Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4IRL0U)

• DOT Name: Multimerin-2 (MMRN2)
• Synonyms: EMILIN-3; Elastin microfibril interface located protein 3; Elastin microfibril interfacer 3; EndoGlyx-1 p125/p140 subunit
• Gene Name: MMRN2
• Related Disease:
  Metastatic malignant neoplasm
  Pancreatic cancer
  Skin neoplasm
• UniProt ID: MMRN2_HUMAN
• Pfam ID: PF00386 ; PF07546
• Sequence:
  MILSLLFSLGGPLGWGLLGAWAQASSTSLSDLQSSRTPGVWKAEAEDTGKDPVGRNWCPY
  PMSKLVTLLALCKTEKFLIHSQQPCPQGAPDCQKVKVMYRMAHKPVYQVKQKVLTSLAWR
  CCPGYTGPNCEHHDSMAIPEPADPGDSHQEPQDGPVSFKPGHLAAVINEVEVQQEQQEHL
  LGDLQNDVHRVADSLPGLWKALPGNLTAAVMEANQTGHEFPDRSLEQVLLPHVDTFLQVH
  FSPIWRSFNQSLHSLTQAIRNLSLDVEANRQAISRVQDSAVARADFQELGAKFEAKVQEN
  TQRVGQLRQDVEDRLHAQHFTLHRSISELQADVDTKLKRLHKAQEAPGTNGSLVLATPGA
  GARPEPDSLQARLGQLQRNLSELHMTTARREEELQYTLEDMRATLTRHVDEIKELYSESD
  ETFDQISKVERQVEELQVNHTALRELRVILMEKSLIMEENKEEVERQLLELNLTLQHLQG
  GHADLIKYVKDCNCQKLYLDLDVIREGQRDATRALEETQVSLDERRQLDGSSLQALQNAV
  DAVSLAVDAHKAEGERARAATSRLRSQVQALDDEVGALKAAAAEARHEVRQLHSAFAALL
  EDALRHEAVLAALFGEEVLEEMSEQTPGPLPLSYEQIRVALQDAASGLQEQALGWDELAA
  RVTALEQASEPPRPAEHLEPSHDAGREEAATTALAGLARELQSLSNDVKNVGRCCEAEAG
  AGAASLNASLHGLHNALFATQRSLEQHQRLFHSLFGNFQGLMEANVSLDLGKLQTMLSRK
  GKKQQKDLEAPRKRDKKEAEPLVDIRVTGPVPGALGAALWEAGSPVAFYASFSEGTAALQ
  TVKFNTTYINIGSSYFPEHGYFRAPERGVYLFAVSVEFGPGPGTGQLVFGGHHRTPVCTT
  GQGSGSTATVFAMAELQKGERVWFELTQGSITKRSLSGTAFGGFLMFKT
• Function: Inhibits endothelial cells motility and acts as a negative regulator of angiogenesis; it down-regulates KDR activation by binding VEGFA.
• Tissue Specificity: Endothelium.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[1]
Pancreatic cancer	DISJC981	Strong	Biomarker	[2]
Skin neoplasm	DIS16DDV	Strong	Altered Expression	[1]

3 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 Multimerin-2 (MMRN2).	[3]
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Multimerin-2 (MMRN2).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Multimerin-2 (MMRN2).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Multimerin-2 (MMRN2).	[4]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Multimerin-2 (MMRN2).	[6]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Multimerin-2 (MMRN2).	[7]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Multimerin-2 (MMRN2).	[9]

References

• [1] Expression of stromal cell markers in distinct compartments of human skin cancers.J Cutan Pathol. 2006 Feb;33(2):145-55. doi: 10.1111/j.0303-6987.2006.00446.x.
• [2] Multimerin-2 is a ligand for group 14 family C-type lectins CLEC14A, CD93 and CD248 spanning the endothelial pericyte interface.Oncogene. 2017 Nov 2;36(44):6097-6108. doi: 10.1038/onc.2017.214. Epub 2017 Jul 3.
• [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] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [5] Epigenetic changes in individuals with arsenicosis. Chem Res Toxicol. 2011 Feb 18;24(2):165-7. doi: 10.1021/tx1004419. Epub 2011 Feb 4.
• [6] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [7] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [8] 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.
• [9] 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.