Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRDWN2V)

DOT Name Platelet-activating factor acetylhydrolase IB subunit alpha2 (PAFAH1B2)
Synonyms EC 3.1.1.47; PAF acetylhydrolase 30 kDa subunit; PAF-AH 30 kDa subunit; PAF-AH subunit beta; PAFAH subunit beta
Gene Name PAFAH1B2
Related Disease
Alzheimer disease ( )
Advanced cancer ( )
Matthew-Wood syndrome ( )
Neoplasm ( )
Pancreatic cancer ( )
Pancreatic ductal carcinoma ( )
UniProt ID
PA1B2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1VYH
EC Number
3.1.1.47
Pfam ID
PF13472
Sequence
MSQGDSNPAAIPHAAEDIQGDDRWMSQHNRFVLDCKDKEPDVLFVGDSMVQLMQQYEIWR
ELFSPLHALNFGIGGDTTRHVLWRLKNGELENIKPKVIVVWVGTNNHENTAEEVAGGIEA
IVQLINTRQPQAKIIVLGLLPRGEKPNPLRQKNAKVNQLLKVSLPKLANVQLLDTDGGFV
HSDGAISCHDMFDFLHLTGGGYAKICKPLHELIMQLLEETPEEKQTTIA
Function
Alpha2 catalytic subunit of the cytosolic type I platelet-activating factor (PAF) acetylhydrolase (PAF-AH (I)) heterotetrameric enzyme that catalyzes the hydrolyze of the acetyl group at the sn-2 position of PAF and its analogs and modulates the action of PAF. The activity and substrate specificity of PAF-AH (I) are affected by its subunit composition. The alpha2/alpha2 homodimer (PAFAH1B2/PAFAH1B2 homodimer) hydrolyzes PAF and 1-O-alkyl-2-acetyl-sn-glycero-3-phosphorylethanolamine (AAGPE) more efficiently than 1-O-alkyl-2-acetyl-sn-glycero-3-phosphoric acid (AAGPA). In contrast, the alpha1/alpha2 heterodimer(PAFAH1B3/PAFAH1B3 heterodimer) hydrolyzes AAGPA more efficiently than PAF, but has little hydrolytic activity towards AAGPE. May play a role in male germ cell meiosis during the late pachytenestage and meiotic divisions as well as early spermiogenesis.
Tissue Specificity Ubiquitous.
KEGG Pathway
Ether lipid metabolism (hsa00565 )
Metabolic pathways (hsa01100 )
Reactome Pathway
COPI-independent Golgi-to-ER retrograde traffic (R-HSA-6811436 )
Neutrophil degranulation (R-HSA-6798695 )

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Alzheimer disease DISF8S70 Strong Genetic Variation [1]
Advanced cancer DISAT1Z9 Limited Biomarker [2]
Matthew-Wood syndrome DISA7HR7 Limited Biomarker [3]
Neoplasm DISZKGEW Limited Biomarker [2]
Pancreatic cancer DISJC981 Limited Biomarker [3]
Pancreatic ductal carcinoma DIS26F9Q Limited Altered Expression [3]
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⏷ Show the Full List of 6 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
5 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Platelet-activating factor acetylhydrolase IB subunit alpha2 (PAFAH1B2). [4]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Platelet-activating factor acetylhydrolase IB subunit alpha2 (PAFAH1B2). [5]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Platelet-activating factor acetylhydrolase IB subunit alpha2 (PAFAH1B2). [6]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Platelet-activating factor acetylhydrolase IB subunit alpha2 (PAFAH1B2). [7]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Platelet-activating factor acetylhydrolase IB subunit alpha2 (PAFAH1B2). [8]
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1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Coumarin DM0N8ZM Investigative Coumarin increases the phosphorylation of Platelet-activating factor acetylhydrolase IB subunit alpha2 (PAFAH1B2). [9]
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References

1 RNA editing alterations in a multi-ethnic Alzheimer disease cohort converge on immune and endocytic molecular pathways.Hum Mol Genet. 2019 Sep 15;28(18):3053-3061. doi: 10.1093/hmg/ddz110.
2 Selective inhibitor of platelet-activating factor acetylhydrolases 1b2 and 1b3 that impairs cancer cell survival.ACS Chem Biol. 2015 Apr 17;10(4):925-32. doi: 10.1021/cb500893q. Epub 2015 Jan 20.
3 PAFAH1B2 is a HIF1a target gene and promotes metastasis in pancreatic cancer.Biochem Biophys Res Commun. 2018 Jun 27;501(3):654-660. doi: 10.1016/j.bbrc.2018.05.039. Epub 2018 May 16.
4 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.
5 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
6 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.
7 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.
8 Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.
9 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.