Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2CJ91O)

• DOT Name: Tyrosine aminotransferase (TAT)
• Synonyms: TAT; EC 2.6.1.5; L-tyrosine:2-oxoglutarate aminotransferase
• Gene Name: TAT
• Related Disease:
  Epilepsy
  Meningioma
  Neuroblastoma
  Type-1 diabetes
  Tyrosinemia type II
  Acquired immune deficiency syndrome
  Acute myelogenous leukaemia
  Advanced cancer
  Alzheimer disease
  Analgesia
  Astrocytoma
  Atrial fibrillation
  B-cell neoplasm
  Bone osteosarcoma
  Cardiovascular disease
  Cervical cancer
  Cervical carcinoma
  Depression
  Glioma
  Hepatitis C virus infection
  Hepatocellular carcinoma
  HIV infectious disease
  Immunodeficiency
  Intellectual disability
  Liver cancer
  Neoplasm
  Non-small-cell lung cancer
  Obesity
  Osteosarcoma
  Pancreatic cancer
  Progressive multifocal leukoencephalopathy
  Prostate cancer
  Tuberculosis
  Type-1/2 diabetes
  Adult glioblastoma
  Glioblastoma multiforme
  Head-neck squamous cell carcinoma
  Neuralgia
  Osteoarthritis
  Tyrosinemia
  Colorectal carcinoma
  Kaposi sarcoma
  Keratitis
  Lymphoma
  Melanoma
  Nasopharyngeal carcinoma
  Prostate carcinoma
  Rheumatoid arthritis
  Stroke
• UniProt ID: ATTY_HUMAN
• PDB ID: 3DYD
• EC Number: 2.6.1.5
• Pfam ID: PF00155 ; PF07706
• Sequence:
  MDPYMIQMSSKGNLPSILDVHVNVGGRSSVPGKMKGRKARWSVRPSDMAKKTFNPIRAIV
  DNMKVKPNPNKTMISLSIGDPTVFGNLPTDPEVTQAMKDALDSGKYNGYAPSIGFLSSRE
  EIASYYHCPEAPLEAKDVILTSGCSQAIDLCLAVLANPGQNILVPRPGFSLYKTLAESMG
  IEVKLYNLLPEKSWEIDLKQLEYLIDEKTACLIVNNPSNPCGSVFSKRHLQKILAVAARQ
  CVPILADEIYGDMVFSDCKYEPLATLSTDVPILSCGGLAKRWLVPGWRLGWILIHDRRDI
  FGNEIRDGLVKLSQRILGPCTIVQGALKSILCRTPGEFYHNTLSFLKSNADLCYGALAAI
  PGLRPVRPSGAMYLMVGIEMEHFPEFENDVEFTERLVAEQSVHCLPATCFEYPNFIRVVI
  TVPEVMMLEACSRIQEFCEQHYHCAEGSQEECDK
• Function: Transaminase involved in tyrosine breakdown. Converts tyrosine to p-hydroxyphenylpyruvate. Can catalyze the reverse reaction, using glutamic acid, with 2-oxoglutarate as cosubstrate (in vitro). Has much lower affinity and transaminase activity towards phenylalanine.
• KEGG Pathway:
  Ubiquinone and other terpenoid-quinone biosynthesis (hsa00130)
  Cysteine and methionine metabolism (hsa00270)
  Tyrosine metabolism (hsa00350)
  Phenylalanine metabolism (hsa00360)
  Phenylalanine, tyrosine and tryptophan biosynthesis (hsa00400)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Tyrosine catabolism (R-HSA-8963684)
• BioCyc Pathway: MetaCyc:HS06761-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Epilepsy	DISBB28L	Definitive	Biomarker	[1]
Meningioma	DISPT4TG	Definitive	Biomarker	[2]
Neuroblastoma	DISVZBI4	Definitive	Biomarker	[3]
Type-1 diabetes	DIS7HLUB	Definitive	Biomarker	[4]
Tyrosinemia type II	DIS4CW3M	Definitive	Autosomal recessive	[5]
Acquired immune deficiency syndrome	DISL5UOX	Strong	Biomarker	[6]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[7]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[8]
Alzheimer disease	DISF8S70	Strong	Biomarker	[9]
Analgesia	DISK3TVI	Strong	Biomarker	[10]
Astrocytoma	DISL3V18	Strong	Altered Expression	[11]
Atrial fibrillation	DIS15W6U	Strong	Biomarker	[12]
B-cell neoplasm	DISVY326	Strong	Biomarker	[13]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[14]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[15]
Cervical cancer	DISFSHPF	Strong	Altered Expression	[16]
Cervical carcinoma	DIST4S00	Strong	Altered Expression	[16]
Depression	DIS3XJ69	Strong	Biomarker	[17]
Glioma	DIS5RPEH	Strong	Biomarker	[18]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[19]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[20]
HIV infectious disease	DISO97HC	Strong	Altered Expression	[21]
Immunodeficiency	DIS093I0	Strong	Biomarker	[22]
Intellectual disability	DISMBNXP	Strong	Biomarker	[23]
Liver cancer	DISDE4BI	Strong	Biomarker	[24]
Neoplasm	DISZKGEW	Strong	Biomarker	[25]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[26]
Obesity	DIS47Y1K	Strong	Biomarker	[27]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[14]
Pancreatic cancer	DISJC981	Strong	Biomarker	[28]
Progressive multifocal leukoencephalopathy	DISX02WS	Strong	Biomarker	[29]
Prostate cancer	DISF190Y	Strong	Biomarker	[30]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[31]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[32]
Adult glioblastoma	DISVP4LU	moderate	Biomarker	[33]
Glioblastoma multiforme	DISK8246	moderate	Biomarker	[33]
Head-neck squamous cell carcinoma	DISF7P24	moderate	Biomarker	[34]
Neuralgia	DISWO58J	moderate	Biomarker	[35]
Osteoarthritis	DIS05URM	moderate	Biomarker	[36]
Tyrosinemia	DISI8Q9Q	moderate	Genetic Variation	[37]
Colorectal carcinoma	DIS5PYL0	Disputed	Biomarker	[38]
Kaposi sarcoma	DISC1H1Z	Limited	Biomarker	[39]
Keratitis	DISMFOEI	Limited	Biomarker	[40]
Lymphoma	DISN6V4S	Limited	Altered Expression	[41]
Melanoma	DIS1RRCY	Limited	Biomarker	[42]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Biomarker	[43]
Prostate carcinoma	DISMJPLE	Limited	Altered Expression	[44]
Rheumatoid arthritis	DISTSB4J	Limited	Biomarker	[45]
Stroke	DISX6UHX	Limited	Biomarker	[46]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Methylprednisolone	DM4BDON	Approved	Tyrosine aminotransferase (TAT) increases the Hepatotoxicity ADR of Methylprednisolone.	[62]

19 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 Tyrosine aminotransferase (TAT).	[47]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Tyrosine aminotransferase (TAT).	[48]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Tyrosine aminotransferase (TAT).	[49]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Tyrosine aminotransferase (TAT).	[48]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Tyrosine aminotransferase (TAT).	[50]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Tyrosine aminotransferase (TAT).	[51]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Tyrosine aminotransferase (TAT).	[52]
Colchicine	DM2POTE	Approved	Colchicine decreases the expression of Tyrosine aminotransferase (TAT).	[53]
Bosentan	DMIOGBU	Approved	Bosentan affects the expression of Tyrosine aminotransferase (TAT).	[54]
Miconazole	DMPMYE8	Approved	Miconazole decreases the expression of Tyrosine aminotransferase (TAT).	[55]
Urethane	DM7NSI0	Phase 4	Urethane affects the expression of Tyrosine aminotransferase (TAT).	[56]
Mapracorat	DMR23M1	Phase 3	Mapracorat affects the activity of Tyrosine aminotransferase (TAT).	[57]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 decreases the expression of Tyrosine aminotransferase (TAT).	[58]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Tyrosine aminotransferase (TAT).	[59]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Tyrosine aminotransferase (TAT).	[58]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Tyrosine aminotransferase (TAT).	[60]
Mivebresib	DMCPF90	Phase 1	Mivebresib decreases the expression of Tyrosine aminotransferase (TAT).	[58]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Tyrosine aminotransferase (TAT).	[61]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of Tyrosine aminotransferase (TAT).	[61]

References

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