Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTURQ2G)

• DTT Name: Glutamate decarboxylase (GLUL)
• Synonyms: Glutamateammonia ligase
• Gene Name: GLUL
• DTT Type: Discontinued target; [1]
• BioChemical Class: Carbon-nitrogen ligase
• UniProt ID: GLNA_HUMAN
• TTD ID: T37735
• EC Number: EC 6.3.1.2
• Sequence:
  MTTSASSHLNKGIKQVYMSLPQGEKVQAMYIWIDGTGEGLRCKTRTLDSEPKCVEELPEW
  NFDGSSTLQSEGSNSDMYLVPAAMFRDPFRKDPNKLVLCEVFKYNRRPAETNLRHTCKRI
  MDMVSNQHPWFGMEQEYTLMGTDGHPFGWPSNGFPGPQGPYYCGVGADRAYGRDIVEAHY
  RACLYAGVKIAGTNAEVMPAQWEFQIGPCEGISMGDHLWVARFILHRVCEDFGVIATFDP
  KPIPGNWNGAGCHTNFSTKAMREENGLKYIEEAIEKLSKRHQYHIRAYDPKGGLDNARRL
  TGFHETSNINDFSAGVANRSASIRIPRTVGQEKKGYFEDRRPSANCDPFSVTEALIRTCL
  LNETGDEPFQYKN
• Function: Its role depends on tissue localization: in the brain, it regulates the levels of toxic ammonia and converts neurotoxic glutamate to harmless glutamine, whereas in the liver, it is one of the enzymes responsible for the removal of ammonia. Essential for proliferation of fetal skin fibroblasts. Independently of its glutamine synthetase activity, required for endothelial cell migration during vascular development: acts by regulating membrane localization and activation of the GTPase RHOJ, possibly by promoting RHOJ palmitoylation. May act as a palmitoyltransferase for RHOJ: able to autopalmitoylate and then transfer the palmitoyl group to RHOJ. Plays a role in ribosomal 40S subunit biogenesis. Glutamine synthetase that catalyzes the ATP-dependent conversion of glutamate and ammonia to glutamine.
• KEGG Pathway:
  Alanine, aspartate and glutamate metabolism (hsa00250)
  Arginine and proline metabolism (hsa00330)
  Glyoxylate and dicarboxylate metabolism (hsa00630)
  Nitrogen metabolism (hsa00910)
  Metabolic pathways (hsa01100)
  Biosynthesis of amino acids (hsa01230)
  Glutamatergic synapse (hsa04724)
  GABAergic synapse (hsa04727)
• Reactome Pathway: Amino acid synthesis and interconversion (transamination) (R-HSA-70614)
• BioCyc Pathway: MetaCyc:HS06066-MON

Molecular Interaction Atlas (MIA) of This DTT

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
NLX-P101	DM6NPUJ	Parkinson disease	8A00.0	Discontinued in Phase 2	[1]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Parkinson's disease	8A00.0	Substantia nigra tissue	2.45E-01	-0.23	-0.4

The Drug-Metabolizing Enzyme (DME) Role of This DTT

• DTT DME Name: Glutamine synthetase (GLUL) DME Info
• Gene Name: GLUL

1 Approved Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ammonia	DMOEVK6	Coronary artery disease	BA80	Approved	[2]

References

• [1] NLX-P101, an adeno-associated virus gene therapy encoding glutamic acid decarboxylase, for the potential treatment of Parkinson's disease. Curr Opin Investig Drugs. 2010 Jul;11(7):813-22.
• [2] Ammonia metabolism capacity of HepG2 cells with high expression of human glutamine synthetase. Hepatobiliary Pancreat Dis Int. 2008 Dec;7(6):621-7.