Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8W6Y1J)

• DOT Name: Serine/threonine/tyrosine-interacting protein (STYX)
• Synonyms: Inactive tyrosine-protein phosphatase STYX; Phosphoserine/threonine/tyrosine interaction protein
• Gene Name: STYX
• Related Disease:
  Autoimmune disease
  Breast cancer
  Breast carcinoma
  Colorectal carcinoma
  Neoplasm
• UniProt ID: STYX_HUMAN
• PDB ID: 2R0B
• Pfam ID: PF00782
• Sequence:
  MEDVKLEFPSLPQCKEDAEEWTYPMRREMQEILPGLFLGPYSSAMKSKLPVLQKHGITHI
  ICIRQNIEANFIKPNFQQLFRYLVLDIADNPVENIIRFFPMTKEFIDGSLQMGGKVLVHG
  NAGISRSAAFVIAYIMETFGMKYRDAFAYVQERRFCINPNAGFVHQLQEYEAIYLAKLTI
  QMMSPLQIERSLSVHSGTTGSLKRTHEEEDDFGTMQVATAQNG
• Function: Catalytically inactive phosphatase. Acts as a nuclear anchor for MAPK1/MAPK3 (ERK1/ERK2). Modulates cell-fate decisions and cell migration by spatiotemporal regulation of MAPK1/MAPK3 (ERK1/ERK2). By binding to the F-box of FBXW7, prevents the assembly of FBXW7 into the SCF E3 ubiquitin-protein ligase complex, and thereby inhibits degradation of its substrates. Plays a role in spermatogenesis.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autoimmune disease	DISORMTM	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[2]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[2]
Colorectal carcinoma	DIS5PYL0	moderate	Biomarker	[3]
Neoplasm	DISZKGEW	Limited	Altered Expression	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Serine/threonine/tyrosine-interacting protein (STYX).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Serine/threonine/tyrosine-interacting protein (STYX).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Serine/threonine/tyrosine-interacting protein (STYX).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Serine/threonine/tyrosine-interacting protein (STYX).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Serine/threonine/tyrosine-interacting protein (STYX).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Serine/threonine/tyrosine-interacting protein (STYX).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Serine/threonine/tyrosine-interacting protein (STYX).	[10]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Serine/threonine/tyrosine-interacting protein (STYX).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Serine/threonine/tyrosine-interacting protein (STYX).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Serine/threonine/tyrosine-interacting protein (STYX).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Serine/threonine/tyrosine-interacting protein (STYX).	[13]

References

• [1] Self-reported lower respiratory tract infections and development of islet autoimmunity in children with the type 1 diabetes high-risk HLA genotype: the MIDIA study.Diabetes Metab Res Rev. 2011 Nov;27(8):834-7. doi: 10.1002/dmrr.1258.
• [2] The pseudophosphatase STYX targets the F-box of FBXW7 and inhibits SCFFBXW7 function.EMBO J. 2017 Feb 1;36(3):260-273. doi: 10.15252/embj.201694795. Epub 2016 Dec 22.
• [3] Pseudophosphatase STYX promotes tumor growth and metastasis by inhibiting FBXW7 function in colorectal cancer.Cancer Lett. 2019 Jul 10;454:53-65. doi: 10.1016/j.canlet.2019.04.014. Epub 2019 Apr 11.
• [4] 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.
• [5] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Analysis of the in vitro synergistic effect of 5-fluorouracil and cisplatin on cervical carcinoma cells. Int J Gynecol Cancer. 2006 May-Jun;16(3):1321-9.
• [8] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [9] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [10] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [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] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.