Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO61X27)

• DOT Name: Rab GTPase-binding effector protein 2 (RABEP2)
• Synonyms: Rabaptin-5beta
• Gene Name: RABEP2
• Related Disease:
  Adenocarcinoma
  Epithelial ovarian cancer
  Autism spectrum disorder
  Barrett esophagus
  Breast neoplasm
  Chagas disease
  Fragile X syndrome
  Lung cancer
  Lung carcinoma
  Mood disorder
  Obesity
  Parkinson disease
  Pyogenic arthritis-pyoderma gangrenosum-acne syndrome
  Triple negative breast cancer
  Squamous cell carcinoma
  Cervical cancer
  Neoplasm
  G6PD deficiency
  Gastritis
  Intellectual disability
  Membranous glomerulonephritis
  Precancerous condition
  Stroke
• UniProt ID: RABE2_HUMAN
• Pfam ID: PF09311 ; PF03528
• Sequence:
  MAAAAPVAADDDERRRRPGAALEDSRSQEGANGEAESGELSRLRAELAGALAEMETMKAV
  AEVSESTKAEAVAAVQRQCQEEVASLQAILKDSISSYEAQITALKQERQQQQQDCEEKER
  ELGRLKQLLSRAYPLDSLEKQMEKAHEDSEKLREIVLPMEKEIEELKAKLLRAEELIQEI
  QRRPRHAPSLHGSTELLPLSRDPSPPLEPLEELSGDGGPAAEAFAHNCDDSASISSFSLG
  GGVGSSSSLPQSRQGLSPEQEETASLVSTGTLVPEGIYLPPPGYQLVPDTQWEQLQTEGR
  QLQKDLESVSRERDELQEGLRRSNEDCAKQMQVLLAQVQNSEQLLRTLQGTVSQAQERVQ
  LQMAELVTTHKCLHHEVKRLNEENQGLRAEQLPSSAPQGSQQEQGEEESLPSSVPELQQL
  LCCTRQEARARLQAQEHGAERLRIEIVTLREALEEETVARASLEGQLRVQREETEVLEAS
  LCSLRTEMERVQQEQSKAQLPDLLSEQRAKVLRLQAELETSEQVQRDFVRLSQALQVRLE
  RIRQAETLEQVRSIMDEAPLTDVRDIKDT
• Function: Plays a role in membrane trafficking and in homotypic early endosome fusion. Participates in arteriogenesis by regulating vascular endothelial growth factor receptor 2/VEGFR2 cell surface expression and endosomal trafficking. By interacting with SDCCAG8, localizes to centrosomes and plays a critical role in ciliogenesis.

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Definitive	Altered Expression	[1]
Epithelial ovarian cancer	DIS56MH2	Definitive	Altered Expression	[1]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[2]
Barrett esophagus	DIS416Y7	Strong	Genetic Variation	[3]
Breast neoplasm	DISNGJLM	Strong	Genetic Variation	[4]
Chagas disease	DIS8KNVF	Strong	Biomarker	[5]
Fragile X syndrome	DISE8W3A	Strong	Genetic Variation	[6]
Lung cancer	DISCM4YA	Strong	Biomarker	[7]
Lung carcinoma	DISTR26C	Strong	Biomarker	[7]
Mood disorder	DISLVMWO	Strong	Biomarker	[6]
Obesity	DIS47Y1K	Strong	Genetic Variation	[8]
Parkinson disease	DISQVHKL	Strong	Genetic Variation	[9]
Pyogenic arthritis-pyoderma gangrenosum-acne syndrome	DIS7E15X	Strong	Genetic Variation	[10]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[11]
Squamous cell carcinoma	DISQVIFL	moderate	Biomarker	[12]
Cervical cancer	DISFSHPF	Disputed	Biomarker	[13]
Neoplasm	DISZKGEW	Disputed	Biomarker	[14]
G6PD deficiency	DISYF1GO	Limited	Biomarker	[15]
Gastritis	DIS8G07K	Limited	Altered Expression	[16]
Intellectual disability	DISMBNXP	Limited	Genetic Variation	[15]
Membranous glomerulonephritis	DISFSUKQ	Limited	Biomarker	[17]
Precancerous condition	DISV06FL	Limited	Altered Expression	[16]
Stroke	DISX6UHX	Limited	Biomarker	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Rab GTPase-binding effector protein 2 (RABEP2).	[19]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Rab GTPase-binding effector protein 2 (RABEP2).	[20]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Rab GTPase-binding effector protein 2 (RABEP2).	[21]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Rab GTPase-binding effector protein 2 (RABEP2).	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Rab GTPase-binding effector protein 2 (RABEP2).	[23]

References

• [1] Expression of folate receptors alpha and beta in normal and cancerous gynecologic tissues: correlation of expression of the beta isoform with macrophage markers.J Ovarian Res. 2015 May 14;8:29. doi: 10.1186/s13048-015-0156-0.
• [2] Facilitation of biological motion processing by group-based autism specific social skills training.Autism Res. 2018 Oct;11(10):1376-1387. doi: 10.1002/aur.2013. Epub 2018 Oct 15.
• [3] Deletion at fragile sites is a common and early event in Barrett's esophagus.Mol Cancer Res. 2010 Aug;8(8):1084-94. doi: 10.1158/1541-7786.MCR-09-0529. Epub 2010 Jul 20.
• [4] FHIT alterations in breast cancer.Semin Cancer Biol. 2001 Oct;11(5):361-6. doi: 10.1006/scbi.2001.0391.
• [5] Chagas disease-specific antigens: characterization of epitopes in CRA/FRA by synthetic peptide mapping and evaluation by ELISA-peptide assay.BMC Infect Dis. 2013 Dec 3;13:568. doi: 10.1186/1471-2334-13-568.
• [6] Variation at the fragile X locus does not influence susceptibility to bipolar disorder.Am J Med Genet. 1994 Jun 15;54(2):141-3. doi: 10.1002/ajmg.1320540209.
• [7] Chemo-biologic combinatorial drug delivery using folate receptor-targeted dendrimer nanoparticles for lung cancer treatment.Nanomedicine. 2018 Feb;14(2):373-384. doi: 10.1016/j.nano.2017.11.010. Epub 2017 Nov 16.
• [8] Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture.Nat Genet. 2013 May;45(5):501-12. doi: 10.1038/ng.2606. Epub 2013 Apr 7.
• [9] Genome-wide mapping of IBD segments in an Ashkenazi PD cohort identifies associated haplotypes.Hum Mol Genet. 2014 Sep 1;23(17):4693-702. doi: 10.1093/hmg/ddu158. Epub 2014 May 19.
• [10] Circulatory disease mortality and diabetes incidence in 27 families with Friedreich ataxia.Genet Epidemiol. 1988;5(6):445-52. doi: 10.1002/gepi.1370050608.
• [11] IgA Fc-folate conjugate activates and recruits neutrophils to directly target triple-negative breast cancer cells.Breast Cancer Res Treat. 2018 Dec;172(3):551-560. doi: 10.1007/s10549-018-4941-5. Epub 2018 Aug 28.
• [12] Folate receptor alpha expression in lung cancer: diagnostic and prognostic significance.Oncotarget. 2012 Apr;3(4):414-425. doi: 10.18632/oncotarget.519.
• [13] Prognostic significance of HPV physical status and integration sites in cervical cancer.Asian Pac J Cancer Prev. 2009 Jul-Sep;10(3):355-60.
• [14] MORAb-202, an Antibody-Drug Conjugate Utilizing Humanized Anti-human FR Farletuzumab and the Microtubule-targeting Agent Eribulin, has Potent Antitumor Activity.Mol Cancer Ther. 2018 Dec;17(12):2665-2675. doi: 10.1158/1535-7163.MCT-17-1215. Epub 2018 Sep 27.
• [15] Mental retardation in heterozygotes for the fragile-X mutation: evidence in favor of an X inactivation-dependent effect.Am J Hum Genet. 1990 Apr;46(4):738-43.
• [16] Carcinogenic Helicobacter pylori Strains Selectively Dysregulate the In Vivo Gastric Proteome, Which May Be Associated with Stomach Cancer Progression.Mol Cell Proteomics. 2019 Feb;18(2):352-371. doi: 10.1074/mcp.RA118.001181. Epub 2018 Nov 19.
• [17] Value of immunofluorescence-mediated detection of Ig, C1q, C3, and FRA for the identification and diagnosis of atypical membranous nephropathy.Eur Rev Med Pharmacol Sci. 2017 Dec;21(23):5415-5419. doi: 10.26355/eurrev_201712_13929.
• [18] Cerebral Collateral Circulation: A Review in the Context of Ischemic Stroke and Mechanical Thrombectomy.World Neurosurg. 2019 Feb;122:33-42. doi: 10.1016/j.wneu.2018.10.066. Epub 2018 Oct 18.
• [19] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [20] 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.
• [21] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [22] Zoledronate dysregulates fatty acid metabolism in renal tubular epithelial cells to induce nephrotoxicity. Arch Toxicol. 2018 Jan;92(1):469-485.
• [23] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.