Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXHWO6M)

• DOT Name: Arfaptin-1 (ARFIP1)
• Synonyms: ADP-ribosylation factor-interacting protein 1
• Gene Name: ARFIP1
• Related Disease:
  Fibrosarcoma
  Vibrio cholerae infection
• UniProt ID: ARFP1_HUMAN
• Pfam ID: PF06456
• Sequence:
  MAQESPKNSAAEIPVTSNGEVDDSREHSFNRDLKHSLPSGLGLSETQITSHGFDNTKEGV
  IEAGAFQGSPAPPLPSVMSPSRVAASRLAQQGSDLIVPAGGQRTQTKSGPVILADEIKNP
  AMEKLELVRKWSLNTYKCTRQIISEKLGRGSRTVDLELEAQIDILRDNKKKYENILKLAQ
  TLSTQLFQMVHTQRQLGDAFADLSLKSLELHEEFGYNADTQKLLAKNGETLLGAINFFIA
  SVNTLVNKTIEDTLMTVKQYESARIEYDAYRTDLEELNLGPRDANTLPKIEQSQHLFQAH
  KEKYDKMRNDVSVKLKFLEENKVKVLHNQLVLFHNAIAAYFAGNQKQLEQTLKQFHIKLK
  TPGVDAPSWLEEQ
• Function: Plays a role in controlling biogenesis of secretory granules at the trans-Golgi network. Mechanistically, binds ARF-GTP at the neck of a growing secretory granule precursor and forms a protective scaffold. Once the granule precursor has been completely loaded, active PRKD1 phosphorylates ARFIP1 and releases it from ARFs. In turn, ARFs induce fission. Through this mechanism, ensures proper secretory granule formation at the Golgi of pancreatic beta cells.
• Tissue Specificity: Ubiquitously expressed . Higher levels in liver, pancreas, placenta, skeletal muscle and heart .

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Fibrosarcoma	DISWX7MU	Strong	Biomarker	[1]
Vibrio cholerae infection	DISW7E3U	Strong	Altered Expression	[1]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Arfaptin-1 (ARFIP1) affects the response to substance of Methotrexate.	[10]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Arfaptin-1 (ARFIP1).	[2]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Arfaptin-1 (ARFIP1).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Arfaptin-1 (ARFIP1).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Arfaptin-1 (ARFIP1).	[4]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Arfaptin-1 (ARFIP1).	[5]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Arfaptin-1 (ARFIP1).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Arfaptin-1 (ARFIP1).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Arfaptin-1 (ARFIP1).	[9]

References

• [1] Arfaptin 1 inhibits ADP-ribosylation factor-dependent matrix metalloproteinase-9 secretion induced by phorbol ester in HT 1080 fibrosarcoma cells.FEBS Lett. 2003 Feb 27;537(1-3):91-5. doi: 10.1016/s0014-5793(03)00098-x.
• [2] 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.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [5] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [6] 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.
• [7] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [8] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [9] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [10] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.