Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWQFP8F)

• DOT Name: Short transient receptor potential channel 5 (TRPC5)
• Synonyms: TrpC5; Transient receptor protein 5; TRP-5; hTRP-5; hTRP5
• Gene Name: TRPC5
• UniProt ID: TRPC5_HUMAN
• PDB ID: 6YSN; 7D4P; 7D4Q; 7E4T; 7WDB; 7X6C; 7X6I; 8GVW; 8GVX
• Pfam ID: PF00023 ; PF12796 ; PF00520 ; PF08344
• Sequence:
  MAQLYYKKVNYSPYRDRIPLQIVRAETELSAEEKAFLNAVEKGDYATVKQALQEAEIYYN
  VNINCMDPLGRSALLIAIENENLEIMELLLNHSVYVGDALLYAIRKEVVGAVELLLSYRR
  PSGEKQVPTLMMDTQFSEFTPDITPIMLAAHTNNYEIIKLLVQKRVTIPRPHQIRCNCVE
  CVSSSEVDSLRHSRSRLNIYKALASPSLIALSSEDPILTAFRLGWELKELSKVENEFKAE
  YEELSQQCKLFAKDLLDQARSSRELEIILNHRDDHSEELDPQKYHDLAKLKVAIKYHQKE
  FVAQPNCQQLLATLWYDGFPGWRRKHWVVKLLTCMTIGFLFPMLSIAYLISPRSNLGLFI
  KKPFIKFICHTASYLTFLFMLLLASQHIVRTDLHVQGPPPTVVEWMILPWVLGFIWGEIK
  EMWDGGFTEYIHDWWNLMDFAMNSLYLATISLKIVAYVKYNGSRPREEWEMWHPTLIAEA
  LFAISNILSSLRLISLFTANSHLGPLQISLGRMLLDILKFLFIYCLVLLAFANGLNQLYF
  YYETRAIDEPNNCKGIRCEKQNNAFSTLFETLQSLFWSVFGLLNLYVTNVKARHEFTEFV
  GATMFGTYNVISLVVLLNMLIAMMNNSYQLIADHADIEWKFARTKLWMSYFDEGGTLPPP
  FNIIPSPKSFLYLGNWFNNTFCPKRDPDGRRRRRNLRSFTERNADSLIQNQHYQEVIRNL
  VKRYVAAMIRNSKTHEGLTEENFKELKQDISSFRYEVLDLLGNRKHPRSFSTSSTELSQR
  DDNNDGSGGARAKSKSVSFNLGCKKKTCHGPPLIRTMPRSSGAQGKSKAESSSKRSFMGP
  SLKKLGLLFSKFNGHMSEPSSEPMYTISDGIVQQHCMWQDIRYSQMEKGKAEACSQSEIN
  LSEVELGEVQGAAQSSECPLACSSSLHCASSICSSNSKLLDSSEDVFETWGEACDLLMHK
  WGDGQEEQVTTRL
• Function: Thought to form a receptor-activated non-selective calcium permeant cation channel. Probably is operated by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases or G-protein coupled receptors. Has also been shown to be calcium-selective. May also be activated by intracellular calcium store depletion. Mediates calcium-dependent phosphatidylserine externalization and apoptosis in neurons via its association with PLSCR1.
• Tissue Specificity: Expressed in brain with higher levels in fetal brain. Found in cerebellum and occipital pole.
• KEGG Pathway:
  Axon guidance (hsa04360)
  GnRH secretion (hsa04929)
• Reactome Pathway:
  Role of second messengers in netrin-1 signaling (R-HSA-418890)
  TRP channels (R-HSA-3295583)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Succimer	DME81IY	Approved	Succimer increases the activity of Short transient receptor potential channel 5 (TRPC5).	[1]
1,4-Dithiothreitol	DMIFOXE	Investigative	1,4-Dithiothreitol increases the activity of Short transient receptor potential channel 5 (TRPC5).	[1]
pCMPS	DMGIS5Q	Investigative	pCMPS increases the activity of Short transient receptor potential channel 5 (TRPC5).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Short transient receptor potential channel 5 (TRPC5).	[2]

References

• [1] Activation of TRPC cationic channels by mercurial compounds confers the cytotoxicity of mercury exposure. Toxicol Sci. 2012 Jan;125(1):56-68. doi: 10.1093/toxsci/kfr268. Epub 2011 Oct 9.
• [2] 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.