Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8Q40G2)

• DOT Name: Putative hydrolase DDAH2 (DDAH2)
• Synonyms: EC 3.-.-.-; DDAHII; Inactive N(G),N(G)-dimethylarginine dimethylaminohydrolase 2; DDAH-2; Inactive dimethylarginine dimethylaminohydrolase 2; Protein G6a; S-phase protein
• Gene Name: DDAH2
• Related Disease:
  Nephropathy
  Arteriosclerosis
  Atherosclerosis
  Bronchopulmonary dysplasia
  Castration-resistant prostate carcinoma
  Congestive heart failure
  Coronary atherosclerosis
  Coronary heart disease
  Diabetic kidney disease
  Dilated cardiomyopathy 1A
  Endometritis
  Insomnia
  Melanoma
  Obesity
  Pre-eclampsia
  Stroke
  Type-1/2 diabetes
  Cardiovascular disease
  Non-insulin dependent diabetes
  Erectile dysfunction
  Hyperglycemia
  Myocardial infarction
  Type-1 diabetes
• UniProt ID: DDAH2_HUMAN
• EC Number: 3.-.-.-
• Sequence:
  MGTPGEGLGRCSHALIRGVPESLASGEGAGAGLPALDLAKAQREHGVLGGKLRQRLGLQL
  LELPPEESLPLGPLLGDTAVIQGDTALITRPWSPARRPEVDGVRKALQDLGLRIVEIGDE
  NATLDGTDVLFTGREFFVGLSKWTNHRGAEIVADTFRDFAVSTVPVSGPSHLRGLCGMGG
  PRTVVAGSSDAAQKAVRAMAVLTDHPYASLTLPDDAAADCLFLRPGLPGVPPFLLHRGGG
  DLPNSQEALQKLSDVTLVPVSCSELEKAGAGLSSLCLVLSTRPHS
• Function: Putative hydrolase with unknown substrate (Probable). Does not hydrolyze N(G),N(G)-dimethyl-L-arginine (ADMA) which acts as an inhibitor of NOS. In endothelial cells, induces expression of vascular endothelial growth factor (VEGF) via phosphorylation of the transcription factor SP1 by PKA in a process that is independent of NO and NO synthase. Similarly, enhances pancreatic insulin secretion through SP1-mediated transcriptional up-regulation of secretagogin/SCGN, an insulin vesicle docking protein. Upon viral infection, relocates to mitochondria where it promotes mitochondrial fission through activation of DNM1L leading to the inhibition of innate response activation mediated by MAVS.
• Tissue Specificity: Detected in heart, placenta, lung, liver, skeletal muscle, kidney and pancreas, and at very low levels in brain.
• BioCyc Pathway: MetaCyc:HS03493-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Nephropathy	DISXWP4P	Definitive	Biomarker	[1]
Arteriosclerosis	DISK5QGC	Strong	Posttranslational Modification	[2]
Atherosclerosis	DISMN9J3	Strong	Posttranslational Modification	[2]
Bronchopulmonary dysplasia	DISO0BY5	Strong	Biomarker	[3]
Castration-resistant prostate carcinoma	DISVGAE6	Strong	Biomarker	[4]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[5]
Coronary atherosclerosis	DISKNDYU	Strong	Genetic Variation	[6]
Coronary heart disease	DIS5OIP1	Strong	Genetic Variation	[6]
Diabetic kidney disease	DISJMWEY	Strong	Genetic Variation	[7]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Biomarker	[8]
Endometritis	DISHGJ6G	Strong	Biomarker	[9]
Insomnia	DIS0AFR7	Strong	Biomarker	[10]
Melanoma	DIS1RRCY	Strong	Biomarker	[11]
Obesity	DIS47Y1K	Strong	Genetic Variation	[12]
Pre-eclampsia	DISY7Q29	Strong	Biomarker	[13]
Stroke	DISX6UHX	Strong	Genetic Variation	[14]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[8]
Cardiovascular disease	DIS2IQDX	moderate	Genetic Variation	[15]
Non-insulin dependent diabetes	DISK1O5Z	moderate	Genetic Variation	[15]
Erectile dysfunction	DISD8MTH	Limited	Genetic Variation	[16]
Hyperglycemia	DIS0BZB5	Limited	Altered Expression	[17]
Myocardial infarction	DIS655KI	Limited	Genetic Variation	[6]
Type-1 diabetes	DIS7HLUB	Limited	Genetic Variation	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Putative hydrolase DDAH2 (DDAH2) affects the response to substance of Fluorouracil.	[42]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Putative hydrolase DDAH2 (DDAH2).	[19]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Putative hydrolase DDAH2 (DDAH2).	[20]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Putative hydrolase DDAH2 (DDAH2).	[21]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Putative hydrolase DDAH2 (DDAH2).	[22]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Putative hydrolase DDAH2 (DDAH2).	[23]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Putative hydrolase DDAH2 (DDAH2).	[24]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Putative hydrolase DDAH2 (DDAH2).	[25]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Putative hydrolase DDAH2 (DDAH2).	[26]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Putative hydrolase DDAH2 (DDAH2).	[27]
Selenium	DM25CGV	Approved	Selenium increases the expression of Putative hydrolase DDAH2 (DDAH2).	[28]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Putative hydrolase DDAH2 (DDAH2).	[29]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol affects the expression of Putative hydrolase DDAH2 (DDAH2).	[30]
Iron Dextran	DM5OY70	Approved	Iron Dextran decreases the expression of Putative hydrolase DDAH2 (DDAH2).	[31]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Putative hydrolase DDAH2 (DDAH2).	[32]
Genistein	DM0JETC	Phase 2/3	Genistein affects the expression of Putative hydrolase DDAH2 (DDAH2).	[30]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Putative hydrolase DDAH2 (DDAH2).	[28]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Putative hydrolase DDAH2 (DDAH2).	[33]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Putative hydrolase DDAH2 (DDAH2).	[34]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Putative hydrolase DDAH2 (DDAH2).	[35]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Putative hydrolase DDAH2 (DDAH2).	[36]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Putative hydrolase DDAH2 (DDAH2).	[37]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Putative hydrolase DDAH2 (DDAH2).	[38]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Putative hydrolase DDAH2 (DDAH2).	[39]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Putative hydrolase DDAH2 (DDAH2).	[40]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Putative hydrolase DDAH2 (DDAH2).	[41]

References

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