Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2F591M)

• DOT Name: Phosphatidate cytidylyltransferase 1 (CDS1)
• Synonyms: EC 2.7.7.41; CDP-DAG synthase 1; CDP-DG synthase 1; CDP-diacylglycerol synthase 1; CDS 1; CDP-diglyceride pyrophosphorylase 1; CDP-diglyceride synthase 1; CTP:phosphatidate cytidylyltransferase 1
• Gene Name: CDS1
• Related Disease:
  Carcinoma
  Adult glioblastoma
  Appendicitis
  B-cell neoplasm
  Bipolar I disorder
  Cardiac failure
  Chondrosarcoma
  Colorectal carcinoma
  Congestive heart failure
  Disorder of orbital region
  Familial isolated congenital asplenia
  Glioblastoma multiforme
  Neoplasm
  Panic disorder
  Undifferentiated carcinoma
  Advanced cancer
  B-cell lymphoma
  Meningitis
  Myasthenia gravis
• UniProt ID: CDS1_HUMAN
• EC Number: 2.7.7.41
• Pfam ID: PF01148
• Sequence:
  MLELRHRGSCPGPREAVSPPHREGEAAGGDHETESTSDKETDIDDRYGDLDSRTDSDIPE
  IPPSSDRTPEILKKALSGLSSRWKNWWIRGILTLTMISLFFLIIYMGSFMLMLLVLGIQV
  KCFHEIITIGYRVYHSYDLPWFRTLSWYFLLCVNYFFYGETVADYFATFVQREEQLQFLI
  RYHRFISFALYLAGFCMFVLSLVKKHYRLQFYMFAWTHVTLLITVTQSHLVIQNLFEGMI
  WFLVPISSVICNDITAYLFGFFFGRTPLIKLSPKKTWEGFIGGFFSTVVFGFIAAYVLSK
  YQYFVCPVEYRSDVNSFVTECEPSELFQLQTYSLPPFLKAVLRQERVSLYPFQIHSIALS
  TFASLIGPFGGFFASGFKRAFKIKDFANTIPGHGGIMDRFDCQYLMATFVHVYITSFIRG
  PNPSKVLQQLLVLQPEQQLNIYKTLKTHLIEKGILQPTLKV
• Function: Catalyzes the conversion of phosphatidic acid (PA) to CDP-diacylglycerol (CDP-DAG), an essential intermediate in the synthesis of phosphatidylglycerol, cardiolipin and phosphatidylinositol. Exhibits almost no acyl chain preference for PA, showing no discrimination for the sn-1/sn-2 acyl chain composition of PAs. Plays an important role in regulating the growth of lipid droplets which are storage organelles at the center of lipid and energy homeostasis. Positively regulates the differentiation and development of adipocytes.
• Tissue Specificity: Expressed in adult tissues such as placenta, brain, small intestine, ovary, testis and prostate. Highly expressed in fetal kidney, lung and brain. Lower level in fetal liver.
• KEGG Pathway:
  Glycerophospholipid metabolism (hsa00564)
  Metabolic pathways (hsa01100)
  Phosphatidylinositol sig.ling system (hsa04070)
• Reactome Pathway: Synthesis of PI (R-HSA-1483226)

Molecular Interaction Atlas (MIA) of This DOT

19 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma	DISH9F1N	Definitive	Biomarker	[1]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[2]
Appendicitis	DIS4GOLF	Strong	Biomarker	[3]
B-cell neoplasm	DISVY326	Strong	Genetic Variation	[4]
Bipolar I disorder	DISD09EH	Strong	Biomarker	[5]
Cardiac failure	DISDC067	Strong	Altered Expression	[6]
Chondrosarcoma	DIS4I7JB	Strong	Biomarker	[7]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[8]
Congestive heart failure	DIS32MEA	Strong	Altered Expression	[6]
Disorder of orbital region	DISH0ECJ	Strong	Biomarker	[9]
Familial isolated congenital asplenia	DIS60HWJ	Strong	Biomarker	[10]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[11]
Panic disorder	DISD3VNY	Strong	Biomarker	[12]
Undifferentiated carcinoma	DISIAZST	Disputed	Biomarker	[1]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[13]
B-cell lymphoma	DISIH1YQ	Limited	Biomarker	[13]
Meningitis	DISQABAA	Limited	Biomarker	[14]
Myasthenia gravis	DISELRCI	Limited	Genetic Variation	[15]

17 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 Phosphatidate cytidylyltransferase 1 (CDS1).	[16]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Phosphatidate cytidylyltransferase 1 (CDS1).	[17]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Phosphatidate cytidylyltransferase 1 (CDS1).	[18]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Phosphatidate cytidylyltransferase 1 (CDS1).	[19]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Phosphatidate cytidylyltransferase 1 (CDS1).	[20]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Phosphatidate cytidylyltransferase 1 (CDS1).	[21]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Phosphatidate cytidylyltransferase 1 (CDS1).	[22]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Phosphatidate cytidylyltransferase 1 (CDS1).	[23]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Phosphatidate cytidylyltransferase 1 (CDS1).	[24]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Phosphatidate cytidylyltransferase 1 (CDS1).	[25]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Phosphatidate cytidylyltransferase 1 (CDS1).	[26]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Phosphatidate cytidylyltransferase 1 (CDS1).	[27]
Nicotine	DMWX5CO	Approved	Nicotine increases the splicing of Phosphatidate cytidylyltransferase 1 (CDS1).	[28]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Phosphatidate cytidylyltransferase 1 (CDS1).	[27]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Phosphatidate cytidylyltransferase 1 (CDS1).	[30]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Phosphatidate cytidylyltransferase 1 (CDS1).	[31]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Phosphatidate cytidylyltransferase 1 (CDS1).	[20]

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 decreases the methylation of Phosphatidate cytidylyltransferase 1 (CDS1).	[29]

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