Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXFGK9H)

• DOT Name: mRNA (PCIF1)
• Synonyms: 2'-O-methyladenosine-N(6)-)-methyltransferase (EC 2.1.1.62; Cap-specific adenosine methyltransferase; CAPAM; hCAPAM; Phosphorylated CTD-interacting factor 1; hPCIF1; Protein phosphatase 1 regulatory subunit 121
• Gene Name: PCIF1
• Related Disease:
  Abdominal aortic aneurysm
  Type-1/2 diabetes
• UniProt ID: CAPAM_HUMAN
• PDB ID: 2JX8; 6IRV; 6IRW
• EC Number: 2.1.1.62
• Pfam ID: PF12237 ; PF00397
• Sequence:
  MANENHGSPREEASLLSHSPGTSNQSQPCSPKPIRLVQDLPEELVHAGWEKCWSRRENRP
  YYFNRFTNQSLWEMPVLGQHDVISDPLGLNATPLPQDSSLVETPPAENKPRKRQLSEEQP
  SGNGVKKPKIEIPVTPTGQSVPSSPSIPGTPTLKMWGTSPEDKQQAALLRPTEVYWDLDI
  QTNAVIKHRGPSEVLPPHPEVELLRSQLILKLRQHYRELCQQREGIEPPRESFNRWMLER
  KVVDKGSDPLLPSNCEPVVSPSMFREIMNDIPIRLSRIKFREEAKRLLFKYAEAARRLIE
  SRSASPDSRKVVKWNVEDTFSWLRKDHSASKEDYMDRLEHLRRQCGPHVSAAAKDSVEGI
  CSKIYHISLEYVKRIREKHLAILKENNISEEVEAPEVEPRLVYCYPVRLAVSAPPMPSVE
  MHMENNVVCIRYKGEMVKVSRNYFSKLWLLYRYSCIDDSAFERFLPRVWCLLRRYQMMFG
  VGLYEGTGLQGSLPVHVFEALHRLFGVSFECFASPLNCYFRQYCSAFPDTDGYFGSRGPC
  LDFAPLSGSFEANPPFCEELMDAMVSHFERLLESSPEPLSFIVFIPEWREPPTPALTRME
  QSRFKRHQLILPAFEHEYRSGSQHICKKEEMHYKAVHNTAVLFLQNDPGFAKWAPTPERL
  QELSAAYRQSGRSHSSGSSSSSSSEAKDRDSGREQGPSREPHPT
• Function: Cap-specific adenosine methyltransferase that catalyzes formation of N(6),2'-O-dimethyladenosine cap (m6A(m)) by methylating the adenosine at the second transcribed position of capped mRNAs. Recruited to the early elongation complex of RNA polymerase II (RNAPII) via interaction with POLR2A and mediates formation of m6A(m) co-transcriptionally.
• Tissue Specificity: Ubiquitous.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Abdominal aortic aneurysm	DISD06OF	Strong	Genetic Variation	[1]
Type-1/2 diabetes	DISIUHAP	Limited	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of mRNA (PCIF1).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of mRNA (PCIF1).	[4]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of mRNA (PCIF1).	[5]
Marinol	DM70IK5	Approved	Marinol increases the expression of mRNA (PCIF1).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of mRNA (PCIF1).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of mRNA (PCIF1).	[8]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of mRNA (PCIF1).	[8]

References

• [1] Replication of Newly Identified Genetic Associations Between Abdominal Aortic Aneurysm and SMYD2, LINC00540, PCIF1/MMP9/ZNF335, and ERG.Eur J Vasc Endovasc Surg. 2020 Jan;59(1):92-97. doi: 10.1016/j.ejvs.2019.02.017. Epub 2019 Nov 1.
• [2] PLTP activity inversely correlates with CAAD: effects of PON1 enzyme activity and genetic variants on PLTP activity.J Lipid Res. 2015 Jul;56(7):1351-62. doi: 10.1194/jlr.P058032. Epub 2015 May 25.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population. Environ Health Perspect. 2008 Apr;116(4):524-31. doi: 10.1289/ehp.10861.
• [6] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] 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.