Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTN4NR7)

• DOT Name: Motile sperm domain-containing protein 2 (MOSPD2)
• Gene Name: MOSPD2
• Related Disease:
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Neoplasm
  Obsolete male infertility with azoospermia or oligozoospermia due to single gene mutation
• UniProt ID: MSPD2_HUMAN
• PDB ID: 6TQS; 6TQT; 6TQU
• Pfam ID: PF00650 ; PF00635
• Sequence:
  MAENHAQNKAKLISETRRRFEAEYVTDKSDKYDARDVERLQQDDNWVESYLSWRHNIVDE
  TLKMLDESFQWRKEISVNDLNESSIPRWLLEIGVIYLHGYDKEGNKLFWIRVKYHVKDQK
  TILDKKKLIAFWLERYAKRENGKPVTVMFDLSETGINSIDMDFVRFIINCFKVYYPKYLS
  KIVIFDMPWLMNAAFKIVKTWLGPEAVSLLKFTSKNEVQDYVSVEYLPPHMGGTDPFKYS
  YPPLVDDDFQTPLCENGPITSEDETSSKEDIESDGKETLETISNEEQTPLLKKINPTEST
  SKAEENEKVDSKVKAFKKPLSVFKGPLLHISPAEELYFGSTESGEKKTLIVLTNVTKNIV
  AFKVRTTAPEKYRVKPSNSSCDPGASVDIVVSPHGGLTVSAQDRFLIMAAEMEQSSGTGP
  AELTQFWKEVPRNKVMEHRLRCHTVESSKPNTLTLKDNAFNMSDKTSEDICLQLSRLLES
  NRKLEDQVQRCIWFQQLLLSLTMLLLAFVTSFFYLLYS
• Function: Endoplasmic reticulum-anchored protein that mediates the formation of contact sites between the endoplasmic (ER) and endosomes, mitochondria or Golgi through interaction with conventional- and phosphorylated-FFAT-containing organelle-bound proteins. In addition, forms endoplasmic reticulum (ER)-lipid droplets (LDs) contacts through a direct protein-membrane interaction and participates in LDs homeostasis. The attachment mechanism involves an amphipathic helix that has an affinity for lipid packing defects present at the surface of LDs. Promotes migration of primary monocytes and neutrophils, in response to various chemokines.
• Tissue Specificity: Highly expressed in CD14(+) monocytes, and at lower levels in neutrophils. Does not show significant expression in B-cells or T-cells.
• Reactome Pathway:
  RHOD GTPase cycle (R-HSA-9013405)
  Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Limited	Biomarker	[1]
Breast cancer	DIS7DPX1	Limited	Biomarker	[1]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[1]
Breast neoplasm	DISNGJLM	Limited	Posttranslational Modification	[1]
Neoplasm	DISZKGEW	Limited	Altered Expression	[1]
Obsolete male infertility with azoospermia or oligozoospermia due to single gene mutation	DIS56JR8	Limited	X-linked	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Motile sperm domain-containing protein 2 (MOSPD2).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Motile sperm domain-containing protein 2 (MOSPD2).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Motile sperm domain-containing protein 2 (MOSPD2).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Motile sperm domain-containing protein 2 (MOSPD2).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Motile sperm domain-containing protein 2 (MOSPD2).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Motile sperm domain-containing protein 2 (MOSPD2).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Motile sperm domain-containing protein 2 (MOSPD2).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Motile sperm domain-containing protein 2 (MOSPD2).	[8]
Clorgyline	DMCEUJD	Approved	Clorgyline increases the expression of Motile sperm domain-containing protein 2 (MOSPD2).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Motile sperm domain-containing protein 2 (MOSPD2).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Motile sperm domain-containing protein 2 (MOSPD2).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Motile sperm domain-containing protein 2 (MOSPD2).	[13]

References

• [1] Newly characterized motile sperm domain-containing protein 2 promotes human breast cancer metastasis.Int J Cancer. 2019 Jan 1;144(1):125-135. doi: 10.1002/ijc.31665. Epub 2018 Oct 29.
• [2] A genomics approach to male infertility. Genet Med. 2020 Dec;22(12):1967-1975. doi: 10.1038/s41436-020-0916-0. Epub 2020 Jul 28.
• [3] 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.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] 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.
• [6] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [7] 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.
• [8] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [9] Anti-oncogenic and pro-differentiation effects of clorgyline, a monoamine oxidase A inhibitor, on high grade prostate cancer cells. BMC Med Genomics. 2009 Aug 20;2:55. doi: 10.1186/1755-8794-2-55.
• [10] 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.
• [11] 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.
• [12] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.