Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTSUSB8)

• DOT Name: SLIT and NTRK-like protein 5 (SLITRK5)
• Synonyms: Leucine-rich repeat-containing protein 11
• Gene Name: SLITRK5
• Related Disease:
  Alopecia
  Anxiety
  Anxiety disorder
  Obsessive compulsive disorder
  Nasopharyngeal carcinoma
• UniProt ID: SLIK5_HUMAN
• Pfam ID: PF13855
• Sequence:
  MHTCCPPVTLEQDLHRKMHSWMLQTLAFAVTSLVLSCAETIDYYGEICDNACPCEEKDGI
  LTVSCENRGIISLSEISPPRFPIYHLLLSGNLLNRLYPNEFVNYTGASILHLGSNVIQDI
  ETGAFHGLRGLRRLHLNNNKLELLRDDTFLGLENLEYLQVDYNYISVIEPNAFGKLHLLQ
  VLILNDNLLSSLPNNLFRFVPLTHLDLRGNRLKLLPYVGLLQHMDKVVELQLEENPWNCS
  CELISLKDWLDSISYSALVGDVVCETPFRLHGRDLDEVSKQELCPRRLISDYEMRPQTPL
  STTGYLHTTPASVNSVATSSSAVYKPPLKPPKGTRQPNKPRVRPTSRQPSKDLGYSNYGP
  SIAYQTKSPVPLECPTACSCNLQISDLGLNVNCQERKIESIAELQPKPYNPKKMYLTENY
  IAVVRRTDFLEATGLDLLHLGNNRISMIQDRAFGDLTNLRRLYLNGNRIERLSPELFYGL
  QSLQYLFLQYNLIREIQSGTFDPVPNLQLLFLNNNLLQAMPSGVFSGLTLLRLNLRSNHF
  TSLPVSGVLDQLKSLIQIDLHDNPWDCTCDIVGMKLWVEQLKVGVLVDEVICKAPKKFAE
  TDMRSIKSELLCPDYSDVVVSTPTPSSIQVPARTSAVTPAVRLNSTGAPASLGAGGGASS
  VPLSVLILSLLLVFIMSVFVAAGLFVLVMKRRKKNQSDHTSTNNSDVSSFNMQYSVYGGG
  GGTGGHPHAHVHHRGPALPKVKTPAGHVYEYIPHPLGHMCKNPIYRSREGNSVEDYKDLH
  ELKVTYSSNHHLQQQQQPPPPPQQPQQQPPPQLQLQPGEEERRESHHLRSPAYSVSTIEP
  REDLLSPVQDADRFYRGILEPDKHCSTTPAGNSLPEYPKFPCSPAAYTFSPNYDLRRPHQ
  YLHPGAGDSRLREPVLYSPPSAVFVEPNRNEYLELKAKLNVEPDYLEVLEKQTTFSQF
• Function: Suppresses neurite outgrowth.
• Tissue Specificity: Expressed predominantly in the cerebral cortex of the brain but also at low levels in the spinal cord and medulla.
• KEGG Pathway: Cell adhesion molecules (hsa04514)
• Reactome Pathway:
  RAC2 GTPase cycle (R-HSA-9013404)
  RAC3 GTPase cycle (R-HSA-9013423)
  Receptor-type tyrosine-protein phosphatases (R-HSA-388844)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alopecia	DIS37HU4	Strong	Biomarker	[1]
Anxiety	DISIJDBA	Strong	Biomarker	[1]
Anxiety disorder	DISBI2BT	Strong	Biomarker	[1]
Obsessive compulsive disorder	DIS1ZMM2	Strong	Biomarker	[2]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Altered Expression	[3]

3 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 SLIT and NTRK-like protein 5 (SLITRK5).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of SLIT and NTRK-like protein 5 (SLITRK5).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of SLIT and NTRK-like protein 5 (SLITRK5).	[11]

8 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 SLIT and NTRK-like protein 5 (SLITRK5).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of SLIT and NTRK-like protein 5 (SLITRK5).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of SLIT and NTRK-like protein 5 (SLITRK5).	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of SLIT and NTRK-like protein 5 (SLITRK5).	[9]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of SLIT and NTRK-like protein 5 (SLITRK5).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of SLIT and NTRK-like protein 5 (SLITRK5).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of SLIT and NTRK-like protein 5 (SLITRK5).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of SLIT and NTRK-like protein 5 (SLITRK5).	[14]

References

• [1] Molecular and cellular basis of obsessive-compulsive disorder-like behaviors: emerging view from mouse models.Curr Opin Neurol. 2011 Apr;24(2):114-8. doi: 10.1097/WCO.0b013e32834451fb.
• [2] Amelioration of obsessive-compulsive disorder in three mouse models treated with one epigenetic drug: unraveling the underlying mechanism.Sci Rep. 2019 Jun 19;9(1):8741. doi: 10.1038/s41598-019-45325-6.
• [3] Genome-wide analyses of long noncoding RNA expression profiles correlated with radioresistance in nasopharyngeal carcinoma via next-generation deep sequencing.BMC Cancer. 2016 Sep 6;16(1):719. doi: 10.1186/s12885-016-2755-6.
• [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] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [6] 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.
• [7] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [8] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [9] 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.
• [10] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [11] 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.
• [12] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [13] 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.
• [14] Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.