Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZXBSS4)

• DOT Name: Angio-associated migratory cell protein (AAMP)
• Gene Name: AAMP
• Related Disease:
  Lung cancer
  Lung carcinoma
  Non-small-cell lung cancer
  Ductal breast carcinoma in situ
  Advanced cancer
  Breast cancer
  Breast carcinoma
• UniProt ID: AAMP_HUMAN
• Pfam ID: PF00400
• Sequence:
  MESESESGAAADTPPLETLSFHGDEEIIEVVELDPGPPDPDDLAQEMEDVDFEEEEEEEG
  NEEGWVLEPQEGVVGSMEGPDDSEVTFALHSASVFCVSLDPKTNTLAVTGGEDDKAFVWR
  LSDGELLFECAGHKDSVTCAGFSHDSTLVATGDMSGLLKVWQVDTKEEVWSFEAGDLEWM
  EWHPRAPVLLAGTADGNTWMWKVPNGDCKTFQGPNCPATCGRVLPDGKRAVVGYEDGTIR
  IWDLKQGSPIHVLKGTEGHQGPLTCVAANQDGSLILTGSVDCQAKLVSATTGKVVGVFRP
  ETVASQPSLGEGEESESNSVESLGFCSVMPLAAVGYLDGTLAIYDLATQTLRHQCQHQSG
  IVQLLWEAGTAVVYTCSLDGIVRLWDARTGRLLTDYRGHTAEILDFALSKDASLVVTTSG
  DHKAKVFCVQRPDR
• Function: Plays a role in angiogenesis and cell migration. In smooth muscle cell migration, may act through the RhoA pathway.
• Tissue Specificity: Expressed in metastatic melanoma, liver, skin, kidney, heart, lung, lymph node, skeletal muscle and brain, and also in A2058 melanoma cells and activated T-cells (at protein level). Expressed in blood vessels. Strongly expressed in endothelial cells, cytotrophoblasts, and poorly differentiated. colon adenocarcinoma cells found in lymphatics.
• Reactome Pathway:
  Signaling by EGFR (R-HSA-177929)
  Signaling by VEGF (R-HSA-194138)
  Thromboxane signalling through TP receptor (R-HSA-428930)
  NOD1/2 Signaling Pathway (R-HSA-168638)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung cancer	DISCM4YA	Strong	Biomarker	[1]
Lung carcinoma	DISTR26C	Strong	Biomarker	[1]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[1]
Ductal breast carcinoma in situ	DISLCJY7	moderate	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[3]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[3]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Angio-associated migratory cell protein (AAMP).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Angio-associated migratory cell protein (AAMP).	[5]
Selenium	DM25CGV	Approved	Selenium increases the expression of Angio-associated migratory cell protein (AAMP).	[6]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Angio-associated migratory cell protein (AAMP).	[7]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Angio-associated migratory cell protein (AAMP).	[8]
Bicalutamide	DMZMSPF	Approved	Bicalutamide increases the expression of Angio-associated migratory cell protein (AAMP).	[9]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Angio-associated migratory cell protein (AAMP).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Angio-associated migratory cell protein (AAMP).	[10]

References

• [1] Angio-associated migratory cell protein interacts with epidermal growth factor receptor and enhances proliferation and drug resistance in human non-small cell lung cancer cells.Cell Signal. 2019 Sep;61:10-19. doi: 10.1016/j.cellsig.2019.05.004. Epub 2019 May 7.
• [2] Analysis of gene expression in ductal carcinoma in situ of the breast.Clin Cancer Res. 2002 Dec;8(12):3788-95.
• [3] The impact of angio-associated migratory cell protein (AAMP) on breast cancer cells in vitro and its clinical significance.Anticancer Res. 2013 Apr;33(4):1499-509.
• [4] 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.
• [5] 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.
• [6] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [7] Progestins regulate genes that can elicit both proliferative and antiproliferative effects in breast cancer cells. Oncol Rep. 2008 Jun;19(6):1627-34.
• [8] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [9] Differentially expressed genes in the prostate cancer cell line LNCaP after exposure to androgen and anti-androgen. Cancer Genet Cytogenet. 2006 Apr 15;166(2):130-8. doi: 10.1016/j.cancergencyto.2005.09.012.
• [10] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.