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Overview

Uniprot IDP15531
Protein NameNucleoside diphosphate kinase A
Gene NameNME1
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
100 ETNPADSKPGTIRGD
12 ERTFIAIKPDGVQRG
26 GLVGEIIKRFEQKGF
31 IIKRFEQKGFRLVGL
49 QASEDLLKEHYVDLK

Function

Catalyzes the transfer of a gamma-phosphoryl group from a nucleoside triphosphate, mainly ATP, to a nucleoside diphosphate via a ping-pong mechanism involving a phosphohistidine intermediate, therefore contributing to the nucleoside triphosphate homeostasis (PubMed:10952986, PubMed:14960567, PubMed:16313181, PubMed:1851158, PubMed:23519676, PubMed:33903070, PubMed:8810265, PubMed:9038158). Also phosphorylates geranyl pyrophosphate (GPP) and farnesyl pyrophosphate (FPP), linking it to isoprenoid metabolism (PubMed:10952986). Additionally, functions as a non-specific serine/threonine kinase and histidine protein kinase, transferring phosphoryl groups from its active site to target proteins (PubMed:8529641, PubMed:9038158). May function as a Mg(2+)-dependent single-stranded DNA endonuclease as part of the SET complex, cooperating with the 3'-5' exonuclease TREX1 to mediate apoptotic DNA fragmentation in cytotoxic T lymphocytes (PubMed:12628186, PubMed:16818237). Reported to nick one DNA strand, enabling TREX1 to remove nucleotides from the free 3' end, enhancing DNA damage and suppressing DNA end reannealing and repair (PubMed:16818237). Has been shown to cleave double strands DNA within the 3'-portions of both 5'-SHS silencer and NHE basal promoter element of the PDGFA gene, potentially repressing its transcription (PubMed:11694515). May also function as a Mg(2+)-dependent 3'-5' DNA exonuclease, excising nucleotides from 3' single-stranded DNA or DNA with 3' single strand overhangs, suggesting a role in DNA nucleolytic processing (PubMed:14960567, PubMed:16313181). Involved in the regulation of tumor metastasis and cellular differentiation (By similarity). Also required for cell motility (PubMed:8270257, PubMed:25582197). May control, with NME2, AcCoA usage between histone acetylation and fatty acid synthesis, possibly by binding and releasing AcCoA at transcriptionally active chromatin regions in proximity to histone acetyltransferase (HAT) (By similarity)

Protein Sequence

10 MANCERTFIA 20 IKPDGVQRGL 30 VGEIIKRFEQ 40 KGFRLVGLKF 50 MQASEDLLKE 60 HYVDLKDRPF 70 FAGLVKYMHS 80 GPVVAMVWEG 90 LNVVKTGRVM 100 LGETNPADSK 110 PGTIRGDFCI 120 QVGRNIIHGS 130 DSVESAEKEI 140 GLWFHPEELV 150 DYTSCAQNWI YE

Gene Ontology

Classification GO ID Description
Biological Process GO:0007399 nervous system development
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005829 cytosol
Cellular Component GO:0005769 early endosome
Cellular Component GO:0070062 extracellular exosome
Cellular Component GO:0016020 membrane
Cellular Component GO:0005634 nucleus
Cellular Component GO:0032587 ruffle membrane
Molecular Function GO:0008296 3'-5'-DNA exonuclease activity
Molecular Function GO:1905502 acetyl-CoA binding
Molecular Function GO:0043531 ADP binding
Molecular Function GO:0005524 ATP binding
Molecular Function GO:0120225 coenzyme A binding
Molecular Function GO:0003677 DNA binding
Molecular Function GO:0004520 DNA endonuclease activity
Molecular Function GO:0004536 DNA nuclease activity
Molecular Function GO:0047887 farnesyl diphosphate kinase activity
Molecular Function GO:0019003 GDP binding
Molecular Function GO:0042802 identical protein binding
Molecular Function GO:0016301 kinase activity
Molecular Function GO:0000287 magnesium ion binding
Molecular Function GO:0004550 nucleoside diphosphate kinase activity
Molecular Function GO:0016776 phosphotransferase activity, phosphate group as acceptor
Molecular Function GO:0004673 protein histidine kinase activity
Molecular Function GO:0106310 protein serine kinase activity
Molecular Function GO:0004674 protein serine/threonine kinase activity
Molecular Function GO:0043024 ribosomal small subunit binding
Molecular Function GO:0003723 RNA binding
Molecular Function GO:0120226 succinyl-CoA binding
Biological Process GO:0046356 acetyl-CoA catabolic process
Biological Process GO:0006309 apoptotic DNA fragmentation
Biological Process GO:0030154 cell differentiation
Biological Process GO:0006241 CTP biosynthetic process
Biological Process GO:0006308 DNA catabolic process
Biological Process GO:0006897 endocytosis
Biological Process GO:0006183 GTP biosynthetic process
Biological Process GO:0006720 isoprenoid metabolic process
Biological Process GO:0046042 ITP biosynthetic process
Biological Process GO:0008285 negative regulation of cell population proliferation
Biological Process GO:0009132 nucleoside diphosphate metabolic process
Biological Process GO:0009142 nucleoside triphosphate biosynthetic process
Biological Process GO:0050679 positive regulation of epithelial cell proliferation
Biological Process GO:0034214 protein hexamerization
Biological Process GO:0042981 regulation of apoptotic process
Biological Process GO:0042304 regulation of fatty acid biosynthetic process
Biological Process GO:0006228 UTP biosynthetic process

Reference

[1] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.

[2] Shi CM, Wang QC, Li XL, Yang YH, Tang XY et al.. Global Profiling of Protein Lactylation in Human Hippocampi.. Proteomics Clin Appl 19(2):e202400061. 2025 Mar. PMID: 39610256.