Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHJUCO1)

DOT Name Rho GTPase-activating protein 44 (ARHGAP44)
Synonyms NPC-A-10; Rho-type GTPase-activating protein RICH2; RhoGAP interacting with CIP4 homologs protein 2; RICH-2
Gene Name ARHGAP44
Related Disease
Hepatocellular carcinoma ( )
Neoplasm ( )
Phobic disorder ( )
UniProt ID
RHG44_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF03114 ; PF00620
Sequence
MKKQFNRMRQLANQTVGRAEKTEVLSEDLLQVEKRLELVKQVSHSTHKKLTACLQGQQGA
EADKRSKKLPLTTLAQCLMEGSAILGDDTLLGKMLKLCGETEDKLAQELIHFELQVERDV
IEPLFLLAEVEIPNIQKQRKHLAKLVLDMDSSRTRWQQTSKSSGLSSSLQPAGAKADALR
EEMEEAANRVEICRDQLSADMYSFVAKEIDYANYFQTLIEVQAEYHRKSLTLLQAVLPQI
KAQQEAWVEKPSFGKPLEEHLTISGREIAFPIEACVTMLLECGMQEEGLFRVAPSASKLK
KLKAALDCCVVDVQEYSADPHAIAGALKSYLRELPEPLMTFELYDEWIQASNVQEQDKKL
QALWNACEKLPKANHNNIRYLIKFLSKLSEYQDVNKMTPSNMAIVLGPNLLWPQAEGNIT
EMMTTVSLQIVGIIEPIIQHADWFFPGEIEFNITGNYGSPVHVNHNANYSSMPSPDMDPA
DRRQPEQARRPLSVATDNMMLEFYKKDGLRKIQSMGVRVMDTNWVARRGSSAGRKVSCAP
PSMQPPAPPAELAAPLPSPLPEQPLDSPAAPALSPSGLGLQPGPERTSTTKSKELSPGSA
QKGSPGSSQGTACAGTQPGAQPGAQPGASPSPSQPPADQSPHTLRKVSKKLAPIPPKVPF
GQPGAMADQSAGQPSPVSLSPTPPSTPSPYGLSYPQGYSLASGQLSPAAAPPLASPSVFT
STLSKSRPTPKPRQRPTLPPPQPPTVNLSASSPQSTEAPMLDGMSPGESMSTDLVHFDIP
SIHIELGSTLRLSPLEHMRRHSVTDKRDSEEESESTAL
Function
GTPase-activating protein (GAP) that stimulates the GTPase activity of Rho-type GTPases. Thereby, controls Rho-type GTPases cycling between their active GTP-bound and inactive GDP-bound states. Acts as a GAP at least for CDC42 and RAC1. In neurons, is involved in dendritic spine formation and synaptic plasticity in a specific RAC1-GAP activity. Limits the initiation of exploratory dendritic filopodia. Recruited to actin-patches that seed filopodia, binds specifically to plasma membrane sections that are deformed inward by acto-myosin mediated contractile forces. Acts through GAP activity on RAC1 to reduce actin polymerization necessary for filopodia formation. In association with SHANK3, promotes GRIA1 exocytosis from recycling endosomes and spine morphological changes associated to long-term potentiation.
Tissue Specificity Highly expressed in brain. Expressed at weak level in other tissues.
Reactome Pathway
CDC42 GTPase cycle (R-HSA-9013148 )
RAC1 GTPase cycle (R-HSA-9013149 )
RHOA GTPase cycle (R-HSA-8980692 )

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Hepatocellular carcinoma DIS0J828 Definitive Biomarker [1]
Neoplasm DISZKGEW Definitive Biomarker [1]
Phobic disorder DISX6DUL Limited Biomarker [2]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
7 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of Rho GTPase-activating protein 44 (ARHGAP44). [3]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Rho GTPase-activating protein 44 (ARHGAP44). [4]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Rho GTPase-activating protein 44 (ARHGAP44). [5]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Rho GTPase-activating protein 44 (ARHGAP44). [6]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Rho GTPase-activating protein 44 (ARHGAP44). [7]
Cytarabine DMZD5QR Approved Cytarabine decreases the expression of Rho GTPase-activating protein 44 (ARHGAP44). [8]
OXYQUINOLINE DMZVS9Y Investigative OXYQUINOLINE decreases the expression of Rho GTPase-activating protein 44 (ARHGAP44). [7]
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⏷ Show the Full List of 7 Drug(s)
2 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 GTPase-activating protein 44 (ARHGAP44). [9]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Rho GTPase-activating protein 44 (ARHGAP44). [10]
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References

1 RICH2, a potential tumor suppressor in hepatocellular carcinoma.Front Biosci (Landmark Ed). 2019 Jun 1;24(8):1363-1376. doi: 10.2741/4784.
2 Object Phobia and Altered RhoA Signaling in Amygdala of Mice Lacking RICH2.Front Mol Neurosci. 2017 Jun 8;10:180. doi: 10.3389/fnmol.2017.00180. eCollection 2017.
3 Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
4 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
5 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.
6 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
7 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.
8 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.
9 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.
10 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.