Details of Drug Off-Target (DOT)

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

• DOT Name: Lipid droplet-regulating VLDL assembly factor AUP1 (AUP1)
• Synonyms: Ancient ubiquitous protein 1
• Gene Name: AUP1
• UniProt ID: AUP1_HUMAN
• PDB ID: 2EKF; 7LEW
• Pfam ID: PF02845
• Sequence:
  MELPSGPGPERLFDSHRLPGDCFLLLVLLLYAPVGFCLLVLRLFLGIHVFLVSCALPDSV
  LRRFVVRTMCAVLGLVARQEDSGLRDHSVRVLISNHVTPFDHNIVNLLTTCSTPLLNSPP
  SFVCWSRGFMEMNGRGELVESLKRFCASTRLPPTPLLLFPEEEATNGREGLLRFSSWPFS
  IQDVVQPLTLQVQRPLVSVTVSDASWVSELLWSLFVPFTVYQVRWLRPVHRQLGEANEEF
  ALRVQQLVAKELGQTGTRLTPADKAEHMKRQRHPRLRPQSAQSSFPPSPGPSPDVQLATL
  AQRVKEVLPHVPLGVIQRDLAKTGCVDLTITNLLEGAVAFMPEDITKGTQSLPTASASKF
  PSSGPVTPQPTALTFAKSSWARQESLQERKQALYEYARRRFTERRAQEAD
• Function: Plays a role in the translocation of terminally misfolded proteins from the endoplasmic reticulum lumen to the cytoplasm and their degradation by the proteasome. Plays a role in lipid droplet formation. Induces lipid droplet clustering. Recruits ubiquitin-conjugating enzyme UBE2G2 to lipid droplets which facilitates its interaction with ubiquitin ligases AMFR/gp78 and RNF139/TRC8, leading to sterol-induced ubiquitination of HMGCR and its subsequent proteasomal degradation. Also required for the degradation of INSIG1, SREBF1 and SREBF2. Plays a role in regulating assembly and secretion of very low density lipoprotein particles and stability of apolipoprotein APOB ; (Microbial infection) Following Dengue virus infection, required for induction of lipophagy which facilitates production of virus progeny particles.
• Tissue Specificity: Detected in blood platelets and leukocytes (at protein level). Ubiquitous. Highly expressed in placenta, liver, kidney, skeletal muscle, heart and brain.

Molecular Interaction Atlas (MIA) of This DOT

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 Lipid droplet-regulating VLDL assembly factor AUP1 (AUP1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Lipid droplet-regulating VLDL assembly factor AUP1 (AUP1).	[2]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Lipid droplet-regulating VLDL assembly factor AUP1 (AUP1).	[3]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Lipid droplet-regulating VLDL assembly factor AUP1 (AUP1).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Lipid droplet-regulating VLDL assembly factor AUP1 (AUP1).	[6]

1 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 decreases the phosphorylation of Lipid droplet-regulating VLDL assembly factor AUP1 (AUP1).	[5]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [4] 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.
• [5] 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.
• [6] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.