Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8C6PKL)

• DOT Name: Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 3 (AGAP3)
• Synonyms: AGAP-3; CRAM-associated GTPase; CRAG; Centaurin-gamma-3; Cnt-g3; MR1-interacting protein; MRIP-1
• Gene Name: AGAP3
• Related Disease:
  Colorectal adenoma
  Colorectal carcinoma
  Schizophrenia
  Melanoma
  Neuroblastic tumor
• UniProt ID: AGAP3_HUMAN
• PDB ID: 3IHW
• Pfam ID: PF12796 ; PF01412 ; PF00071
• Sequence:
  MNFQAGGGQSPQQQQQLAGGPPQQFALSNSAAIRAEIQRFESVHPNIYAIYDLIERIEDL
  ALQNQIREHVISIEDSFVNSQEWTLSRSVPELKVGIVGNLSSGKSALVHRYLTGTYVQEE
  SPEGGRFKKEIVVDGQSYLLLIRDEGGPPELQFAAWVDAVVFVFSLEDEISFQTVYNYFL
  RLCSFRNASEVPMVLVGTQDAISAANPRVIDDSRARKLSTDLKRCTYYETCATYGLNVER
  VFQDVAQKVVALRKKQQLAIGPCKSLPNSPSHSAVSAASIPAVHINQATNGGGSAFSDYS
  SSVPSTPSISQRELRIETIAASSTPTPIRKQSKRRSNIFTSRKGADLDREKKAAECKVDS
  IGSGRAIPIKQGILLKRSGKSLNKEWKKKYVTLCDNGLLTYHPSLHDYMQNIHGKEIDLL
  RTTVKVPGKRLPRATPATAPGTSPRANGLSVERSNTQLGGGTGAPHSASSASLHSERPLS
  SSAWAGPRPEGLHQRSCSVSSADQWSEATTSLPPGMQHPASGPAEVLSSSPKLDPPPSPH
  SNRKKHRRKKSTGTPRPDGPSSATEEAEESFEFVVVSLTGQTWHFEASTAEERELWVQSV
  QAQILASLQGCRSAKDKTRLGNQNAALAVQAVRTVRGNSFCIDCDAPNPDWASLNLGALM
  CIECSGIHRHLGAHLSRVRSLDLDDWPPELLAVMTAMGNALANSVWEGALGGYSKPGPDA
  CREEKERWIRAKYEQKLFLAPLPSSDVPLGQQLLRAVVEDDLRLLVMLLAHGSKEEVNET
  YGDGDGRTALHLSSAMANVVFTQLLIWYGVDVRSRDARGLTPLAYARRAGSQECADILIQ
  HGCPGEGCGLAPTPNREPANGTNPSAELHRSPSLL
• Function: GTPase-activating protein for the ADP ribosylation factor family (Potential). GTPase which may be involved in the degradation of expanded polyglutamine proteins through the ubiquitin-proteasome pathway.
• Tissue Specificity: Widely expressed.
• KEGG Pathway: Endocytosis (hsa04144)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal adenoma	DISTSVHM	Strong	Altered Expression	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[1]
Schizophrenia	DISSRV2N	Strong	Biomarker	[2]
Melanoma	DIS1RRCY	Limited	Biomarker	[3]
Neuroblastic tumor	DISKWPS1	Limited	Biomarker	[4]

2 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 Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 3 (AGAP3).	[5]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 3 (AGAP3).	[7]

9 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 3 (AGAP3).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 3 (AGAP3).	[8]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 3 (AGAP3).	[9]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 3 (AGAP3).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 3 (AGAP3).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 3 (AGAP3).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 3 (AGAP3).	[13]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 3 (AGAP3).	[14]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 3 (AGAP3).	[15]

References

• [1] CRMP5-associated GTPase (CRAG) Is a Candidate Driver Gene for Colorectal Cancer Carcinogenesis.Anticancer Res. 2019 Jan;39(1):99-106. doi: 10.21873/anticanres.13084.
• [2] Family study of schizophrenia: exploratory analysis for relevant factors.Schizophr Bull. 1986;12(1):120-8. doi: 10.1093/schbul/12.1.120.
• [3] BRAF Fusion as a Novel Mechanism of Acquired Resistance to Vemurafenib in BRAF(V600E) Mutant Melanoma.Clin Cancer Res. 2017 Sep 15;23(18):5631-5638. doi: 10.1158/1078-0432.CCR-16-0758. Epub 2017 May 24.
• [4] Exome sequencing identifies predisposing and fusion gene in ganglioneuroma, ganglioneuroblastoma and neuroblastoma.Math Biosci Eng. 2019 Aug 8;16(6):7217-7229. doi: 10.3934/mbe.2019362.
• [5] 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.
• [6] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [7] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [8] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [9] Gene expression in endometrial cancer cells (Ishikawa) after short time high dose exposure to progesterone. Steroids. 2008 Jan;73(1):116-28.
• [10] Cellular response to 5-fluorouracil (5-FU) in 5-FU-resistant colon cancer cell lines during treatment and recovery. Mol Cancer. 2006 May 18;5:20. doi: 10.1186/1476-4598-5-20.
• [11] Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
• [12] 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.
• [13] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [14] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.
• [15] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.