Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTC7616F)

• DOT Name: Serine protease HTRA2, mitochondrial (HTRA2)
• Synonyms: EC 3.4.21.108; High temperature requirement protein A2; HtrA2; Omi stress-regulated endoprotease; Serine protease 25; Serine proteinase OMI
• Gene Name: HTRA2
• Related Disease:
  3-methylglutaconic aciduria type 8
  Cerebral infarction
  3-methylglutaconic aciduria
  Advanced cancer
  Alzheimer disease
  Amyloidosis
  Attention deficit hyperactivity disorder
  Autosomal recessive juvenile Parkinson disease 2
  B-cell neoplasm
  Benign prostatic hyperplasia
  Breast cancer
  Breast carcinoma
  Cervical cancer
  Cervical carcinoma
  Colitis
  Colonic neoplasm
  DiGeorge syndrome
  Essential tremor
  Hepatocellular carcinoma
  Huntington disease
  Juvenile-onset Parkinson disease
  Late-onset Parkinson disease
  Liver cirrhosis
  Melanoma
  Movement disorder
  Neoplasm
  Non-small-cell lung cancer
  Pancreatic cancer
  Parkinsonian disorder
  Premature aging syndrome
  Prostate cancer
  Prostate carcinoma
  Renal cell carcinoma
  Wilms tumor
  Epithelial ovarian cancer
  Ovarian cancer
  Ovarian neoplasm
  Spinal muscular atrophy
  Amyotrophic lateral sclerosis
  Benign neoplasm
  Coronary heart disease
  Cryptorchidism
  Endometrial cancer
  Endometrial carcinoma
  Neuroblastoma
  Status epilepticus seizure
• UniProt ID: HTRA2_HUMAN
• PDB ID: 1LCY; 2PZD; 5FHT; 5M3N; 5M3O; 5TNY; 5TNZ; 5TO0; 5TO1; 5WYN; 7VGE; 8AUK; 8E2K
• EC Number: 3.4.21.108
• Pfam ID: PF17820 ; PF13365
• Sequence:
  MAAPRAGRGAGWSLRAWRALGGIRWGRRPRLTPDLRALLTSGTSDPRARVTYGTPSLWAR
  LSVGVTEPRACLTSGTPGPRAQLTAVTPDTRTREASENSGTRSRAWLAVALGAGGAVLLL
  LWGGGRGPPAVLAAVPSPPPASPRSQYNFIADVVEKTAPAVVYIEILDRHPFLGREVPIS
  NGSGFVVAADGLIVTNAHVVADRRRVRVRLLSGDTYEAVVTAVDPVADIATLRIQTKEPL
  PTLPLGRSADVRQGEFVVAMGSPFALQNTITSGIVSSAQRPARDLGLPQTNVEYIQTDAA
  IDFGNSGGPLVNLDGEVIGVNTMKVTAGISFAIPSDRLREFLHRGEKKNSSSGISGSQRR
  YIGVMMLTLSPSILAELQLREPSFPDVQHGVLIHKVILGSPAHRAGLRPGDVILAIGEQM
  VQNAEDVYEAVRTQSQLAVQIRRGRETLTLYVTPEVTE
• Function: Serine protease that shows proteolytic activity against a non-specific substrate beta-casein. Promotes or induces cell death either by direct binding to and inhibition of BIRC proteins (also called inhibitor of apoptosis proteins, IAPs), leading to an increase in caspase activity, or by a BIRC inhibition-independent, caspase-independent and serine protease activity-dependent mechanism. Cleaves THAP5 and promotes its degradation during apoptosis. Isoform 2 seems to be proteolytically inactive.
• Tissue Specificity: .Ubiquitously expressed.
• KEGG Pathway:
  Apoptosis (hsa04210)
  Apoptosis - multiple species (hsa04215)
  Parkinson disease (hsa05012)
  Pathways of neurodegeneration - multiple diseases (hsa05022)

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
3-methylglutaconic aciduria type 8	DISQG1OS	Definitive	Autosomal recessive	[1]
Cerebral infarction	DISR1WNP	Definitive	Biomarker	[2]
3-methylglutaconic aciduria	DIS8G1WP	Strong	Biomarker	[3]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[4]
Alzheimer disease	DISF8S70	Strong	Biomarker	[5]
Amyloidosis	DISHTAI2	Strong	Biomarker	[6]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Altered Expression	[7]
Autosomal recessive juvenile Parkinson disease 2	DISNSTD1	Strong	Biomarker	[8]
B-cell neoplasm	DISVY326	Strong	Biomarker	[9]
Benign prostatic hyperplasia	DISI3CW2	Strong	Altered Expression	[10]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[11]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[11]
Cervical cancer	DISFSHPF	Strong	Biomarker	[12]
Cervical carcinoma	DIST4S00	Strong	Altered Expression	[12]
Colitis	DISAF7DD	Strong	Biomarker	[13]
Colonic neoplasm	DISSZ04P	Strong	Altered Expression	[14]
DiGeorge syndrome	DIST1RKO	Strong	Genetic Variation	[15]
Essential tremor	DIS7GBKQ	Strong	Genetic Variation	[16]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[17]
Huntington disease	DISQPLA4	Strong	Biomarker	[18]
Juvenile-onset Parkinson disease	DISNT5BI	Strong	Biomarker	[8]
Late-onset Parkinson disease	DIS9IOUI	Strong	Genetic Variation	[19]
Liver cirrhosis	DIS4G1GX	Strong	Altered Expression	[20]
Melanoma	DIS1RRCY	Strong	Biomarker	[21]
Movement disorder	DISOJJ2D	Strong	Biomarker	[22]
Neoplasm	DISZKGEW	Strong	Altered Expression	[17]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[4]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[23]
Parkinsonian disorder	DISHGY45	Strong	Genetic Variation	[24]
Premature aging syndrome	DIS51AGT	Strong	Biomarker	[25]
Prostate cancer	DISF190Y	Strong	Altered Expression	[10]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[10]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[26]
Wilms tumor	DISB6T16	Strong	Biomarker	[27]
Epithelial ovarian cancer	DIS56MH2	moderate	Altered Expression	[28]
Ovarian cancer	DISZJHAP	moderate	Altered Expression	[28]
Ovarian neoplasm	DISEAFTY	moderate	Altered Expression	[28]
Spinal muscular atrophy	DISTLKOB	moderate	Altered Expression	[29]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Biomarker	[30]
Benign neoplasm	DISDUXAD	Limited	Altered Expression	[31]
Coronary heart disease	DIS5OIP1	Limited	Biomarker	[32]
Cryptorchidism	DISYUD2P	Limited	Biomarker	[33]
Endometrial cancer	DISW0LMR	Limited	Biomarker	[34]
Endometrial carcinoma	DISXR5CY	Limited	Biomarker	[34]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[35]
Status epilepticus seizure	DISY3BIC	Limited	Biomarker	[36]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Serine protease HTRA2, mitochondrial (HTRA2) affects the response to substance of Methotrexate.	[57]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Serine protease HTRA2, mitochondrial (HTRA2).	[37]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Serine protease HTRA2, mitochondrial (HTRA2).	[38]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Serine protease HTRA2, mitochondrial (HTRA2).	[39]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Serine protease HTRA2, mitochondrial (HTRA2).	[40]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Serine protease HTRA2, mitochondrial (HTRA2).	[41]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Serine protease HTRA2, mitochondrial (HTRA2).	[42]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Serine protease HTRA2, mitochondrial (HTRA2).	[43]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Serine protease HTRA2, mitochondrial (HTRA2).	[44]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Serine protease HTRA2, mitochondrial (HTRA2).	[45]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Serine protease HTRA2, mitochondrial (HTRA2).	[45]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Serine protease HTRA2, mitochondrial (HTRA2).	[46]
MG-132	DMKA2YS	Preclinical	MG-132 increases the expression of Serine protease HTRA2, mitochondrial (HTRA2).	[51]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone decreases the expression of Serine protease HTRA2, mitochondrial (HTRA2).	[53]
Okadaic acid	DM47CO1	Investigative	Okadaic acid affects the expression of Serine protease HTRA2, mitochondrial (HTRA2).	[55]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bortezomib	DMNO38U	Approved	Bortezomib affects the localization of Serine protease HTRA2, mitochondrial (HTRA2).	[47]
Simvastatin	DM30SGU	Approved	Simvastatin affects the localization of Serine protease HTRA2, mitochondrial (HTRA2).	[48]
2-deoxyglucose	DMIAHVU	Approved	2-deoxyglucose decreases the localization of Serine protease HTRA2, mitochondrial (HTRA2).	[49]
Flavopiridol	DMKSUOI	Phase 2	Flavopiridol affects the localization of Serine protease HTRA2, mitochondrial (HTRA2).	[50]
Paraquat	DMR8O3X	Investigative	Paraquat increases the transport of Serine protease HTRA2, mitochondrial (HTRA2).	[52]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde affects the localization of Serine protease HTRA2, mitochondrial (HTRA2).	[54]
Nitrosoglutathione	DMZ9WI4	Investigative	Nitrosoglutathione affects the localization of Serine protease HTRA2, mitochondrial (HTRA2).	[56]

References

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