Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPVI22J)

• DOT Name: SLIT and NTRK-like protein 2 (SLITRK2)
• Gene Name: SLITRK2
• Related Disease:
  Bipolar disorder
  Neoplasm
• UniProt ID: SLIK2_HUMAN
• Pfam ID: PF13855
• Sequence:
  MLSGVWFLSVLTVAGILQTESRKTAKDICKIRCLCEEKENVLNINCENKGFTTVSLLQPP
  QYRIYQLFLNGNLLTRLYPNEFVNYSNAVTLHLGNNGLQEIRTGAFSGLKTLKRLHLNNN
  KLEILREDTFLGLESLEYLQADYNYISAIEAGAFSKLNKLKVLILNDNLLLSLPSNVFRF
  VLLTHLDLRGNRLKVMPFAGVLEHIGGIMEIQLEENPWNCTCDLLPLKAWLDTITVFVGE
  IVCETPFRLHGKDVTQLTRQDLCPRKSASDSSQRGSHADTHVQRLSPTMNPALNPTRAPK
  ASRPPKMRNRPTPRVTVSKDRQSFGPIMVYQTKSPVPLTCPSSCVCTSQSSDNGLNVNCQ
  ERKFTNISDLQPKPTSPKKLYLTGNYLQTVYKNDLLEYSSLDLLHLGNNRIAVIQEGAFT
  NLTSLRRLYLNGNYLEVLYPSMFDGLQSLQYLYLEYNVIKEIKPLTFDALINLQLLFLNN
  NLLRSLPDNIFGGTALTRLNLRNNHFSHLPVKGVLDQLPAFIQIDLQENPWDCTCDIMGL
  KDWTEHANSPVIINEVTCESPAKHAGEILKFLGREAICPDSPNLSDGTVLSMNHNTDTPR
  SLSVSPSSYPELHTEVPLSVLILGLLVVFILSVCFGAGLFVFVLKRRKGVPSVPRNTNNL
  DVSSFQLQYGSYNTETHDKTDGHVYNYIPPPVGQMCQNPIYMQKEGDPVAYYRNLQEFSY
  SNLEEKKEEPATPAYTISATELLEKQATPREPELLYQNIAERVKELPSAGLVHYNFCTLP
  KRQFAPSYESRRQNQDRINKTVLYGTPRKCFVGQSKPNHPLLQAKPQSEPDYLEVLEKQT
  AISQL
• Function: It is involved in synaptogenesis and promotes excitatory synapse differentiation. Suppresses neurite outgrowth. Involved in the negative regulation of NTRK2.
• Tissue Specificity: Expressed predominantly in the cerebral cortex of the brain but also at low levels in the spinal cord and medulla. Also expressed in some astrocytic brain tumors such as astrocytomas, oligodendrogliomas, glioblastomas, gangliogliomas and primitive neuroectodermal tumors.
• KEGG Pathway: Cell adhesion molecules (hsa04514)
• Reactome Pathway: Receptor-type tyrosine-protein phosphatases (R-HSA-388844)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bipolar disorder	DISAM7J2	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of SLIT and NTRK-like protein 2 (SLITRK2).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of SLIT and NTRK-like protein 2 (SLITRK2).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of SLIT and NTRK-like protein 2 (SLITRK2).	[4]
Folic acid	DMEMBJC	Approved	Folic acid increases the expression of SLIT and NTRK-like protein 2 (SLITRK2).	[5]
Gemcitabine	DMSE3I7	Approved	Gemcitabine increases the expression of SLIT and NTRK-like protein 2 (SLITRK2).	[6]

References

• [1] Genome-wide association study of bipolar disorder in European American and African American individuals.Mol Psychiatry. 2009 Aug;14(8):755-63. doi: 10.1038/mp.2009.43. Epub 2009 Jun 2.
• [2] Mutational landscape of penile squamous cell carcinoma in a Chinese population.Int J Cancer. 2019 Sep 1;145(5):1280-1289. doi: 10.1002/ijc.32373. Epub 2019 May 8.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] 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.
• [6] Gene expression profiling of breast cancer cells in response to gemcitabine: NF-kappaB pathway activation as a potential mechanism of resistance. Breast Cancer Res Treat. 2007 Apr;102(2):157-72.
• [7] 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.