Target Information

Target General Infomation
Target ID
T59045
Former ID
TTDS00024
Target Name
4-aminobutyrate aminotransferase, mitochondrial
Gene Name
ABAT
Synonyms
(S)-3-amino-2-methylpropionate transaminase; GABA aminotransferase; GABA transaminase; GABA-AT; GABA-T; Gamma-amino-N-butyrate transaminase; L-AIBAT; ABAT
Target Type
Successful
Disease Dietary shortage [ICD9: 260-269; ICD10: E40-E46]
Dietary shortage; Glioma [ICD9:260-269, 191; ICD10: E40-E46, C71]
Dementia [ICD9: 290-294; ICD10: F01-F07]
Epilepsy; Infantile spasms; Complex partial seizures [ICD9: 345, 345.4, 345.5, 345.9, 728.85, 780.3; ICD10: G40, G40.2, P90, R25.2, R56]
Infantile spasms [ICD10: G40.4]
Seizures [ICD9: 345.9, 780.3; ICD10: G40, P90, R56]
Substance dependence [ICD10: F10-F19]
Function
Catalyzes the conversion of gamma-aminobutyrate and L- beta-aminoisobutyrate to succinate semialdehyde and methylmalonate semialdehyde, respectively. Can also convert delta-aminovalerate andbeta-alanine.
BioChemical Class
Transferases of nitrogenous groups
Target Validation
T59045
UniProt ID
P80404
EC Number
EC 2.6.1.22
Sequence
MASMLLAQRLACSFQHSYRLLVPGSRHISQAAAKVDVEFDYDGPLMKTEVPGPRSQELMK
QLNIIQNAEAVHFFCNYEESRGNYLVDVDGNRMLDLYSQISSVPIGYSHPALLKLIQQPQ
NASMFVNRPALGILPPENFVEKLRQSLLSVAPKGMSQLITMACGSCSNENALKTIFMWYR
SKERGQRGFSQEELETCMINQAPGCPDYSILSFMGAFHGRTMGCLATTHSKAIHKIDIPS
FDWPIAPFPRLKYPLEEFVKENQQEEARCLEEVEDLIVKYRKKKKTVAGIIVEPIQSEGG
DNHASDDFFRKLRDIARKHGCAFLVDEVQTGGGCTGKFWAHEHWGLDDPADVMTFSKKMM
TGGFFHKEEFRPNAPYRIFNTWLGDPSKNLLLAEVINIIKREDLLNNAAHAGKALLTGLL
DLQARYPQFISRVRGRGTFCSFDTPDDSIRNKLILIARNKGVVLGGCGDKSIRFRPTLVF
RDHHAHLFLNIFSDILADFK
Drugs and Mode of Action
Drug(s) Divalproex sodium Drug Info Approved Seizures [550982]
L-Alanine Drug Info Approved Dietary shortage; Glioma [542213], [550116], [551871]
Pyridoxal Phosphate Drug Info Approved Dietary shortage [540717], [550672]
Pyruvic acid Drug Info Approved Dietary shortage [468040], [538216]
Vigabatrin Drug Info Approved Epilepsy; Infantile spasms; Complex partial seizures [468053], [530677]
K-828-AB Drug Info Phase 2 Dementia [551074]
CPP -15 Drug Info Phase 1 Infantile spasms [549894]
CPP-115 Drug Info Phase 1 Substance dependence [523732], [543038]
Inhibitor (4e)-4-Aminohex-4-Enoic Acid Drug Info [551393]
1-(4-hydroxyphenyl)prop-2-en-1-one Drug Info [527869]
3-chloro-1-(4-hydroxyphenyl)propan-1-one Drug Info [529916]
4-Amino Hexanoic Acid Drug Info [551393]
4-hydroxy-3-nitrobenzaldehyde Drug Info [527869]
4-hydroxybenzaldehyde Drug Info [529916]
4-hydroxybenzylamine Drug Info [527869]
Acetate Ion Drug Info [551393]
CPP-115 Drug Info [549893]
Divalproex sodium Drug Info [536555]
Gamma-acetylenic GABA Drug Info [537793]
K-828-AB Drug Info [550353]
L-Alanine Drug Info [536555]
NIPECOTIC ACID Drug Info [533540]
OXAMATE Drug Info [533540]
Pyridoxal Phosphate Drug Info [536555]
Pyruvic acid Drug Info [536555]
Sodium valproate Drug Info [537744]
VANILLIN Drug Info [527869]
Vigabatrin Drug Info [530677], [535575], [536166], [537757]
Modulator CPP -15 Drug Info [549893]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
BioCyc Pathway GABA shunt
Valine degradation
Beta-alanine degradation
4-aminobutyrate degradation
KEGG Pathway Alanine, aspartate and glutamate metabolism
Valine, leucine and isoleucine degradation
beta-Alanine metabolism
Propanoate metabolism
Butanoate metabolism
Metabolic pathways
GABAergic synapse
PANTHER Pathway Aminobutyrate degradation
Pyrimidine Metabolism
Gamma-aminobutyric acid synthesis
PathWhiz Pathway Aspartate Metabolism
Glutamate Metabolism
Beta-Alanine Metabolism
Valine, Leucine and Isoleucine Degradation
Propanoate Metabolism
WikiPathways GABA synthesis, release, reuptake and degradation
Alanine and aspartate metabolism
References
Ref 468040(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4809).
Ref 468053(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4821).
Ref 523732ClinicalTrials.gov (NCT01493596) A Safety, Tolerability and Pharmacokinetic Study of CPP-115. U.S. National Institutes of Health.
Ref 530677Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
Ref 538216FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 065200.
Ref 540717(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5249).
Ref 542213(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 720).
Ref 543038(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8284).
Ref 549894Clinical pipeline report, company report or official report of Catalyst Pharma.
Ref 550116Drug information of L-Alanine, Health Canada, 2008. (drugid: 7638)
Ref 550672Drug information of Pyridoxal Phosphate, 2008. eduDrugs.
Ref 550982FDA approved drugs (1996) in CenterWatch
Ref 551074Clinical pipeline report, company report or official report of Kowa Co Ltd.
Ref 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 527869Bioorg Med Chem Lett. 2006 Feb;16(3):592-5. Epub 2005 Nov 14.Inhibition of GABA shunt enzymes' activity by 4-hydroxybenzaldehyde derivatives.
Ref 529916Bioorg Med Chem Lett. 2009 Feb 1;19(3):731-4. Epub 2008 Dec 11.Inactivation of GABA transaminase by 3-chloro-1-(4-hydroxyphenyl)propan-1-one.
Ref 530677Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
Ref 533540J Med Chem. 1982 Feb;25(2):113-6.Aminomethyl-1,2,4-benzothiadiazines as potential analogues of gamma-aminobutyric acid. Unexpected discovery of a taurine antagonist.
Ref 535575Gamma-vinyl GABA, an irreversible inhibitor of GABA transaminase, alters the acquisition and expression of cocaine-induced sensitization in male rats. Synapse. 2002 Dec 15;46(4):240-50.
Ref 536166Glutamate- and GABA-based CNS therapeutics. Curr Opin Pharmacol. 2006 Feb;6(1):7-17.
Ref 536555DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29.
Ref 537744Influence of a GABA transaminase inhibitor on central nervous system oxygen toxicity. Aviat Space Environ Med. 1978 Jul;49(7):877-9.
Ref 537757Vigabatrin for refractory complex partial seizures: multicenter single-blind study with long-term follow-up. Neurology. 1987 Feb;37(2):184-9.
Ref 537793Treatment of Huntington disease with gamma-acetylenic GABA an irreversible inhibitor of GABA-transaminase: increased CSF GABA and homocarnosine without clinical amelioration. Neurology. 1981 Feb;31(2):207-11.
Ref 549893Clinical pipeline report, company report or official report of Catalyst Pharma.
Ref 550353Phase II clinical trial of K-828-AB for treating behavioral and psychological symptoms of dementia. Kowa Co. Ltd.
Ref 551393How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.

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