Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9ZS72C)

DOT Name SLIT-ROBO Rho GTPase-activating protein 3 (SRGAP3)
Synonyms srGAP3; Mental disorder-associated GAP; Rho GTPase-activating protein 14; WAVE-associated Rac GTPase-activating protein; WRP
Gene Name SRGAP3
Related Disease
Neurodevelopmental disorder ( )
Schizophrenia ( )
High blood pressure ( )
Infantile epileptic-dyskinetic encephalopathy ( )
Intellectual disability ( )
Myopathy ( )
Neoplasm ( )
Neuroblastoma ( )
Parkinson disease ( )
UniProt ID
SRGP3_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00611 ; PF00620 ; PF00018
Sequence
MSSQTKFKKDKEIIAEYEAQIKEIRTQLVEQFKCLEQQSESRLQLLQDLQEFFRRKAEIE
LEYSRSLEKLAERFSSKIRSSREHQFKKDQYLLSPVNCWYLVLHQTRRESRDHATLNDIF
MNNVIVRLSQISEDVIRLFKKSKEIGLQMHEELLKVTNELYTVMKTYHMYHAESISAESK
LKEAEKQEEKQFNKSGDLSMNLLRHEDRPQRRSSVKKIEKMKEKRQAKYSENKLKCTKAR
NDYLLNLAATNAAISKYYIHDVSDLIDCCDLGFHASLARTFRTYLSAEYNLETSRHEGLD
VIENAVDNLDSRSDKHTVMDMCNQVFCPPLKFEFQPHMGDEVCQVSAQQPVQTELLMRYH
QLQSRLATLKIENEEVRKTLDATMQTLQDMLTVEDFDVSDAFQHSRSTESVKSAASETYM
SKINIAKRRANQQETEMFYFTKFKEYVNGSNLITKLQAKHDLLKQTLGEGERAECGTTRP
PCLPPKPQKMRRPRPLSVYSHKLFNGSMEAFIKDSGQAIPLVVESCIRYINLYGLQQQGI
FRVPGSQVEVNDIKNSFERGEDPLVDDQNERDINSVAGVLKLYFRGLENPLFPKERFQDL
ISTIKLENPAERVHQIQQILVTLPRVVIVVMRYLFAFLNHLSQYSDENMMDPYNLAICFG
PTLMHIPDGQDPVSCQAHINEVIKTIIIHHEAIFPSPRELEGPVYEKCMAGGEEYCDSPH
SEPGAIDEVDHDNGTEPHTSDEEVEQIEAIAKFDYMGRSPRELSFKKGASLLLYHRASED
WWEGRHNGVDGLIPHQYIVVQDMDDAFSDSLSQKADSEASSGPLLDDKASSKNDLQSPTE
HISDYGFGGVMGRVRLRSDGAAIPRRRSGGDTHSPPRGLGPSIDTPPRAAACPSSPHKIP
LTRGRIESPEKRRMATFGSAGSINYPDKKALSEGHSMRSTCGSTRHSSLGDHKSLEAEAL
AEDIEKTMSTALHELRELERQNTVKQAPDVVLDTLEPLKNPPGPVSSEPASPLHTIVIRD
PDAAMRRSSSSSTEMMTTFKPALSARLAGAQLRPPPMRPVRPVVQHRSSSSSSSGVGSPA
VTPTEKMFPNSSADKSGTM
Function GTPase-activating protein for RAC1 and perhaps Cdc42, but not for RhoA small GTPase. May attenuate RAC1 signaling in neurons.
Tissue Specificity Highly expressed in adult and fetal brain. Expressed at low levels in kidney. Isoform 3 is expressed in the kidney but is absent in the brain.
KEGG Pathway
Axon guidance (hsa04360 )
Reactome Pathway
CDC42 GTPase cycle (R-HSA-9013148 )
RAC1 GTPase cycle (R-HSA-9013149 )
Inactivation of CDC42 and RAC1 (R-HSA-428543 )

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Neurodevelopmental disorder DIS372XH Definitive Biomarker [1]
Schizophrenia DISSRV2N Definitive Biomarker [2]
High blood pressure DISY2OHH Strong Genetic Variation [3]
Infantile epileptic-dyskinetic encephalopathy DISD2ZNC Strong Genetic Variation [4]
Intellectual disability DISMBNXP Strong Biomarker [5]
Myopathy DISOWG27 Strong Biomarker [6]
Neoplasm DISZKGEW Limited Biomarker [7]
Neuroblastoma DISVZBI4 Limited Biomarker [8]
Parkinson disease DISQVHKL Limited Biomarker [9]
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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
4 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of SLIT-ROBO Rho GTPase-activating protein 3 (SRGAP3). [10]
Ciclosporin DMAZJFX Approved Ciclosporin increases the methylation of SLIT-ROBO Rho GTPase-activating protein 3 (SRGAP3). [11]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of SLIT-ROBO Rho GTPase-activating protein 3 (SRGAP3). [19]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of SLIT-ROBO Rho GTPase-activating protein 3 (SRGAP3). [20]
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12 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of SLIT-ROBO Rho GTPase-activating protein 3 (SRGAP3). [12]
Estradiol DMUNTE3 Approved Estradiol affects the expression of SLIT-ROBO Rho GTPase-activating protein 3 (SRGAP3). [13]
Quercetin DM3NC4M Approved Quercetin increases the expression of SLIT-ROBO Rho GTPase-activating protein 3 (SRGAP3). [14]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of SLIT-ROBO Rho GTPase-activating protein 3 (SRGAP3). [15]
Dexamethasone DMMWZET Approved Dexamethasone increases the expression of SLIT-ROBO Rho GTPase-activating protein 3 (SRGAP3). [16]
Cytarabine DMZD5QR Approved Cytarabine increases the expression of SLIT-ROBO Rho GTPase-activating protein 3 (SRGAP3). [17]
2-deoxyglucose DMIAHVU Approved 2-deoxyglucose decreases the expression of SLIT-ROBO Rho GTPase-activating protein 3 (SRGAP3). [18]
Resveratrol DM3RWXL Phase 3 Resveratrol increases the expression of SLIT-ROBO Rho GTPase-activating protein 3 (SRGAP3). [16]
Camptothecin DM6CHNJ Phase 3 Camptothecin decreases the expression of SLIT-ROBO Rho GTPase-activating protein 3 (SRGAP3). [18]
Trichostatin A DM9C8NX Investigative Trichostatin A affects the expression of SLIT-ROBO Rho GTPase-activating protein 3 (SRGAP3). [21]
Sulforaphane DMQY3L0 Investigative Sulforaphane decreases the expression of SLIT-ROBO Rho GTPase-activating protein 3 (SRGAP3). [22]
Apicidin DM83WVF Investigative Apicidin decreases the expression of SLIT-ROBO Rho GTPase-activating protein 3 (SRGAP3). [18]
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⏷ Show the Full List of 12 Drug(s)

References

1 Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases. Nat Genet. 2017 Apr;49(4):515-526. doi: 10.1038/ng.3792. Epub 2017 Feb 13.
2 Srgap3??mice present a neurodevelopmental disorder with schizophrenia-related intermediate phenotypes.FASEB J. 2012 Nov;26(11):4418-28. doi: 10.1096/fj.11-202317. Epub 2012 Jul 20.
3 A genome-wide linkage and association scan reveals novel loci for hypertension and blood pressure traits.PLoS One. 2012;7(2):e31489. doi: 10.1371/journal.pone.0031489. Epub 2012 Feb 24.
4 Early infantile epileptic encephalopathy associated with the disrupted gene encoding Slit-Robo Rho GTPase activating protein 2 (SRGAP2).Am J Med Genet A. 2012 Jan;158A(1):199-205. doi: 10.1002/ajmg.a.34363. Epub 2011 Nov 21.
5 Regulation of synaptic architecture and synaptic vesicle pools by Nervous wreck at Drosophila Type 1b glutamatergic synapses.Exp Mol Med. 2018 Mar 23;50(3):e462. doi: 10.1038/emm.2017.303.
6 Interstitial 3p25.3-p26.1 deletion in a patient with intellectual disability.Am J Med Genet A. 2012 Oct;158A(10):2587-90. doi: 10.1002/ajmg.a.35562. Epub 2012 Sep 10.
7 A tumor suppressor role for srGAP3 in mammary epithelial cells.Oncogene. 2013 Oct;32(40):4854-60. doi: 10.1038/onc.2012.489. Epub 2012 Oct 29.
8 The inverse F-BAR domain protein srGAP2 acts through srGAP3 to modulate neuronal differentiation and neurite outgrowth of mouse neuroblastoma cells.PLoS One. 2013;8(3):e57865. doi: 10.1371/journal.pone.0057865. Epub 2013 Mar 7.
9 Single-cell expression profiling of dopaminergic neurons combined with association analysis identifies pyridoxal kinase as Parkinson's disease gene.Ann Neurol. 2009 Dec;66(6):792-8. doi: 10.1002/ana.21780.
10 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
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 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
13 Research resource: STR DNA profile and gene expression comparisons of human BG-1 cells and a BG-1/MCF-7 clonal variant. Mol Endocrinol. 2014 Dec;28(12):2072-81.
14 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.
15 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
16 Influence of resveratrol on rheumatoid fibroblast-like synoviocytes analysed with gene chip transcription. Phytomedicine. 2013 Feb 15;20(3-4):310-8. doi: 10.1016/j.phymed.2012.09.020. Epub 2012 Nov 6.
17 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.
18 Development and validation of the TGx-HDACi transcriptomic biomarker to detect histone deacetylase inhibitors in human TK6 cells. Arch Toxicol. 2021 May;95(5):1631-1645. doi: 10.1007/s00204-021-03014-2. Epub 2021 Mar 26.
19 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.
20 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.
21 A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
22 Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.