Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5CPOJE)

• DOT Name: MARVEL domain-containing protein 1 (MARVELD1)
• Gene Name: MARVELD1
• Related Disease:
  Epithelial neoplasm
  Breast cancer
  Breast carcinoma
  Carcinoma of liver and intrahepatic biliary tract
  Liver cancer
  Neoplasm
  Non-small-cell lung cancer
  Hepatocellular carcinoma
  Lung cancer
  Lung carcinoma
• UniProt ID: MALD1_HUMAN
• Pfam ID: PF01284
• Sequence:
  MLPPPPRQPPPQARAARGAVRLQRPFLRSPLGVLRLLQLLAGAAFWITIATSKYQGPVHF
  ALFVSVLFWLLTLGLYFLTLLGKHELVPVLGSRWLMVNVAHDVLAAALYGAATGIMSDQM
  QRHSYCNLKDYPLPCAYHAFLAAAVCGGVCHGLYLLSALYGCGRRCQGKQEVA
• Function: Microtubule-associated protein that exhibits cell cycle-dependent localization and can inhibit cell proliferation and migration.
• Tissue Specificity: Widely expressed in normal tissues. Down-regulated in multiple primary tumors.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Epithelial neoplasm	DIS0T594	Definitive	Altered Expression	[1]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[2]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[2]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Altered Expression	[3]
Liver cancer	DISDE4BI	Strong	Altered Expression	[3]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[4]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[1]
Lung cancer	DISCM4YA	moderate	Biomarker	[5]
Lung carcinoma	DISTR26C	moderate	Biomarker	[5]

This DOT Affected the Drug Response of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	MARVEL domain-containing protein 1 (MARVELD1) decreases the response to substance of Arsenic trioxide.	[3]
Paclitaxel	DMLB81S	Approved	MARVEL domain-containing protein 1 (MARVELD1) increases the response to substance of Paclitaxel.	[13]
Gefitinib	DM15F0X	Approved	MARVEL domain-containing protein 1 (MARVELD1) decreases the response to substance of Gefitinib.	[13]
Epirubicin	DMPDW6T	Approved	MARVEL domain-containing protein 1 (MARVELD1) increases the response to substance of Epirubicin.	[3]

2 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 MARVEL domain-containing protein 1 (MARVELD1).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of MARVEL domain-containing protein 1 (MARVELD1).	[11]

7 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 MARVEL domain-containing protein 1 (MARVELD1).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of MARVEL domain-containing protein 1 (MARVELD1).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of MARVEL domain-containing protein 1 (MARVELD1).	[9]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of MARVEL domain-containing protein 1 (MARVELD1).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of MARVEL domain-containing protein 1 (MARVELD1).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of MARVEL domain-containing protein 1 (MARVELD1).	[12]
BETULIN	DMGQRON	Investigative	BETULIN decreases the expression of MARVEL domain-containing protein 1 (MARVELD1).	[13]

References

• [1] MARVELD1 interacting with catalase regulates reactive oxygen species metabolism and mediates the sensitivity to chemotherapeutic drugs in epithelial tumors of the reproductive system.Mol Carcinog. 2019 Aug;58(8):1410-1426. doi: 10.1002/mc.23024. Epub 2019 May 7.
• [2] Identification and characterization of MARVELD1, a novel nuclear protein that is down-regulated in multiple cancers and silenced by DNA methylation.Cancer Lett. 2009 Sep 8;282(1):77-86. doi: 10.1016/j.canlet.2009.03.008. Epub 2009 Apr 11.
• [3] MARVELD1 attenuates arsenic trioxide-induced apoptosis in liver cancer cells by inhibiting reactive oxygen species production. Ann Transl Med. 2019 May;7(9):200. doi: 10.21037/atm.2019.04.38.
• [4] MARVELD1 modulates cell surface morphology and suppresses epithelial-mesenchymal transition in non-small cell lung cancer.Mol Carcinog. 2016 Nov;55(11):1714-1727. doi: 10.1002/mc.22421. Epub 2015 Oct 28.
• [5] Biological and clinical significance of epigenetic silencing of MARVELD1 gene in lung cancer.Sci Rep. 2014 Dec 18;4:7545. doi: 10.1038/srep07545.
• [6] 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.
• [7] 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.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [10] 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.
• [11] 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.
• [12] Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.
• [13] Inhibition of SREBP increases gefitinib sensitivity in non-small cell lung cancer cells. Oncotarget. 2016 Aug 9;7(32):52392-52403.
• [14] MARVELD1 attenuates arsenic trioxide-induced apoptosis in liver cancer cells by inhibiting reactive oxygen species production. Ann Transl Med. 2019 May;7(9):200. doi: 10.21037/atm.2019.04.38.
• [15] Inhibition of SREBP increases gefitinib sensitivity in non-small cell lung cancer cells. Oncotarget. 2016 Aug 9;7(32):52392-52403.