Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6SD4OK)

• DOT Name: Translocating chain-associated membrane protein 1-like 1 (TRAM1L1)
• Gene Name: TRAM1L1
• UniProt ID: TR1L1_HUMAN
• Pfam ID: PF03798
• Sequence:
  MGLRKKSTKNPPVLSQEFILQNHADIVSCVGMFFLLGLVFEGTAEASIVFLTLQHSVAVP
  AAEEQATGSKSLYYYGVKDLATVFFYMLVAIIIHATIQEYVLDKINKRMQFTKAKQNKFN
  ESGQFSVFYFFSCIWGTFILISENCLSDPTLIWKARPHSMMTFQMKFFYISQLAYWFHAF
  PELYFQKTKKQDIPRQLVYIGLHLFHITGAYLLYLNHLGLLLLVLHYFVELLSHMCGLFY
  FSDEKYQKGISLWAIVFILGRLVTLIVSVLTVGFHLAGSQNRNPDALTGNVNVLAAKIAV
  LSSSCTIQAYVTWNLITLWLQRWVEDSNIQASCMKKKRSRSSKKRTENGVGVETSNRVDC
  PPKRKEKSS
• Function: Stimulatory or required for the translocation of secretory proteins across the ER membrane.
• KEGG Pathway: Protein processing in endoplasmic reticulum (hsa04141)

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 decreases the methylation of Translocating chain-associated membrane protein 1-like 1 (TRAM1L1).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Translocating chain-associated membrane protein 1-like 1 (TRAM1L1).	[9]

10 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 Translocating chain-associated membrane protein 1-like 1 (TRAM1L1).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Translocating chain-associated membrane protein 1-like 1 (TRAM1L1).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Translocating chain-associated membrane protein 1-like 1 (TRAM1L1).	[4]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Translocating chain-associated membrane protein 1-like 1 (TRAM1L1).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Translocating chain-associated membrane protein 1-like 1 (TRAM1L1).	[6]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Translocating chain-associated membrane protein 1-like 1 (TRAM1L1).	[7]
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of Translocating chain-associated membrane protein 1-like 1 (TRAM1L1).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Translocating chain-associated membrane protein 1-like 1 (TRAM1L1).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Translocating chain-associated membrane protein 1-like 1 (TRAM1L1).	[10]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Translocating chain-associated membrane protein 1-like 1 (TRAM1L1).	[11]

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] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [6] 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.
• [7] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [10] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [11] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.