Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTACZZJ0)

DOT Name Pikachurin (EGFLAM)
Synonyms Agrin-like protein; EGF-like, fibronectin type-III and laminin G-like domain-containing protein
Gene Name EGFLAM
Related Disease
46,XY sex reversal 11 ( )
Adult glioblastoma ( )
Dengue ( )
Glioblastoma multiforme ( )
Influenza ( )
Major depressive disorder ( )
Mood disorder ( )
Muscular dystrophy ( )
Narcolepsy ( )
Rabies ( )
Oral mucosa leukoplakia ( )
UniProt ID
EGFLA_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
7ZC9; 7ZCB; 8D1B
Pfam ID
PF00008 ; PF00041 ; PF00054 ; PF02210
Sequence
MDLIRGVLLRLLLLASSLGPGAVSLRAAIRKPGKVGPPLDIKLGALNCTAFSIQWKMPRH
PGSPILGYTVFYSEVGADKSLQEQLHSVPLSRDIPTTEEVIGDLKPGTEYRVSIAAYSQA
GKGRLSSPRHVTTLSQDSCLPPAAPQQPHVIVVSDSEVALSWKPGASEGSAPIQYYSVEF
IRPDFDKKWTSIHERIQMDSMVIKGLDPDTNYQFAVRAMNSHGPSPRSWPSDIIRTLCPE
EAGSGRYGPRYITDMGAGEDDEGFEDDLDLDISFEEVKPLPATKGGNKKFLVESKKMSIS
NPKTISRLIPPTSASLPVTTVAPQPIPIQRKGKNGVAIMSRLFDMPCDETLCSADSFCVN
DYTWGGSRCQCTLGKGGESCSEDIVIQYPQFFGHSYVTFEPLKNSYQAFQITLEFRAEAE
DGLLLYCGENEHGRGDFMSLAIIRRSLQFRFNCGTGVAIIVSETKIKLGGWHTVMLYRDG
LNGLLQLNNGTPVTGQSQGQYSKITFRTPLYLGGAPSAYWLVRATGTNRGFQGCVQSLAV
NGRRIDMRPWPLGKALSGADVGECSSGICDEASCIHGGTCTAIKADSYICLCPLGFKGRH
CEDAFTLTIPQFRESLRSYAATPWPLEPQHYLSFMEFEITFRPDSGDGVLLYSYDTGSKD
FLSINLAGGHVEFRFDCGSGTGVLRSEDPLTLGNWHELRVSRTAKNGILQVDKQKIVEGM
AEGGFTQIKCNTDIFIGGVPNYDDVKKNSGVLKPFSGSIQKIILNDRTIHVKHDFTSGVN
VENAAHPCVRAPCAHGGSCRPRKEGYDCDCPLGFEGLHCQKECGNYCLNTIIEAIEIPQF
IGRSYLTYDNPDILKRVSGSRSNVFMRFKTTAKDGLLLWRGDSPMRPNSDFISLGLRDGA
LVFSYNLGSGVASIMVNGSFNDGRWHRVKAVRDGQSGKITVDDYGARTGKSPGMMRQLNI
NGALYVGGMKEIALHTNRQYMRGLVGCISHFTLSTDYHISLVEDAVDGKNINTCGAK
Function
Involved in both the retinal photoreceptor ribbon synapse formation and physiological functions of visual perception. Plays a key role in the synaptic organization of photoreceptors by mediating transsynaptic interaction between alpha-dystroglycan and GPR179 on the postsynaptic membrane. Necessary for proper bipolar dendritic tip apposition to the photoreceptor ribbon synapse. Promotes matrix assembly and cell adhesiveness.

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
46,XY sex reversal 11 DISYJTLT Definitive Genetic Variation [1]
Adult glioblastoma DISVP4LU Strong Biomarker [2]
Dengue DISKH221 Strong Biomarker [3]
Glioblastoma multiforme DISK8246 Strong Biomarker [2]
Influenza DIS3PNU3 Strong Biomarker [4]
Major depressive disorder DIS4CL3X Strong Genetic Variation [5]
Mood disorder DISLVMWO Strong Genetic Variation [5]
Muscular dystrophy DISJD6P7 Strong Biomarker [6]
Narcolepsy DISLCNLI Strong Genetic Variation [7]
Rabies DISSC4V5 Strong Biomarker [8]
Oral mucosa leukoplakia DISJTL5X Limited Biomarker [9]
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⏷ Show the Full List of 11 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Aspirin DM672AH Approved Pikachurin (EGFLAM) increases the Adverse reaction ADR of Aspirin. [23]
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9 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Pikachurin (EGFLAM). [10]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Pikachurin (EGFLAM). [12]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Pikachurin (EGFLAM). [13]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Pikachurin (EGFLAM). [14]
Vorinostat DMWMPD4 Approved Vorinostat increases the expression of Pikachurin (EGFLAM). [16]
Dexamethasone DMMWZET Approved Dexamethasone increases the expression of Pikachurin (EGFLAM). [17]
Cytarabine DMZD5QR Approved Cytarabine decreases the expression of Pikachurin (EGFLAM). [18]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Pikachurin (EGFLAM). [19]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Pikachurin (EGFLAM). [22]
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⏷ Show the Full List of 9 Drug(s)
4 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the methylation of Pikachurin (EGFLAM). [11]
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Pikachurin (EGFLAM). [15]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Pikachurin (EGFLAM). [20]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Pikachurin (EGFLAM). [21]
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References

1 Structural divergence of essential triad ribbon synapse proteins among placental mammals - Implications for preclinical trials in photoreceptor transplantation therapy.Exp Eye Res. 2017 Jun;159:156-167. doi: 10.1016/j.exer.2017.03.005. Epub 2017 Mar 18.
2 EGFLAM correlates with cell proliferation, migration, invasion and poor prognosis in glioblastoma.Cancer Biomark. 2019;24(3):343-350. doi: 10.3233/CBM-181740.
3 Adjuvant PIKA protects hepatoma cells from dengue virus infection by promoting a TBK-1-dependent innate immune response.Arch Virol. 2013 Apr;158(4):829-38. doi: 10.1007/s00705-012-1556-8. Epub 2012 Dec 7.
4 A TLR3 ligand that exhibits potent inhibition of influenza virus replication and has strong adjuvant activity has the potential for dual applications in an influenza pandemic.Vaccine. 2009 Feb 25;27(9):1354-64. doi: 10.1016/j.vaccine.2008.12.048. Epub 2009 Jan 15.
5 Analysis of 23andMe antidepressant efficacy survey data: implication of circadian rhythm and neuroplasticity in bupropion response.Transl Psychiatry. 2016 Sep 13;6(9):e889. doi: 10.1038/tp.2016.171.
6 Post-translational maturation of dystroglycan is necessary for pikachurin binding and ribbon synaptic localization.J Biol Chem. 2010 Oct 8;285(41):31208-16. doi: 10.1074/jbc.M110.116343. Epub 2010 Aug 3.
7 Genome-wide association database developed in the Japanese Integrated Database Project.J Hum Genet. 2009 Sep;54(9):543-6. doi: 10.1038/jhg.2009.68. Epub 2009 Jul 24.
8 An accelerated rabies vaccine schedule based on toll-like receptor 3 (TLR3) agonist PIKA adjuvant augments rabies virus specific antibody and T cell response in healthy adult volunteers.Vaccine. 2017 Feb 22;35(8):1175-1183. doi: 10.1016/j.vaccine.2016.12.031. Epub 2017 Jan 22.
9 High-risk oral leukoplakia is associated with aberrant promoter methylation of multiple genes.BMC Cancer. 2016 Jun 3;16:350. doi: 10.1186/s12885-016-2371-5.
10 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
11 Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
12 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
13 Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
14 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.
15 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
16 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
17 Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
18 Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
19 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.
20 Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
21 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.
22 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
23 Genome-wide pharmacogenomic study of citalopram-induced side effects in STAR*D. Transl Psychiatry. 2012 Jul 3;2(7):e129. doi: 10.1038/tp.2012.57.