Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVI6YFP)

DOT Name FERM domain-containing protein 4B (FRMD4B)
Synonyms GRP1-binding protein GRSP1
Gene Name FRMD4B
Related Disease
Atrial fibrillation ( )
Cardiac failure ( )
Coeliac disease ( )
Congestive heart failure ( )
Enhanced S-cone syndrome ( )
Familial atrial fibrillation ( )
UniProt ID
FRM4B_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF11819 ; PF09380 ; PF00373 ; PF09379
Sequence
MASVFMCGVEDLLFSGSRFVWNLTVSTLRRWYTERLRACHQVLRTWCGLQDVYQMTEGRH
CQVHLLDDRRLELLVQPKLLARELLDLVASHFNLKEKEYFGITFIDDTGQQNWLQLDHRV
LDHDLPKKPGPTILHFAVRFYIESISFLKDKTTVELFFLNAKACVHKGQIEVESETIFKL
AAFILQEAKGDYTSDENARKDLKTLPAFPTKTLQEHPSLAYCEDRVIEHYLKIKGLTRGQ
AVVQYMKIVEALPTYGVHYYAVKDKQGLPWWLGISYKGIGQYDIQDKVKPRKLFQWKQLE
NLYFREKKFAVEVHDPRRISVSRRTFGQSGLFVQTWYANSSLIKSIWVMAISQHQFYLDR
KQSKAKIPSARSLDEIAMDLTETGTQRASKLVTLETKSQFIMASNGSLISSGSQDSEVSE
EQKREKILELKKKEKLLQEKLLKKVEELKKICLREAELTGKMPKEYPLNIGEKPPQVRRR
VGTAFKLDDNLLPSEEDPALQELESNFLIQQKLVEAAKKLANEPDLCKTVKKKRKQDYTD
AMKKLQEIENAINEYRIRCGKKPSQKATVLPEDIIPSESSSLSDTTTYDDPSDAFTFPGQ
RSSSVPHSPRILPPKSLGIERIHFRKSSINEQFVDTRQSREMLSTHSSPYKTLERRPQGG
RSMPTTPVLTRNAYSSSHLEPESSSQHCRQRSGSLESQSHLLSEMDSDKPFFSLSKSQRS
SSTEILDDGSSYTSQSSTEYYCVTPVTGPYYTTQTLDTRTRGRRRSKKQNVSTSNSGSMP
NLAQKDSLRNGVYSKSQEPPSSSYYIAGYTPYAECDFYYSGGYVYENDTEGQYSVNPSYR
SSAHYGYERQRDYSRSFHEDEVDRVPHNPYATLRLPRKAAAKSEHITKNIHKALVAEHLR
GWYQRASGQKDQGHSPQTSFDSDRGSQRCLGFAGLQVPCSPSSRASSYSSVSSTNASGNW
RTQLTIGLSDYETPAHSSYTSCYGNVYNPLPSPSRQYTEISQLDGTDGNQLEDNLESSEQ
RLFWHEDSKPGTLV
Function
Member of GRP1 signaling complexes that are acutely recruited to plasma membrane ruffles in response to insulin receptor signaling. May function as a scaffolding protein that regulates epithelial cell polarity by connecting ARF6 activation with the PAR3 complex. Plays a redundant role with FRMD4A in epithelial polarization.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Atrial fibrillation DIS15W6U Strong Biomarker [1]
Cardiac failure DISDC067 Strong Genetic Variation [2]
Coeliac disease DISIY60C Strong Genetic Variation [3]
Congestive heart failure DIS32MEA Strong Genetic Variation [2]
Enhanced S-cone syndrome DIS2IWS3 Strong Genetic Variation [4]
Familial atrial fibrillation DISL4AGF moderate Biomarker [1]
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⏷ Show the Full List of 6 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
13 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 FERM domain-containing protein 4B (FRMD4B). [5]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of FERM domain-containing protein 4B (FRMD4B). [6]
Tretinoin DM49DUI Approved Tretinoin increases the expression of FERM domain-containing protein 4B (FRMD4B). [7]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of FERM domain-containing protein 4B (FRMD4B). [8]
Estradiol DMUNTE3 Approved Estradiol increases the expression of FERM domain-containing protein 4B (FRMD4B). [9]
Quercetin DM3NC4M Approved Quercetin decreases the expression of FERM domain-containing protein 4B (FRMD4B). [10]
Amphotericin B DMTAJQE Approved Amphotericin B decreases the expression of FERM domain-containing protein 4B (FRMD4B). [11]
Melphalan DMOLNHF Approved Melphalan decreases the expression of FERM domain-containing protein 4B (FRMD4B). [12]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of FERM domain-containing protein 4B (FRMD4B). [13]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of FERM domain-containing protein 4B (FRMD4B). [14]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of FERM domain-containing protein 4B (FRMD4B). [15]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of FERM domain-containing protein 4B (FRMD4B). [16]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of FERM domain-containing protein 4B (FRMD4B). [5]
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⏷ Show the Full List of 13 Drug(s)

References

1 Multi-ethnic genome-wide association study for atrial fibrillation.Nat Genet. 2018 Jun 11;50(9):1225-1233. doi: 10.1038/s41588-018-0133-9.
2 Common variants in HSPB7 and FRMD4B associated with advanced heart failure.Circ Cardiovasc Genet. 2010 Apr;3(2):147-54. doi: 10.1161/CIRCGENETICS.109.898395. Epub 2010 Feb 2.
3 Genome-wide association study of celiac disease in North America confirms FRMD4B as new celiac locus.PLoS One. 2014 Jul 7;9(7):e101428. doi: 10.1371/journal.pone.0101428. eCollection 2014.
4 An FRMD4B variant suppresses dysplastic photoreceptor lesions in models of enhanced S-cone syndrome and of Nrl deficiency.Hum Mol Genet. 2018 Oct 1;27(19):3340-3352. doi: 10.1093/hmg/ddy238.
5 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.
6 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
7 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.
8 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.
9 Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
10 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
11 Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
12 Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
13 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
14 Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
15 Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
16 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.