Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFKXQ1O)

• DOT Name: Serine--tRNA ligase, cytoplasmic (SARS1)
• Synonyms: EC 6.1.1.11; Seryl-tRNA synthetase; SerRS; Seryl-tRNA(Ser/Sec) synthetase
• Gene Name: SARS1
• Related Disease:
  Brain disease
  Bronchitis
  Chikungunya virus infection
  Colon carcinoma
  Common cold
  Dengue
  Ebola virus infection
  Encephalitis
  Enterovirus infection
  Gastroenteritis
  Hepatitis
  Hepatitis A virus infection
  Hepatocellular carcinoma
  Intellectual disability
  Lung cancer
  Lung carcinoma
  Measles
  Melanoma
  Middle East Respiratory Syndrome (MERS)
  Neoplasm
  Pneumonitis
  Prostate cancer
  Prostate carcinoma
  Pulmonary fibrosis
  Respiratory disease
  Respiratory failure
  Syphilis
  Tuberculosis
  Advanced cancer
  Coronary heart disease
  Influenza
  Neurodevelopmental disorder with microcephaly, ataxia, and seizures
  Pancreatic cancer
  Stroke
  Autosomal recessive non-syndromic intellectual disability
  Adult respiratory distress syndrome
  Pneumonia
  Rabies
  Breast cancer
  Breast carcinoma
  Carcinoma of liver and intrahepatic biliary tract
  Encephalitis/encephalopathy, mild, with reversible myelin vacuolization
  Gonorrhea
  Lassa fever
  Liver cancer
  Multiple sclerosis
  Pneumococcal infection
  Pulmonary disease
  Sexually transmitted infection
  Type-1 diabetes
• UniProt ID: SYSC_HUMAN
• PDB ID: 3VBB; 4L87; 4RQE; 4RQF
• EC Number: 6.1.1.11
• Pfam ID: PF02403 ; PF00587
• Sequence:
  MVLDLDLFRVDKGGDPALIRETQEKRFKDPGLVDQLVKADSEWRRCRFRADNLNKLKNLC
  SKTIGEKMKKKEPVGDDESVPENVLSFDDLTADALANLKVSQIKKVRLLIDEAILKCDAE
  RIKLEAERFENLREIGNLLHPSVPISNDEDVDNKVERIWGDCTVRKKYSHVDLVVMVDGF
  EGEKGAVVAGSRGYFLKGVLVFLEQALIQYALRTLGSRGYIPIYTPFFMRKEVMQEVAQL
  SQFDEELYKVIGKGSEKSDDNSYDEKYLIATSEQPIAALHRDEWLRPEDLPIKYAGLSTC
  FRQEVGSHGRDTRGIFRVHQFEKIEQFVYSSPHDNKSWEMFEEMITTAEEFYQSLGIPYH
  IVNIVSGSLNHAASKKLDLEAWFPGSGAFRELVSCSNCTDYQARRLRIRYGQTKKMMDKV
  EFVHMLNATMCATTRTICAILENYQTEKGITVPEKLKEFMPPGLQELIPFVKPAPIEQEP
  SKKQKKQHEGSKKKAAARDVTLENRLQNMEVTDA
• Function: Catalyzes the attachment of serine to tRNA(Ser) in a two-step reaction: serine is first activated by ATP to form Ser-AMP and then transferred to the acceptor end of tRNA(Ser). Is probably also able to aminoacylate tRNA(Sec) with serine, to form the misacylated tRNA L-seryl-tRNA(Sec), which will be further converted into selenocysteinyl-tRNA(Sec). In the nucleus, binds to the VEGFA core promoter and prevents MYC binding and transcriptional activation by MYC. Recruits SIRT2 to the VEGFA promoter, promoting deacetylation of histone H4 at 'Lys-16' (H4K16). Thereby, inhibits the production of VEGFA and sprouting angiogenesis mediated by VEGFA.
• Tissue Specificity: Brain.
• KEGG Pathway: Aminoacyl-tR. biosynthesis (hsa00970)
• Reactome Pathway:
  Cytosolic tRNA aminoacylation (R-HSA-379716)
  Selenocysteine synthesis (R-HSA-2408557)

Molecular Interaction Atlas (MIA) of This DOT

50 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Brain disease	DIS6ZC3X	Strong	Biomarker	[1]
Bronchitis	DISBM6EQ	Strong	Biomarker	[2]
Chikungunya virus infection	DISDXEHY	Strong	Biomarker	[3]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[4]
Common cold	DIS3MADM	Strong	Genetic Variation	[5]
Dengue	DISKH221	Strong	Genetic Variation	[6]
Ebola virus infection	DISJAVM1	Strong	Biomarker	[7]
Encephalitis	DISLD1RL	Strong	Biomarker	[8]
Enterovirus infection	DISH2UDP	Strong	Biomarker	[9]
Gastroenteritis	DISXQCG5	Strong	Biomarker	[2]
Hepatitis	DISXXX35	Strong	Biomarker	[10]
Hepatitis A virus infection	DISUMFQV	Strong	Biomarker	[10]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[11]
Intellectual disability	DISMBNXP	Strong	Genetic Variation	[12]
Lung cancer	DISCM4YA	Strong	Biomarker	[13]
Lung carcinoma	DISTR26C	Strong	Biomarker	[13]
Measles	DISXSUID	Strong	Genetic Variation	[14]
Melanoma	DIS1RRCY	Strong	Altered Expression	[15]
Middle East Respiratory Syndrome (MERS)	DIS5VPYU	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Biomarker	[16]
Pneumonitis	DIS88E0K	Strong	Biomarker	[17]
Prostate cancer	DISF190Y	Strong	Biomarker	[18]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[18]
Pulmonary fibrosis	DISQKVLA	Strong	Biomarker	[19]
Respiratory disease	DISGGAGJ	Strong	Biomarker	[20]
Respiratory failure	DISVMYJO	Strong	Genetic Variation	[1]
Syphilis	DISJ73BS	Strong	Biomarker	[21]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[22]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[23]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[24]
Influenza	DIS3PNU3	moderate	Genetic Variation	[25]
Neurodevelopmental disorder with microcephaly, ataxia, and seizures	DIS7D5RO	Moderate	Autosomal recessive	[26]
Pancreatic cancer	DISJC981	moderate	Biomarker	[27]
Stroke	DISX6UHX	moderate	Biomarker	[25]
Autosomal recessive non-syndromic intellectual disability	DISJWRZZ	Supportive	Autosomal recessive	[12]
Adult respiratory distress syndrome	DISIJV47	Disputed	Biomarker	[28]
Pneumonia	DIS8EF3M	Disputed	Biomarker	[29]
Rabies	DISSC4V5	Disputed	Biomarker	[30]
Breast cancer	DIS7DPX1	Limited	Biomarker	[31]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[31]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Biomarker	[32]
Encephalitis/encephalopathy, mild, with reversible myelin vacuolization	DIS4VEZH	Limited	Genetic Variation	[33]
Gonorrhea	DISQ5AO6	Limited	Biomarker	[34]
Lassa fever	DISKFYGZ	Limited	Biomarker	[35]
Liver cancer	DISDE4BI	Limited	Biomarker	[32]
Multiple sclerosis	DISB2WZI	Limited	Biomarker	[36]
Pneumococcal infection	DIS6SXQD	Limited	Biomarker	[37]
Pulmonary disease	DIS6060I	Limited	Altered Expression	[38]
Sexually transmitted infection	DISIVIAL	Limited	Biomarker	[34]
Type-1 diabetes	DIS7HLUB	Limited	Biomarker	[36]

32 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--tRNA ligase, cytoplasmic (SARS1).	[39]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Serine--tRNA ligase, cytoplasmic (SARS1).	[40]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Serine--tRNA ligase, cytoplasmic (SARS1).	[41]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Serine--tRNA ligase, cytoplasmic (SARS1).	[42]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Serine--tRNA ligase, cytoplasmic (SARS1).	[43]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Serine--tRNA ligase, cytoplasmic (SARS1).	[44]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Serine--tRNA ligase, cytoplasmic (SARS1).	[45]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Serine--tRNA ligase, cytoplasmic (SARS1).	[46]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Serine--tRNA ligase, cytoplasmic (SARS1).	[47]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Serine--tRNA ligase, cytoplasmic (SARS1).	[48]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Serine--tRNA ligase, cytoplasmic (SARS1).	[49]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Serine--tRNA ligase, cytoplasmic (SARS1).	[50]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Serine--tRNA ligase, cytoplasmic (SARS1).	[48]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Serine--tRNA ligase, cytoplasmic (SARS1).	[51]
Clozapine	DMFC71L	Approved	Clozapine decreases the expression of Serine--tRNA ligase, cytoplasmic (SARS1).	[52]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the expression of Serine--tRNA ligase, cytoplasmic (SARS1).	[53]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol affects the expression of Serine--tRNA ligase, cytoplasmic (SARS1).	[54]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of Serine--tRNA ligase, cytoplasmic (SARS1).	[45]
Ifosfamide	DMCT3I8	Approved	Ifosfamide increases the expression of Serine--tRNA ligase, cytoplasmic (SARS1).	[45]
Benzatropine	DMF7EXL	Approved	Benzatropine decreases the expression of Serine--tRNA ligase, cytoplasmic (SARS1).	[52]
Haloperidol	DM96SE0	Approved	Haloperidol decreases the expression of Serine--tRNA ligase, cytoplasmic (SARS1).	[52]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Serine--tRNA ligase, cytoplasmic (SARS1).	[55]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Serine--tRNA ligase, cytoplasmic (SARS1).	[56]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Serine--tRNA ligase, cytoplasmic (SARS1).	[58]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Serine--tRNA ligase, cytoplasmic (SARS1).	[59]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Serine--tRNA ligase, cytoplasmic (SARS1).	[60]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Serine--tRNA ligase, cytoplasmic (SARS1).	[61]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Serine--tRNA ligase, cytoplasmic (SARS1).	[62]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Serine--tRNA ligase, cytoplasmic (SARS1).	[63]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Serine--tRNA ligase, cytoplasmic (SARS1).	[64]
AM251	DMTAWHL	Investigative	AM251 increases the expression of Serine--tRNA ligase, cytoplasmic (SARS1).	[65]
(E)-4-(3,5-dimethoxystyryl)phenol	DMYXI2V	Investigative	(E)-4-(3,5-dimethoxystyryl)phenol increases the expression of Serine--tRNA ligase, cytoplasmic (SARS1).	[66]

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 increases the methylation of Serine--tRNA ligase, cytoplasmic (SARS1).	[57]

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