Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTU0NZU0)

DOT Name Ras-related protein Rab-38 (RAB38)
Synonyms Melanoma antigen NY-MEL-1
Gene Name RAB38
Related Disease
Frontotemporal dementia ( )
Alzheimer disease ( )
Clear cell renal carcinoma ( )
Glioblastoma multiforme ( )
Glioma ( )
Hypopigmentation of the skin ( )
Metastatic malignant neoplasm ( )
Non-small-cell lung cancer ( )
Oculocutaneous albinism ( )
Carcinoid tumor ( )
Hermansky-Pudlak syndrome ( )
Neoplasm ( )
Pancreatic adenocarcinoma ( )
Pancreatic cancer ( )
Small-cell lung cancer ( )
Advanced cancer ( )
Bladder cancer ( )
Choroideremia ( )
Diabetic kidney disease ( )
Melanoma ( )
Type-1/2 diabetes ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
UniProt ID
RAB38_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
6HDU; 6S5H
Pfam ID
PF00071
Sequence
MQAPHKEHLYKLLVIGDLGVGKTSIIKRYVHQNFSSHYRATIGVDFALKVLHWDPETVVR
LQLWDIAGQERFGNMTRVYYREAMGAFIVFDVTRPATFEAVAKWKNDLDSKLSLPNGKPV
SVVLLANKCDQGKDVLMNNGLKMDQFCKEHGFVGWFETSAKENINIDEASRCLVKHILAN
ECDLMESIEPDVVKPHLTSTKVASCSGCAKS
Function
May be involved in melanosomal transport and docking. Involved in the proper sorting of TYRP1. Involved in peripheral melanosomal distribution of TYRP1 in melanocytes; the function, which probably is implicating vesicle-trafficking, includes cooperation with ANKRD27 and VAMP7. Plays a role in the maturation of phagosomes that engulf pathogens, such as S.aureus and M.tuberculosis. Plays an important role in the control of melanin production and melanosome biogenesis. In concert with RAB32, regulates the proper trafficking of melanogenic enzymes TYR, TYRP1 and DCT/TYRP2 to melanosomes in melanocytes.
Tissue Specificity Expressed in melanocytes.
Reactome Pathway
RAB GEFs exchange GTP for GDP on RABs (R-HSA-8876198 )
RAB geranylgeranylation (R-HSA-8873719 )

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Frontotemporal dementia DISKYHXL Definitive Genetic Variation [1]
Alzheimer disease DISF8S70 Strong Genetic Variation [2]
Clear cell renal carcinoma DISBXRFJ Strong Genetic Variation [3]
Glioblastoma multiforme DISK8246 Strong Genetic Variation [4]
Glioma DIS5RPEH Strong Altered Expression [4]
Hypopigmentation of the skin DIS39YKC Strong Biomarker [5]
Metastatic malignant neoplasm DIS86UK6 Strong Biomarker [6]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [6]
Oculocutaneous albinism DISJS7CU Strong Biomarker [5]
Carcinoid tumor DISMNRDC moderate Genetic Variation [7]
Hermansky-Pudlak syndrome DISCY0HQ moderate Biomarker [8]
Neoplasm DISZKGEW moderate Biomarker [9]
Pancreatic adenocarcinoma DISKHX7S moderate Altered Expression [9]
Pancreatic cancer DISJC981 moderate Biomarker [9]
Small-cell lung cancer DISK3LZD moderate Genetic Variation [7]
Advanced cancer DISAT1Z9 Limited Altered Expression [6]
Bladder cancer DISUHNM0 Limited Biomarker [10]
Choroideremia DISH4N9B Limited Biomarker [11]
Diabetic kidney disease DISJMWEY Limited Altered Expression [12]
Melanoma DIS1RRCY Limited Biomarker [13]
Type-1/2 diabetes DISIUHAP Limited Genetic Variation [12]
Urinary bladder cancer DISDV4T7 Limited Biomarker [10]
Urinary bladder neoplasm DIS7HACE Limited Biomarker [10]
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⏷ Show the Full List of 23 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
9 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-38 (RAB38). [14]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Ras-related protein Rab-38 (RAB38). [15]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Ras-related protein Rab-38 (RAB38). [16]
Vorinostat DMWMPD4 Approved Vorinostat increases the expression of Ras-related protein Rab-38 (RAB38). [17]
Triclosan DMZUR4N Approved Triclosan increases the expression of Ras-related protein Rab-38 (RAB38). [18]
Isotretinoin DM4QTBN Approved Isotretinoin decreases the expression of Ras-related protein Rab-38 (RAB38). [19]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Ras-related protein Rab-38 (RAB38). [20]
THAPSIGARGIN DMDMQIE Preclinical THAPSIGARGIN decreases the expression of Ras-related protein Rab-38 (RAB38). [21]
chloropicrin DMSGBQA Investigative chloropicrin decreases the expression of Ras-related protein Rab-38 (RAB38). [22]
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⏷ Show the Full List of 9 Drug(s)

References

1 Frontotemporal dementia and its subtypes: a genome-wide association study.Lancet Neurol. 2014 Jul;13(7):686-99. doi: 10.1016/S1474-4422(14)70065-1.
2 Association of Frontotemporal Dementia GWAS Loci with Late-Onset Alzheimer's Disease in a Northern Han Chinese Population.J Alzheimers Dis. 2016 Feb 26;52(1):43-50. doi: 10.3233/JAD-151073.
3 Pervasive transcription read-through promotes aberrant expression of oncogenes and RNA chimeras in renal carcinoma.Elife. 2015 Nov 17;4:e09214. doi: 10.7554/eLife.09214.
4 RAB38 confers a poor prognosis, associated with malignant progression and subtype preference in glioma.Oncol Rep. 2013 Nov;30(5):2350-6. doi: 10.3892/or.2013.2730. Epub 2013 Sep 10.
5 Analysis of ocular hypopigmentation in Rab38cht/cht mice.Invest Ophthalmol Vis Sci. 2007 Sep;48(9):3905-13. doi: 10.1167/iovs.06-1464.
6 RAB38 is a potential prognostic factor for tumor recurrence in non-small cell lung cancer.Oncol Lett. 2019 Sep;18(3):2598-2604. doi: 10.3892/ol.2019.10547. Epub 2019 Jun 28.
7 Pathways Impacted by Genomic Alterations in Pulmonary Carcinoid Tumors.Clin Cancer Res. 2018 Apr 1;24(7):1691-1704. doi: 10.1158/1078-0432.CCR-17-0252. Epub 2018 Jan 19.
8 The BLOC-3 subunit HPS4 is required for activation of Rab32/38 GTPases in melanogenesis, but its Rab9 activity is dispensable for melanogenesis.J Biol Chem. 2019 Apr 26;294(17):6912-6922. doi: 10.1074/jbc.RA119.007345. Epub 2019 Mar 5.
9 High expression of RAB38 promotes malignant progression of pancreatic cancer.Mol Med Rep. 2019 Feb;19(2):909-918. doi: 10.3892/mmr.2018.9732. Epub 2018 Dec 10.
10 RAB38 promotes bladder cancer growth by promoting cell proliferation and motility.World J Urol. 2019 Sep;37(9):1889-1897. doi: 10.1007/s00345-018-2596-9. Epub 2018 Dec 10.
11 Rab GTPase prenylation hierarchy and its potential role in choroideremia disease.PLoS One. 2013 Dec 16;8(12):e81758. doi: 10.1371/journal.pone.0081758. eCollection 2013.
12 Genome-wide Association Studies Identify Genetic Loci Associated With Albuminuria in Diabetes.Diabetes. 2016 Mar;65(3):803-17. doi: 10.2337/db15-1313. Epub 2015 Dec 2.
13 A Targeted Quantitative Proteomic Approach Assesses the Reprogramming of Small GTPases during Melanoma Metastasis.Cancer Res. 2018 Sep 15;78(18):5431-5445. doi: 10.1158/0008-5472.CAN-17-3811. Epub 2018 Aug 2.
14 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
15 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.
16 Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
17 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.
18 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
19 Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
20 Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
21 Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.
22 Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.