Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBZYSR3)

• DOT Name: Protein FAM72A (FAM72A)
• Synonyms: Latent membrane protein 1-induced protein; LMP1-induced protein; LMPIP
• Gene Name: FAM72A
• Related Disease:
  Adult lymphoma
  Advanced cancer
  Alzheimer disease
  Dementia
  Epstein barr virus infection
  Gastric cancer
  Hepatitis C virus infection
  HIV infectious disease
  Lymphoma
  Neoplasm
  Non-hodgkin lymphoma
  Pediatric lymphoma
  Pulmonary fibrosis
  Retinopathy
  Factor IX deficiency
  Nasopharyngeal carcinoma
• UniProt ID: FA72A_HUMAN
• Pfam ID: PF14976
• Sequence:
  MSTNICSFKDRCVSILCCKFCKQVLSSRGMKAVLLADTEIDLFSTDIPPTNAVDFTGRCY
  FTKICKCKLKDIACLKCGNIVGYHVIVPCSSCLLSCNNGHFWMFHSQAVYDINRLDSTGV
  NVLLWGNLPEIEESTDEDVLNISAEECIR
• Function: May play a role in the regulation of cellular reactive oxygen species metabolism. May participate in cell growth regulation.
• Tissue Specificity: May be up-regulated in malignant colon cancers, compared to normal colon and colon adenomas. Expression is also elevated in other common cancer types, including breast, lung, uterus, and ovary.

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult lymphoma	DISK8IZR	Strong	Genetic Variation	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Dementia	DISXL1WY	Strong	Biomarker	[4]
Epstein barr virus infection	DISOO0WT	Strong	Biomarker	[5]
Gastric cancer	DISXGOUK	Strong	Genetic Variation	[6]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[7]
HIV infectious disease	DISO97HC	Strong	Biomarker	[8]
Lymphoma	DISN6V4S	Strong	Genetic Variation	[1]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[9]
Non-hodgkin lymphoma	DISS2Y8A	Strong	Biomarker	[10]
Pediatric lymphoma	DIS51BK2	Strong	Genetic Variation	[1]
Pulmonary fibrosis	DISQKVLA	Strong	Biomarker	[11]
Retinopathy	DISB4B0F	Strong	Biomarker	[12]
Factor IX deficiency	DISHN9SC	moderate	Biomarker	[13]
Nasopharyngeal carcinoma	DISAOTQ0	moderate	Altered Expression	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein FAM72A (FAM72A).	[15]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Protein FAM72A (FAM72A).	[16]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Protein FAM72A (FAM72A).	[17]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein FAM72A (FAM72A).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein FAM72A (FAM72A).	[19]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Protein FAM72A (FAM72A).	[20]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Protein FAM72A (FAM72A).	[21]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Protein FAM72A (FAM72A).	[22]

References

• [1] Lymphomagenic properties of a HIV p17 variant derived from a splenic marginal zone lymphoma occurred in a HIV-infected patient.Hematol Oncol. 2019 Apr;37(2):176-184. doi: 10.1002/hon.2562. Epub 2018 Nov 6.
• [2] Mechanistic insights into avian reovirus p17-modulated suppression of cell cycle CDK-cyclin complexes and enhancement of p53 and cyclin H interaction.J Biol Chem. 2018 Aug 10;293(32):12542-12562. doi: 10.1074/jbc.RA118.002341. Epub 2018 Jun 15.
• [3] Identification and characterisation of the novel amyloid-beta peptide-induced protein p17.FEBS Lett. 2009 Oct 6;583(19):3247-53. doi: 10.1016/j.febslet.2009.09.018. Epub 2009 Sep 13.
• [4] p17 from HIV induces brain endothelial cell angiogenesis through EGFR-1-mediated cell signalling activation.Lab Invest. 2019 Feb;99(2):180-190. doi: 10.1038/s41374-018-0147-z. Epub 2018 Nov 2.
• [5] A natural HIV p17 protein variant up-regulates the LMP-1 EBV oncoprotein and promotes the growth of EBV-infected B-lymphocytes: implications for EBV-driven lymphomagenesis in the HIV setting.Int J Cancer. 2015 Sep 15;137(6):1374-85. doi: 10.1002/ijc.29494. Epub 2015 Mar 9.
• [6] Inactivating mutations of the caspase-10 gene in gastric cancer.Oncogene. 2002 Apr 25;21(18):2919-25. doi: 10.1038/sj.onc.1205394.
• [7] Molecular characterization of human immunodeficiency virus type 1 and hepatitis C virus in paid blood donors and injection drug users in china.J Virol. 2004 Dec;78(24):13591-9. doi: 10.1128/JVI.78.24.13591-13599.2004.
• [8] A CXCR1 haplotype hampers HIV-1 matrix protein p17 biological activity.AIDS. 2014 Oct 23;28(16):2355-64. doi: 10.1097/QAD.0000000000000423.
• [9] A lymphomagenic role for HIV beyond immune suppression?.Blood. 2016 Mar 17;127(11):1403-9. doi: 10.1182/blood-2015-11-681411. Epub 2016 Jan 14.
• [10] In-depth analysis of compartmentalization of HIV-1 matrix protein p17 in PBMC and plasma.New Microbiol. 2017 Jan;40(1):58-61. Epub 2017 Jan 9.
• [11] Therapeutic effect of a peptide inhibitor of TGF- on pulmonary fibrosis.Cytokine. 2011 Mar;53(3):327-33. doi: 10.1016/j.cyto.2010.11.019. Epub 2010 Dec 23.
• [12] elemene inhibits oxygeninduced retinal neovascularization via promoting miR?7a and reducing VEGF expression.Mol Med Rep. 2019 Mar;19(3):2307-2316. doi: 10.3892/mmr.2019.9863. Epub 2019 Jan 15.
• [13] The genetic diversification of the HIV type 1 gag p17 gene in patients infected from a common source.AIDS Res Hum Retroviruses. 1995 Oct;11(10):1197-201. doi: 10.1089/aid.1995.11.1197.
• [14] Functional interaction of Ugene and EBV infection mediates tumorigenic effects.Oncogene. 2011 Jun 30;30(26):2921-32. doi: 10.1038/onc.2011.16. Epub 2011 Feb 14.
• [15] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [16] 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.
• [17] Lucanthone is a novel inhibitor of autophagy that induces cathepsin D-mediated apoptosis. J Biol Chem. 2011 Feb 25;286(8):6602-13.
• [18] 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.
• [19] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [20] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [21] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [22] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.