Details of Drug-Metabolizing Enzyme (DME)

General Information of DME (ID: DMEN002)
DME Name Nucleoside diphosphate kinase A (NME1), Homo sapiens
Gene Name NME1
UniProt ID
NDKA_HUMAN
EC Number    EC: 2.7.1.30     (Click to Show/Hide the Complete EC Tree)
Transferase
Kinase
Phosphotransferase
EC: 2.7.1.30
Lineage    Species: Homo sapiens     (Click to Show/Hide the Complete Species Lineage)
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
      Click to Show/Hide the Molecular/Functional Data (Sequence/Structure/Pathway/Function) of This DME
Sequence
MANCERTFIAIKPDGVQRGLVGEIIKRFEQKGFRLVGLKFMQASEDLLKEHYVDLKDRPF
FAGLVKYMHSGPVVAMVWEGLNVVKTGRVMLGETNPADSKPGTIRGDFCIQVGRNIIHGS
DSVESAEKEIGLWFHPEELVDYTSCAQNWIYE
Structure
1JXV ; 1UCN ; 2HVD ; 2HVE ; 3L7U ; 4ENO ; 5UI4 ;
Function Major role in the synthesis of nucleoside triphosphates other than ATP. The ATP gamma phosphate is transferred to the NDP beta phosphate via a ping-pong mechanism, using a phosphorylated active-site intermediate. Possesses nucleoside-diphosphate kinase, serine/threonine-specific protein kinase, geranyl and farnesyl pyrophosphate kinase, histidine protein kinase and 3'-5' exonuclease activities. Involved in cell proliferation, differentiation and development, signal transduction, G protein-coupled receptor endocytosis, and gene expression. Required for neural development including neural patterning and cell fate determination. During GZMA-mediated cell death, works in concert with TREX1. NME1 nicks one strand of DNA and TREX1 removes bases from the free 3' end to enhance DNA damage and prevent DNA end reannealing and rapid repair.
Full List of Drug(s) Metabolized by This DME
      Drugs Approved by FDA Click to Show/Hide the Full List of Drugs:          4 Drugs
Adenosine
 Drug Info Approved Atrial fibrillation ICD11: BC81 [1]
Sofosbuvir
 Drug Info Approved Viral hepatitis ICD11: 1E51 [2]
Sofosbuvir
 Drug Info Approved Viral hepatitis ICD11: 1E51 [3]
Adefovir dipivoxil
 Drug Info Approved Viral hepatitis ICD11: 1E51 [4]
Full List of Metabolic Reactions (MR) Catalyzed by This DME
MR ID Reactant Product MR Type Source Drug REF
MR000063 Adefovir monophosphate Adefovir Diphosphate Other reaction - Phosphorylation Adefovir dipivoxil [5]
MR000073 ADP ATP Other reaction - Phosphorylation Adenosine [1], [6]
References
1 Adenosine Metabolism: Emerging Concepts for Cancer Therapy Cancer Cell. 2019 Dec 9;36(6):582-596. doi: 10.1016/j.ccell.2019.10.007.
2 Effects of rifampin, itraconazole and esomeprazole on the pharmacokinetics of alisertib, an investigational aurora a kinase inhibitor in patients with advanced malignancies. Invest New Drugs. 2018 Apr;36(2):248-258. doi: 10.1007/s10637-017-0499-z.
3 Species differences in liver accumulation and metabolism of nucleotide prodrug sofosbuvir
4 Liquid oral suspension adefovir dipivoxil (GS-02-526): an update on treatments for hepatitis B infection. Expert Rev Anti Infect Ther. 2014 Aug;12(8):919-28. doi: 10.1586/14787210.2014.928588.
5 Effective metabolism and long intracellular half life of the anti-hepatitis B agent adefovir in hepatic cells Biochem Pharmacol. 2004 Nov 1;68(9):1825-31. doi: 10.1016/j.bcp.2004.07.010.
6 Purine signaling pathway dysfunction in autism spectrum disorders: Evidence from multiple omics data. Front Mol Neurosci. 2023 Feb 3;16:1089871. doi: 10.3389/fnmol.2023.1089871.

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