Molecule Information

General Information of the Molecule (ID: Mol01024)

• Name: Nucleoside diphosphate kinase A (NME1) ,Homo sapiens
• Synonyms: NDK A; NDP kinase A; Granzyme A-activated DNase; GAAD; Metastasis inhibition factor nm23; NM23-H1; Tumor metastatic process-associated protein; NDPKA; NM23
• Molecule Type: Protein
• Gene Name: NME1
• Gene ID: 4830
• Location: chr17:51153559-51162428[+]
• Sequence:
  MANCERTFIAIKPDGVQRGLVGEIIKRFEQKGFRLVGLKFMQASEDLLKEHYVDLKDRPF
  FAGLVKYMHSGPVVAMVWEGLNVVKTGRVMLGETNPADSKPGTIRGDFCIQVGRNIIHGS
  DSVESAEKEIGLWFHPEELVDYTSCAQNWIYE
• 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.
• Uniprot ID: NDKA_HUMAN
• Ensembl ID: ENSG00000239672
• HGNC ID: HGNC:7849

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  DISM: Drug Inactivation by Structure Modification

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Cytarabine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Disease Class: Leukemia [1]

• Resistant Disease: Leukemia [ICD-11: 2B33.6]
• Resistant Drug: Cytarabine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Activation of cytarabine occurs by means of the step wise de novo synthesis of 5'-mono-, di-, and triphosphate derivatives throughout the sequential action of deoxycytidine kinase (DCk), deoxycytidine monophosphate kinase (dCMk), and nucleoside diphosphate kinase (NDk) encoded by the NME1 gene. Phosphorylated cytarabine metabolites interfere with the cellular pool of natural nucleosides, are incorporated into DNA and inhibit DNA synthesis in a competitive fashion. In vitro studies have revealed that the intracellular concentrations of cytarabine-triphosphate are higher in cytarabine sensitive cells than in resistant cells.

Disease Class: Lymphoma [1]

• Resistant Disease: Lymphoma [ICD-11: 2A90- 2A85]
• Resistant Drug: Cytarabine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Activation of cytarabine occurs by means of the step wise de novo synthesis of 5'-mono-, di-, and triphosphate derivatives throughout the sequential action of deoxycytidine kinase (DCk), deoxycytidine monophosphate kinase (dCMk), and nucleoside diphosphate kinase (NDk) encoded by the NME1 gene. Phosphorylated cytarabine metabolites interfere with the cellular pool of natural nucleosides, are incorporated into DNA and inhibit DNA synthesis in a competitive fashion. In vitro studies have revealed that the intracellular concentrations of cytarabine-triphosphate are higher in cytarabine sensitive cells than in resistant cells.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Lymphoma [ICD-11: 2A90- 2A85]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Tonsil tissue
• The Specified Disease: Lymphoma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 5.03E-01; Fold-change: 2.97E-01; Z-score: 7.23E-01

References

• Ref 1: Response and Toxicity to Cytarabine Therapy in Leukemia and Lymphoma: From Dose Puzzle to Pharmacogenomic Biomarkers. Cancers (Basel). 2021 Feb 25;13(5):966. doi: 10.3390/cancers13050966.