Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJIVR84)

• DOT Name: AP-4 complex accessory subunit Tepsin (TEPSIN)
• Synonyms: ENTH domain-containing protein 2; Epsin for AP-4; Tetra-epsin
• Gene Name: TEPSIN
• Related Disease:
  Frontotemporal dementia
  Psoriasis
• UniProt ID: AP4AT_HUMAN
• PDB ID: 5WF9; 5WFB
• Pfam ID: PF01417
• Sequence:
  MAAAPPLRDRLSFLHRLPILLKGTSDDDVPCPGYLFEEIAKISHESPGSSQCLLEYLLSR
  LHSSSGHGKLKVLKILLYLCSHGSSFFLLILKRNSAFIQEAAAFAGPPDPLHGNSLYQKV
  RAAAQDLGSTLFSDTVLPLAPSQPLGTPPATGMGSQARPHSTLQGFGYSKEHGRTAVRHQ
  PGQAGGGWDELDSGPSSQNSSQNSDLSRVSDSGSHSGSDSHSGASREPGDLAERVEVVAL
  SDCQQELSLVRTVTRGPRAFLSREEAQHFIKACGLLNCEAVLQLLTCHLRGTSECTQLRA
  LCAIASLGSSDLLPQEHILLRTRPWLQELSMGSPGPVTNKATKILRHFEASCGQLSPARG
  TSAEPGPTAALPGPSDLLTDAVPLPGSQVFLQPLSSTPVSSRSPAPSSGMPSSPVPTPPP
  DASPIPAPGDPSEAEARLAESRRWRPERIPGGTDSPKRGPSSCAWSRDSLFAGMELVACP
  RLVGAGAAAGESCPDAPRAPQTSSQRTAAKEPPGSEPSAFAFLNA
• Function: Associates with the adapter-like complex 4 (AP-4) and may therefore play a role in vesicular trafficking of proteins at the trans-Golgi network.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Frontotemporal dementia	DISKYHXL	Strong	Genetic Variation	[1]
Psoriasis	DIS59VMN	Strong	Genetic Variation	[2]

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 AP-4 complex accessory subunit Tepsin (TEPSIN).	[3]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of AP-4 complex accessory subunit Tepsin (TEPSIN).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of AP-4 complex accessory subunit Tepsin (TEPSIN).	[4]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of AP-4 complex accessory subunit Tepsin (TEPSIN).	[5]
Menadione	DMSJDTY	Approved	Menadione affects the expression of AP-4 complex accessory subunit Tepsin (TEPSIN).	[6]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of AP-4 complex accessory subunit Tepsin (TEPSIN).	[8]

References

• [1] A genome-wide screening and SNPs-to-genes approach to identify novel genetic risk factors associated with frontotemporal dementia.Neurobiol Aging. 2015 Oct;36(10):2904.e13-26. doi: 10.1016/j.neurobiolaging.2015.06.005. Epub 2015 Jun 12.
• [2] A promoter sequence variant of ZNF750 is linked with familial psoriasis.J Invest Dermatol. 2008 Jul;128(7):1662-8. doi: 10.1038/jid.2008.1. Epub 2008 Feb 7.
• [3] 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.
• [4] 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.
• [5] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [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.
• [8] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.