Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVP97ZV)

• DOT Name: Semaphorin-4F (SEMA4F)
• Synonyms: Semaphorin-M; Sema M; Semaphorin-W; Sema W
• Gene Name: SEMA4F
• Related Disease:
  Advanced cancer
  Benign neoplasm
  Breast cancer
  Breast carcinoma
  Malignant mesothelioma
  Neoplasm
  Prostate cancer
  Prostate carcinoma
• UniProt ID: SEM4F_HUMAN
• Pfam ID: PF01437 ; PF01403 ; PF19428
• Sequence:
  MPASAARPRPGPGQPTASPFPLLLLAVLSGPVSGRVPRSVPRTSLPISEADSCLTRFAVP
  HTYNYSVLLVDPASHTLYVGARDTIFALSLPFSGERPRRIDWMVPEAHRQNCRKKGKKED
  ECHNFVQILAIANASHLLTCGTFAFDPKCGVIDVSRFQQVERLESGRGKCPFEPAQRSAA
  VMAGGVLYAATVKNYLGTEPIITRAVGRAEDWIRTDTLPSWLNAPAFVAAVALSPAEWGD
  EDGDDEIYFFFTETSRAFDSYERIKVPRVARVCAGDLGGRKTLQQRWTTFLKADLLCPGP
  EHGRASSVLQDVAVLRPELGAGTPIFYGIFSSQWEGATISAVCAFRPQDIRTVLNGPFRE
  LKHDCNRGLPVVDNDVPQPRPGECITNNMKLRHFGSSLSLPDRVLTFIRDHPLMDRPVFP
  ADGHPLLVTTDTAYLRVVAHRVTSLSGKEYDVLYLGTEDGHLHRAVRIGAQLSVLEDLAL
  FPEPQPVENMKLYHSWLLVGSRTEVTQVNTTNCGRLQSCSECILAQDPVCAWSFRLDECV
  AHAGEHRGLVQDIESADVSSLCPKEPGERPVVFEVPVATAAHVVLPCSPSSAWASCVWHQ
  PSGVTALTPRRDGLEVVVTPGAMGAYACECQEGGAAHVVAAYSLVWGSQRDAPSRAHTVG
  AGLAGFFLGILAASLTLILIGRRQQRRRQRELLARDKVGLDLGAPPSGTTSYSQDPPSPS
  PEDERLPLALAKRGSGFGGFSPPFLLDPCPSPAHIRLTGAPLATCDETSI
• Function: Probable cell surface receptor that regulates oligodendroglial precursor cell migration. Might also regulate differentiation of oligodendroglial precursor cells. Has growth cone collapse activity against retinal ganglion-cell axons.
• KEGG Pathway: Axon guidance (hsa04360)
• Reactome Pathway: RND3 GTPase cycle (R-HSA-9696264)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Benign neoplasm	DISDUXAD	Strong	Altered Expression	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Malignant mesothelioma	DISTHJGH	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Prostate cancer	DISF190Y	Strong	Biomarker	[1]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Semaphorin-4F (SEMA4F).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Semaphorin-4F (SEMA4F).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Semaphorin-4F (SEMA4F).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Semaphorin-4F (SEMA4F).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Semaphorin-4F (SEMA4F).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Semaphorin-4F (SEMA4F).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Semaphorin-4F (SEMA4F).	[11]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Semaphorin-4F (SEMA4F).	[12]
Methyl Mercury Ion	DM6YEW4	Investigative	Methyl Mercury Ion decreases the expression of Semaphorin-4F (SEMA4F).	[12]

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 affects the methylation of Semaphorin-4F (SEMA4F).	[9]

References

• [1] Semaphorin 4F as a critical regulator of neuroepithelial interactions and a biomarker of aggressive prostate cancer.Clin Cancer Res. 2013 Nov 15;19(22):6101-11. doi: 10.1158/1078-0432.CCR-12-3669. Epub 2013 Oct 4.
• [2] Semaphorin-plexin signalling genes associated with human breast tumourigenesis.Gene. 2011 Dec 10;489(2):63-9. doi: 10.1016/j.gene.2011.08.024. Epub 2011 Sep 2.
• [3] MicroRNA and mRNA features of malignant pleural mesothelioma and benign asbestos-related pleural effusion.Biomed Res Int. 2015;2015:635748. doi: 10.1155/2015/635748. Epub 2015 Feb 1.
• [4] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [5] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [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] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] 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.
• [10] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [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] Inhibition of CXCL12-mediated chemotaxis of Jurkat cells by direct immunotoxicants. Arch Toxicol. 2016 Jul;90(7):1685-94. doi: 10.1007/s00204-015-1585-7. Epub 2015 Aug 28.