Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWBCJ8O)

• DOT Name: Protein shisa-6 (SHISA6)
• Gene Name: SHISA6
• Related Disease:
  Myopia
  Acute myelogenous leukaemia
  Refractive error
• UniProt ID: SHSA6_HUMAN
• Pfam ID: PF13908
• Sequence:
  MALRRLLLLLLLSLESLDLLPSVHGARGRAANRTLSAGGAAVGGRRAGGALARGGRELNG
  TARAPGIPEAGSRRGQPAAAVAAAASAAVTYETCWGYYDVSGQYDKEFECNNSESGYLYC
  CGTCYYRFCCKKRHEKLDQRQCTNYQSPVWVQTPSTKVVSPGPENKYDPEKDKTNFTVYI
  TCGVIAFVIVAGVFAKVSYDKAHRPPREMNIHRALADILRQQGPIPIAHCERETISAIDT
  SPKENTPVRSSSKNHYTPVRTAKQTPEKPRMNNILTSATEPYDLSFSRSFQNLAHLPPSY
  ESAVKTNPSKYSSLKRLTDKEADEYYMRRRHLPDLAARGTLPLNVIQMSQQKPLPRERPR
  RPIRAMSQDRVLSPDRGLPDEFSMPYDRILSDEQLLSTERLHSQDPLLSPERTAFPEQSL
  SRAISHTDVFVSTPVLDRYRMSKMHSHPSASNNSYATLGQSQTAAKRHAFASRRHNTVEQ
  LHYIPGHHTCYTASKTEVTV
• Function: Involved in maintenance of high-frequency synaptic transmission at hippocampal CA3-CA1 synapses. Regulates AMPA-type glutamate receptor (AMPAR) immobilization at postsynaptic density keeping the channels in an activated state in the presence of glutamate and preventing synaptic depression. May play a role in self-renewal and differentiation of spermatogonial stem cells by inhibiting canonical Wnt signaling pathway.
• Tissue Specificity: Expressed in the developing ventral mesencephalon.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Myopia	DISK5S60	Strong	Genetic Variation	[1]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[2]
Refractive error	DISWNEQ1	moderate	Genetic Variation	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Protein shisa-6 (SHISA6).	[4]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Protein shisa-6 (SHISA6).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Protein shisa-6 (SHISA6).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Protein shisa-6 (SHISA6).	[8]

3 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 Protein shisa-6 (SHISA6).	[5]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Protein shisa-6 (SHISA6).	[6]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Protein shisa-6 (SHISA6).	[7]

References

• [1] Detection and interpretation of shared genetic influences on 42 human traits.Nat Genet. 2016 Jul;48(7):709-17. doi: 10.1038/ng.3570. Epub 2016 May 16.
• [2] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [3] Education influences the association between genetic variants and refractive error: a meta-analysis of five Singapore studies.Hum Mol Genet. 2014 Jan 15;23(2):546-54. doi: 10.1093/hmg/ddt431. Epub 2013 Sep 6.
• [4] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [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] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [7] 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.
• [8] 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.
• [9] 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.