Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS5VF7N)

• DOT Name: Alanine aminotransferase 2 (GPT2)
• Synonyms: ALT2; EC 2.6.1.2; Glutamate pyruvate transaminase 2; GPT 2; Glutamic--alanine transaminase 2; Glutamic--pyruvic transaminase 2
• Gene Name: GPT2
• Related Disease:
  Glutamate pyruvate transaminase 2 deficiency
  Breast cancer
  Breast carcinoma
  Chronic hepatitis B virus infection
  Colorectal carcinoma
  Esophageal squamous cell carcinoma
  Hepatitis
  Hepatitis B virus infection
  Intellectual disability
  Isolated congenital microcephaly
  Liver cirrhosis
  Non-insulin dependent diabetes
  Onchocerciasis
  Filarial disease
  Hepatocellular carcinoma
  Neoplasm
  Advanced cancer
  Complex hereditary spastic paraplegia
  Hereditary spastic paraplegia
  Movement disorder
  Nervous system disease
  Type-1 diabetes
• UniProt ID: ALAT2_HUMAN
• PDB ID: 3IHJ
• EC Number: 2.6.1.2
• Pfam ID: PF00155
• Sequence:
  MQRAAALVRRGCGPRTPSSWGRSQSSAAAEASAVLKVRPERSRRERILTLESMNPQVKAV
  EYAVRGPIVLKAGEIELELQRGIKKPFTEVIRANIGDAQAMGQQPITFLRQVMALCTYPN
  LLDSPSFPEDAKKRARRILQACGGNSLGSYSASQGVNCIREDVAAYITRRDGGVPADPDN
  IYLTTGASDGISTILKILVSGGGKSRTGVMIPIPQYPLYSAVISELDAIQVNYYLDEENC
  WALNVNELRRAVQEAKDHCDPKVLCIINPGNPTGQVQSRKCIEDVIHFAWEEKLFLLADE
  VYQDNVYSPDCRFHSFKKVLYEMGPEYSSNVELASFHSTSKGYMGECGYRGGYMEVINLH
  PEIKGQLVKLLSVRLCPPVSGQAAMDIVVNPPVAGEESFEQFSREKESVLGNLAKKAKLT
  EDLFNQVPGIHCNPLQGAMYAFPRIFIPAKAVEAAQAHQMAPDMFYCMKLLEETGICVVP
  GSGFGQREGTYHFRMTILPPVEKLKTVLQKVKDFHINFLEKYA
• Function: Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate.
• Tissue Specificity: Expressed at high levels in muscle, adipose tissue, kidney and brain and at lower levels in the liver and breast.
• KEGG Pathway:
  Arginine biosynthesis (hsa00220)
  Alanine, aspartate and glutamate metabolism (hsa00250)
  Metabolic pathways (hsa01100)
  Carbon metabolism (hsa01200)
  2-Oxocarboxylic acid metabolism (hsa01210)
  Biosynthesis of amino acids (hsa01230)
• BioCyc Pathway: MetaCyc:HS09332-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

22 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glutamate pyruvate transaminase 2 deficiency	DIS05BFD	Definitive	Autosomal recessive	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Chronic hepatitis B virus infection	DISHL4NT	Strong	Biomarker	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[4]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[5]
Hepatitis	DISXXX35	Strong	Genetic Variation	[6]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[7]
Intellectual disability	DISMBNXP	Strong	Genetic Variation	[8]
Isolated congenital microcephaly	DISUXHZ6	Strong	Genetic Variation	[8]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[3]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[9]
Onchocerciasis	DISEPYEA	Strong	Biomarker	[10]
Filarial disease	DISWBRRN	moderate	Biomarker	[11]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[3]
Neoplasm	DISZKGEW	moderate	Altered Expression	[12]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[13]
Complex hereditary spastic paraplegia	DIS9KXQY	Limited	Genetic Variation	[14]
Hereditary spastic paraplegia	DISGZQV1	Limited	Genetic Variation	[14]
Movement disorder	DISOJJ2D	Limited	CausalMutation	[8]
Nervous system disease	DISJ7GGT	Limited	Genetic Variation	[15]
Type-1 diabetes	DIS7HLUB	Limited	Genetic Variation	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Alanine aminotransferase 2 (GPT2) increases the Hyperglycaemia ADR of Acetaminophen.	[35]

2 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 Alanine aminotransferase 2 (GPT2).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Alanine aminotransferase 2 (GPT2).	[30]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Alanine aminotransferase 2 (GPT2).	[17]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Alanine aminotransferase 2 (GPT2).	[18]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Alanine aminotransferase 2 (GPT2).	[19]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate affects the expression of Alanine aminotransferase 2 (GPT2).	[20]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Alanine aminotransferase 2 (GPT2).	[21]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Alanine aminotransferase 2 (GPT2).	[22]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Alanine aminotransferase 2 (GPT2).	[23]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Alanine aminotransferase 2 (GPT2).	[24]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Alanine aminotransferase 2 (GPT2).	[25]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Alanine aminotransferase 2 (GPT2).	[26]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Alanine aminotransferase 2 (GPT2).	[27]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Alanine aminotransferase 2 (GPT2).	[28]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide decreases the expression of Alanine aminotransferase 2 (GPT2).	[24]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial increases the expression of Alanine aminotransferase 2 (GPT2).	[29]
Motexafin gadolinium	DMEJKRF	Approved	Motexafin gadolinium increases the expression of Alanine aminotransferase 2 (GPT2).	[29]
Lindane	DMB8CNL	Approved	Lindane increases the expression of Alanine aminotransferase 2 (GPT2).	[24]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Alanine aminotransferase 2 (GPT2).	[31]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Alanine aminotransferase 2 (GPT2).	[32]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Alanine aminotransferase 2 (GPT2).	[33]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Alanine aminotransferase 2 (GPT2).	[24]
CH-223191	DMMJZYC	Investigative	CH-223191 increases the expression of Alanine aminotransferase 2 (GPT2).	[34]

References

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