Details of Drug Off-Target (DOT)

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

• DOT Name: Ras-related protein Rab-43 (RAB43)
• Synonyms: Ras-related protein Rab-41
• Gene Name: RAB43
• Related Disease:
  Advanced cancer
  Colon cancer
  Colon carcinoma
  Glioma
• UniProt ID: RAB43_HUMAN
• PDB ID: 2HUP
• Pfam ID: PF00071
• Sequence:
  MAGPGPGPGDPDEQYDFLFKLVLVGDASVGKTCVVQRFKTGAFSERQGSTIGVDFTMKTL
  EIQGKRVKLQIWDTAGQERFRTITQSYYRSANGAILAYDITKRSSFLSVPHWIEDVRKYA
  GSNIVQLLIGNKSDLSELREVSLAEAQSLAEHYDILCAIETSAKDSSNVEEAFLRVATEL
  IMRHGGPLFSEKSPDHIQLNSKDIGEGWGCGC
• Function: The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. The low intrinsic GTPase activity of RAB43 is activated by USP6NL. Involved in retrograde transport from the endocytic pathway to the Golgi apparatus. Involved in the transport of Shiga toxin from early and recycling endosomes to the trans-Golgi network. Required for the structural integrity of the Golgi complex. Plays a role in the maturation of phagosomes that engulf pathogens, such as S.aureus and M.tuberculosis.
• Tissue Specificity: Widely expressed in brain, testis, lung, heart, ovary, colon, kidney, uterus and spleen but not in liver.
• Reactome Pathway:
  RAB geranylgeranylation (R-HSA-8873719)
  Retrograde transport at the Trans-Golgi-Network (R-HSA-6811440)

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	Altered Expression	[1]
Colon cancer	DISVC52G	Strong	Genetic Variation	[1]
Colon carcinoma	DISJYKUO	Strong	Genetic Variation	[1]
Glioma	DIS5RPEH	Strong	Altered Expression	[2]

1 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 Ras-related protein Rab-43 (RAB43).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Ras-related protein Rab-43 (RAB43).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Ras-related protein Rab-43 (RAB43).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Ras-related protein Rab-43 (RAB43).	[6]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Ras-related protein Rab-43 (RAB43).	[7]
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of Ras-related protein Rab-43 (RAB43).	[8]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Ras-related protein Rab-43 (RAB43).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Ras-related protein Rab-43 (RAB43).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Ras-related protein Rab-43 (RAB43).	[11]

References

• [1] A germline mutation in Rab43 gene identified from a cancer family predisposes to a hereditary liver-colon cancer syndrome.BMC Cancer. 2019 Jun 21;19(1):613. doi: 10.1186/s12885-019-5845-4.
• [2] High expression of RAB43 predicts poor prognosis and is associated with epithelial-mesenchymal transition in gliomas.Oncol Rep. 2017 Feb;37(2):903-912. doi: 10.3892/or.2017.5349. Epub 2017 Jan 3.
• [3] 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.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] Transcriptional responses to estrogen and progesterone in mammary gland identify networks regulating p53 activity. Endocrinology. 2008 Oct;149(10):4809-20. doi: 10.1210/en.2008-0035. Epub 2008 Jun 12.
• [7] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [8] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [11] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.