Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGKRR3C)

• DOT Name: Ras-related protein Rab-3D (RAB3D)
• Gene Name: RAB3D
• Related Disease:
  Alzheimer disease
  Analgesia
  B-cell neoplasm
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Esophageal squamous cell carcinoma
  Major depressive disorder
  Neoplasm
  Osteosarcoma
  Sjogren syndrome
  Systemic lupus erythematosus
  Colorectal carcinoma
  Metastatic malignant neoplasm
  Advanced cancer
  Lung cancer
  Lung carcinoma
• UniProt ID: RAB3D_HUMAN
• PDB ID: 2GF9
• Pfam ID: PF00071
• Sequence:
  MASAGDTQAGPRDAADQNFDYMFKLLLIGNSSVGKTSFLFRYADDSFTPAFVSTVGIDFK
  VKTVYRHDKRIKLQIWDTAGQERYRTITTAYYRGAMGFLLMYDIANQESFAAVQDWATQI
  KTYSWDNAQVILVGNKCDLEDERVVPAEDGRRLADDLGFEFFEASAKENINVKQVFERLV
  DVICEKMNESLEPSSSSGSNGKGPAVGDAPAPQPSSCSC
• Function: Protein transport. Probably involved in regulated exocytosis.
• Tissue Specificity: Highly expressed in granulocytes of peripheral blood. Constitutively expressed at low levels in all hematopoietic cell lines investigated.
• KEGG Pathway: Pancreatic secretion (hsa04972)
• Reactome Pathway:
  RAB geranylgeranylation (R-HSA-8873719)
  Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[1]
Analgesia	DISK3TVI	Strong	Biomarker	[2]
B-cell neoplasm	DISVY326	Strong	Biomarker	[3]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[5]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[5]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[6]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[7]
Neoplasm	DISZKGEW	Strong	Altered Expression	[8]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[4]
Sjogren syndrome	DISUBX7H	Strong	Altered Expression	[9]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[3]
Colorectal carcinoma	DIS5PYL0	moderate	Biomarker	[10]
Metastatic malignant neoplasm	DIS86UK6	moderate	Biomarker	[11]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[6]
Lung cancer	DISCM4YA	Limited	Genetic Variation	[12]
Lung carcinoma	DISTR26C	Limited	Genetic Variation	[12]

10 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 Rab-3D (RAB3D).	[13]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Ras-related protein Rab-3D (RAB3D).	[14]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ras-related protein Rab-3D (RAB3D).	[15]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Ras-related protein Rab-3D (RAB3D).	[16]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Ras-related protein Rab-3D (RAB3D).	[17]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ras-related protein Rab-3D (RAB3D).	[18]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Ras-related protein Rab-3D (RAB3D).	[19]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Ras-related protein Rab-3D (RAB3D).	[20]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Ras-related protein Rab-3D (RAB3D).	[22]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Ras-related protein Rab-3D (RAB3D).	[23]

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 Rab-3D (RAB3D).	[21]

References

• [1] Family-based association analyses of imputed genotypes reveal genome-wide significant association of Alzheimer's disease with OSBPL6, PTPRG, and PDCL3.Mol Psychiatry. 2016 Nov;21(11):1608-1612. doi: 10.1038/mp.2015.218. Epub 2016 Feb 2.
• [2] Desmetramadol Has the Safety and Analgesic Profile of Tramadol Without Its Metabolic Liabilities: Consecutive Randomized, Double-Blind, Placebo- and Active Comparator-Controlled Trials.J Pain. 2019 Oct;20(10):1218-1235. doi: 10.1016/j.jpain.2019.04.005. Epub 2019 Apr 18.
• [3] Exposure-Response Analyses of the Effects of Venetoclax, a Selective BCL-2 Inhibitor, on B-Lymphocyte and Total Lymphocyte Counts in Women with Systemic Lupus Erythematosus.Clin Pharmacokinet. 2020 Mar;59(3):335-347. doi: 10.1007/s40262-019-00818-5.
• [4] The lncRNA HOXA11-AS regulates Rab3D expression by sponging miR-125a-5p promoting metastasis of osteosarcoma.Cancer Manag Res. 2019 May 16;11:4505-4518. doi: 10.2147/CMAR.S196025. eCollection 2019.
• [5] Effect of the secretory small GTPase Rab27B on breast cancer growth, invasion, and metastasis.J Natl Cancer Inst. 2010 Jun 16;102(12):866-80. doi: 10.1093/jnci/djq153. Epub 2010 May 18.
• [6] Silencing of Rab3D suppresses the proliferation and invasion of esophageal squamous cell carcinoma cells.Biomed Pharmacother. 2017 Jul;91:402-407. doi: 10.1016/j.biopha.2017.04.010. Epub 2017 May 2.
• [7] Effects of continuation electroconvulsive therapy on quality of life in elderly depressed patients: A randomized clinical trial.J Psychiatr Res. 2018 Feb;97:65-69. doi: 10.1016/j.jpsychires.2017.11.001. Epub 2017 Nov 16.
• [8] MicroRNA-506-3p inhibits osteosarcoma cell proliferation and metastasis by suppressing RAB3D expression.Aging (Albany NY). 2018 Jun 10;10(6):1294-1305. doi: 10.18632/aging.101468.
• [9] Changes in Rab3D expression and distribution in the acini of Sjgren's syndrome patients are associated with loss of cell polarity and secretory dysfunction.Arthritis Rheum. 2011 Oct;63(10):3126-35. doi: 10.1002/art.30500.
• [10] MiR-27b directly targets Rab3D to inhibit the malignant phenotype in colorectal cancer.Oncotarget. 2017 Dec 12;9(3):3830-3841. doi: 10.18632/oncotarget.23237. eCollection 2018 Jan 9.
• [11] High expression of small GTPase Rab3D promotes cancer progression and metastasis.Oncotarget. 2015 May 10;6(13):11125-38. doi: 10.18632/oncotarget.3575.
• [12] A polymorphism in miR-1262 regulatory region confers the risk of lung cancer in Chinese population.Int J Cancer. 2017 Sep 1;141(5):958-966. doi: 10.1002/ijc.30788. Epub 2017 May 29.
• [13] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [14] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [15] 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.
• [16] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [17] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [18] 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.
• [19] Gene expression signatures after ethanol exposure in differentiating embryoid bodies. Toxicol In Vitro. 2018 Feb;46:66-76.
• [20] Comparative proteomics reveals concordant and discordant biochemical effects of caffeine versus epigallocatechin-3-gallate in human endothelial cells. Toxicol Appl Pharmacol. 2019 Sep 1;378:114621. doi: 10.1016/j.taap.2019.114621. Epub 2019 Jun 10.
• [21] 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.
• [22] 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.
• [23] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.