Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0RRSG9)

• DOT Name: Dual specificity protein phosphatase 19 (DUSP19)
• Synonyms: EC 3.1.3.16; EC 3.1.3.48; Dual specificity phosphatase TS-DSP1; Low molecular weight dual specificity phosphatase 3; LMW-DSP3; Protein phosphatase SKRP1; Stress-activated protein kinase pathway-regulating phosphatase 1; SAPK pathway-regulating phosphatase 1
• Gene Name: DUSP19
• Related Disease:
  Cone-rod dystrophy 2
  Osteoarthritis
• UniProt ID: DUS19_HUMAN
• PDB ID: 3S4E; 4D3P; 4D3Q; 4D3R
• EC Number: 3.1.3.16; 3.1.3.48
• Pfam ID: PF00782
• Sequence:
  MYSLNQEIKAFSRNNLRKQCTRVTTLTGKKIIETWKDARIHVVEEVEPSSGGGCGYVQDL
  SSDLQVGVIKPWLLLGSQDAAHDLDTLKKNKVTHILNVAYGVENAFLSDFTYKSISILDL
  PETNILSYFPECFEFIEEAKRKDGVVLVHCNAGVSRAAAIVIGFLMNSEQTSFTSAFSLV
  KNARPSICPNSGFMEQLRTYQEGKESNKCDRIQENSS
• Function: Has a dual specificity toward Ser/Thr and Tyr-containing proteins.
• Tissue Specificity: Expressed in the heart, lung, liver, and pancreas. The expression level in the pancreas is the highest.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cone-rod dystrophy 2	DISX2RWY	Definitive	Biomarker	[1]
Osteoarthritis	DIS05URM	Strong	Biomarker	[2]

6 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Dual specificity protein phosphatase 19 (DUSP19).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Dual specificity protein phosphatase 19 (DUSP19).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Dual specificity protein phosphatase 19 (DUSP19).	[5]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Dual specificity protein phosphatase 19 (DUSP19).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Dual specificity protein phosphatase 19 (DUSP19).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Dual specificity protein phosphatase 19 (DUSP19).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Dual specificity protein phosphatase 19 (DUSP19).	[6]

References

• [1] DUSP19 mediates spinal cord injury-induced apoptosis and inflammation in mouse primary microglia cells via the NF-kB signaling pathway.Neurol Res. 2020 Jan;42(1):31-38. doi: 10.1080/01616412.2019.1685068. Epub 2019 Dec 8.
• [2] DUSP19, a downstream effector of leptin, inhibits chondrocyte apoptosis via dephosphorylating JNK during osteoarthritis pathogenesis.Mol Biosyst. 2016 Mar;12(3):721-8. doi: 10.1039/c5mb00776c.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [6] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [7] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [8] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.
• [9] Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.