Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSY5NQ9)

• DOT Name: Reticulon-4 receptor-like 2 (RTN4RL2)
• Synonyms: Nogo receptor-like 3; Nogo-66 receptor homolog 1; Nogo-66 receptor-related protein 2; NgR2
• Gene Name: RTN4RL2
• Related Disease: Colorectal carcinoma
• UniProt ID: R4RL2_HUMAN
• Pfam ID: PF13855
• Sequence:
  MLPGLRRLLQAPASACLLLMLLALPLAAPSCPMLCTCYSSPPTVSCQANNFSSVPLSLPP
  STQRLFLQNNLIRTLRPGTFGSNLLTLWLFSNNLSTIYPGTFRHLQALEELDLGDNRHLR
  SLEPDTFQGLERLQSLHLYRCQLSSLPGNIFRGLVSLQYLYLQENSLLHLQDDLFADLAN
  LSHLFLHGNRLRLLTEHVFRGLGSLDRLLLHGNRLQGVHRAAFRGLSRLTILYLFNNSLA
  SLPGEALADLPSLEFLRLNANPWACDCRARPLWAWFQRARVSSSDVTCATPPERQGRDLR
  ALREADFQACPPAAPTRPGSRARGNSSSNHLYGVAEAGAPPADPSTLYRDLPAEDSRGRQ
  GGDAPTEDDYWGGYGGEDQRGEQMCPGAACQAPPDSRGPALSAGLPSPLLCLLLLVPHHL
• Function: Cell surface receptor that plays a functionally redundant role in the inhibition of neurite outgrowth mediated by MAG. Plays a functionally redundant role in postnatal brain development. Contributes to normal axon migration across the brain midline and normal formation of the corpus callosum. Does not seem to play a significant role in regulating axon regeneration in the adult central nervous system. Protects motoneurons against apoptosis; protection against apoptosis is probably mediated by MAG. Like other family members, plays a role in restricting the number dendritic spines and the number of synapses that are formed during brain development. Signaling mediates activation of Rho and downstream reorganization of the actin cytoskeleton.
• Tissue Specificity: Highly expressed in brain and liver. Expressed at lower levels in kidney, mammary gland, placenta, skeletal muscle, spleen and thyroid.
• Reactome Pathway: Post-translational modification (R-HSA-163125)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Reticulon-4 receptor-like 2 (RTN4RL2).	[2]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Reticulon-4 receptor-like 2 (RTN4RL2).	[3]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Reticulon-4 receptor-like 2 (RTN4RL2).	[4]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid increases the expression of Reticulon-4 receptor-like 2 (RTN4RL2).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Reticulon-4 receptor-like 2 (RTN4RL2).	[5]

References

• [1] Downregulation of epidermal growth factor receptor family receptors and ligands in a mutant K-ras group of patients with colorectal cancer.Mol Med Rep. 2016 Apr;13(4):3514-20. doi: 10.3892/mmr.2016.4951. Epub 2016 Mar 1.
• [2] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [3] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [4] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [5] 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.
• [6] MS4A3-HSP27 target pathway reveals potential for haematopoietic disorder treatment in alimentary toxic aleukia. Cell Biol Toxicol. 2023 Feb;39(1):201-216. doi: 10.1007/s10565-021-09639-4. Epub 2021 Sep 28.