Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQ75KF2)

• DOT Name: Phosphatidate phosphatase LPIN1 (LPIN1)
• Synonyms: EC 3.1.3.4; Lipin-1
• Gene Name: LPIN1
• Related Disease:
  Hepatocellular carcinoma
  Myoglobinuria, acute recurrent, autosomal recessive
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Carcinoma
  Cardiovascular disease
  Cervical Intraepithelial neoplasia
  Chronic renal failure
  Dysplasia of cervix
  End-stage renal disease
  Fatty liver disease
  Hereditary myoglobinuria
  High blood pressure
  Human papillomavirus infection
  Hyperinsulinemia
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Myopathy
  Neoplasm
  Neuralgia
  Non-alcoholic fatty liver disease
  Obesity
  Polycystic ovarian syndrome
  Triple negative breast cancer
  Type-1/2 diabetes
  Very long chain acyl-CoA dehydrogenase deficiency
  Adrenoleukodystrophy
  Retinitis pigmentosa 9
  Hereditary recurrent myoglobinuria
  46,XY sex reversal 2
  Charcot-Marie-Tooth disease type 3
  Colitis
  Colon cancer
  Colon carcinoma
  Colonic neoplasm
  Congenital generalized lipodystrophy
  Generalized lipodystrophy
  Prostate cancer
  Skeletal muscle disorder
  Small lymphocytic lymphoma
• UniProt ID: LPIN1_HUMAN
• EC Number: 3.1.3.4
• Pfam ID: PF16876 ; PF04571 ; PF08235
• Sequence:
  MNYVGQLAGQVFVTVKELYKGLNPATLSGCIDIIVIRQPNGNLQCSPFHVRFGKMGVLRS
  REKVVDIEINGESVDLHMKLGDNGEAFFVQETDNDQEVIPMHLATSPILSEGASRMECQL
  KRGSVDRMRGLDPSTPAQVIAPSETPSSSSVVKKRRKRRRKSQLDSLKRDDNMNTSEDED
  MFPIEMSSDEAMELLESSRTLPNDIPPFQDDIPEENLSLAVIYPQSASYPNSDREWSPTP
  SPSGSRPSTPKSDSELVSKSTERTGQKNPEMLWLWGELPQAAKSSSPHKMKESSPLSSRK
  ICDKSHFQAIHSESSDTFSDQSPTLVGGALLDQNKPQTEMQFVNEEDLETLGAAAPLLPM
  IEELKPPSASVVQTANKTDSPSRKRDKRSRHLGADGVYLDDLTDMDPEVAALYFPKNGDP
  SGLAKHASDNGARSANQSPQSVGSSGVDSGVESTSDGLRDLPSIAISLCGGLSDHREITK
  DAFLEQAVSYQQFVDNPAIIDDPNLVVKIGSKYYNWTTAAPLLLAMQAFQKPLPKATVES
  IMRDKMPKKGGRWWFSWRGRNTTIKEESKPEQCLAGKAHSTGEQPPQLSLATRVKHESSS
  SDEERAAAKPSNAGHLPLLPNVSYKKTLRLTSEQLKSLKLKNGPNDVVFSVTTQYQGTCR
  CEGTIYLWNWDDKVIISDIDGTITRSDTLGHILPTLGKDWTHQGIAKLYHKVSQNGYKFL
  YCSARAIGMADMTRGYLHWVNERGTVLPQGPLLLSPSSLFSALHREVIEKKPEKFKVQCL
  TDIKNLFFPNTEPFYAAFGNRPADVYSYKQVGVSLNRIFTVNPKGELVQEHAKTNISSYV
  RLCEVVDHVFPLLKRSHSSDFPCSDTFSNFTFWREPLPPFENQDIHSASA
• Function: Acts as a magnesium-dependent phosphatidate phosphatase enzyme which catalyzes the conversion of phosphatidic acid to diacylglycerol during triglyceride, phosphatidylcholine and phosphatidylethanolamine biosynthesis and therefore controls the metabolism of fatty acids at different levels. Is involved in adipocyte differentiation. Acts also as nuclear transcriptional coactivator for PPARGC1A/PPARA regulatory pathway to modulate lipid metabolism gene expression. Recruited at the mitochondrion outer membrane and is involved in mitochondrial fission by converting phosphatidic acid to diacylglycerol.
• Tissue Specificity: Specifically expressed in skeletal muscle. Also abundant in adipose tissue. Lower levels in some portions of the digestive tract.
• KEGG Pathway:
  Glycerolipid metabolism (hsa00561)
  Glycerophospholipid metabolism (hsa00564)
  Metabolic pathways (hsa01100)
  mTOR sig.ling pathway (hsa04150)
  Alcoholic liver disease (hsa04936)
• Reactome Pathway:
  Synthesis of PE (R-HSA-1483213)
  Depolymerization of the Nuclear Lamina (R-HSA-4419969)
  Triglyceride biosynthesis (R-HSA-75109)
  Synthesis of PC (R-HSA-1483191)

Molecular Interaction Atlas (MIA) of This DOT

42 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Definitive	Biomarker	[1]
Myoglobinuria, acute recurrent, autosomal recessive	DIS1M9AQ	Definitive	Autosomal recessive	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[4]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[4]
Carcinoma	DISH9F1N	Strong	Genetic Variation	[5]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[6]
Cervical Intraepithelial neoplasia	DISXP757	Strong	Altered Expression	[7]
Chronic renal failure	DISGG7K6	Strong	Biomarker	[8]
Dysplasia of cervix	DISOAROS	Strong	Altered Expression	[7]
End-stage renal disease	DISXA7GG	Strong	Biomarker	[8]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[9]
Hereditary myoglobinuria	DIS9GJQA	Strong	Biomarker	[10]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[11]
Human papillomavirus infection	DISX61LX	Strong	Biomarker	[12]
Hyperinsulinemia	DISIDWT6	Strong	Genetic Variation	[13]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[14]
Lung cancer	DISCM4YA	Strong	Biomarker	[14]
Lung carcinoma	DISTR26C	Strong	Biomarker	[14]
Myopathy	DISOWG27	Strong	Genetic Variation	[15]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Neuralgia	DISWO58J	Strong	Biomarker	[16]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Genetic Variation	[17]
Obesity	DIS47Y1K	Strong	Biomarker	[18]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Genetic Variation	[19]
Triple negative breast cancer	DISAMG6N	Strong	Altered Expression	[3]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[20]
Very long chain acyl-CoA dehydrogenase deficiency	DISB7TEQ	Strong	Altered Expression	[21]
Adrenoleukodystrophy	DISTUD1F	moderate	Biomarker	[22]
Retinitis pigmentosa 9	DISHLM3S	moderate	Genetic Variation	[23]
Hereditary recurrent myoglobinuria	DIS4RAUG	Supportive	Autosomal dominant	[24]
46,XY sex reversal 2	DIS0USUN	Limited	Altered Expression	[5]
Charcot-Marie-Tooth disease type 3	DIS6DQK1	Limited	Altered Expression	[5]
Colitis	DISAF7DD	Limited	Altered Expression	[25]
Colon cancer	DISVC52G	Limited	Altered Expression	[5]
Colon carcinoma	DISJYKUO	Limited	Altered Expression	[5]
Colonic neoplasm	DISSZ04P	Limited	Genetic Variation	[5]
Congenital generalized lipodystrophy	DIS4XF8N	Limited	Genetic Variation	[26]
Generalized lipodystrophy	DISC6HI8	Limited	Genetic Variation	[26]
Prostate cancer	DISF190Y	Limited	Altered Expression	[27]
Skeletal muscle disorder	DISR9DGU	Limited	Biomarker	[28]
Small lymphocytic lymphoma	DIS30POX	Limited	Biomarker	[29]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Rosiglitazone	DMILWZR	Approved	Phosphatidate phosphatase LPIN1 (LPIN1) increases the response to substance of Rosiglitazone.	[60]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Phosphatidate phosphatase LPIN1 (LPIN1).	[30]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Phosphatidate phosphatase LPIN1 (LPIN1).	[53]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Phosphatidate phosphatase LPIN1 (LPIN1).	[55]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Phosphatidate phosphatase LPIN1 (LPIN1).	[58]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Phosphatidate phosphatase LPIN1 (LPIN1).	[31]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Phosphatidate phosphatase LPIN1 (LPIN1).	[32]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Phosphatidate phosphatase LPIN1 (LPIN1).	[33]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Phosphatidate phosphatase LPIN1 (LPIN1).	[34]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Phosphatidate phosphatase LPIN1 (LPIN1).	[35]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Phosphatidate phosphatase LPIN1 (LPIN1).	[36]
Triclosan	DMZUR4N	Approved	Triclosan affects the expression of Phosphatidate phosphatase LPIN1 (LPIN1).	[37]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Phosphatidate phosphatase LPIN1 (LPIN1).	[38]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Phosphatidate phosphatase LPIN1 (LPIN1).	[39]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Phosphatidate phosphatase LPIN1 (LPIN1).	[40]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Phosphatidate phosphatase LPIN1 (LPIN1).	[41]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Phosphatidate phosphatase LPIN1 (LPIN1).	[42]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Phosphatidate phosphatase LPIN1 (LPIN1).	[43]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Phosphatidate phosphatase LPIN1 (LPIN1).	[44]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid decreases the expression of Phosphatidate phosphatase LPIN1 (LPIN1).	[45]
Phenytoin	DMNOKBV	Approved	Phenytoin increases the expression of Phosphatidate phosphatase LPIN1 (LPIN1).	[46]
Fluoxetine	DM3PD2C	Approved	Fluoxetine increases the expression of Phosphatidate phosphatase LPIN1 (LPIN1).	[47]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Phosphatidate phosphatase LPIN1 (LPIN1).	[48]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Phosphatidate phosphatase LPIN1 (LPIN1).	[49]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Phosphatidate phosphatase LPIN1 (LPIN1).	[32]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Phosphatidate phosphatase LPIN1 (LPIN1).	[50]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Phosphatidate phosphatase LPIN1 (LPIN1).	[39]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Phosphatidate phosphatase LPIN1 (LPIN1).	[51]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Phosphatidate phosphatase LPIN1 (LPIN1).	[52]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Phosphatidate phosphatase LPIN1 (LPIN1).	[54]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Phosphatidate phosphatase LPIN1 (LPIN1).	[56]
MG-132	DMKA2YS	Preclinical	MG-132 increases the expression of Phosphatidate phosphatase LPIN1 (LPIN1).	[49]
Celastrol	DMWQIJX	Preclinical	Celastrol increases the expression of Phosphatidate phosphatase LPIN1 (LPIN1).	[57]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Phosphatidate phosphatase LPIN1 (LPIN1).	[59]

References

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