Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY0K84R)

• DOT Name: AP-1 complex subunit beta-1 (AP1B1)
• Synonyms: Adaptor protein complex AP-1 subunit beta-1; Adaptor-related protein complex 1 subunit beta-1; Beta-1-adaptin; Beta-adaptin 1; Clathrin assembly protein complex 1 beta large chain; Golgi adaptor HA1/AP1 adaptin beta subunit
• Gene Name: AP1B1
• Related Disease:
  Meningioma
  Analgesia
  Ichthyosiform erythroderma, corneal involvement, and hearing loss
  Non-syndromic ichthyosis
  Intellectual disability
  MEDNIK syndrome
  Neoplasm
• UniProt ID: AP1B1_HUMAN
• PDB ID: 4HMY; 4P6Z; 6CM9; 6CRI; 6D83; 6D84; 6DFF; 7R4H; 7UX3; 8D4C; 8D4D; 8D4E; 8D4F; 8D4G; 8D9R; 8D9S; 8D9T; 8D9U; 8D9V; 8D9W
• Pfam ID: PF01602 ; PF02883 ; PF09066
• Sequence:
  MTDSKYFTTTKKGEIFELKAELNSDKKEKKKEAVKKVIASMTVGKDVSALFPDVVNCMQT
  DNLELKKLVYLYLMNYAKSQPDMAIMAVNTFVKDCEDPNPLIRALAVRTMGCIRVDKITE
  YLCEPLRKCLKDEDPYVRKTAAVCVAKLHDINAQLVEDQGFLDTLKDLISDSNPMVVANA
  VAALSEIAESHPSSNLLDLNPQSINKLLTALNECTEWGQIFILDCLANYMPKDDREAQSI
  CERVTPRLSHANSAVVLSAVKVLMKFMEMLSKDLDYYGTLLKKLAPPLVTLLSAEPELQY
  VALRNINLIVQKRPEILKHEMKVFFVKYNDPIYVKLEKLDIMIRLASQANIAQVLAELKE
  YATEVDVDFVRKAVRAIGRCAIKVEQSAERCVSTLLDLIQTKVNYVVQEAIVVIKDIFRK
  YPNKYESVIATLCENLDSLDEPEARAAMIWIVGEYAERIDNADELLESFLEGFHDESTQV
  QLQLLTAIVKLFLKKPTETQELVQQVLSLATQDSDNPDLRDRGYIYWRLLSTDPVAAKEV
  VLAEKPLISEETDLIEPTLLDELICYIGTLASVYHKPPSAFVEGGRGVVHKSLPPRTASS
  ESAESPETAPTGAPPGEQPDVIPAQGDLLGDLLNLDLGPPVSGPPLATSSVQMGAVDLLG
  GGLDSLMGDEPEGIGGTNFVAPPTAAVPANLGAPIGSGLSDLFDLTSGVGTLSGSYVAPK
  AVWLPAMKAKGLEISGTFTRQVGSISMDLQLTNKALQVMTDFAIQFNRNSFGLAPAAPLQ
  VHAPLSPNQTVEISLPLSTVGSVMKMEPLNNLQVAVKNNIDVFYFSTLYPLHILFVEDGK
  MDRQMFLATWKDIPNENEAQFQIRDCPLNAEAASSKLQSSNIFTVAKRNVEGQDMLYQSL
  KLTNGIWVLAELRIQPGNPSCTDLELSLKCRAPEVSQHVYQAYETILKN
• Function: Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes. The AP complexes mediate both the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules.
• Tissue Specificity: Widely expressed.
• KEGG Pathway:
  Lysosome (hsa04142)
  Human immunodeficiency virus 1 infection (hsa05170)
• Reactome Pathway:
  MHC class II antigen presentation (R-HSA-2132295)
  Lysosome Vesicle Biogenesis (R-HSA-432720)
  Golgi Associated Vesicle Biogenesis (R-HSA-432722)
  Nef mediated downregulation of MHC class I complex cell surface expression (R-HSA-164940)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Meningioma	DISPT4TG	Definitive	Biomarker	[1]
Analgesia	DISK3TVI	Strong	Biomarker	[2]
Ichthyosiform erythroderma, corneal involvement, and hearing loss	DISQSVSF	Strong	Autosomal recessive	[3]
Non-syndromic ichthyosis	DISZ9QBQ	Strong	Genetic Variation	[3]
Intellectual disability	DISMBNXP	moderate	Biomarker	[4]
MEDNIK syndrome	DISRF06E	Supportive	Autosomal recessive	[4]
Neoplasm	DISZKGEW	Limited	Biomarker	[5]

10 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 AP-1 complex subunit beta-1 (AP1B1).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of AP-1 complex subunit beta-1 (AP1B1).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of AP-1 complex subunit beta-1 (AP1B1).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of AP-1 complex subunit beta-1 (AP1B1).	[10]
Selenium	DM25CGV	Approved	Selenium increases the expression of AP-1 complex subunit beta-1 (AP1B1).	[11]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of AP-1 complex subunit beta-1 (AP1B1).	[12]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of AP-1 complex subunit beta-1 (AP1B1).	[13]
APR-246	DMNFADH	Phase 2	APR-246 affects the expression of AP-1 complex subunit beta-1 (AP1B1).	[15]
SB-431542	DM0YOXQ	Preclinical	SB-431542 increases the expression of AP-1 complex subunit beta-1 (AP1B1).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of AP-1 complex subunit beta-1 (AP1B1).	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of AP-1 complex subunit beta-1 (AP1B1).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of AP-1 complex subunit beta-1 (AP1B1).	[16]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of AP-1 complex subunit beta-1 (AP1B1).	[14]

References

• [1] Pathological classification and molecular genetics of meningiomas.J Neurooncol. 2010 Sep;99(3):379-91. doi: 10.1007/s11060-010-0342-2. Epub 2010 Sep 1.
• [2] Oligomerization of MrgC11 and -opioid receptors in sensory neurons enhances morphine analgesia.Sci Signal. 2018 Jun 19;11(535):eaao3134. doi: 10.1126/scisignal.aao3134.
• [3] Recessive Mutations in AP1B1 Cause Ichthyosis, Deafness, and Photophobia. Am J Hum Genet. 2019 Nov 7;105(5):1023-1029. doi: 10.1016/j.ajhg.2019.09.021. Epub 2019 Oct 17.
• [4] Homozygous Loss-of-Function Mutations in AP1B1, Encoding Beta-1 Subunit of Adaptor-Related Protein Complex 1, Cause MEDNIK-like Syndrome. Am J Hum Genet. 2019 Nov 7;105(5):1016-1022. doi: 10.1016/j.ajhg.2019.09.020. Epub 2019 Oct 17.
• [5] Molecular genetics of meningiomas.Neurosurg Focus. 2005 Nov 15;19(5):E9. doi: 10.3171/foc.2005.19.5.10.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 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.
• [9] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [10] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [11] 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.
• [12] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [13] Effects of acute ethanol treatment on NCCIT cells and NCCIT cell-derived embryoid bodies (EBs). Toxicol In Vitro. 2010 Sep;24(6):1696-704. doi: 10.1016/j.tiv.2010.05.017. Epub 2010 May 26.
• [14] Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
• [15] Mutant p53 reactivation by PRIMA-1MET induces multiple signaling pathways converging on apoptosis. Oncogene. 2010 Mar 4;29(9):1329-38. doi: 10.1038/onc.2009.425. Epub 2009 Nov 30.
• [16] 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.
• [17] Activin/nodal signaling switches the terminal fate of human embryonic stem cell-derived trophoblasts. J Biol Chem. 2015 Apr 3;290(14):8834-48.
• [18] 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.