Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4HBPHE)

• DOT Name: Ras-related protein Rap-2c (RAP2C)
• Synonyms: EC 3.6.5.2
• Gene Name: RAP2C
• Related Disease: Neoplasm
• UniProt ID: RAP2C_HUMAN
• EC Number: 3.6.5.2
• Pfam ID: PF00071
• Sequence:
  MREYKVVVLGSGGVGKSALTVQFVTGTFIEKYDPTIEDFYRKEIEVDSSPSVLEILDTAG
  TEQFASMRDLYIKNGQGFILVYSLVNQQSFQDIKPMRDQIVRVKRYEKVPLILVGNKVDL
  EPEREVMSSEGRALAQEWGCPFMETSAKSKSMVDELFAEIVRQMNYSSLPEKQDQCCTTC
  VVQ
• Function: Small GTP-binding protein which cycles between a GDP-bound inactive and a GTP-bound active form. May play a role in cytoskeletal rearrangements and regulate cell spreading through activation of the effector TNIK. May play a role in SRE-mediated gene transcription.
• Tissue Specificity: Expressed in liver, skeletal muscle, prostate, uterus, rectum, stomach, and bladder and to a lower extent in brain, kidney, pancreas, and bone marrow. Expressed in mononuclear leukocytes and megakaryocytes.
• KEGG Pathway: Tight junction (hsa04530)
• Reactome Pathway: Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Strong	Biomarker	[1]

8 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 Rap-2c (RAP2C).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Ras-related protein Rap-2c (RAP2C).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Ras-related protein Rap-2c (RAP2C).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ras-related protein Rap-2c (RAP2C).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Ras-related protein Rap-2c (RAP2C).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Ras-related protein Rap-2c (RAP2C).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Ras-related protein Rap-2c (RAP2C).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Ras-related protein Rap-2c (RAP2C).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Ras-related protein Rap-2c (RAP2C).	[8]

References

• [1] Ras-related protein Rap2c promotes the migration and invasion of human osteosarcoma cells.Oncol Lett. 2018 Apr;15(4):5352-5358. doi: 10.3892/ol.2018.7987. Epub 2018 Feb 7.
• [2] Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [5] 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.
• [6] 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.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [9] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [10] 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.