Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZLM5UB)

• DOT Name: Aspartate aminotransferase, cytoplasmic (GOT1)
• Synonyms: cAspAT; EC 2.6.1.1; EC 2.6.1.3; Cysteine aminotransferase, cytoplasmic; Cysteine transaminase, cytoplasmic; cCAT; Glutamate oxaloacetate transaminase 1; Transaminase A
• Gene Name: GOT1
• UniProt ID: AATC_HUMAN
• PDB ID: 3II0; 3WZF; 6DNA; 6DNB; 6DND; 6LIG
• EC Number: 2.6.1.1; 2.6.1.3
• Pfam ID: PF00155
• Sequence:
  MAPPSVFAEVPQAQPVLVFKLTADFREDPDPRKVNLGVGAYRTDDCHPWVLPVVKKVEQK
  IANDNSLNHEYLPILGLAEFRSCASRLALGDDSPALKEKRVGGVQSLGGTGALRIGADFL
  ARWYNGTNNKNTPVYVSSPTWENHNAVFSAAGFKDIRSYRYWDAEKRGLDLQGFLNDLEN
  APEFSIVVLHACAHNPTGIDPTPEQWKQIASVMKHRFLFPFFDSAYQGFASGNLERDAWA
  IRYFVSEGFEFFCAQSFSKNFGLYNERVGNLTVVGKEPESILQVLSQMEKIVRITWSNPP
  AQGARIVASTLSNPELFEEWTGNVKTMADRILTMRSELRARLEALKTPGTWNHITDQIGM
  FSFTGLNPKQVEYLVNEKHIYLLPSGRINVSGLTTKNLDYVATSIHEAVTKIQ
• Function: Biosynthesis of L-glutamate from L-aspartate or L-cysteine. Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system. Acts as a scavenger of glutamate in brain neuroprotection. The aspartate aminotransferase activity is involved in hepatic glucose synthesis during development and in adipocyte glyceroneogenesis. Using L-cysteine as substrate, regulates levels of mercaptopyruvate, an important source of hydrogen sulfide. Mercaptopyruvate is converted into H(2)S via the action of 3-mercaptopyruvate sulfurtransferase (3MST). Hydrogen sulfide is an important synaptic modulator and neuroprotectant in the brain. In addition, catalyzes (2S)-2-aminobutanoate, a by-product in the cysteine biosynthesis pathway.
• KEGG Pathway:
  Arginine biosynthesis (hsa00220)
  Alanine, aspartate and glutamate metabolism (hsa00250)
  Cysteine and methionine metabolism (hsa00270)
  Arginine and proline metabolism (hsa00330)
  Tyrosine metabolism (hsa00350)
  Phenylalanine metabolism (hsa00360)
  Phenylalanine, tyrosine and tryptophan biosynthesis (hsa00400)
  Metabolic pathways (hsa01100)
  Carbon metabolism (hsa01200)
  2-Oxocarboxylic acid metabolism (hsa01210)
  Biosynthesis of amino acids (hsa01230)
• Reactome Pathway:
  Gluconeogenesis (R-HSA-70263)
  Aspartate and asparagine metabolism (R-HSA-8963693)
  Methionine salvage pathway (R-HSA-1237112)
• BioCyc Pathway: MetaCyc:HS04361-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Aspartate aminotransferase, cytoplasmic (GOT1) increases the Death ADR of Methotrexate.	[24]
Formaldehyde	DM7Q6M0	Investigative	Aspartate aminotransferase, cytoplasmic (GOT1) affects the response to substance of Formaldehyde.	[25]

27 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 Aspartate aminotransferase, cytoplasmic (GOT1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Aspartate aminotransferase, cytoplasmic (GOT1).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Aspartate aminotransferase, cytoplasmic (GOT1).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Aspartate aminotransferase, cytoplasmic (GOT1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Aspartate aminotransferase, cytoplasmic (GOT1).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Aspartate aminotransferase, cytoplasmic (GOT1).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Aspartate aminotransferase, cytoplasmic (GOT1).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Aspartate aminotransferase, cytoplasmic (GOT1).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Aspartate aminotransferase, cytoplasmic (GOT1).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Aspartate aminotransferase, cytoplasmic (GOT1).	[10]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Aspartate aminotransferase, cytoplasmic (GOT1).	[11]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Aspartate aminotransferase, cytoplasmic (GOT1).	[12]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Aspartate aminotransferase, cytoplasmic (GOT1).	[2]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Aspartate aminotransferase, cytoplasmic (GOT1).	[13]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Aspartate aminotransferase, cytoplasmic (GOT1).	[14]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of Aspartate aminotransferase, cytoplasmic (GOT1).	[2]
Ibuprofen	DM8VCBE	Approved	Ibuprofen increases the expression of Aspartate aminotransferase, cytoplasmic (GOT1).	[2]
Enzalutamide	DMGL19D	Approved	Enzalutamide affects the expression of Aspartate aminotransferase, cytoplasmic (GOT1).	[16]
Adefovir dipivoxil	DMMAWY1	Approved	Adefovir dipivoxil decreases the expression of Aspartate aminotransferase, cytoplasmic (GOT1).	[2]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Aspartate aminotransferase, cytoplasmic (GOT1).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Aspartate aminotransferase, cytoplasmic (GOT1).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Aspartate aminotransferase, cytoplasmic (GOT1).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Aspartate aminotransferase, cytoplasmic (GOT1).	[20]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Aspartate aminotransferase, cytoplasmic (GOT1).	[7]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Aspartate aminotransferase, cytoplasmic (GOT1).	[21]
D-glucose	DMMG2TO	Investigative	D-glucose increases the expression of Aspartate aminotransferase, cytoplasmic (GOT1).	[22]
Oxalacetic acid	DMPZSV1	Investigative	Oxalacetic acid increases the expression of Aspartate aminotransferase, cytoplasmic (GOT1).	[22]

2 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Diclofenac	DMPIHLS	Approved	Diclofenac increases the secretion of Aspartate aminotransferase, cytoplasmic (GOT1).	[15]
Icariside II	DM3DB8X	Investigative	Icariside II increases the secretion of Aspartate aminotransferase, cytoplasmic (GOT1).	[23]

References

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