Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4YPNTF)

• DOT Name: Serine/threonine-protein kinase 25 (STK25)
• Synonyms: EC 2.7.11.1; Ste20-like kinase; Sterile 20/oxidant stress-response kinase 1; SOK-1; Ste20/oxidant stress response kinase 1
• Gene Name: STK25
• Related Disease:
  Arteriosclerosis
  Atherosclerosis
  Breast cancer
  Breast carcinoma
  Cardiovascular disease
  Colorectal carcinoma
  Fatty liver disease
  Glioma
  Hypothyroidism
  Metabolic disorder
  Non-alcoholic fatty liver disease
  Pancreas disorder
  Pseudohypoparathyroidism type 1A
  High blood pressure
  Neoplasm
  Neuroblastoma
  Pseudohypoparathyroidism
  Pseudopseudohypoparathyroidism
• UniProt ID: STK25_HUMAN
• PDB ID: 2XIK; 3W8H; 4NZW; 7Z4V
• EC Number: 2.7.11.1
• Pfam ID: PF20929 ; PF00069
• Sequence:
  MAHLRGFANQHSRVDPEELFTKLDRIGKGSFGEVYKGIDNHTKEVVAIKIIDLEEAEDEI
  EDIQQEITVLSQCDSPYITRYFGSYLKSTKLWIIMEYLGGGSALDLLKPGPLEETYIATI
  LREILKGLDYLHSERKIHRDIKAANVLLSEQGDVKLADFGVAGQLTDTQIKRNTFVGTPF
  WMAPEVIKQSAYDFKADIWSLGITAIELAKGEPPNSDLHPMRVLFLIPKNSPPTLEGQHS
  KPFKEFVEACLNKDPRFRPTAKELLKHKFITRYTKKTSFLTELIDRYKRWKSEGHGEESS
  SEDSDIDGEAEDGEQGPIWTFPPTIRPSPHSKLHKGTALHSSQKPAEPVKRQPRSQCLST
  LVRPVFGELKEKHKQSGGSVGALEELENAFSLAEESCPGISDKLMVHLVERVQRFSHNRN
  HLTSTR
• Function: Oxidant stress-activated serine/threonine kinase that may play a role in the response to environmental stress. Targets to the Golgi apparatus where it appears to regulate protein transport events, cell adhesion, and polarity complexes important for cell migration.
• Tissue Specificity: Ubiquitously expressed. Highest levels are found in testis, large intestine, brain and stomach followed by heart and lung.

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[1]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[3]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[4]
Glioma	DIS5RPEH	Strong	Altered Expression	[5]
Hypothyroidism	DISR0H6D	Strong	Genetic Variation	[6]
Metabolic disorder	DIS71G5H	Strong	Biomarker	[7]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[1]
Pancreas disorder	DISDH7NI	Strong	Biomarker	[7]
Pseudohypoparathyroidism type 1A	DISSOR3M	Strong	Biomarker	[8]
High blood pressure	DISY2OHH	moderate	Biomarker	[9]
Neoplasm	DISZKGEW	moderate	Altered Expression	[3]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[10]
Pseudohypoparathyroidism	DIS183OJ	Limited	Biomarker	[11]
Pseudopseudohypoparathyroidism	DISRRO5I	Limited	Biomarker	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Serine/threonine-protein kinase 25 (STK25).	[12]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Serine/threonine-protein kinase 25 (STK25).	[13]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Serine/threonine-protein kinase 25 (STK25).	[15]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Serine/threonine-protein kinase 25 (STK25).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Serine/threonine-protein kinase 25 (STK25).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Serine/threonine-protein kinase 25 (STK25).	[17]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Serine/threonine-protein kinase 25 (STK25).	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Serine/threonine-protein kinase 25 (STK25).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Serine/threonine-protein kinase 25 (STK25).	[14]

References

• [1] STK25 Regulates Cardiovascular Disease Progression in a Mouse Model of Hypercholesterolemia.Arterioscler Thromb Vasc Biol. 2018 Aug;38(8):1723-1737. doi: 10.1161/ATVBAHA.118.311241.
• [2] The Ste20-like kinase SLK is required for ErbB2-driven breast cancer cell motility.Oncogene. 2009 Aug 6;28(31):2839-48. doi: 10.1038/onc.2009.146. Epub 2009 Jun 15.
• [3] STK25-induced inhibition of aerobic glycolysis via GOLPH3-mTOR pathway suppresses cell proliferation in colorectal cancer.J Exp Clin Cancer Res. 2018 Jul 11;37(1):144. doi: 10.1186/s13046-018-0808-1.
• [4] Overexpression of protein kinase STK25 in mice exacerbates ectopic lipid accumulation, mitochondrial dysfunction and insulin resistance in skeletal muscle.Diabetologia. 2017 Mar;60(3):553-567. doi: 10.1007/s00125-016-4171-5. Epub 2016 Dec 16.
• [5] Ste20-like kinase is upregulated in glioma and induces glioma invasion.Neoplasma. 2018;65(2):185-191. doi: 10.4149/neo_2018_170318N193.
• [6] Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
• [7] Protein kinase STK25 aggravates the severity of non-alcoholic fatty pancreas disease in mice.J Endocrinol. 2017 Jul;234(1):15-27. doi: 10.1530/JOE-17-0018. Epub 2017 Apr 25.
• [8] Molecular delineation of deletions on 2q37.3 in three cases with an Albright hereditary osteodystrophy-like phenotype.Clin Genet. 2004 Dec;66(6):537-44. doi: 10.1111/j.1399-0004.2004.00363.x.
• [9] MST3 (mammalian Ste20-like protein kinase 3), a novel gene involved in ion homeostasis and renal regulation of blood pressure in spontaneous hypertensive rats.Int Urol Nephrol. 2018 Dec;50(12):2299-2307. doi: 10.1007/s11255-018-2011-x. Epub 2018 Oct 16.
• [10] STK25 protein mediates TrkA and CCM2 protein-dependent death in pediatric tumor cells of neural origin.J Biol Chem. 2012 Aug 24;287(35):29285-9. doi: 10.1074/jbc.C112.345397. Epub 2012 Jul 10.
• [11] STK25 is a candidate gene for pseudopseudohypoparathyroidism.Genomics. 2001 Sep;77(1-2):2-4. doi: 10.1006/geno.2001.6605.
• [12] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [13] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [14] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [15] Gingival Stromal Cells as an In Vitro Model: Cannabidiol Modulates Genes Linked With Amyotrophic Lateral Sclerosis. J Cell Biochem. 2017 Apr;118(4):819-828. doi: 10.1002/jcb.25757. Epub 2016 Nov 28.
• [16] Effects of tobacco compounds on gene expression in fetal lung fibroblasts. Environ Toxicol. 2008 Aug;23(4):423-34.
• [17] 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.
• [18] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.