General Information of Drug Off-Target (DOT) (ID: OTD5TJIN)

DOT Name ADP-ribosylation factor-like protein 8B (ARL8B)
Synonyms EC 3.6.5.2; ADP-ribosylation factor-like protein 10C; Novel small G protein indispensable for equal chromosome segregation 1
Gene Name ARL8B
Related Disease
Systemic lupus erythematosus ( )
Prostate cancer ( )
Prostate carcinoma ( )
UniProt ID
ARL8B_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2AL7
EC Number
3.6.5.2
Pfam ID
PF00025
Sequence
MLALISRLLDWFRSLFWKEEMELTLVGLQYSGKTTFVNVIASGQFSEDMIPTVGFNMRKV
TKGNVTIKIWDIGGQPRFRSMWERYCRGVNAIVYMIDAADREKIEASRNELHNLLDKPQL
QGIPVLVLGNKRDLPNALDEKQLIEKMNLSAIQDREICCYSISCKEKDNIDITLQWLIQH
SKSRRS
Function
Small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins playing a key role in the regulation of lysosomal positioning which is important for nutrient sensing, natural killer cell-mediated cytotoxicity and antigen presentation. Along with its effectors, orchestrates lysosomal transport and fusion. Localizes specifically to lysosomal membranes and mediates anterograde lysosomal motility by recruiting PLEKHM2, which in turn recruits the motor protein kinesin-1 on lysosomes. Required for lysosomal and cytolytic granule exocytosis. Critical factor involved in NK cell-mediated cytotoxicity. Drives the polarization of cytolytic granules and microtubule-organizing centers (MTOCs) toward the immune synapse between effector NK lymphocytes and target cells. In neurons, mediates the anterograde axonal long-range transport of presynaptic lysosome-related vesicles required for presynaptic biogenesis and synaptic function. Also acts as a regulator of endosome to lysosome trafficking pathways of special significance for host defense. Regulates cargo trafficking to lysosomes by binding to PLEKHM1 and recruiting the HOPS subunit VPS41, resulting in functional assembly of the HOPS complex on lysosomal membranes. Plays an important role in cargo delivery to lysosomes for antigen presentation and microbial killing. Directs the intersection of CD1d with lipid antigens in lysosomes, and plays a role in intersecting phagosomes with lysosomes to generate phagolysosomes that kill microbes. Involved in the process of MHC II presentation. Regulates the delivery of antigens to lysosomes and the formation of MHC II-peptide complexes through the recruitment of the HOPS complex to lysosomes allowing the fusion of late endosomes to lysosomes. May play a role in chromosome segregation ; (Microbial infection) During Mycobacterium tuberculosis (Mtb) infection, is required for plasma membrane repair by controlling the exocytosis of lysosomes in macrophages. ARL8B secretion pathway is crucial to control the type of cell death of the M. tuberculosis-infected macrophages, distinguishing avirulent from virulent Mtb induced necrotic cell death; (Microbial infection) During infection, coronaviruses such as SARS-CoV-2 and the chaperone HSPA5/GRP78 are probably co-released through ARL8B-dependent lysosomal exocytic pathway for unconventional egress.
Tissue Specificity Ubiquitously expressed.
KEGG Pathway
Salmonella infection (hsa05132 )

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Systemic lupus erythematosus DISI1SZ7 Strong Biomarker [1]
Prostate cancer DISF190Y Disputed Biomarker [2]
Prostate carcinoma DISMJPLE Disputed Biomarker [2]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
13 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 ADP-ribosylation factor-like protein 8B (ARL8B). [3]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of ADP-ribosylation factor-like protein 8B (ARL8B). [4]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of ADP-ribosylation factor-like protein 8B (ARL8B). [5]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of ADP-ribosylation factor-like protein 8B (ARL8B). [6]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of ADP-ribosylation factor-like protein 8B (ARL8B). [7]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of ADP-ribosylation factor-like protein 8B (ARL8B). [8]
Testosterone DM7HUNW Approved Testosterone decreases the expression of ADP-ribosylation factor-like protein 8B (ARL8B). [9]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of ADP-ribosylation factor-like protein 8B (ARL8B). [10]
Diethylstilbestrol DMN3UXQ Approved Diethylstilbestrol decreases the expression of ADP-ribosylation factor-like protein 8B (ARL8B). [11]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of ADP-ribosylation factor-like protein 8B (ARL8B). [12]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of ADP-ribosylation factor-like protein 8B (ARL8B). [14]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of ADP-ribosylation factor-like protein 8B (ARL8B). [15]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of ADP-ribosylation factor-like protein 8B (ARL8B). [16]
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⏷ Show the Full List of 13 Drug(s)
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 ADP-ribosylation factor-like protein 8B (ARL8B). [13]
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References

1 ADP-ribosylation factor-like 8b is required for the development of mouse models of systemic lupus erythematosus.Int Immunol. 2019 Mar 28;31(4):225-237. doi: 10.1093/intimm/dxy084.
2 The Arf-like GTPase Arl8b is essential for three-dimensional invasive growth of prostate cancer in vitro and xenograft formation and growth in vivo.Oncotarget. 2016 May 24;7(21):31037-52. doi: 10.18632/oncotarget.8832.
3 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
4 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.
5 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.
6 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
7 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.
8 Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
9 The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
10 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.
11 Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
12 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
13 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.
14 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.
15 Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
16 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.