Details of Drug Off-Target (DOT)

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

DOT Name Rab GTPase-binding effector protein 1 (RABEP1)
Synonyms Rabaptin-4; Rabaptin-5; Rabaptin-5alpha; Renal carcinoma antigen NY-REN-17
Gene Name RABEP1
Related Disease
Advanced cancer ( )
Alzheimer disease ( )
Breast neoplasm ( )
Chronic myelomonocytic leukaemia ( )
Chronic myelomonocytic leukemia ( )
Gastric cancer ( )
Rheumatoid arthritis ( )
Sickle-cell anaemia ( )
Stomach cancer ( )
UniProt ID
RABE1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1P4U; 1TU3; 1X79; 4N3Y; 4N3Z; 4Q9U
Pfam ID
PF09311 ; PF03528
Sequence
MAQPGPASQPDVSLQQRVAELEKINAEFLRAQQQLEQEFNQKRAKFKELYLAKEEDLKRQ
NAVLQAAQDDLGHLRTQLWEAQAEMENIKAIATVSENTKQEAIDEVKRQWREEVASLQAV
MKETVRDYEHQFHLRLEQERTQWAQYRESAEREIADLRRRLSEGQEEENLENEMKKAQED
AEKLRSVVMPMEKEIAALKDKLTEAEDKIKELEASKVKELNHYLEAEKSCRTDLEMYVAV
LNTQKSVLQEDAEKLRKELHEVCHLLEQERQQHNQLKHTWQKANDQFLESQRLLMRDMQR
MEIVLTSEQLRQVEELKKKDQEDDEQQRLNKRKDHKKADVEEEIKIPVVCALTQEESSAQ
LSNEEEHLDSTRGSVHSLDAGLLLPSGDPFSKSDNDMFKDGLRRAQSTDSLGTSGSLQSK
ALGYNYKAKSAGNLDESDFGPLVGADSVSENFDTASLGSLQMPSGFMLTKDQERAIKAMT
PEQEETASLLSSVTQGMESAYVSPSGYRLVSETEWNLLQKEVHNAGNKLGRRCDMCSNYE
KQLQGIQIQEAETRDQVKKLQLMLRQANDQLEKTMKDKQELEDFIKQSSEDSSHQISALV
LRAQASEILLEELQQGLSQAKRDVQEQMAVLMQSREQVSEELVRLQKDNDSLQGKHSLHV
SLQQAEDFILPDTTEALRELVLKYREDIINVRTAADHVEEKLKAEILFLKEQIQAEQCLK
ENLEETLQLEIENCKEEIASISSLKAELERIKVEKGQLESTLREKSQQLESLQEIKISLE
EQLKKETAAKATVEQLMFEEKNKAQRLQTELDVSEQVQRDFVKLSQTLQVQLERIRQADS
LERIRAILNDTKLTDINQLPET
Function
Rab effector protein acting as linker between gamma-adaptin, RAB4A and RAB5A. Involved in endocytic membrane fusion and membrane trafficking of recycling endosomes. Involved in KCNH1 channels trafficking to and from the cell membrane. Stimulates RABGEF1 mediated nucleotide exchange on RAB5A. Mediates the traffic of PKD1:PKD2 complex from the endoplasmic reticulum through the Golgi to the cilium.
KEGG Pathway
Endocytosis (hsa04144 )
Reactome Pathway
TBC/RABGAPs (R-HSA-8854214 )

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Strong Biomarker [1]
Alzheimer disease DISF8S70 Strong Biomarker [2]
Breast neoplasm DISNGJLM Strong Altered Expression [3]
Chronic myelomonocytic leukaemia DISDN5P7 Strong Biomarker [4]
Chronic myelomonocytic leukemia DISIL8UR Strong Genetic Variation [5]
Gastric cancer DISXGOUK Strong Biomarker [6]
Rheumatoid arthritis DISTSB4J Strong Genetic Variation [7]
Sickle-cell anaemia DIS5YNZB Strong Genetic Variation [8]
Stomach cancer DISKIJSX Strong Biomarker [6]
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⏷ Show the Full List of 9 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
4 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 Rab GTPase-binding effector protein 1 (RABEP1). [9]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Rab GTPase-binding effector protein 1 (RABEP1). [17]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Rab GTPase-binding effector protein 1 (RABEP1). [19]
Coumarin DM0N8ZM Investigative Coumarin decreases the phosphorylation of Rab GTPase-binding effector protein 1 (RABEP1). [17]
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9 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Rab GTPase-binding effector protein 1 (RABEP1). [10]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Rab GTPase-binding effector protein 1 (RABEP1). [11]
Temozolomide DMKECZD Approved Temozolomide increases the expression of Rab GTPase-binding effector protein 1 (RABEP1). [12]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Rab GTPase-binding effector protein 1 (RABEP1). [13]
Methotrexate DM2TEOL Approved Methotrexate increases the expression of Rab GTPase-binding effector protein 1 (RABEP1). [14]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Rab GTPase-binding effector protein 1 (RABEP1). [15]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Rab GTPase-binding effector protein 1 (RABEP1). [16]
Geldanamycin DMS7TC5 Discontinued in Phase 2 Geldanamycin increases the expression of Rab GTPase-binding effector protein 1 (RABEP1). [18]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Rab GTPase-binding effector protein 1 (RABEP1). [20]
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⏷ Show the Full List of 9 Drug(s)

References

1 CVID-Associated Tumors: Czech Nationwide Study Focused on Epidemiology, Immunology, and Genetic Background in a Cohort of Patients With CVID.Front Immunol. 2019 Jan 22;9:3135. doi: 10.3389/fimmu.2018.03135. eCollection 2018.
2 Endocytic pathway abnormalities precede amyloid beta deposition in sporadic Alzheimer's disease and Down syndrome: differential effects of APOE genotype and presenilin mutations.Am J Pathol. 2000 Jul;157(1):277-86. doi: 10.1016/s0002-9440(10)64538-5.
3 Regulation of endocytosis via the oxygen-sensing pathway.Nat Med. 2009 Mar;15(3):319-24. doi: 10.1038/nm.1922. Epub 2009 Mar 1.
4 Rabaptin-5 is a novel fusion partner to platelet-derived growth factor beta receptor in chronic myelomonocytic leukemia.Blood. 2001 Oct 15;98(8):2518-25. doi: 10.1182/blood.v98.8.2518.
5 Activity of STI571 in chronic myelomonocytic leukemia with a platelet-derived growth factor beta receptor fusion oncogene.Blood. 2002 Aug 1;100(3):1088-91. doi: 10.1182/blood-2002-01-0165.
6 HDAC6 sustains growth stimulation by prolonging the activation of EGF receptor through the inhibition of rabaptin-5-mediated early endosome fusion in gastric cancer.Cancer Lett. 2014 Nov 1;354(1):97-106. doi: 10.1016/j.canlet.2014.07.041. Epub 2014 Aug 8.
7 Genetic influences on susceptibility to rheumatoid arthritis in African-Americans.Hum Mol Genet. 2019 Mar 1;28(5):858-874. doi: 10.1093/hmg/ddy395.
8 Genome-wide association study of erythrocyte density in sickle cell disease patients.Blood Cells Mol Dis. 2017 Jun;65:60-65. doi: 10.1016/j.bcmd.2017.05.005. Epub 2017 May 13.
9 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.
10 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
11 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.
12 Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
13 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
14 Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
15 Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
16 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.
17 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.
18 Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
19 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
20 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.