Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT734R7X)

• DOT Name: Ras-related protein Ral-A (RALA)
• Synonyms: EC 3.6.5.2
• Gene Name: RALA
• Related Disease:
  Carcinoma of liver and intrahepatic biliary tract
  Liver cancer
  Advanced cancer
  Cervical cancer
  Cervical carcinoma
  Complex neurodevelopmental disorder
  Hiatt-Neu-Cooper neurodevelopmental syndrome
  Intellectual disability
  Lung neoplasm
  Microcephaly
  Pancreatic cancer
  Pancreatic tumour
  Prostate cancer
  Prostate carcinoma
  Urinary bladder neoplasm
  Hepatocellular carcinoma
  leukaemia
  Leukemia
  Onchocerciasis
  Squamous cell carcinoma
  Non-small-cell lung cancer
• UniProt ID: RALA_HUMAN
• PDB ID: 1UAD; 1ZC3; 1ZC4; 2A78; 2A9K; 2BOV; 6P0I; 6P0J; 6P0K; 6P0L; 6P0M; 6P0N; 6P0O; 7NQC; 8FJH; 8FJI
• EC Number: 3.6.5.2
• Pfam ID: PF00071
• Sequence:
  MAANKPKGQNSLALHKVIMVGSGGVGKSALTLQFMYDEFVEDYEPTKADSYRKKVVLDGE
  EVQIDILDTAGQEDYAAIRDNYFRSGEGFLCVFSITEMESFAATADFREQILRVKEDENV
  PFLLVGNKSDLEDKRQVSVEEAKNRAEQWNVNYVETSAKTRANVDKVFFDLMREIRARKM
  EDSKEKNGKKKRKSLAKRIRERCCIL
• Function: Multifunctional GTPase involved in a variety of cellular processes including gene expression, cell migration, cell proliferation, oncogenic transformation and membrane trafficking. Accomplishes its multiple functions by interacting with distinct downstream effectors. Acts as a GTP sensor for GTP-dependent exocytosis of dense core vesicles. The RALA-exocyst complex regulates integrin-dependent membrane raft exocytosis and growth signaling. Key regulator of LPAR1 signaling and competes with GRK2 for binding to LPAR1 thus affecting the signaling properties of the receptor. Required for anchorage-independent proliferation of transformed cells. During mitosis, supports the stabilization and elongation of the intracellular bridge between dividing cells. Cooperates with EXOC2 to recruit other components of the exocyst to the early midbody. During mitosis, also controls mitochondrial fission by recruiting to the mitochondrion RALBP1, which mediates the phosphorylation and activation of DNM1L by the mitotic kinase cyclin B-CDK1.
• KEGG Pathway:
  Ras sig.ling pathway (hsa04014)
  Rap1 sig.ling pathway (hsa04015)
  Phospholipase D sig.ling pathway (hsa04072)
  Salmonella infection (hsa05132)
  Pathways in cancer (hsa05200)
  Colorectal cancer (hsa05210)
  Pancreatic cancer (hsa05212)
• Reactome Pathway:
  p38MAPK events (R-HSA-171007)
  Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation (R-HSA-8950505)
  Translocation of SLC2A4 (GLUT4) to the plasma membrane (R-HSA-1445148)

Molecular Interaction Atlas (MIA) of This DOT

21 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Definitive	Altered Expression	[1]
Liver cancer	DISDE4BI	Definitive	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Cervical cancer	DISFSHPF	Strong	Genetic Variation	[3]
Cervical carcinoma	DIST4S00	Strong	Genetic Variation	[3]
Complex neurodevelopmental disorder	DISB9AFI	Strong	Autosomal dominant	[4]
Hiatt-Neu-Cooper neurodevelopmental syndrome	DISTRJXA	Strong	Autosomal dominant	[5]
Intellectual disability	DISMBNXP	Strong	Genetic Variation	[5]
Lung neoplasm	DISVARNB	Strong	Biomarker	[6]
Microcephaly	DIS2GRD8	Strong	CausalMutation	[5]
Pancreatic cancer	DISJC981	Strong	Genetic Variation	[7]
Pancreatic tumour	DIS3U0LK	Strong	Biomarker	[8]
Prostate cancer	DISF190Y	Strong	Biomarker	[9]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[9]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[10]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[1]
leukaemia	DISS7D1V	moderate	Biomarker	[11]
Leukemia	DISNAKFL	moderate	Biomarker	[11]
Onchocerciasis	DISEPYEA	moderate	Biomarker	[12]
Squamous cell carcinoma	DISQVIFL	moderate	Altered Expression	[13]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Biomarker	[14]

20 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 Ras-related protein Ral-A (RALA).	[15]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Ras-related protein Ral-A (RALA).	[16]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Ras-related protein Ral-A (RALA).	[17]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Ras-related protein Ral-A (RALA).	[18]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Ras-related protein Ral-A (RALA).	[19]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ras-related protein Ral-A (RALA).	[20]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Ras-related protein Ral-A (RALA).	[21]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Ras-related protein Ral-A (RALA).	[22]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Ras-related protein Ral-A (RALA).	[23]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of Ras-related protein Ral-A (RALA).	[19]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Ras-related protein Ral-A (RALA).	[24]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Ras-related protein Ral-A (RALA).	[25]
Nefazodone	DM4ZS8M	Approved	Nefazodone increases the expression of Ras-related protein Ral-A (RALA).	[26]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Ras-related protein Ral-A (RALA).	[27]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Ras-related protein Ral-A (RALA).	[28]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Ras-related protein Ral-A (RALA).	[24]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Ras-related protein Ral-A (RALA).	[29]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Ras-related protein Ral-A (RALA).	[30]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Ras-related protein Ral-A (RALA).	[31]
Glyphosate	DM0AFY7	Investigative	Glyphosate increases the expression of Ras-related protein Ral-A (RALA).	[32]

References

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• [18] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [19] Arsenite and cadmium promote the development of mammary tumors. Carcinogenesis. 2020 Jul 14;41(7):1005-1014. doi: 10.1093/carcin/bgz176.
• [20] 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.
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• [23] Zoledronate dysregulates fatty acid metabolism in renal tubular epithelial cells to induce nephrotoxicity. Arch Toxicol. 2018 Jan;92(1):469-485.
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