Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGB32NG)

• DOT Name: Prenylated Rab acceptor protein 1 (RABAC1)
• Synonyms: PRA1 family protein 1
• Gene Name: RABAC1
• Related Disease:
  Advanced cancer
  Malignant glioma
  Neoplasm
  Hepatocellular carcinoma
• UniProt ID: PRAF1_HUMAN
• Pfam ID: PF03208
• Sequence:
  MAAQKDQQKDAEAEGLSGTTLLPKLIPSGAGREWLERRRATIRPWSTFVDQQRFSRPRNL
  GELCQRLVRNVEYYQSNYVFVFLGLILYCVVTSPMLLVALAVFFGACYILYLRTLESKLV
  LFGREVSPAHQYALAGGISFPFFWLAGAGSAVFWVLGATLVVIGSHAAFHQIEAVDGEEL
  QMEPV
• Function: General Rab protein regulator required for vesicle formation from the Golgi complex. May control vesicle docking and fusion by mediating the action of Rab GTPases to the SNARE complexes. In addition it inhibits the removal of Rab GTPases from the membrane by GDI.
• Tissue Specificity: Ubiquitous. Strongest expression found in placenta, pituitary gland, kidney, lung and stomach.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Malignant glioma	DISFXKOV	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Prenylated Rab acceptor protein 1 (RABAC1).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Prenylated Rab acceptor protein 1 (RABAC1).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Prenylated Rab acceptor protein 1 (RABAC1).	[7]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Prenylated Rab acceptor protein 1 (RABAC1).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Prenylated Rab acceptor protein 1 (RABAC1).	[9]
Selenium	DM25CGV	Approved	Selenium increases the expression of Prenylated Rab acceptor protein 1 (RABAC1).	[10]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Prenylated Rab acceptor protein 1 (RABAC1).	[10]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Prenylated Rab acceptor protein 1 (RABAC1).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Prenylated Rab acceptor protein 1 (RABAC1).	[12]

References

• [1] Prenylated Rab acceptor RABAC1 inhibits anti-apoptotic protein BCL2A1 and induces apoptosis.Biochem Biophys Res Commun. 2019 Jun 11;513(4):940-946. doi: 10.1016/j.bbrc.2019.04.080. Epub 2019 Apr 17.
• [2] Subcellular distribution and expression of prenylated Rab acceptor 1 domain family, member 2 (PRAF2) in malignant glioma: Influence on cell survival and migration.Cancer Sci. 2010 Jul;101(7):1624-31. doi: 10.1111/j.1349-7006.2010.01570.x. Epub 2010 Mar 19.
• [3] Comparison of protein expression between formalin-fixed core-cut biopsies and surgical excision specimens using a novel multiplex approach.Breast Cancer Res Treat. 2019 Jun;175(2):317-326. doi: 10.1007/s10549-019-05163-6. Epub 2019 Feb 22.
• [4] PRAF2 expression indicates unfavorable clinical outcome in hepatocellular carcinoma.Cancer Manag Res. 2018 Jul 25;10:2241-2248. doi: 10.2147/CMAR.S166789. eCollection 2018.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [7] 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.
• [8] 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.
• [9] Gene microarray analysis of human renal cell carcinoma: the effects of HDAC inhibition and retinoid treatment. Cancer Biol Ther. 2008 Oct;7(10):1607-18.
• [10] 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.
• [11] Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.