Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI66SAJ)

• DOT Name: Phospholipase A and acyltransferase 4 (PLAAT4)
• Synonyms: EC 2.3.1.-; EC 3.1.1.32; EC 3.1.1.4; HRAS-like suppressor 4; HRSL4; RAR-responsive protein TIG3; Retinoic acid receptor responder protein 3; Retinoid-inducible gene 1 protein; Tazarotene-induced gene 3 protein
• Gene Name: PLAAT4
• Related Disease:
  Psoriasis
  Acute myelogenous leukaemia
  Adult glioblastoma
  Advanced cancer
  Autoimmune disease
  Carcinoma of liver and intrahepatic biliary tract
  Chronic hepatitis B virus infection
  Chronic obstructive pulmonary disease
  Colorectal carcinoma
  Dengue
  Dermatomyositis
  Glioblastoma multiforme
  Graft-versus-host disease
  Hepatitis B virus infection
  Hepatitis C virus infection
  Hepatocellular carcinoma
  Herpes simplex infection
  IgA nephropathy
  Inclusion body myositis
  Liver cancer
  Lung cancer
  Lung carcinoma
  Lupus nephritis
  Measles
  Melanoma
  Nasopharyngeal carcinoma
  Neuroblastoma
  Osteoarthritis
  Polymyositis
  Respiratory syncytial virus infection
  Rheumatoid arthritis
  Singleton-Merten dysplasia
  Skin disease
  Systemic lupus erythematosus
  Zika virus infection
  Breast cancer
  Breast carcinoma
  Colon cancer
  Colon carcinoma
  Head-neck squamous cell carcinoma
  Influenza
  Non-small-cell lung cancer
  Breast neoplasm
  Ebola virus infection
  Neoplasm
  Type-1 diabetes
• UniProt ID: PLAT4_HUMAN
• PDB ID: 2LKT; 2MY9; 7ZOT
• EC Number: 2.3.1.-; 3.1.1.32; 3.1.1.4
• Pfam ID: PF04970
• Sequence:
  MASPHQEPKPGDLIEIFRLGYEHWALYIGDGYVIHLAPPSEYPGAGSSSVFSVLSNSAEV
  KRERLEDVVGGCCYRVNNSLDHEYQPRPVEVIISSAKEMVGQKMKYSIVSRNCEHFVTQL
  RYGKSRCKQVEKAKVEVGVATALGILVVAGCSFAIRRYQKKATA
• Function: Exhibits both phospholipase A1/2 and acyltransferase activities. Shows phospholipase A1 (PLA1) and A2 (PLA2), catalyzing the calcium-independent release of fatty acids from the sn-1 or sn-2 position of glycerophospholipids. For most substrates, PLA1 activity is much higher than PLA2 activity. Shows O-acyltransferase activity, catalyzing the transfer of a fatty acyl group from glycerophospholipid to the hydroxyl group of lysophospholipid. Shows N-acyltransferase activity, catalyzing the calcium-independent transfer of a fatty acyl group at the sn-1 position of phosphatidylcholine (PC) and other glycerophospholipids to the primary amine of phosphatidylethanolamine (PE), forming N-acylphosphatidylethanolamine (NAPE), which serves as precursor for N-acylethanolamines (NAEs). Promotes keratinocyte differentiation via activation of TGM1.
• Tissue Specificity: Widely expressed.
• Reactome Pathway: Acyl chain remodelling of PE (R-HSA-1482839)
• BioCyc Pathway: MetaCyc:ENSG00000133321-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Psoriasis	DIS59VMN	Definitive	Biomarker	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[2]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Autoimmune disease	DISORMTM	Strong	Genetic Variation	[5]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Biomarker	[6]
Chronic hepatitis B virus infection	DISHL4NT	Strong	Altered Expression	[7]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Altered Expression	[8]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[9]
Dengue	DISKH221	Strong	Altered Expression	[10]
Dermatomyositis	DIS50C5O	Strong	Altered Expression	[11]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[3]
Graft-versus-host disease	DIS0QADF	Strong	Biomarker	[12]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[13]
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[14]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[15]
Herpes simplex infection	DISL1SAV	Strong	Biomarker	[16]
IgA nephropathy	DISZ8MTK	Strong	Altered Expression	[17]
Inclusion body myositis	DISZXXG5	Strong	Altered Expression	[18]
Liver cancer	DISDE4BI	Strong	Biomarker	[6]
Lung cancer	DISCM4YA	Strong	Altered Expression	[19]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[19]
Lupus nephritis	DISCVGPZ	Strong	Biomarker	[20]
Measles	DISXSUID	Strong	Altered Expression	[21]
Melanoma	DIS1RRCY	Strong	Biomarker	[22]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Biomarker	[23]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[24]
Osteoarthritis	DIS05URM	Strong	Biomarker	[25]
Polymyositis	DIS5DHFP	Strong	Altered Expression	[18]
Respiratory syncytial virus infection	DIS7FWHY	Strong	Biomarker	[26]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[27]
Singleton-Merten dysplasia	DISYNAVB	Strong	Genetic Variation	[28]
Skin disease	DISDW8R6	Strong	Altered Expression	[1]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[29]
Zika virus infection	DISQUCTY	Strong	Biomarker	[30]
Breast cancer	DIS7DPX1	moderate	Biomarker	[31]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[31]
Colon cancer	DISVC52G	moderate	Biomarker	[32]
Colon carcinoma	DISJYKUO	moderate	Biomarker	[32]
Head-neck squamous cell carcinoma	DISF7P24	moderate	Altered Expression	[33]
Influenza	DIS3PNU3	moderate	Biomarker	[34]
Non-small-cell lung cancer	DIS5Y6R9	moderate	Biomarker	[35]
Breast neoplasm	DISNGJLM	Limited	Biomarker	[31]
Ebola virus infection	DISJAVM1	Limited	Biomarker	[36]
Neoplasm	DISZKGEW	Limited	Biomarker	[2]
Type-1 diabetes	DIS7HLUB	Limited	Biomarker	[37]

23 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 Phospholipase A and acyltransferase 4 (PLAAT4).	[38]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Phospholipase A and acyltransferase 4 (PLAAT4).	[39]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Phospholipase A and acyltransferase 4 (PLAAT4).	[40]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Phospholipase A and acyltransferase 4 (PLAAT4).	[41]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Phospholipase A and acyltransferase 4 (PLAAT4).	[42]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Phospholipase A and acyltransferase 4 (PLAAT4).	[43]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Phospholipase A and acyltransferase 4 (PLAAT4).	[44]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Phospholipase A and acyltransferase 4 (PLAAT4).	[45]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Phospholipase A and acyltransferase 4 (PLAAT4).	[45]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Phospholipase A and acyltransferase 4 (PLAAT4).	[43]
Marinol	DM70IK5	Approved	Marinol increases the expression of Phospholipase A and acyltransferase 4 (PLAAT4).	[46]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Phospholipase A and acyltransferase 4 (PLAAT4).	[47]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Phospholipase A and acyltransferase 4 (PLAAT4).	[48]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Phospholipase A and acyltransferase 4 (PLAAT4).	[49]
Alitretinoin	DMME8LH	Approved	Alitretinoin increases the expression of Phospholipase A and acyltransferase 4 (PLAAT4).	[50]
Vitamin A	DMJ2AH4	Approved	Vitamin A increases the expression of Phospholipase A and acyltransferase 4 (PLAAT4).	[50]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Phospholipase A and acyltransferase 4 (PLAAT4).	[40]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Phospholipase A and acyltransferase 4 (PLAAT4).	[51]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Phospholipase A and acyltransferase 4 (PLAAT4).	[52]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Phospholipase A and acyltransferase 4 (PLAAT4).	[53]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Phospholipase A and acyltransferase 4 (PLAAT4).	[54]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Phospholipase A and acyltransferase 4 (PLAAT4).	[47]
all-trans-4-oxo-retinoic acid	DMM2R1N	Investigative	all-trans-4-oxo-retinoic acid increases the expression of Phospholipase A and acyltransferase 4 (PLAAT4).	[50]

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