Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY2ZW1H)

• DOT Name: Pre-mRNA-splicing factor SYF2 (SYF2)
• Synonyms: CCNDBP1-interactor; p29
• Gene Name: SYF2
• Related Disease:
  Gastric cancer
  Melanoma
  Stomach cancer
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Encephalitis
  Epithelial ovarian cancer
  Fanconi anemia complementation group A
  Fanconi's anemia
  Glioblastoma multiforme
  Glioma
  Hepatocellular carcinoma
  Neoplasm
  Non-small-cell lung cancer
  Cutaneous melanoma
  Cystitis
• UniProt ID: SYF2_HUMAN
• PDB ID: 5MQF; 5XJC; 5YZG; 6ICZ; 6ID0; 6ID1; 6QDV; 7A5P; 7W59; 7W5A; 7W5B; 8C6J
• Pfam ID: PF08231
• Sequence:
  MAAIAASEVLVDSAEEGSLAAAAELAAQKREQRLRKFRELHLMRNEARKLNHQEVVEEDK
  RLKLPANWEAKKARLEWELKEEEKKKECAARGEDYEKVKLLEISAEDAERWERKKKRKNP
  DLGFSDYAAAQLRQYHRLTKQIKPDMETYERLREKHGEEFFPTSNSLLHGTHVPSTEEID
  RMVIDLEKQIEKRDKYSRRRPYNDDADIDYINERNAKFNKKAERFYGKYTAEIKQNLERG
  TAV
• Function: Involved in pre-mRNA splicing as component of the spliceosome.
• Tissue Specificity: Abundantly expressed in the heart, skeletal muscle and kidney. Expressed at lower level other tissues.
• KEGG Pathway: Spliceosome (hsa03040)
• Reactome Pathway: mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gastric cancer	DISXGOUK	Definitive	Biomarker	[1]
Melanoma	DIS1RRCY	Definitive	Genetic Variation	[2]
Stomach cancer	DISKIJSX	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Encephalitis	DISLD1RL	Strong	Biomarker	[5]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[6]
Fanconi anemia complementation group A	DIS8PZLI	Strong	Biomarker	[7]
Fanconi's anemia	DISGW6Q8	Strong	Biomarker	[7]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[3]
Glioma	DIS5RPEH	Strong	Biomarker	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[8]
Neoplasm	DISZKGEW	Strong	Altered Expression	[4]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[9]
Cutaneous melanoma	DIS3MMH9	Limited	Genetic Variation	[2]
Cystitis	DIS2D4B9	Limited	Biomarker	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Pre-mRNA-splicing factor SYF2 (SYF2).	[11]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Pre-mRNA-splicing factor SYF2 (SYF2).	[12]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Pre-mRNA-splicing factor SYF2 (SYF2).	[13]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Pre-mRNA-splicing factor SYF2 (SYF2).	[14]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Pre-mRNA-splicing factor SYF2 (SYF2).	[15]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Pre-mRNA-splicing factor SYF2 (SYF2).	[16]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Pre-mRNA-splicing factor SYF2 (SYF2).	[18]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Pre-mRNA-splicing factor SYF2 (SYF2).	[19]

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 decreases the methylation of Pre-mRNA-splicing factor SYF2 (SYF2).	[17]

References

• [1] Influence of miR-376c-3p/SYF2 Axis on the Progression of Gastric Cancer.Technol Cancer Res Treat. 2019 Jan 1;18:1533033819874808. doi: 10.1177/1533033819874808.
• [2] RAC1(P29S) Induces a Mesenchymal Phenotypic Switch via Serum Response Factor to Promote Melanoma Development and Therapy Resistance.Cancer Cell. 2019 Jul 8;36(1):68-83.e9. doi: 10.1016/j.ccell.2019.05.015. Epub 2019 Jun 27.
• [3] Knocking down the expression of SYF2 inhibits the proliferation of glioma cells.Med Oncol. 2014 Aug;31(8):101. doi: 10.1007/s12032-014-0101-x. Epub 2014 Jul 2.
• [4] Overexpression of SYF2 promotes cell proliferation and correlates with poor prognosis in human breast cancer.Oncotarget. 2017 May 23;8(51):88453-88463. doi: 10.18632/oncotarget.18188. eCollection 2017 Oct 24.
• [5] Upregulation of SYF2 is associated with neuronal apoptosis caused by reactive astrogliosis to neuroinflammation.J Neurosci Res. 2014 Mar;92(3):318-28. doi: 10.1002/jnr.23312. Epub 2013 Dec 2.
• [6] SYF2 is upregulated in human epithelial ovarian cancer and promotes cell proliferation.Tumour Biol. 2015 Jun;36(6):4633-42. doi: 10.1007/s13277-015-3111-1. Epub 2015 Jan 28.
• [7] Disruption of murine mp29/Syf2/Ntc31 gene results in embryonic lethality with aberrant checkpoint response.PLoS One. 2012;7(3):e33538. doi: 10.1371/journal.pone.0033538. Epub 2012 Mar 20.
• [8] Overexpression of SYF2 correlates with enhanced cell growth and poor prognosis in human hepatocellular carcinoma.Mol Cell Biochem. 2015 Dec;410(1-2):1-9. doi: 10.1007/s11010-015-2533-9. Epub 2015 Aug 11.
• [9] LncRNA HOST2 enhances gefitinib-resistance in non-small cell lung cancer by down-regulating miRNA-621.Eur Rev Med Pharmacol Sci. 2019 Nov;23(22):9939-9946. doi: 10.26355/eurrev_201911_19560.
• [10] MicroRNA-mediated GABA A-1 receptor subunit down-regulation in adult spinal cord following neonatal cystitis-induced chronic visceral pain in rats.Pain. 2013 Jan;154(1):59-70. doi: 10.1016/j.pain.2012.09.002.
• [11] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [12] 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.
• [13] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [14] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [15] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [16] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [17] 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.
• [18] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [19] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.