Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDYDBN7)

DOT Name	Dual specificity phosphatase 28 (DUSP28)
Synonyms	EC 3.1.3.16; EC 3.1.3.48
Gene Name	DUSP28
Related Disease	Advanced cancer ( ) Hepatocellular carcinoma ( ) Neoplasm ( ) Pancreatic cancer ( )
UniProt ID	DUS28_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	5Y15; 5Y16
EC Number	3.1.3.16; 3.1.3.48
Pfam ID	PF00782
Sequence	MGPAEAGRRGAASPVPPPLVRVAPSLFLGSARAAGAEEQLARAGVTLCVNVSRQQPGPRA PGVAELRVPVFDDPAEDLLAHLEPTCAAMEAAVRAGGACLVYCKNGRSRSAAVCTAYLMR HRGLSLAKAFQMVKSARPVAEPNPGFWSQLQKYEEALQAQSCLQGEPPALGLGPEA
Function	Has phosphatase activity with the synthetic substrate 6,8-difluoro-4-methylumbelliferyl phosphate (in vitro). Has almost no detectable activity with phosphotyrosine, even less activity with phosphothreonine and displays complete lack of activity with phosphoserine. The poor activity with phosphotyrosine may be due to steric hindrance by bulky amino acid sidechains that obstruct access to the active site.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Pancreatic cancer	DISJC981	Limited	Biomarker	[1]
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Molecular Interaction Atlas (MIA)

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Dual specificity phosphatase 28 (DUSP28).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Dual specificity phosphatase 28 (DUSP28).	[7]
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3 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Dual specificity phosphatase 28 (DUSP28).	[5]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Dual specificity phosphatase 28 (DUSP28).	[6]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Dual specificity phosphatase 28 (DUSP28).	[8]
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References

1	Scattered DUSP28 is a novel biomarker responsible for aggravating malignancy via the autocrine and paracrine signaling in metastatic pancreatic cancer.Cancer Lett. 2019 Aug 1;456:1-12. doi: 10.1016/j.canlet.2019.03.006. Epub 2019 Mar 19.
2	DUSP28 contributes to human hepatocellular carcinoma via regulation of the p38 MAPK signaling.Int J Oncol. 2014 Dec;45(6):2596-604. doi: 10.3892/ijo.2014.2653. Epub 2014 Sep 16.
3	Autocrine DUSP28 signaling mediates pancreatic cancer malignancy via regulation of PDGF-A.Sci Rep. 2017 Oct 6;7(1):12760. doi: 10.1038/s41598-017-13023-w.
4	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.
5	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.
6	Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
7	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.
8	Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.