Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKM7N7P)

• DOT Name: Selenoprotein K (SELENOK)
• Synonyms: SelK
• Gene Name: SELENOK
• Related Disease:
  Melanoma
  Cystic fibrosis
  Hepatocellular carcinoma
  Lyme disease
  Choriocarcinoma
  Congenital contractural arachnodactyly
  Prostate cancer
  Prostate carcinoma
  Advanced cancer
  Neoplasm
• UniProt ID: SELK_HUMAN
• PDB ID: 6DO3
• Pfam ID: PF10961
• Sequence:
  MVYISNGQVLDSRSQSPWRLSLITDFFWGIAEFVVLFFKTLLQQDVKKRRSYGNSSDSRY
  DDGRGPPGNPPRRMGRINHLRGPSPPPMAGGUGR
• Function: Required for Ca(2+) flux in immune cells and plays a role in T-cell proliferation and in T-cell and neutrophil migration. Involved in endoplasmic reticulum-associated degradation (ERAD) of soluble glycosylated proteins. Required for palmitoylation and cell surface expression of CD36 and involved in macrophage uptake of low-density lipoprotein and in foam cell formation. Together with ZDHHC6, required for palmitoylation of ITPR1 in immune cells, leading to regulate ITPR1 stability and function. Plays a role in protection of cells from ER stress-induced apoptosis. Protects cells from oxidative stress when overexpressed in cardiomyocytes.
• Tissue Specificity: Highly expressed in heart.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Melanoma	DIS1RRCY	Definitive	Biomarker	[1]
Cystic fibrosis	DIS2OK1Q	Strong	Biomarker	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[3]
Lyme disease	DISO70G5	Strong	Biomarker	[4]
Choriocarcinoma	DISDBVNL	moderate	Biomarker	[5]
Congenital contractural arachnodactyly	DISOM1K7	moderate	Altered Expression	[5]
Prostate cancer	DISF190Y	moderate	Biomarker	[6]
Prostate carcinoma	DISMJPLE	moderate	Biomarker	[6]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[1]
Neoplasm	DISZKGEW	Limited	Biomarker	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Selenoprotein K (SELENOK).	[8]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Selenoprotein K (SELENOK).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Selenoprotein K (SELENOK).	[10]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Selenoprotein K (SELENOK).	[11]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Selenoprotein K (SELENOK).	[12]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Selenoprotein K (SELENOK).	[13]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Selenoprotein K (SELENOK).	[14]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Selenoprotein K (SELENOK).	[15]

References

• [1] Molecular Mechanisms by Which Selenoprotein K Regulates Immunity and Cancer.Biol Trace Elem Res. 2019 Nov;192(1):60-68. doi: 10.1007/s12011-019-01774-8. Epub 2019 Jun 11.
• [2] Superantigen types in Staphylococcus aureus isolated from patients with cystic fibrosis.Folia Microbiol (Praha). 2006;51(6):614-8. doi: 10.1007/BF02931628.
• [3] A study on the structural features of SELK, an over-expressed protein in hepatocellular carcinoma, by molecular dynamics simulations in a lipid-water system.Mol Biosyst. 2016 Oct 20;12(10):3209-22. doi: 10.1039/c6mb00469e. Epub 2016 Aug 15.
• [4] Is selenoprotein K required for Borrelia burgdorferi infection within the tick vector Ixodes scapularis?.Parasit Vectors. 2019 Jun 7;12(1):289. doi: 10.1186/s13071-019-3548-y.
• [5] Selenoprotein K Mediates the Proliferation, Migration, and Invasion of Human Choriocarcinoma Cells by Negatively Regulating Human Chorionic Gonadotropin Expression via ERK, p38 MAPK, and Akt Signaling Pathway.Biol Trace Elem Res. 2018 Jul;184(1):47-59. doi: 10.1007/s12011-017-1155-3. Epub 2017 Oct 6.
• [6] Polymorphisms in thioredoxin reductase and selenoprotein K genes and selenium status modulate risk of prostate cancer.PLoS One. 2012;7(11):e48709. doi: 10.1371/journal.pone.0048709. Epub 2012 Nov 1.
• [7] Selenoprotein K deficiency inhibits melanoma by reducing calcium flux required for tumor growth and metastasis.Oncotarget. 2018 Feb 3;9(17):13407-13422. doi: 10.18632/oncotarget.24388. eCollection 2018 Mar 2.
• [8] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [9] 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.
• [10] 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.
• [11] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [12] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [13] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [14] Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Sci Rep. 2020 Feb 26;10(1):3450. doi: 10.1038/s41598-020-59827-1.
• [15] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.