NME1
entrez
4830
canonical
uniprot
P15531
canonical
ensembl
ENSG00000239672
resolver
ensp
ENSP00000337060
resolver
ensp
ENSP00000376892
resolver
genesymbol
NME1
resolver
genesymbol_syn
NDPKA
resolver
genesymbol_syn
NM23
resolver
hgnc
HGNC:7849
resolver
uniprot
A0A384MTW7
resolver
uniprot
Q6FGK3
resolver
uniprot
Q86XQ2
resolver
uniprot
Q9UDJ6
resolver
uniprot_entry
A0A384MTW7_HUMAN
resolver
uniprot_entry
NDKA_HUMAN
resolver
uniprot_sec
Q6FGK3
resolver
uniprot_sec
Q86XQ2
resolver
uniprot_sec
Q9UDJ6
resolver
activity_regulation
ACTIVITY REGULATION: Autophosphorylation at His-118 increases nucleoside diphosphate kinase activity and serine/threonine protein kinase activity (Probable) (PubMed:1851158, PubMed:8810265). Under cellular stress conditions, nucleoside diphosphate kinase activity is inhibited through both covalent and non-covalent binding by CoenzymeA (CoA); a non-covalent binding of coenzyme A (CoA) via its ADP moiety to the nucleotide-binding pocket of NME1 and a covalent binding of CoA through CoAlation (disulfide linkage to cysteine) at Cys-109 (PubMed:33903070). Nucleoside diphosphate kinase activity is regulated by oxido-reduction system coupled to its oligomeric state; disulfide bond formation, glutathionylation and oxidation at Cys-109 inhibit the nucleoside diphosphate kinase activity; intra- and specific inter-disulfide bonds are reduced through the NADPH-TXNRD1-TXN system thus activating nucleoside diphosphate kinase activity (PubMed:19956735, PubMed:23519676). Interaction with the SET complex inhibits the DNA endonuclease activity (PubMed:12628186). 3'-5'-DNA exonuclease activity is inhibited by potassium chloride (KCL), with the optimal KCl concentration less than or equal to 20 mM and ATP (PubMed:14960567). {ECO:0000269|PubMed:12628186, ECO:0000269|PubMed:14960567, ECO:0000269|PubMed:1851158, ECO:0000269|PubMed:19956735, ECO:0000269|PubMed:23519676, ECO:0000269|PubMed:33903070, ECO:0000269|PubMed:8810265, ECO:0000305|PubMed:8529641}.
uniprot
proteins
amino_acid_sequence
MANCERTFIAIKPDGVQRGLVGEIIKRFEQKGFRLVGLKFMQASEDLLKEHYVDLKDRPFFAGLVKYMHSGPVVAMVWEGLNVVKTGRVMLGETNPADSKPGTIRGDFCIQVGRNIIHGSDSVESAEKEIGLWFHPEELVDYTSCAQNWIYE
uniprot
proteins
ec_number
2.7.11.1
uniprot
proteins
ec_number
2.7.13.3
uniprot
proteins
ec_number
2.7.4.18
uniprot
proteins
ec_number
2.7.4.6
uniprot
proteins
ec_number
3.1.11.-
uniprot
proteins
ec_number
3.1.24.-
uniprot
proteins
function
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). {ECO:0000250|UniProtKB:P15532, ECO:0000269|PubMed:10952986, ECO:0000269|PubMed:11694515, ECO:0000269|PubMed:12628186, ECO:0000269|PubMed:14960567, ECO:0000269|PubMed:16313181, ECO:0000269|PubMed:16818237, ECO:0000269|PubMed:1851158, ECO:0000269|PubMed:23519676, ECO:0000269|PubMed:25582197, ECO:0000269|PubMed:33903070, ECO:0000269|PubMed:8270257, ECO:0000269|PubMed:8529641, ECO:0000269|PubMed:8810265, ECO:0000269|PubMed:9038158}.
uniprot
proteins
mass_dalton
17149
uniprot
proteins
mutagenesis
MUTAGEN 4; /note="C->S: Increases resistance to oxidative stress. Impairs intramolecular disulfide bonds formation under oxidative stress. Decreases oxidative modification at Cys-109."; /evidence="ECO:0000269|PubMed:23519676"; MUTAGEN 5; /note="E->A: Almost completely loss of 3'-5'-DNA exonuclease activity. Slightly decreases nucleoside diphoshate kinase activity."; /evidence="ECO:0000269|PubMed:16313181"; MUTAGEN 5; /note="E->Q: Reduces of about 80% of wild type 3'-5'-DNA exonuclease activity. Slightly decreases nucleoside diphoshate kinase activity."; /evidence="ECO:0000269|PubMed:16313181"; MUTAGEN 12; /note="K->Q: Does not affect homohexamer formation. Dramatically reduces nucleoside diphosphate kinase activity. Markedly decreases 3'-5'-DNA exonuclease activity."; /evidence="ECO:0000269|PubMed:14960567, ECO:0000269|PubMed:16313181"; MUTAGEN 33; /note="F->A: Almost completely loss of 3'-5'-DNA exonuclease activity."; /evidence="ECO:0000269|PubMed:16313181"; MUTAGEN 34; /note="R->A: Does not affect homohexamer formation. Slightly reduces nucleoside diphosphate kinase activity. Markedly decreases 3'-5'-DNA exonuclease activity."; /evidence="ECO:0000269|PubMed:14960567"; MUTAGEN 44; /note="S->A: Does not affect autophosphorylation. Significantly decreases nucleoside diphosphate kinase activity."; /evidence="ECO:0000269|PubMed:9038158"; MUTAGEN 54; /note="D->A: Almost completely loss of 3'-5'-DNA exonuclease activity. Slightly decreases nucleoside diphoshate kinase activity."; /evidence="ECO:0000269|PubMed:16313181"; MUTAGEN 56; /note="K->Q: Reduced interaction with FBXO24."; /evidence="ECO:0000269|PubMed:25582197"; MUTAGEN 56; /note="K->R: Increased interaction with FBXO24."; /evidence="ECO:0000269|PubMed:25582197"; MUTAGEN 58; /note="R->E: Abolishes CoA binding."; /evidence="ECO:0000269|PubMed:37298313"; MUTAGEN 60; /note="F->W: Does not affect GTP binding; when associated with Gly-118. Does not affect ATP binding; when associated with Gly-118."; /evidence="ECO:0000269|PubMed:12972261"; MUTAGEN 85; /note="K->A: Less ubiquitinated than WT in vitro."; /evidence="ECO:0000269|PubMed:25582197"; MUTAGEN 94; /note="T->D: Abolishes CoA binding."; /evidence="ECO:0000269|PubMed:37298313"; MUTAGEN 96; /note="P->S: Increases motility of carcinoma cells. Decreases farnesyl diphosphate kinase activity. Decreases geranyl-diphosphate kinase activity. Does not affect autophosphorylation. Significantly decreases histidine kinase activity."; /evidence="ECO:0000269|PubMed:10952986, ECO:0000269|PubMed:8810265, ECO:0000269|PubMed:9038158"; MUTAGEN 109; /note="C->A: Does not affect nucleoside diphosphate kinase activity. Impairs glutathionylation. Does not affect nucleoside diphosphate kinase activity under oxidative stress. Does not affect metastasis suppressor activity under oxidative stress."; /evidence="ECO:0000269|PubMed:19956735, ECO:0000269|PubMed:33903070"; MUTAGEN 109; /note="C->S: Significantly increases resistance to oxidative stress. Does not affect intramolecular disulfide bonds formation under oxidative stress."; /evidence="ECO:0000269|PubMed:23519676"; MUTAGEN 118; /note="H->F: Decreases autophosphorylation. Some loss of motility of carcinoma cells. Loss of farnesyl diphosphate kinase activity. Loss of geranyl-diphosphate kinase activity. Does not affect homohexamer formation. Dramatically reduces nucleoside diphosphate kinase activity. Significantly decreases 3'-5'-DNA exonuclease activity. Loss of autophosphorylation. Loss of histidine kinase activity. Loss of nucleoside diphosphate kinase activity under this oxidative stress."; /evidence="ECO:0000269|PubMed:10952986, ECO:0000269|PubMed:14960567, ECO:0000269|PubMed:16313181, ECO:0000269|PubMed:19956735, ECO:0000269|PubMed:8810265, ECO:0000269|PubMed:9038158"; MUTAGEN 118; /note="H->G: Does not affect GTP binding; when associated with Trp-60. Does not affect ATP binding; when associated with Trp-60."; /evidence="ECO:0000269|PubMed:12972261"; MUTAGEN 120; /note="S->A: Limited increase in motility of carcinoma cells. Increases farnesyl diphosphate kinase activity. Increases geranyl-diphosphate kinase activity. Significantly decreases autophosphorylation."; /evidence="ECO:0000269|PubMed:10952986, ECO:0000269|PubMed:8810265, ECO:0000269|PubMed:9038158"; MUTAGEN 121; /note="D->A: Almost completely loss of 3'-5'-DNA exonuclease activity."; /evidence="ECO:0000269|PubMed:16313181"; MUTAGEN 129; /note="E->A: Almost completely loss of 3'-5'-DNA exonuclease activity. Completely lost nucleoside diphoshate kinase activity."; /evidence="ECO:0000269|PubMed:16313181"; MUTAGEN 129; /note="E->Q: Almost completely loss of 3'-5'-DNA exonuclease activity. Completely lost nucleoside diphoshate kinase activity."; /evidence="ECO:0000269|PubMed:16313181"; MUTAGEN 145; /note="C->S: Increases resistance to oxidative stress. Impairs intramolecular disulfide bonds formation under oxidative stress. Decreases oxidative modification at Cys-109."; /evidence="ECO:0000269|PubMed:23519676
uniprot
proteins
post_translational_modification
PTM: Autophosphorylated at His-118 results in the formation of a phospho-enzyme intermediate and consequently activation of nucleoside diphosphate kinase activity and serine/threonine protein kinase activity. {ECO:0000269|PubMed:1851158, ECO:0000269|PubMed:8810265, ECO:0000305|PubMed:8529641}.; PTM: Cys-109 is oxidized to various oxidation states including intra- and inter-disulfide cross-links, glutathionylation and sulfonic acid formation in response to oxidative stress (PubMed:19956735). Glutathionylation and sulfonic acid formation lead to the loss of nucleoside diphosphate activity (PubMed:19956735). Glutathionylation, and sulfonic acid formation are dependent of dimeric state and intramolecular disulfide bond formation between Cys-4 and Cys-145 (PubMed:23519676). {ECO:0000269|PubMed:19956735, ECO:0000269|PubMed:23519676}.; PTM: The intramolecular disulfide bond between Cys-4 and Cys-145 is formed under oxidative stress and triggers a large conformational change that destabilizes and dissociates the hexamer into dimers thus creating a suitable environment for the oxidation of Cys-109 to sulfonic acid and glutathionylation. {ECO:0000269|PubMed:19956735, ECO:0000269|PubMed:23519676}.; PTM: An intra-disulfide cross-link can be reduced through the NADPH-TXNRD1-TXN system resulting into a fully activated hexamer; this system reduces the Cys-4-Cys-145 intra-disulfide bond to free sulfhydryls by interacting with the redox-active center of TXN that can be sequentially reduced by TXNRD1 and NADPH. {ECO:0000269|PubMed:19956735}.; PTM: CoAlation at Cys-109, in response to oxidative stress, negatively regulates the nucleoside diphosphate kinase activity. {ECO:0000269|PubMed:33903070}.; PTM: The N-terminus is blocked. {ECO:0000250|UniProtKB:P52175}.; PTM: Acetylated by GCN5, which prevents recognition by the SCF-FBXO24 E3 ubiquitin ligase, thereby protecting the protein from ubiquitination and proteasomal degradation. {ECO:0000269|PubMed:25582197}.; PTM: Ubiquitinated by the SCF-FBXO24 E3 ubiquitin ligase, leading to proteasomal degradation. {ECO:0000269|PubMed:25582197}.
uniprot
proteins
protein_family
NDK family
uniprot
proteins
pubmed
10512675
uniprot
proteins
pubmed
10952986
uniprot
proteins
pubmed
11694515
uniprot
proteins
pubmed
11835509
uniprot
proteins
pubmed
12601555
uniprot
proteins
pubmed
12628186
uniprot
proteins
pubmed
12972261
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
14960567
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16313181
uniprot
proteins
pubmed
16442775
uniprot
proteins
pubmed
16625196
uniprot
proteins
pubmed
16818237
uniprot
proteins
pubmed
16944299
uniprot
proteins
pubmed
17906697
uniprot
proteins
pubmed
1851158
uniprot
proteins
pubmed
19956735
uniprot
proteins
pubmed
2056128
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
22905912
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23519676
uniprot
proteins
pubmed
2509941
uniprot
proteins
pubmed
25582197
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
33903070
uniprot
proteins
pubmed
37298313
uniprot
proteins
pubmed
7916650
uniprot
proteins
pubmed
8047138
uniprot
proteins
pubmed
8270257
uniprot
proteins
pubmed
8529641
uniprot
proteins
pubmed
8810265
uniprot
proteins
pubmed
9038158
uniprot
proteins
sequence_length
152
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12628186, ECO:0000269|PubMed:16313181, ECO:0000269|PubMed:16442775, ECO:0000269|PubMed:2509941}. Nucleus {ECO:0000269|PubMed:12628186, ECO:0000269|PubMed:16313181, ECO:0000269|PubMed:16442775, ECO:0000269|PubMed:2509941}. Cell membrane {ECO:0000250|UniProtKB:P52175}. Note=Cell-cycle dependent nuclear localization which can be induced by degradation of the SET complex by GzmA (PubMed:12628186). In response to DNA damage, translocates to the nucleus where it might participate in DNA nucleolytic processing (PubMed:16313181). {ECO:0000269|PubMed:12628186, ECO:0000269|PubMed:16313181}.
uniprot
proteins