Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7TSF7I)

• DOT Name: Noelin-2 (OLFM2)
• Synonyms: Olfactomedin-2
• Gene Name: OLFM2
• Related Disease:
  Disorder of orbital region
  Open-angle glaucoma
  Hepatocellular carcinoma
  Smith-McCort dysplasia 1
  Coloboma
  Microphthalmia
• UniProt ID: NOE2_HUMAN
• Pfam ID: PF12308 ; PF02191
• Sequence:
  MWPLTVPPPLLLLLCSGLAGQTLFQNPEEGWQLYTSAQAPDGKCICTAVIPAQSTCSRDG
  RSRELRQLMEKVQNVSQSMEVLELRTYRDLQYVRGMETLMRSLDARLRAADGSLSAKSFQ
  ELKDRMTELLPLSSVLEQYKADTRTIVRLREEVRNLSGSLAAIQEEMGAYGYEDLQQRVM
  ALEARLHACAQKLGCGKLTGVSNPITVRAMGSRFGSWMTDTMAPSADSRVWYMDGYYKGR
  RVLEFRTLGDFIKGQNFIQHLLPQPWAGTGHVVYNGSLFYNKYQSNVVVKYHFRSRSVLV
  QRSLPGAGYNNTFPYSWGGFSDMDFMVDESGLWAVYTTNQNAGNIVVSRLDPHTLEVMRS
  WDTGYPKRSAGEAFMICGVLYVTNSHLAGAKVYFAYFTNTSSYEYTDVPFHNQYSHISML
  DYNPRERALYTWNNGHQVLYNVTLFHVISTSGDP
• Function: Involved in transforming growth factor beta (TGF-beta)-induced smooth muscle differentiation. TGF-beta induces expression and translocation of OLFM2 to the nucleus where it binds to SRF, causing its dissociation from the transcriptional repressor HEY2/HERP1 and facilitating binding of SRF to target genes. Plays a role in AMPAR complex organization. Is a regulator of vascular smooth-muscle cell (SMC) phenotypic switching, that acts by promoting RUNX2 and inhibiting MYOCD binding to SRF. SMC phenotypic switching is the process through which vascular SMCs undergo transition between a quiescent contractile phenotype and a proliferative synthetic phenotype in response to pathological stimuli. SMC phenotypic plasticity is essential for vascular development and remodeling.
• Tissue Specificity: Expressed in aortic smooth muscle (at protein level) . In the fetus, expressed in the brain and ocular tissues including lens vesicle and optic cup .

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Disorder of orbital region	DISH0ECJ	Definitive	Genetic Variation	[1]
Open-angle glaucoma	DISSZEE8	Definitive	Biomarker	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[2]
Smith-McCort dysplasia 1	DIS8072R	Strong	Altered Expression	[3]
Coloboma	DISP39N5	Limited	Biomarker	[1]
Microphthalmia	DISGEBES	Limited	Biomarker	[1]

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 Noelin-2 (OLFM2).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Noelin-2 (OLFM2).	[5]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Noelin-2 (OLFM2).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Noelin-2 (OLFM2).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Noelin-2 (OLFM2).	[7]

References

• [1] Identification and functional characterisation of genetic variants in OLFM2 in children with developmental eye disorders.Hum Genet. 2017 Jan;136(1):119-127. doi: 10.1007/s00439-016-1745-8. Epub 2016 Nov 14.
• [2] Mining featured biomarkers associated with vascular invasion in HCC by bioinformatics analysis with TCGA RNA sequencing data.Biomed Pharmacother. 2019 Oct;118:109274. doi: 10.1016/j.biopha.2019.109274. Epub 2019 Aug 28.
• [3] Olfactomedin 2 Regulates Smooth Muscle Phenotypic Modulation and Vascular Remodeling Through Mediating Runt-Related Transcription Factor 2 Binding to Serum Response Factor.Arterioscler Thromb Vasc Biol. 2017 Mar;37(3):446-454. doi: 10.1161/ATVBAHA.116.308606. Epub 2017 Jan 5.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] RNA sequence analysis of inducible pluripotent stem cell-derived cardiomyocytes reveals altered expression of DNA damage and cell cycle genes in response to doxorubicin. Toxicol Appl Pharmacol. 2018 Oct 1;356:44-53.
• [6] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [7] 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.
• [8] 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.