Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDOMEH6)

DOT Name Rho guanine nucleotide exchange factor 11 (ARHGEF11)
Synonyms PDZ-RhoGEF
Gene Name ARHGEF11
Related Disease
Nephropathy ( )
Non-insulin dependent diabetes ( )
Adult glioblastoma ( )
Advanced cancer ( )
Breast cancer ( )
Breast carcinoma ( )
Glioblastoma multiforme ( )
Glioma ( )
Hyperinsulinemia ( )
Invasive breast carcinoma ( )
Lung cancer ( )
Lung carcinoma ( )
Lung neoplasm ( )
Neoplasm ( )
Schizophrenia ( )
UniProt ID
ARHGB_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1HTJ; 1XCG; 2DLS; 3KZ1; 3T06; 5E6P; 5JHG; 5JHH; 5TYT
Pfam ID
PF00595 ; PF17838 ; PF09128 ; PF00621
Sequence
MSVRLPQSIDRLSSLSSLGDSAPERKSPSHHRQPSDASETTGLVQRCVIIQKDQHGFGFT
VSGDRIVLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLIKSGAYVALTLL
GSSPSSMGISGLQQDPSPAGAPRITSVIPSPPPPPPLPPPQRITGPKPLQDPEVQKHATQ
ILRNMLRQEEKELQDILPLYGDTSQRPSEGRLSLDSQEGDSGLDSGTERFPSLSESLMNR
NSVLSDPGLDSPRTSPVIMARVAQHHRRQGSDAAVPSTGDQGVDQSPKPLIIGPEEDYDP
GYFNNESDIIFQDLEKLKSRPAHLGVFLRYIFSQADPSPLLFYLCAEVYQQASPKDSRSL
GKDIWNIFLEKNAPLRVKIPEMLQAEIDSRLRNSEDARGVLCEAQEAAMPEIQEQIHDYR
TKRTLGLGSLYGENDLLDLDGDPLRERQVAEKQLAALGDILSKYEEDRSAPMDFALNTYM
SHAGIRLREARPSNTAEKAQSAPDKDKWLPFFPKTKKSSNSKKEKDALEDKKRNPILKYI
GKPKSSSQSTFHIPLSPVEVKPGNVRNIIQHFENNQQYDAPEPGTQRLSTGSFPEDLLES
DSSRSEIRLGRSESLKGREEMKRSRKAENVPRSRSDVDMDAAAEATRLHQSASSSTSSLS
TRSLENPTPPFTPKMGRRSIESPSLGFCTDTLLPHLLEDDLGQLSDLEPEPDAQNWQHTV
GKDVVAGLTQREIDRQEVINELFVTEASHLRTLRVLDLIFYQRMKKENLMPREELARLFP
NLPELIEIHNSWCEAMKKLREEGPIIKEISDLMLARFDGPAREELQQVAAQFCSYQSIAL
ELIKTKQRKESRFQLFMQEAESHPQCRRLQLRDLIISEMQRLTKYPLLLESIIKHTEGGT
SEHEKLCRARDQCREILKYVNEAVKQTENRHRLEGYQKRLDATALERASNPLAAEFKSLD
LTTRKMIHEGPLTWRISKDKTLDLHVLLLEDLLVLLQKQDEKLLLKCHSKTAVGSSDSKQ
TFSPVLKLNAVLIRSVATDKRAFFIICTSKLGPPQIYELVALTSSDKNTWMELLEEAVRN
ATRHPGAAPMPVHPPPPGPREPAQQGPTPSRVELDDSDVFHGEPEPEELPGGTGSQQRVQ
GKHQVLLEDPEQEGSAEEEELGVLPCPSTSLDGENRGIRTRNPIHLAFPGPLFMEGLADS
ALEDVENLRHLILWSLLPGHTMETQAAQEPEDDLTPTPSVISVTSHPWDPGSPGQAPPGG
EGDNTQLAGLEGERPEQEDMGLCSLEHLPPRTRNSGIWESPELDRNLAEDASSTEAAGGY
KVVRKAEVAGSKVVPALPESGQSEPGPPEVEGGTKATGNCFYVSMPSGPPDSSTDHSEAP
MSPPQPDSLPAGQTEPQPQLQGGNDDPRRPSRSPPSLALRDVGMIFHTIEQLTLKLNRLK
DMELAHRELLKSLGGESSGGTTPVGSFHTEAARWTDGSLSPPAKEPLASDSRNSHELGPC
PEDGSDAPLEDSTADAAASPGP
Function
May play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13). Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPase and may act as GTPase-activating protein (GAP) for GNA12 and GNA13. Involved in neurotrophin-induced neurite outgrowth.
Tissue Specificity Ubiquitously expressed.
KEGG Pathway
Vascular smooth muscle contraction (hsa04270 )
Parathyroid hormone synthesis, secretion and action (hsa04928 )
Pathogenic Escherichia coli infection (hsa05130 )
Human cytomegalovirus infection (hsa05163 )
Pathways in cancer (hsa05200 )
Reactome Pathway
G alpha (12/13) signalling events (R-HSA-416482 )
Sema4D induced cell migration and growth-cone collapse (R-HSA-416572 )
RHOA GTPase cycle (R-HSA-8980692 )
RHOB GTPase cycle (R-HSA-9013026 )
RHOC GTPase cycle (R-HSA-9013106 )
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

15 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Nephropathy DISXWP4P Definitive Genetic Variation [1]
Non-insulin dependent diabetes DISK1O5Z Definitive Genetic Variation [2]
Adult glioblastoma DISVP4LU Strong Altered Expression [3]
Advanced cancer DISAT1Z9 Strong Genetic Variation [4]
Breast cancer DIS7DPX1 Strong Biomarker [5]
Breast carcinoma DIS2UE88 Strong Biomarker [5]
Glioblastoma multiforme DISK8246 Strong Altered Expression [3]
Glioma DIS5RPEH Strong Altered Expression [3]
Hyperinsulinemia DISIDWT6 Strong Genetic Variation [6]
Invasive breast carcinoma DISANYTW Strong Altered Expression [5]
Lung cancer DISCM4YA Strong Genetic Variation [4]
Lung carcinoma DISTR26C Strong Genetic Variation [4]
Lung neoplasm DISVARNB Strong Genetic Variation [4]
Neoplasm DISZKGEW Strong Altered Expression [3]
Schizophrenia DISSRV2N Strong Biomarker [2]
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⏷ Show the Full List of 15 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
4 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Rho guanine nucleotide exchange factor 11 (ARHGEF11). [7]
Tacrolimus DMZ7XNQ Approved Tacrolimus increases the expression of Rho guanine nucleotide exchange factor 11 (ARHGEF11). [8]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Rho guanine nucleotide exchange factor 11 (ARHGEF11). [9]
Fasudil DMTCNOM Investigative Fasudil decreases the expression of Rho guanine nucleotide exchange factor 11 (ARHGEF11). [11]
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2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Rho guanine nucleotide exchange factor 11 (ARHGEF11). [10]
Coumarin DM0N8ZM Investigative Coumarin increases the phosphorylation of Rho guanine nucleotide exchange factor 11 (ARHGEF11). [10]
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References

1 Genetic variants in Arhgef11 are associated with kidney injury in the Dahl salt-sensitive rat.Hypertension. 2012 Nov;60(5):1157-68. doi: 10.1161/HYPERTENSIONAHA.112.199240. Epub 2012 Sep 17.
2 Human Rho guanine nucleotide exchange factor 11 gene is associated with schizophrenia in a Japanese population.Hum Psychopharmacol. 2014 Nov;29(6):552-8. doi: 10.1002/hup.2435. Epub 2014 Oct 15.
3 PDZ-RhoGEF Is a Signaling Effector for TROY-Induced Glioblastoma Cell Invasion and Survival.Neoplasia. 2018 Oct;20(10):1045-1058. doi: 10.1016/j.neo.2018.08.008. Epub 2018 Sep 13.
4 A nonsynonymous single-nucleotide polymorphism in the PDZ-Rho guanine nucleotide exchange factor (Ser1416Gly) modulates the risk of lung cancer in Mexican Americans.Cancer. 2006 Jun 15;106(12):2716-24. doi: 10.1002/cncr.21944.
5 The exon 38-containing ARHGEF11 splice isoform is differentially expressed and is required for migration and growth in invasive breast cancer cells.Oncotarget. 2017 Sep 18;8(54):92157-92170. doi: 10.18632/oncotarget.20985. eCollection 2017 Nov 3.
6 Variants in ARHGEF11, a candidate gene for the linkage to type 2 diabetes on chromosome 1q, are nominally associated with insulin resistance and type 2 diabetes in Pima Indians.Diabetes. 2007 May;56(5):1454-9. doi: 10.2337/db06-0640. Epub 2007 Feb 7.
7 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.
8 Calcineurin is an important factor involved in glucose uptake in human adipocytes. Mol Cell Biochem. 2018 Aug;445(1-2):157-168. doi: 10.1007/s11010-017-3261-0. Epub 2018 Jan 27.
9 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
10 Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
11 Allelic Variants in Arhgef11 via the Rho-Rock Pathway Are Linked to Epithelial-Mesenchymal Transition and Contributes to Kidney Injury in the Dahl Salt-Sensitive Rat. PLoS One. 2015 Jul 14;10(7):e0132553. doi: 10.1371/journal.pone.0132553. eCollection 2015.