Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNR61OD)

DOT Name Short transient receptor potential channel 3 (TRPC3)
Synonyms TrpC3; Transient receptor protein 3; TRP-3; hTrp-3; hTrp3
Gene Name TRPC3
Related Disease
Spinocerebellar ataxia type 41 ( )
UniProt ID
TRPC3_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
5ZBG; 6CUD; 6D7L; 6DJS; 7DXB; 7DXC; 7DXD; 7DXE
Pfam ID
PF12796 ; PF00520 ; PF08344
Sequence
MSTKVRKCKEQARVTFPAPEEEEDEGEDEGAEPQRRRRGWRGVNGGLEPRSAPSQREPHG
YCPPPFSHGPDLSMEGSPSLRRMTVMREKGRRQAVRGPAFMFNDRGTSLTAEEERFLDAA
EYGNIPVVRKMLEESKTLNVNCVDYMGQNALQLAVGNEHLEVTELLLKKENLARIGDALL
LAISKGYVRIVEAILNHPGFAASKRLTLSPCEQELQDDDFYAYDEDGTRFSPDITPIILA
AHCQKYEVVHMLLMKGARIERPHDYFCKCGDCMEKQRHDSFSHSRSRINAYKGLASPAYL
SLSSEDPVLTALELSNELAKLANIEKEFKNDYRKLSMQCKDFVVGVLDLCRDSEEVEAIL
NGDLESAEPLEVHRHKASLSRVKLAIKYEVKKFVAHPNCQQQLLTIWYENLSGLREQTIA
IKCLVVLVVALGLPFLAIGYWIAPCSRLGKILRSPFMKFVAHAASFIIFLGLLVFNASDR
FEGITTLPNITVTDYPKQIFRVKTTQFTWTEMLIMVWVLGMMWSECKELWLEGPREYILQ
LWNVLDFGMLSIFIAAFTARFLAFLQATKAQQYVDSYVQESDLSEVTLPPEIQYFTYARD
KWLPSDPQIISEGLYAIAVVLSFSRIAYILPANESFGPLQISLGRTVKDIFKFMVLFIMV
FFAFMIGMFILYSYYLGAKVNAAFTTVEESFKTLFWSIFGLSEVTSVVLKYDHKFIENIG
YVLYGIYNVTMVVVLLNMLIAMINSSYQEIEDDSDVEWKFARSKLWLSYFDDGKTLPPPF
SLVPSPKSFVYFIMRIVNFPKCRRRRLQKDIEMGMGNSKSRLNLFTQSNSRVFESHSFNS
ILNQPTRYQQIMKRLIKRYVLKAQVDKENDEVNEGELKEIKQDISSLRYELLEDKSQATE
ELAILIHKLSEKLNPSMLRCE
Function
Forms a receptor-activated non-selective calcium permeant cation channel. May be operated by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases or G-protein coupled receptors.
Tissue Specificity Expressed predominantly in brain and at much lower levels in ovary, colon, small intestine, lung, prostate, placenta and testis.
KEGG Pathway
Axon guidance (hsa04360 )
Spinocerebellar ataxia (hsa05017 )
Pathways of neurodegeneration - multiple diseases (hsa05022 )
Reactome Pathway
Elevation of cytosolic Ca2+ levels (R-HSA-139853 )
TRP channels (R-HSA-3295583 )
Role of second messengers in netrin-1 signaling (R-HSA-418890 )
MECP2 regulates neuronal receptors and channels (R-HSA-9022699 )
Effects of PIP2 hydrolysis (R-HSA-114508 )

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Spinocerebellar ataxia type 41 DISO90FU Supportive Autosomal dominant [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 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 Short transient receptor potential channel 3 (TRPC3). [2]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Short transient receptor potential channel 3 (TRPC3). [9]
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6 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 Short transient receptor potential channel 3 (TRPC3). [3]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Short transient receptor potential channel 3 (TRPC3). [4]
Vorinostat DMWMPD4 Approved Vorinostat increases the expression of Short transient receptor potential channel 3 (TRPC3). [5]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Short transient receptor potential channel 3 (TRPC3). [6]
Paclitaxel DMLB81S Approved Paclitaxel increases the expression of Short transient receptor potential channel 3 (TRPC3). [7]
Methacholine Chloride DMGS4QH Approved Methacholine Chloride increases the activity of Short transient receptor potential channel 3 (TRPC3). [8]
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⏷ Show the Full List of 6 Drug(s)

References

1 Do mutations in the murine ataxia gene TRPC3 cause cerebellar ataxia in humans?. Mov Disord. 2015 Feb;30(2):284-6. doi: 10.1002/mds.26096. Epub 2014 Dec 5.
2 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.
3 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.
4 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
5 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
6 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
7 Proteomic analysis of anti-cancer effects by paclitaxel treatment in cervical cancer cells. Gynecol Oncol. 2005 Jul;98(1):45-53. doi: 10.1016/j.ygyno.2005.04.010.
8 Dissociation of regulated trafficking of TRPC3 channels to the plasma membrane from their activation by phospholipase C. J Biol Chem. 2006 Apr 28;281(17):11712-20. doi: 10.1074/jbc.M510541200. Epub 2006 Mar 7.
9 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.