Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJLVIQ1)

• DOT Name: Rab-like protein 6 (RABL6)
• Synonyms: GTP-binding protein Parf; Partner of ARF; Rab-like protein 1; RBEL1
• Gene Name: RABL6
• Related Disease:
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Intellectual disability
  Neoplasm
  Bone osteosarcoma
  Osteosarcoma
• UniProt ID: RABL6_HUMAN
• Pfam ID: PF08477
• Sequence:
  MFSALKKLVGSDQAPGRDKNIPAGLQSMNQALQRRFAKGVQYNMKIVIRGDRNTGKTALW
  HRLQGRPFVEEYIPTQEIQVTSIHWSYKTTDDIVKVEVWDVVDKGKCKKRGDGLKMENDP
  QEAESEMALDAEFLDVYKNCNGVVMMFDITKQWTFNYILRELPKVPTHVPVCVLGNYRDM
  GEHRVILPDDVRDFIDNLDRPPGSSYFRYAESSMKNSFGLKYLHKFFNIPFLQLQRETLL
  RQLETNQLDMDATLEELSVQQETEDQNYGIFLEMMEARSRGHASPLAANGQSPSPGSQSP
  VVPAGAVSTGSSSPGTPQPAPQLPLNAAPPSSVPPVPPSEALPPPACPSAPAPRRSIISR
  LFGTSPATEAAPPPPEPVPAAEGPATVQSVEDFVPDDRLDRSFLEDTTPARDEKKVGAKA
  AQQDSDSDGEALGGNPMVAGFQDDVDLEDQPRGSPPLPAGPVPSQDITLSSEEEAEVAAP
  TKGPAPAPQQCSEPETKWSSIPASKPRRGTAPTRTAAPPWPGGVSVRTGPEKRSSTRPPA
  EMEPGKGEQASSSESDPEGPIAAQMLSFVMDDPDFESEGSDTQRRADDFPVRDDPSDVTD
  EDEGPAEPPPPPKLPLPAFRLKNDSDLFGLGLEEAGPKESSEEGKEGKTPSKEKKKKKKK
  GKEEEEKAAKKKSKHKKSKDKEEGKEERRRRQQRPPRSRERTAADELEAFLGGGAPGGRH
  PGGGDYEEL
• Function: May enhance cellular proliferation. May reduce growth inhibitory activity of CDKN2A.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[1]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[2]
Intellectual disability	DISMBNXP	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Bone osteosarcoma	DIST1004	Limited	Biomarker	[4]
Osteosarcoma	DISLQ7E2	Limited	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Rab-like protein 6 (RABL6).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Rab-like protein 6 (RABL6).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Rab-like protein 6 (RABL6).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Rab-like protein 6 (RABL6).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Rab-like protein 6 (RABL6).	[10]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Rab-like protein 6 (RABL6).	[11]
MG-132	DMKA2YS	Preclinical	MG-132 decreases the expression of Rab-like protein 6 (RABL6).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Rab-like protein 6 (RABL6).	[14]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Rab-like protein 6 (RABL6).	[15]
biochanin A	DM0HPWY	Investigative	biochanin A decreases the expression of Rab-like protein 6 (RABL6).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Rab-like protein 6 (RABL6).	[9]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Rab-like protein 6 (RABL6).	[12]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Rab-like protein 6 (RABL6).	[12]

References

• [1] RBEL1 is a novel gene that encodes a nucleocytoplasmic Ras superfamily GTP-binding protein and is overexpressed in breast cancer.J Biol Chem. 2007 Dec 28;282(52):37640-9. doi: 10.1074/jbc.M704760200. Epub 2007 Oct 25.
• [2] Down-regulation of c9orf86 in human breast cancer cells inhibits cell proliferation, invasion and tumor growth and correlates with survival of breast cancer patients.PLoS One. 2013 Aug 14;8(8):e71764. doi: 10.1371/journal.pone.0071764. eCollection 2013.
• [3] Deep sequencing reveals 50 novel genes for recessive cognitive disorders. Nature. 2011 Sep 21;478(7367):57-63. doi: 10.1038/nature10423.
• [4] RBEL1 is required for osteosarcoma cell proliferation via inhibiting retinoblastoma 1.Mol Med Rep. 2016 Feb;13(2):1275-80. doi: 10.3892/mmr.2015.4670. Epub 2015 Dec 10.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 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.
• [9] 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.
• [10] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [11] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [12] 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.
• [13] Proteasome inhibition creates a chromatin landscape favorable to RNA Pol II processivity. J Biol Chem. 2020 Jan 31;295(5):1271-1287. doi: 10.1074/jbc.RA119.011174. Epub 2019 Dec 5.
• [14] Exposure to environmental bisphenol A inhibits HTR-8/SVneo cell migration and invasion. J Biomed Res. 2020 Jun 30;34(5):369-378. doi: 10.7555/JBR.34.20200013.
• [15] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [16] Mechanisms of the growth inhibitory effects of the isoflavonoid biochanin A on LNCaP cells and xenografts. Prostate. 2002 Aug 1;52(3):201-12.