIFSKKYIPPPKEKRPEGRLKEAVDQ
  SDGSRQAPRTEPPCVGAMARTELLVPLPGPREPSPHPGVGLTSGSSRSLEEYRVTRTVRT
  TTVVGGHVDRRMSSSVTVRPVSSGEALPRGRQVSRMVPPVVVGSPPGSPSRSQAVKVLSN
  LVPAGHSPPASHLPRPTAGGPRSTGLGSTVGAALRQLPETGTAELKDSSALASTGIPASA
  HLPKNQDAPAACPDRDQGRAPDARACELWQVLGAPSSTELPLQTSQGQASVPSSPRLETH
  VPSPGLTHPAKQPVVPTHPGARLTPLVLPPKKKDGPVDPPAATVLPMVRSEHVTVPGQPP
  APSTTRRKDVPSPGGLSAPSSPRNKFVQNSENVPVLPFTQREVVKGPGAPAASSPTRKEV
  VQGSSASAASSPTWKEVVKGPGAPAASSPTQKEVVQGSSAPAALFPTWKEVVKGPGAPDA
  SFPTWKEVVKGPGAPAASSPTQKEVVQGSGAPAALSTTPKEVVKGPGAPAASSPTQKEVV
  KGPCAPAASSPTQKEVVQGSGAPAALSPKSTEVVQGPKGSSSIQKEAVQGIAGSLAPPLT
  KEETVQGPIAPATSLPKQDKGVQDSEGSPISSLTQKEVVQDPDALPAPSSSVDRVSPSPG
  GTPAPVPTGAEASTESQLVSDPTEGKTCTETSREEDEVALAADLEIFLDTLRSMEPPEIL
  RTHRLPRAPRSSYLSMYATLPAIEEDQLGPWVLGPGPQEVPSLEEKEEEEEEEPENPYLS
  DDEKLQRRQEKAGPSPSRDLHPARPTQVSCSPLEMMKKHVAGTKGPHSELGLELQGGSRP
  TSRLGGSLLFGSLVPTAKEASTPEPLGTKLSALLPHGAPGLRKVPGQLPLLCSERSSPTE
  KLACSLPLEGWSPALKTQGKLNTRPGKVIFFSESGCQGSGREVWGDIVDASGWAPVASIR
  VVRGCWVLYEEPEFRGQKLVLPEGDMELRTPGTKWSPQGIGSLRRVVWDYSTPEISLFSE
  EGLKGEQVKLTEALKNSQGLEKPLQVASATVSAGLWLLYPKPLFEDTPYILEPGEYPTSE
  AWGTSDPSVGSLKPMRLGCPSVEKPGEPRAVVYEAPGFQGRSWEVSRDIYNLQQPEDSQS
  PHLASVGSLRVLGGCWVGYEKEGFRGHQYLLEEGEYPDWSHWGGYDELLTSLRVIRTDFG
  DPAVVLFEAMDFEGHGVEVSKALPDVELVQHGPSTQAIHVLSGVWVAYQEVGFSGEQYVL
  EKGVYRNCEDWGAGNSTLASLQPVLQVGEHDLHFVSKIQLFSRPDFLGDHFSFEDDQAAL
  PASFRPQSCRVHGGSWILFDETNFEGDQHILSEGEFPTLTAMGCLASTVLGSLQKVSLHF
  SEPSIFLYGLECFEGKEIELSREVRSLQAEGFNNHVLSVRIKGGIWVLCEHSDFRGRQWL
  VGSCEITNWLTYSGTQRVGSLYPIKQRRVYFRLWNAALGGFLAVPDHVEDMKAGRVVVAD
  PQAGGSCIWYYEDGLLKNQMAPTMSLQVIGPPSPGSKVVLWAESRLPRQTWSISESGHIC
  SQMFEGQILDVKGGRGYDRDHVVLWEPDEDRASQIWTIHVL

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Beta/gamma crystallin domain-containing protein 2 (CRYBG2).	[1]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Beta/gamma crystallin domain-containing protein 2 (CRYBG2).	[13]

15 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 Beta/gamma crystallin domain-containing protein 2 (CRYBG2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Beta/gamma crystallin domain-containing protein 2 (CRYBG2).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Beta/gamma crystallin domain-containing protein 2 (CRYBG2).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Beta/gamma crystallin domain-containing protein 2 (CRYBG2).	[5]
Selenium	DM25CGV	Approved	Selenium increases the expression of Beta/gamma crystallin domain-containing protein 2 (CRYBG2).	[6]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Beta/gamma crystallin domain-containing protein 2 (CRYBG2).	[7]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Beta/gamma crystallin domain-containing protein 2 (CRYBG2).	[8]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Beta/gamma crystallin domain-containing protein 2 (CRYBG2).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Beta/gamma crystallin domain-containing protein 2 (CRYBG2).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Beta/gamma crystallin domain-containing protein 2 (CRYBG2).	[11]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Beta/gamma crystallin domain-containing protein 2 (CRYBG2).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Beta/gamma crystallin domain-containing protein 2 (CRYBG2).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Beta/gamma crystallin domain-containing protein 2 (CRYBG2).	[14]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Beta/gamma crystallin domain-containing protein 2 (CRYBG2).	[15]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of Beta/gamma crystallin domain-containing protein 2 (CRYBG2).	[16]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [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] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Comparative Analysis of Transcriptomic Changes including mRNA and microRNA Expression Induced by the Xenoestrogens Zearalenone and Bisphenol A in Human Ovarian Cells. Toxins (Basel). 2023 Feb 9;15(2):140. doi: 10.3390/toxins15020140.
• [6] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [7] 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.
• [8] Endometrial receptivity is affected in women with high circulating progesterone levels at the end of the follicular phase: a functional genomics analysis. Hum Reprod. 2011 Jul;26(7):1813-25.
• [9] Differently expressed long noncoding RNAs and mRNAs in TK6 cells exposed to low dose hydroquinone. Oncotarget. 2017 Oct 4;8(56):95554-95567. doi: 10.18632/oncotarget.21481. eCollection 2017 Nov 10.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [12] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [13] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [14] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [15] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [16] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.