Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLR4HSR)

DOT Name PEX5-related protein (PEX5L)
Synonyms PEX2-related protein; PEX5-like protein; Peroxin-5-related protein; Peroxisome biogenesis factor 5-like; Tetratricopeptide repeat-containing Rab8b-interacting protein; Pex5Rp; TRIP8b
Gene Name PEX5L
Related Disease
Depression ( )
Major depressive disorder ( )
Non-insulin dependent diabetes ( )
Temporal lobe epilepsy ( )
UniProt ID
PEX5R_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF13432 ; PF13181
Sequence
MYQGHMQKSKEQGYGKLSSDEDLEIIVDQKQGKGSRAADKAVAMVMKEIPREESAEEKPL
LTMTSQLVNEQQESRPLLSPSIDDFLCETKSEAIARPVTSNTAVLTTGLDLLDLSEPVSQ
TQTKAKKSEPSSKTSSLKKKADGSDLISTDAEQRGQPLRVPETSSLDLDIQTQLEKWDDV
KFHGDRNTKGHPMAERKSSSSRTGSKELLWSSEHRSQPELSGGKSALNSESASELELVAP
TQARLTKEHRWGSALLSRNHSLEEEFERAKAAVESDTEFWDKMQAEWEEMARRNWISENQ
EAQNQVTISASEKGYYFHTENPFKDWPGAFEEGLKRLKEGDLPVTILFMEAAILQDPGDA
EAWQFLGITQAENENEQAAIVALQRCLELQPNNLKALMALAVSYTNTGHQQDACDALKNW
IKQNPKYKYLVKSKKGSPGLTRRMSKSPVDSSVLEGVKELYLEAAHQNGDMIDPDLQTGL
GVLFHLSGEFNRAIDAFNAALTVRPEDYSLWNRLGATLANGDRSEEAVEAYTRALEIQPG
FIRSRYNLGISCINLGAYREAVSNFLTALSLQRKSRNQQQVPHPAISGNIWAALRIALSL
MDQPELFQAANLGDLDVLLRAFNLDP
Function Accessory subunit of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, regulating their cell-surface expression and cyclic nucleotide dependence.
Tissue Specificity Mainly expressed in brain. Also expressed in pancreas, testis and pituitary.
KEGG Pathway
Peroxisome (hsa04146 )

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Depression DIS3XJ69 Strong Genetic Variation [1]
Major depressive disorder DIS4CL3X Strong Biomarker [2]
Non-insulin dependent diabetes DISK1O5Z Strong Genetic Variation [3]
Temporal lobe epilepsy DISNOPXX Limited Biomarker [4]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Fulvestrant DM0YZC6 Approved Fulvestrant decreases the methylation of PEX5-related protein (PEX5L). [5]
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4 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of PEX5-related protein (PEX5L). [6]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of PEX5-related protein (PEX5L). [7]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of PEX5-related protein (PEX5L). [8]
KOJIC ACID DMP84CS Investigative KOJIC ACID decreases the expression of PEX5-related protein (PEX5L). [9]
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References

1 HCN channels: New targets for the design of an antidepressant with rapid effects.J Affect Disord. 2019 Feb 15;245:764-770. doi: 10.1016/j.jad.2018.11.081. Epub 2018 Nov 13.
2 HCN-channel dendritic targeting requires bipartite interaction with TRIP8b and regulates antidepressant-like behavioral effects.Mol Psychiatry. 2017 Mar;22(3):458-465. doi: 10.1038/mp.2016.99. Epub 2016 Jul 12.
3 Genetic Variants in HSD17B3, SMAD3, and IPO11 Impact Circulating Lipids in Response to Fenofibrate in Individuals With Type 2 Diabetes.Clin Pharmacol Ther. 2018 Apr;103(4):712-721. doi: 10.1002/cpt.798. Epub 2017 Nov 3.
4 Phosphorylation of the HCN channel auxiliary subunit TRIP8b is altered in an animal model of temporal lobe epilepsy and modulates channel function.J Biol Chem. 2019 Oct 25;294(43):15743-15758. doi: 10.1074/jbc.RA119.010027. Epub 2019 Sep 5.
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 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.
7 Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
8 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
9 Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.