Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6SKRF0)

• DOT Name: Tripartite motif-containing protein 43 (TRIM43)
• Gene Name: TRIM43
• Related Disease: Kaposi sarcoma
• UniProt ID: TRI43_HUMAN
• Pfam ID: PF00622 ; PF15227
• Sequence:
  MDSDFSHAFQKELTCVICLNYLVDPVTICCGHSFCRPCLCLSWEEAQSPANCPACREPSP
  KMDFKTNILLKNLVTIARKASLWQFLSSEKQICGTHRQTKKMFCDMDKSLLCLLCSNSQE
  HGAHKHHPIEEAAEEHREKLLKQMRILWKKIQENQRNLYEEGRTAFLWRGNVVLRAQMIR
  NEYRKLHPVLHKEEKQHLERLNKEYQEIFQQLQRSWVKMDQKSKHLKEMYQELMEMCHKP
  DVELLQDLGDIVARSESVLLHMPQPVNPELTAGPITGLVYRLNRFRVEISFHFEVTNHNI
  RLFEDVRSWMFRRGPLNSDRSDYFAAWGARVFSFGKHYWELDVDNSCDWALGVCNNSWIR
  KNSTMVNSEDIFLLLCLKVDNHFNLLTTSPVFPHYIEKPLGRVGVFLDFESGSVSFLNVT
  KSSLIWSYPAGSLTFPVRPFFYTGHR
• Function: E3 ligase that regulates nuclear lamina integrity and the association of viral chromatin with transcriptionally-active host chromatin. Acts thereby as a herpesvirus-specific antiviral factor and mediates the ubiquitination-dependent proteasomal degradation of PCNT.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Kaposi sarcoma	DISC1H1Z	Definitive	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Tripartite motif-containing protein 43 (TRIM43).	[2]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Tripartite motif-containing protein 43 (TRIM43).	[3]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Tripartite motif-containing protein 43 (TRIM43).	[4]
Folic acid	DMEMBJC	Approved	Folic acid increases the expression of Tripartite motif-containing protein 43 (TRIM43).	[5]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Tripartite motif-containing protein 43 (TRIM43).	[3]

References

• [1] Centrosomal protein TRIM43 restricts herpesvirus infection by regulating nuclear lamina integrity.Nat Microbiol. 2019 Jan;4(1):164-176. doi: 10.1038/s41564-018-0285-5. Epub 2018 Nov 12.
• [2] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [3] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [4] Characterization of DOK1, a candidate tumor suppressor gene, in epithelial ovarian cancer. Mol Oncol. 2011 Oct;5(5):438-53. doi: 10.1016/j.molonc.2011.07.003. Epub 2011 Jul 26.
• [5] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.