Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT58M21J)

• DOT Name: Serine protease HTRA4 (HTRA4)
• Synonyms: EC 3.4.21.-; High-temperature requirement factor A4
• Gene Name: HTRA4
• Related Disease:
  Eclampsia
  Advanced cancer
  Brain neoplasm
  Breast cancer
  Breast carcinoma
  Prostate cancer
  Cutaneous mastocytosis
• UniProt ID: HTRA4_HUMAN
• EC Number: 3.4.21.-
• Pfam ID: PF00219 ; PF07648 ; PF13180 ; PF13365
• Sequence:
  MIRPQLRTAGLGRCLLPGLLLLLVPVLWAGAEKLHTQPSCPAVCQPTRCPALPTCALGTT
  PVFDLCRCCRVCPAAEREVCGGAQGQPCAPGLQCLQPLRPGFPSTCGCPTLGGAVCGSDR
  RTYPSMCALRAENRAARRLGKVPAVPVQWGNCGDTGTRSAGPLRRNYNFIAAVVEKVAPS
  VVHVQLWGRLLHGSRLVPVYSGSGFIVSEDGLIITNAHVVRNQQWIEVVLQNGARYEAVV
  KDIDLKLDLAVIKIESNAELPVLMLGRSSDLRAGEFVVALGSPFSLQNTATAGIVSTKQR
  GGKELGMKDSDMDYVQIDATINYGNSGGPLVNLDGDVIGVNSLRVTDGISFAIPSDRVRQ
  FLAEYHEHQMKGKAFSNKKYLGLQMLSLTVPLSEELKMHYPDFPDVSSGVYVCKVVEGTA
  AQSSGLRDHDVIVNINGKPITTTTDVVKALDSDSLSMAVLRGKDNLLLTVIPETIN
• Function: Serine protease.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Eclampsia	DISWPO8U	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[2]
Brain neoplasm	DISY3EKS	moderate	Altered Expression	[2]
Breast cancer	DIS7DPX1	moderate	Biomarker	[2]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[2]
Prostate cancer	DISF190Y	moderate	Altered Expression	[2]
Cutaneous mastocytosis	DISLBZEF	Limited	Altered Expression	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Malathion	DMXZ84M	Approved	Malathion decreases the expression of Serine protease HTRA4 (HTRA4).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Serine protease HTRA4 (HTRA4).	[6]
L-Serine	DM6WPIS	Investigative	L-Serine decreases the expression of Serine protease HTRA4 (HTRA4).	[7]

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 Serine protease HTRA4 (HTRA4).	[5]

References

• [1] Upregulation of HtrA4 in the placentas of patients with severe pre-eclampsia.Placenta. 2012 Nov;33(11):919-26. doi: 10.1016/j.placenta.2012.08.003. Epub 2012 Sep 8.
• [2] HtrA4 Protease Promotes Chemotherapeutic-Dependent Cancer Cell Death.Cells. 2019 Sep 20;8(10):1112. doi: 10.3390/cells8101112.
• [3] Immune response against HtrA proteases in children with cutaneous mastocytosis.Acta Biochim Pol. 2018;65(3):471-478. doi: 10.18388/abp.2018_2623. Epub 2018 Aug 27.
• [4] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [5] 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.
• [6] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [7] Mechanisms of L-Serine Neuroprotection in vitro Include ER Proteostasis Regulation. Neurotox Res. 2018 Jan;33(1):123-132. doi: 10.1007/s12640-017-9829-3. Epub 2017 Nov 2.