Details of Drug Off-Target (DOT)

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

• DOT Name: Leucine-rich repeat transmembrane neuronal protein 2 (LRRTM2)
• Synonyms: Leucine-rich repeat neuronal 2 protein
• Gene Name: LRRTM2
• Related Disease: Acute myelogenous leukaemia
• UniProt ID: LRRT2_HUMAN
• PDB ID: 5Z8X; 5Z8Y
• Pfam ID: PF13855
• Sequence:
  MGLHFKWPLGAPMLAAIYAMSMVLKMLPALGMACPPKCRCEKLLFYCDSQGFHSVPNATD
  KGSLGLSLRHNHITELERDQFASFSQLTWLHLDHNQISTVKEDAFQGLYKLKELILSSNK
  IFYLPNTTFTQLINLQNLDLSFNQLSSLHPELFYGLRKLQTLHLRSNSLRTIPVRLFWDC
  RSLEFLDLSTNRLRSLARNGFAGLIKLRELHLEHNQLTKINFAHFLRLSSLHTLFLQWNK
  ISNLTCGMEWTWGTLEKLDLTGNEIKAIDLTVFETMPNLKILLMDNNKLNSLDSKILNSL
  RSLTTVGLSGNLWECSARICALASWLGSFQGRWEHSILCHSPDHTQGEDILDAVHGFQLC
  WNLSTTVTVMATTYRDPTTEYTKRISSSSYHVGDKEIPTTAGIAVTTEEHFPEPDNAIFT
  QRVITGTMALLFSFFFIIFIVFISRKCCPPTLRRIRQCSMVQNHRQLRSQTRLHMSNMSD
  QGPYNEYEPTHEGPFIIINGYGQCKCQQLPYKECEV
• Function: Involved in the development and maintenance of excitatory synapses in the vertebrate nervous system. Regulates surface expression of AMPA receptors and instructs the development of functional glutamate release sites. Acts as a ligand for the presynaptic receptors NRXN1-A and NRXN1-B.
• Tissue Specificity: Expressed in neuronal tissues.
• Reactome Pathway: Neurexins and neuroligins (R-HSA-6794361)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Leucine-rich repeat transmembrane neuronal protein 2 (LRRTM2).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Leucine-rich repeat transmembrane neuronal protein 2 (LRRTM2).	[3]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Leucine-rich repeat transmembrane neuronal protein 2 (LRRTM2).	[4]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Leucine-rich repeat transmembrane neuronal protein 2 (LRRTM2).	[5]

References

• [1] 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.
• [2] 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.
• [3] 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.
• [4] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [5] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.