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

DOT Name Rho guanine nucleotide exchange factor 15 (ARHGEF15)
Synonyms Ephexin-5; E5; Vsm-RhoGEF
Gene Name ARHGEF15
Related Disease
Alzheimer disease ( )
Autism spectrum disorder ( )
Epilepsy ( )
Bipolar disorder ( )
Infantile spasm ( )
Matthew-Wood syndrome ( )
Pancreatic cancer ( )
Pancreatic ductal carcinoma ( )
Schizophrenia ( )
UniProt ID
ARHGF_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00621
Sequence
MSAQSLPAATPPTQKPPRIIRPRPPSRSRAAQSPGPPHNGSSPQELPRNSNDAPTPMCTP
IFWEPPAASLKPPALLPPSASRASLDSQTSPDSPSSTPTPSPVSRRSASPEPAPRSPVPP
PKPSGSPCTPLLPMAGVLAQNGSASAPGTVRRLAGRFEGGAEGRAQDADAPEPGLQARAD
VNGEREAPLTGSGSQENGAPDAGLACPPCCPCVCHTTRPGLELRWVPVGGYEEVPRVPRR
ASPLRTSRSRPHPPSIGHPAVVLTSYRSTAERKLLPLLKPPKPTRVRQDATIFGDPPQPD
LDLLSEDGIQTGDSPDEAPQNTPPATVEGREEEGLEVLKEQNWELPLQDEPLYQTYRAAV
LSEELWGVGEDGSPSPANAGDAPTFPRPPGPRNTLWQELPAVQASGLLDTLSPQERRMQE
SLFEVVTSEASYLRSLRLLTDTFVLSQALRDTLTPRDHHTLFSNVQRVQGVSERFLATLL
SRVRSSPHISDLCDVVHAHAVGPFSVYVDYVRNQQYQEETYSRLMDTNVRFSAELRRLQS
LPKCERLPLPSFLLLPFQRITRLRMLLQNILRQTEEGSSRQENAQKALGAVSKIIERCSA
EVGRMKQTEELIRLTQRLRFHKVKALPLVSWSRRLEFQGELTELGCRRGGVLFASRPRFT
PLCLLLFSDLLLITQPKSGQRLQVLDYAHRSLVQAQQVPDPSGPPTFRLSLLSNHQGRPT
HRLLQASSLSDMQRWLGAFPTPGPLPCSPDTIYEDCDCSQELCSESSAPAKTEGRSLESR
AAPKHLHKTPEGWLKGLPGAFPAQLVCEVTGEHERRRHLRQNQRLLEAVGSSSGTPNAPP
P
Function
Specific GEF for RhoA activation. Does not activate RAC1 or CDC42. Regulates vascular smooth muscle contractility. Negatively regulates excitatory synapse development by suppressing the synapse-promoting activity of EPHB2.
Tissue Specificity Expressed in the vascular smooth muscle of coronary artery.
Reactome Pathway
G alpha (12/13) signalling events (R-HSA-416482 )
RHOA GTPase cycle (R-HSA-8980692 )
CDC42 GTPase cycle (R-HSA-9013148 )
RAC1 GTPase cycle (R-HSA-9013149 )
NRAGE signals death through JNK (R-HSA-193648 )

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Alzheimer disease DISF8S70 Strong Altered Expression [1]
Autism spectrum disorder DISXK8NV Strong Genetic Variation [2]
Epilepsy DISBB28L Strong Biomarker [3]
Bipolar disorder DISAM7J2 moderate Genetic Variation [4]
Infantile spasm DISZSKDG Limited Autosomal dominant [5]
Matthew-Wood syndrome DISA7HR7 Limited Altered Expression [6]
Pancreatic cancer DISJC981 Limited Altered Expression [6]
Pancreatic ductal carcinoma DIS26F9Q Limited Altered Expression [6]
Schizophrenia DISSRV2N No Known Unknown [7]
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⏷ Show the Full List of 9 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Rho guanine nucleotide exchange factor 15 (ARHGEF15). [8]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Rho guanine nucleotide exchange factor 15 (ARHGEF15). [9]
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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 increases the methylation of Rho guanine nucleotide exchange factor 15 (ARHGEF15). [10]
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References

1 Reducing expression of synapse-restricting protein Ephexin5 ameliorates Alzheimer's-like impairment in mice.J Clin Invest. 2017 May 1;127(5):1646-1650. doi: 10.1172/JCI85504. Epub 2017 Mar 27.
2 EphB-mediated degradation of the RhoA GEF Ephexin5 relieves a developmental brake on excitatory synapse formation.Cell. 2010 Oct 29;143(3):442-55. doi: 10.1016/j.cell.2010.09.038.
3 Exome sequencing reveals new causal mutations in children with epileptic encephalopathies. Epilepsia. 2013 Jul;54(7):1270-81. doi: 10.1111/epi.12201. Epub 2013 May 3.
4 A genome-wide association study identifies two novel susceptibility loci and trans population polygenicity associated with bipolar disorder.Mol Psychiatry. 2018 Mar;23(3):639-647. doi: 10.1038/mp.2016.259. Epub 2017 Jan 24.
5 Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
6 ARHGEF15 overexpression worsens the prognosis in patients with pancreatic ductal adenocarcinoma through enhancing the motility and proliferative activity of the cancer cells.Mol Cancer. 2016 May 4;15(1):32. doi: 10.1186/s12943-016-0516-4.
7 De novo mutations in schizophrenia implicate synaptic networks. Nature. 2014 Feb 13;506(7487):179-84. doi: 10.1038/nature12929. Epub 2014 Jan 22.
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 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
10 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.