Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTF1J0TB)

• DOT Name: Ras-related protein Rab-14 (RAB14)
• Gene Name: RAB14
• Related Disease:
  Hepatocellular carcinoma
  Malaria
  Advanced cancer
  Arthrogryposis
  Cervical cancer
  Cervical carcinoma
  Colorectal carcinoma
  Craniosynostosis
  Gastric cancer
  Hemolytic anemia
  Maturity-onset diabetes of the young
  Myocardial infarction
  Neoplasm
  Non-insulin dependent diabetes
  Non-small-cell lung cancer
  Rheumatoid arthritis
  Stomach cancer
  Pancreatic cancer
  Bladder cancer
  Rett syndrome
  Squamous cell carcinoma
  Urinary bladder cancer
  Urinary bladder neoplasm
• UniProt ID: RAB14_HUMAN
• PDB ID: 1Z0F; 4D0G; 4DRZ
• Pfam ID: PF00071
• Sequence:
  MATAPYNYSYIFKYIIIGDMGVGKSCLLHQFTEKKFMADCPHTIGVEFGTRIIEVSGQKI
  KLQIWDTAGQERFRAVTRSYYRGAAGALMVYDITRRSTYNHLSSWLTDARNLTNPNTVII
  LIGNKADLEAQRDVTYEEAKQFAEENGLLFLEASAKTGENVEDAFLEAAKKIYQNIQDGS
  LDLNAAESGVQHKPSAPQGGRLTSEPQPQREGCGC
• Function: Involved in membrane trafficking between the Golgi complex and endosomes during early embryonic development. Regulates the Golgi to endosome transport of FGFR-containing vesicles during early development, a key process for developing basement membrane and epiblast and primitive endoderm lineages during early postimplantation development. May act by modulating the kinesin KIF16B-cargo association to endosomes. Regulates, together with its guanine nucleotide exchange factor DENND6A, the specific endocytic transport of ADAM10, N-cadherin/CDH2 shedding and cell-cell adhesion.
• KEGG Pathway:
  Efferocytosis (hsa04148)
  AMPK sig.ling pathway (hsa04152)
• Reactome Pathway:
  Synthesis of PIPs at the plasma membrane (R-HSA-1660499)
  Neutrophil degranulation (R-HSA-6798695)
  RAB geranylgeranylation (R-HSA-8873719)
  RAB GEFs exchange GTP for GDP on RABs (R-HSA-8876198)
  Translocation of SLC2A4 (GLUT4) to the plasma membrane (R-HSA-1445148)

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Definitive	Biomarker	[1]
Malaria	DISQ9Y50	Definitive	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Arthrogryposis	DISC81CM	Strong	Genetic Variation	[4]
Cervical cancer	DISFSHPF	Strong	Biomarker	[5]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[5]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[6]
Craniosynostosis	DIS6J405	Strong	Genetic Variation	[7]
Gastric cancer	DISXGOUK	Strong	Biomarker	[8]
Hemolytic anemia	DIS803XQ	Strong	Genetic Variation	[4]
Maturity-onset diabetes of the young	DISG75M5	Strong	Biomarker	[9]
Myocardial infarction	DIS655KI	Strong	Genetic Variation	[10]
Neoplasm	DISZKGEW	Strong	Biomarker	[11]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[9]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[12]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[13]
Stomach cancer	DISKIJSX	Strong	Biomarker	[8]
Pancreatic cancer	DISJC981	moderate	Altered Expression	[14]
Bladder cancer	DISUHNM0	Limited	Biomarker	[11]
Rett syndrome	DISGG5UV	Limited	Biomarker	[15]
Squamous cell carcinoma	DISQVIFL	Limited	Biomarker	[16]
Urinary bladder cancer	DISDV4T7	Limited	Biomarker	[11]
Urinary bladder neoplasm	DIS7HACE	Limited	Biomarker	[11]

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-14 (RAB14).	[17]

8 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 Ras-related protein Rab-14 (RAB14).	[18]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Ras-related protein Rab-14 (RAB14).	[19]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ras-related protein Rab-14 (RAB14).	[20]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Ras-related protein Rab-14 (RAB14).	[21]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Ras-related protein Rab-14 (RAB14).	[22]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Ras-related protein Rab-14 (RAB14).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Ras-related protein Rab-14 (RAB14).	[23]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Ras-related protein Rab-14 (RAB14).	[24]

References

• [1] CHML promotes liver cancer metastasis by facilitating Rab14 recycle.Nat Commun. 2019 Jun 7;10(1):2510. doi: 10.1038/s41467-019-10364-0.
• [2] Rab GTPase regulation of bacteria and protozoa phagocytosis occurs through the modulation of phagocytic receptor surface expression.Sci Rep. 2018 Aug 29;8(1):12998. doi: 10.1038/s41598-018-31171-5.
• [3] Rab14 Act as Oncogene and Induce Proliferation of Gastric Cancer Cells via AKT Signaling Pathway.PLoS One. 2017 Jan 20;12(1):e0170620. doi: 10.1371/journal.pone.0170620. eCollection 2017.
• [4] Human aldolase A natural mutants: relationship between flexibility of the C-terminal region and enzyme function.Biochem J. 2004 May 15;380(Pt 1):51-6. doi: 10.1042/BJ20031941.
• [5] TMPO-AS1 promotes cervical cancer progression by upregulating RAB14 via sponging miR-577.J Gene Med. 2019 Nov;21(11):e3125. doi: 10.1002/jgm.3125. Epub 2019 Nov 17.
• [6] LncRNA-SNHG15 enhances cell proliferation in colorectal cancer by inhibiting miR-338-3p.Cancer Med. 2019 May;8(5):2404-2413. doi: 10.1002/cam4.2105. Epub 2019 Apr 3.
• [7] Differentially Regulated Host Proteins Associated with Chronic Rhinosinusitis Are Correlated with the Sinonasal Microbiome.Front Cell Infect Microbiol. 2017 Dec 6;7:504. doi: 10.3389/fcimb.2017.00504. eCollection 2017.
• [8] Hypermethylation of miR-338-3p and Impact of its Suppression on Cell Metastasis Through N-Cadherin Accumulation at the Cell -Cell Junction and Degradation of MMP in Gastric Cancer.Cell Physiol Biochem. 2018;50(2):411-425. doi: 10.1159/000494153. Epub 2018 Oct 11.
• [9] Fructose-1,6-bisphosphatase: genetic and physical mapping to human chromosome 9q22.3 and evaluation in non-insulin-dependent diabetes mellitus.Genomics. 1995 Sep 1;29(1):187-94. doi: 10.1006/geno.1995.1230.
• [10] Lipid-associated genetic polymorphisms are associated with FBP and LDL-c levels among myocardial infarction patients in Chinese population.Gene. 2018 Nov 15;676:22-28. doi: 10.1016/j.gene.2018.07.016. Epub 2018 Jul 10.
• [11] RAB14 activates MAPK signaling to promote bladder tumorigenesis.Carcinogenesis. 2019 Nov 25;40(11):1341-1351. doi: 10.1093/carcin/bgz039.
• [12] microRNA-338-3p functions as a tumor suppressor in human nonsmallcell lung carcinoma and targets Ras-related protein 14.Mol Med Rep. 2015 Feb;11(2):1400-6. doi: 10.3892/mmr.2014.2880. Epub 2014 Nov 6.
• [13] REL, encoding a member of the NF-kappaB family of transcription factors, is a newly defined risk locus for rheumatoid arthritis.Nat Genet. 2009 Jul;41(7):820-3. doi: 10.1038/ng.395. Epub 2009 Jun 7.
• [14] Rab14 overexpression regulates gemcitabine sensitivity through regulation of Bcl-2 and mitochondrial function in pancreatic cancer.Virchows Arch. 2019 Jan;474(1):59-69. doi: 10.1007/s00428-018-2455-5. Epub 2018 Sep 29.
• [15] Reduced folate transport to the CNS in female Rett patients.Neurology. 2003 Aug 26;61(4):506-15. doi: 10.1212/01.wnl.0000078939.64774.1b.
• [16] Silencing Rab14 represses the proliferation and migration of oral squamous cell carcinoma, and enhances cisplatin sensitivity.Am J Transl Res. 2017 Sep 15;9(9):4195-4205. eCollection 2017.
• [17] 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.
• [18] Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling. Toxicol Sci. 2012 Mar;126(1):101-13.
• [19] 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.
• [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.
• [21] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [22] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [23] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [24] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.