Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO5GKZS)

• DOT Name: Acyl-CoA wax alcohol acyltransferase 2 (AWAT2)
• Synonyms: EC 2.3.1.75; 11-cis-specific retinyl-ester synthase; 11-cis-RE-synthase; Acyl-CoA retinol O-fatty-acyltransferase; ARAT; Retinol O-fatty-acyltransferase; EC 2.3.1.76; Diacylglycerol O-acyltransferase 2-like protein 4; EC 2.3.1.20; Diacylglycerol O-acyltransferase candidate 4; hDC4; Long-chain-alcohol O-fatty-acyltransferase 2; Multifunctional O-acyltransferase; Wax synthase; hWS
• Gene Name: AWAT2
• Related Disease:
  Oral lichen planus
  Legionellosis
• UniProt ID: AWAT2_HUMAN
• EC Number: 2.3.1.20; 2.3.1.75; 2.3.1.76
• Pfam ID: PF03982
• Sequence:
  MLLPSKKDLKTALDVFAVFQWSFSALLITTTVIAVNLYLVVFTPYWPVTVLILTWLAFDW
  KTPQRGGRRFTCVRHWRLWKHYSDYFPLKLLKTHDICPSRNYILVCHPHGLFAHGWFGHF
  ATEASGFSKIFPGITPYILTLGAFFWMPFLREYVMSTGACSVSRSSIDFLLTHKGTGNMV
  IVVIGGLAECRYSLPGSSTLVLKNRSGFVRMALQHGVPLIPAYAFGETDLYDQHIFTPGG
  FVNRFQKWFQSMVHIYPCAFYGRGFTKNSWGLLPYSRPVTTIVGEPLPMPKIENPSQEIV
  AKYHTLYIDALRKLFDQHKTKFGISETQELEII
• Function: Acyltransferase that catalyzes the formation of ester bonds between fatty alcohols and fatty acyl-CoAs to form wax monoesters. Shows a preference for medium chain acyl-CoAs from C12 to C16 in length and fatty alcohols shorter than C20, as the acyl donors and acceptors, respectively. Also possesses acyl-CoA retinol acyltransferase (ARAT) activity that preferentially esterifies 11-cis-retinol, a chromophore precursor of bleached opsin pigments in cone cells. Shows higher catalytic efficiency toward 11-cis-retinol versus 9-cis-retinol, 13-cis-retinol, and all-trans-retinol substrates.
• Tissue Specificity: Highly expressed in skin, where it is primarily restricted to undifferentiated peripheral sebocytes. Also expressed at lower level in other tissues except pancreas.
• KEGG Pathway:
  Retinol metabolism (hsa00830)
  Metabolic pathways (hsa01100)
  Vitamin digestion and absorption (hsa04977)
• Reactome Pathway:
  The retinoid cycle in cones (daylight vision) (R-HSA-2187335)
  Wax biosynthesis (R-HSA-9640463)
  Acyl chain remodeling of DAG and TAG (R-HSA-1482883)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Oral lichen planus	DISVEAJA	Definitive	Altered Expression	[1]
Legionellosis	DISHA0ML	Strong	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Acyl-CoA wax alcohol acyltransferase 2 (AWAT2).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Acyl-CoA wax alcohol acyltransferase 2 (AWAT2).	[4]

References

• [1] Difficulties detecting miRNA-203 in human whole saliva by the use of PCR.Med Oral Patol Oral Cir Bucal. 2015 Mar 1;20(2):e130-4. doi: 10.4317/medoral.20172.
• [2] Sequence-based typing of Legionella pneumophila strains isolated from hospital water distribution systems as a complementary element of risk assessment of legionellosis in Poland.Ann Agric Environ Med. 2013;20(3):436-40.
• [3] 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.
• [4] 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.