Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1P2GJA)

• DOT Name: Adipocyte plasma membrane-associated protein (APMAP)
• Synonyms: Protein BSCv
• Gene Name: APMAP
• Related Disease:
  Alzheimer disease
  Colorectal carcinoma
  Cytomegalovirus infection
  Prostate cancer
  Prostate carcinoma
• UniProt ID: APMAP_HUMAN
• Pfam ID: PF20067 ; PF03088
• Sequence:
  MSEADGLRQRRPLRPQVVTDDDGQAPEAKDGSSFSGRVFRVTFLMLAVSLTVPLLGAMML
  LESPIDPQPLSFKEPPLLLGVLHPNTKLRQAERLFENQLVGPESIAHIGDVMFTGTADGR
  VVKLENGEIETIARFGSGPCKTRDDEPVCGRPLGIRAGPNGTLFVADAYKGLFEVNPWKR
  EVKLLLSSETPIEGKNMSFVNDLTVTQDGRKIYFTDSSSKWQRRDYLLLVMEGTDDGRLL
  EYDTVTREVKVLLDQLRFPNGVQLSPAEDFVLVAETTMARIRRVYVSGLMKGGADLFVEN
  MPGFPDNIRPSSSGGYWVGMSTIRPNPGFSMLDFLSERPWIKRMIFKLFSQETVMKFVPR
  YSLVLELSDSGAFRRSLHDPDGLVATYISEVHEHDGHLYLGSFRSPFLCRLSLQAV
• Function: Exhibits strong arylesterase activity with beta-naphthyl acetate and phenyl acetate. May play a role in adipocyte differentiation.
• Tissue Specificity: Liver, glomerular and tubular structures of the kidney, endothelial cells, arterial wall and pancreatic islets of Langerhans (at protein level). Found ubiquitously in adult as well as in embryonic tissues. In adult tissue, the highest expression is found in the liver, placenta and heart. Found on the cell surface of monocytes. In embryonic tissue, the highest expression levels is found in the liver and the kidney.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[2]
Cytomegalovirus infection	DISCEMGC	Strong	Biomarker	[3]
Prostate cancer	DISF190Y	Strong	Biomarker	[4]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[4]

9 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 Adipocyte plasma membrane-associated protein (APMAP).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Adipocyte plasma membrane-associated protein (APMAP).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Adipocyte plasma membrane-associated protein (APMAP).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Adipocyte plasma membrane-associated protein (APMAP).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Adipocyte plasma membrane-associated protein (APMAP).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Adipocyte plasma membrane-associated protein (APMAP).	[10]
SB-431542	DM0YOXQ	Preclinical	SB-431542 increases the expression of Adipocyte plasma membrane-associated protein (APMAP).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Adipocyte plasma membrane-associated protein (APMAP).	[13]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Adipocyte plasma membrane-associated protein (APMAP).	[14]

1 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 increases the methylation of Adipocyte plasma membrane-associated protein (APMAP).	[11]

References

• [1] The APMAP interactome reveals new modulators of APP processing and beta-amyloid production that are altered in Alzheimer's disease.Acta Neuropathol Commun. 2019 Jan 31;7(1):13. doi: 10.1186/s40478-019-0660-3.
• [2] Chromosome 20p11 gains are associated with liver-specific metastasis in patients with colorectal cancer.Gut. 2013 Jan;62(1):94-101. doi: 10.1136/gutjnl-2011-301587. Epub 2012 Jan 20.
• [3] Identification of adipocyte plasma membrane-associated protein as a novel modulator of human cytomegalovirus infection.PLoS Pathog. 2019 Jul 29;15(7):e1007914. doi: 10.1371/journal.ppat.1007914. eCollection 2019 Jul.
• [4] Cholesterol Induces Epithelial-to-Mesenchymal Transition of Prostate Cancer Cells by Suppressing Degradation of EGFR through APMAP.Cancer Res. 2019 Jun 15;79(12):3063-3075. doi: 10.1158/0008-5472.CAN-18-3295. Epub 2019 Apr 15.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [7] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [8] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [9] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [10] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [11] 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.
• [12] Activin/nodal signaling switches the terminal fate of human embryonic stem cell-derived trophoblasts. J Biol Chem. 2015 Apr 3;290(14):8834-48.
• [13] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [14] Evaluation of an in vitro model of androgen ablation and identification of the androgen responsive proteome in LNCaP cells. Proteomics. 2007 Jan;7(1):47-63.