Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCSXJ9C)

• DOT Name: Surfeit locus protein 4 (SURF4)
• Gene Name: SURF4
• Related Disease:
  Hepatitis C virus infection
  Neoplasm
  Prostate cancer
  Prostate neoplasm
  Venous thromboembolism
• UniProt ID: SURF4_HUMAN
• Pfam ID: PF02077
• Sequence:
  MGQNDLMGTAEDFADQFLRVTKQYLPHVARLCLISTFLEDGIRMWFQWSEQRDYIDTTWN
  CGYLLASSFVFLNLLGQLTGCVLVLSRNFVQYACFGLFGIIALQTIAYSILWDLKFLMRN
  LALGGGLLLLLAESRSEGKSMFAGVPTMRESSPKQYMQLGGRVLLVLMFMTLLHFDASFF
  SIVQNIVGTALMILVAIGFKTKLAALTLVVWLFAINVYFNAFWTIPVYKPMHDFLKYDFF
  QTMSVIGGLLLVVALGPGGVSMDEKKKEW
• Function: Endoplasmic reticulum cargo receptor that mediates the export of lipoproteins by recruiting cargos into COPII vesicles to facilitate their secretion. Acts as a cargo receptor for lipoproteins bearing both APOB and APOA1, thereby regulating lipoprotein delivery and the maintenance of lipid homeostasis. Synergizes with the GTPase SAR1B to mediate transport of circulating lipoproteins. Promotes the secretion of PCSK9. Also mediates the efficient secretion of erythropoietin (EPO). May also play a role in the maintenance of the architecture of the endoplasmic reticulum-Golgi intermediate compartment and of the Golgi.
• Reactome Pathway:
  COPI-dependent Golgi-to-ER retrograde traffic (R-HSA-6811434)
  Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Prostate cancer	DISF190Y	Strong	Biomarker	[3]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[3]
Venous thromboembolism	DISUR7CR	Strong	Genetic Variation	[4]

13 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 Surfeit locus protein 4 (SURF4).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Surfeit locus protein 4 (SURF4).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Surfeit locus protein 4 (SURF4).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Surfeit locus protein 4 (SURF4).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Surfeit locus protein 4 (SURF4).	[9]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Surfeit locus protein 4 (SURF4).	[10]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Surfeit locus protein 4 (SURF4).	[11]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Surfeit locus protein 4 (SURF4).	[12]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Surfeit locus protein 4 (SURF4).	[13]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Surfeit locus protein 4 (SURF4).	[8]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Surfeit locus protein 4 (SURF4).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Surfeit locus protein 4 (SURF4).	[15]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Surfeit locus protein 4 (SURF4).	[16]

References

• [1] Surfeit 4 Contributes to the Replication of Hepatitis C Virus Using Double-Membrane Vesicles.J Virol. 2020 Jan 6;94(2):e00858-19. doi: 10.1128/JVI.00858-19. Print 2020 Jan 6.
• [2] SURF4 has oncogenic potential in NIH3T3 cells.Biochem Biophys Res Commun. 2018 Jul 7;502(1):43-47. doi: 10.1016/j.bbrc.2018.05.116. Epub 2018 May 21.
• [3] Identification of genes potentially involved in the acquisition of androgen-independent and metastatic tumor growth in an autochthonous genetically engineered mouse prostate cancer model.Prostate. 2007 Jan 1;67(1):83-106. doi: 10.1002/pros.20505.
• [4] Genetics of venous thrombosis: insights from a new genome wide association study.PLoS One. 2011;6(9):e25581. doi: 10.1371/journal.pone.0025581. Epub 2011 Sep 27.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] 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.
• [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] Changes in gene expressions elicited by physiological concentrations of genistein on human endometrial cancer cells. Mol Carcinog. 2006 Oct;45(10):752-63.
• [9] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [10] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [11] 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.
• [12] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [13] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [14] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [15] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.
• [16] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.