Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTP1OV78)

• DOT Name: ADP-ribosylation factor-related protein 1 (ARFRP1)
• Synonyms: ARF-related protein 1; ARP
• Gene Name: ARFRP1
• Related Disease:
  Acute leukaemia
  Carcinoma of esophagus
  Choriocarcinoma
  Esophageal cancer
  Esophageal squamous cell carcinoma
  Hepatocellular carcinoma
  Immunodeficiency
  Neoplasm of esophagus
  Pancreatic cancer
  Pancreatitis
  Plasma cell myeloma
  Spinocerebellar ataxia type 5
  Syphilis
• UniProt ID: ARFRP_HUMAN
• Pfam ID: PF00025
• Sequence:
  MYTLLSGLYKYMFQKDEYCILILGLDNAGKTTFLEQSKTRFNKNYKGMSLSKITTTVGLN
  IGTVDVGKARLMFWDLGGQEELQSLWDKYYAECHGVIYVIDSTDEERLAESKQAFEKVVT
  SEALCGVPVLVLANKQDVETCLSIPDIKTAFSDCTSKIGRRDCLTQACSALTGKGVREGI
  EWMVKCVVRNVHRPPRQRDIT
• Function: Trans-Golgi-associated GTPase that regulates protein sorting. Controls the targeting of ARL1 and its effector to the trans-Golgi. Required for the lipidation of chylomicrons in the intestine and required for VLDL lipidation in the liver.
• Tissue Specificity: Found in most tissues.
• Reactome Pathway: Retrograde transport at the Trans-Golgi-Network (R-HSA-6811440)

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute leukaemia	DISDQFDI	Strong	Genetic Variation	[1]
Carcinoma of esophagus	DISS6G4D	Strong	Genetic Variation	[2]
Choriocarcinoma	DISDBVNL	Strong	Altered Expression	[3]
Esophageal cancer	DISGB2VN	Strong	Genetic Variation	[2]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Genetic Variation	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[4]
Immunodeficiency	DIS093I0	Strong	Biomarker	[5]
Neoplasm of esophagus	DISOLKAQ	Strong	Genetic Variation	[2]
Pancreatic cancer	DISJC981	Strong	Genetic Variation	[6]
Pancreatitis	DIS0IJEF	Strong	Biomarker	[7]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[8]
Spinocerebellar ataxia type 5	DISPYXJ0	Strong	Genetic Variation	[9]
Syphilis	DISJ73BS	Limited	Genetic Variation	[10]

3 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 ADP-ribosylation factor-related protein 1 (ARFRP1).	[11]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of ADP-ribosylation factor-related protein 1 (ARFRP1).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of ADP-ribosylation factor-related protein 1 (ARFRP1).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Selenium	DM25CGV	Approved	Selenium increases the expression of ADP-ribosylation factor-related protein 1 (ARFRP1).	[12]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of ADP-ribosylation factor-related protein 1 (ARFRP1).	[14]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of ADP-ribosylation factor-related protein 1 (ARFRP1).	[16]

References

• [1] Identification and characterization of the ARP1 gene, a target for the human acute leukemia ALL1 gene.Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4573-8. doi: 10.1073/pnas.95.8.4573.
• [2] Polymorphic variation of the ARP gene on 3p21 in Japanese esophageal cancer patients.Oncol Rep. 2000 May-Jun;7(3):591-3. doi: 10.3892/or.7.3.591.
• [3] The ARP-1 orphan receptor represses steroid-mediated stimulation of human placental lactogen gene expression.J Mol Endocrinol. 1996 Jun;16(3):221-7. doi: 10.1677/jme.0.0160221.
• [4] Repression by ARP-1 sensitizes apolipoprotein AI gene responsiveness to RXR alpha and retinoic acid.Mol Cell Biol. 1992 Aug;12(8):3380-9. doi: 10.1128/mcb.12.8.3380-3389.1992.
• [5] Rice-based oral antibody fragment prophylaxis and therapy against rotavirus infection.J Clin Invest. 2013 Sep;123(9):3829-38. doi: 10.1172/JCI70266. Epub 2013 Aug 8.
• [6] Lack of association between UGT1A7, UGT1A9, ARP, SPINK1 and CFTR gene polymorphisms and pancreatic cancer in Italian patients.World J Gastroenterol. 2006 Oct 21;12(39):6343-8. doi: 10.3748/wjg.v12.i39.6343.
• [7] An Evaluation of Factors Associated With Pathogenic PRSS1, SPINK1, CTFR, and/or CTRC Genetic Variants in Patients With Idiopathic Pancreatitis.Am J Gastroenterol. 2017 Aug;112(8):1320-1329. doi: 10.1038/ajg.2017.106. Epub 2017 Apr 25.
• [8] DCZ0814 induces apoptosis and G0/G1 phase cell cycle arrest in myeloma by dual inhibition of mTORC1/2.Cancer Manag Res. 2019 May 27;11:4797-4808. doi: 10.2147/CMAR.S194202. eCollection 2019.
• [9] Beta-III spectrin mutation L253P associated with spinocerebellar ataxia type 5 interferes with binding to Arp1 and protein trafficking from the Golgi.Hum Mol Genet. 2010 Sep 15;19(18):3634-41. doi: 10.1093/hmg/ddq279. Epub 2010 Jul 5.
• [10] Multicentre surveillance of prevalence of the 23S rRNA A2058G and A2059G point mutations and molecular subtypes of Treponema pallidum in Taiwan, 2009-2013.Clin Microbiol Infect. 2014 Aug;20(8):802-7. doi: 10.1111/1469-0691.12529. Epub 2014 Feb 13.
• [11] 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.
• [12] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [13] 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.
• [14] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [15] 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.
• [16] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.