Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL5Z9NC)

• DOT Name: SUN domain-containing protein 3 (SUN3)
• Synonyms: Sad1/unc-84 domain-containing protein 1
• Gene Name: SUN3
• Related Disease: Amyotrophic lateral sclerosis
• UniProt ID: SUN3_HUMAN
• Pfam ID: PF07738
• Sequence:
  MSGKTKARRAAMFFRRCSEDASGSASGNALLSEDENPDANGVTRSWKIILSTMLTLTFLL
  VGLLNHQWLKETDVPQKSRQLYAIIAEYGSRLYKYQARLRMPKEQLELLKKESQNLENNF
  RQILFLIEQIDVLKALLRDMKDGMDNNHNWNTHGDPVEDPDHTEEVSNLVNYVLKKLRED
  QVEMADYALKSAGASIIEAGTSESYKNNKAKLYWHGIGFLNHEMPPDIILQPDVYPGKCW
  AFPGSQGHTLIKLATKIIPTAVTMEHISEKVSPSGNISSAPKEFSVYGITKKCEGEEIFL
  GQFIYNKTGTTVQTFELQHAVSEYLLCVKLNIFSNWGHPKYTCLYRFRVHGTPGKHI
• Function: As a probable component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex, involved in the connection between the nuclear lamina and the cytoskeleton. The nucleocytoplasmic interactions established by the LINC complex play an important role in the transmission of mechanical forces across the nuclear envelope and in nuclear movement and positioning. May be involved in nuclear remodeling during sperm head formation in spermatogenesis. A probable SUN3:SYNE1 LINC complex may tether spermatid nuclei to posterior cytoskeletal structures such as the manchette.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Amyotrophic lateral sclerosis	DISF7HVM	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of SUN domain-containing protein 3 (SUN3).	[2]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of SUN domain-containing protein 3 (SUN3).	[5]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of SUN domain-containing protein 3 (SUN3).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of SUN domain-containing protein 3 (SUN3).	[3]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of SUN domain-containing protein 3 (SUN3).	[4]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of SUN domain-containing protein 3 (SUN3).	[6]

References

• [1] A two-stage genome-wide association study of sporadic amyotrophic lateral sclerosis.Hum Mol Genet. 2009 Apr 15;18(8):1524-32. doi: 10.1093/hmg/ddp059. Epub 2009 Feb 4.
• [2] 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.
• [3] 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.
• [4] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [5] 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.
• [6] Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.
• [7] 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.