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Protein

Nucleoside diphosphate kinase A

Gene

NME1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.3 Publications

Catalytic activityi

ATP + nucleoside diphosphate = ADP + nucleoside triphosphate.

Cofactori

Enzyme regulationi

Autophosphorylation at His-118 increases serine/threonine protein kinase activity of the enzyme. Interaction with the SET complex inhibits the endonuclease activity.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei12ATP1
Binding sitei60ATP1
Binding sitei88ATP1
Binding sitei94ATP1
Binding sitei105ATP1
Binding sitei115ATP1
Active sitei118Pros-phosphohistidine intermediate1 Publication1

GO - Molecular functioni

  • ATP binding Source: UniProtKB
  • deoxyribonuclease activity Source: UniProtKB
  • GTP binding Source: UniProtKB
  • identical protein binding Source: IntAct
  • magnesium ion binding Source: UniProtKB
  • nucleoside diphosphate kinase activity Source: UniProtKB
  • poly(A) RNA binding Source: UniProtKB
  • ribosomal small subunit binding Source: UniProtKB
  • RNA polymerase II regulatory region sequence-specific DNA binding Source: Ensembl
  • single-stranded DNA binding Source: Ensembl

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase

Keywords - Biological processi

Differentiation, Endocytosis, Neurogenesis, Nucleotide metabolism

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000011052-MONOMER.
ZFISH:ENSG00000011052-MONOMER.
BRENDAi2.7.4.6. 2681.
ReactomeiR-HSA-499943. Synthesis and interconversion of nucleotide di- and triphosphates.
SIGNORiP15531.

Names & Taxonomyi

Protein namesi
Recommended name:
Nucleoside diphosphate kinase A (EC:2.7.4.6)
Short name:
NDK A
Short name:
NDP kinase A
Alternative name(s):
Granzyme A-activated DNase
Short name:
GAAD
Metastasis inhibition factor nm23
NM23-H1
Tumor metastatic process-associated protein
Gene namesi
Name:NME1
Synonyms:NDPKA, NM23
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:7849. NME1.

Subcellular locationi

  • Cytoplasm 1 Publication
  • Nucleus 1 Publication

  • Note: Cell-cycle dependent nuclear localization which can be induced by interaction with Epstein-barr viral proteins or by degradation of the SET complex by GzmA.

GO - Cellular componenti

  • centrosome Source: Ensembl
  • cytoplasm Source: UniProtKB
  • cytosol Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • intermediate filament Source: Ensembl
  • membrane Source: UniProtKB
  • mitochondrial outer membrane Source: Ensembl
  • nucleus Source: UniProtKB
  • perinuclear region of cytoplasm Source: Ensembl
  • ruffle membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi60F → W: No loss of activity or substrate binding. 1 Publication1
Mutagenesisi96P → S: Increased motility of carcinoma cells. 1 Publication1
Mutagenesisi118H → F: Loss of serine/threonine kinase activity. Some loss of motility of carcinoma cells. 2 Publications1
Mutagenesisi118H → G: Loss of activity. 2 Publications1
Mutagenesisi120S → A: Limited increase in motility of carcinoma cells. 1 Publication1

Organism-specific databases

DisGeNETi4830.
MalaCardsiNME1.
OpenTargetsiENSG00000239672.
PharmGKBiPA249.

Chemistry databases

ChEMBLiCHEMBL2159.
DrugBankiDB00718. Adefovir Dipivoxil.
DB00709. Lamivudine.
DB00300. Tenofovir.

Polymorphism and mutation databases

BioMutaiNME1.
DMDMi127981.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00001371142 – 152Nucleoside diphosphate kinase AAdd BLAST151

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki100Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Modified residuei120PhosphoserineCombined sources1
Modified residuei122PhosphoserineCombined sources1
Modified residuei125PhosphoserineCombined sources1

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP15531.
PaxDbiP15531.
PeptideAtlasiP15531.
PRIDEiP15531.
TopDownProteomicsiP15531-1. [P15531-1]

2D gel databases

DOSAC-COBS-2DPAGEP15531.
OGPiP15531.

PTM databases

iPTMnetiP15531.
PhosphoSitePlusiP15531.
SwissPalmiP15531.

Expressioni

Tissue specificityi

Isoform 1 is expressed in heart, brain, placenta, lung, liver, skeletal muscle, pancreas, spleen and thymus. Expressed in lung carcinoma cell lines but not in normal lung tissues. Isoform 2 is ubiquitously expressed and its expression is also related to tumor differentiation.3 Publications

Gene expression databases

BgeeiENSG00000239672.
CleanExiHS_NME1.
ExpressionAtlasiP15531. baseline and differential.
GenevisibleiP15531. HS.

Organism-specific databases

HPAiCAB040571.
HPA008467.
HPA041113.

Interactioni

Subunit structurei

Hexamer of two different chains: A and B (A6, A5B, A4B2, A3B3, A2B4, AB5, B6). Interacts with PRUNE. Component of the SET complex, composed of at least ANP32A, APEX1, HMGB2, NME1, SET and TREX1. Within this complex, interacts directly with SET. Also interacts with TREX1, but only following translocation to the nucleus.4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself9EBI-741141,EBI-741141
Ksr1Q610977EBI-741141,EBI-1536336From a different organism.
MCF2P109114EBI-741141,EBI-1914514
NME2P223922EBI-741141,EBI-713693
NME3Q132324EBI-741141,EBI-713684
NME4O007464EBI-741141,EBI-744871
PID1Q7Z2X43EBI-741141,EBI-10256685
POLR1CO151607EBI-741141,EBI-1055079
PRUNEQ86TP12EBI-741141,EBI-2127112
SREK1IP1Q8N9Q23EBI-741141,EBI-10268630
STRAPQ9Y3F49EBI-741141,EBI-727414
TNPO2O147873EBI-741141,EBI-431907
WDYHV1Q96HA83EBI-741141,EBI-741158

GO - Molecular functioni

  • identical protein binding Source: IntAct

Protein-protein interaction databases

BioGridi110894. 58 interactors.
DIPiDIP-39164N.
IntActiP15531. 28 interactors.
MINTiMINT-221462.
STRINGi9606.ENSP00000013034.

Structurei

Secondary structure

1152
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi2 – 4Combined sources3
Beta strandi6 – 11Combined sources6
Helixi13 – 17Combined sources5
Helixi21 – 31Combined sources11
Beta strandi34 – 41Combined sources8
Helixi45 – 51Combined sources7
Helixi53 – 55Combined sources3
Beta strandi56 – 58Combined sources3
Helixi61 – 69Combined sources9
Beta strandi73 – 80Combined sources8
Helixi83 – 91Combined sources9
Helixi96 – 98Combined sources3
Helixi104 – 108Combined sources5
Helixi112 – 114Combined sources3
Beta strandi116 – 119Combined sources4
Helixi123 – 133Combined sources11
Helixi136 – 138Combined sources3
Helixi147 – 150Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1JXVX-ray2.20A/B/C/D/E/F1-152[»]
1UCNX-ray2.00A/B/C1-152[»]
2HVDX-ray2.15A/B/C1-152[»]
2HVEX-ray2.40A/B/C1-152[»]
3L7UX-ray2.10A/B/C1-152[»]
4ENOX-ray2.80A/B1-152[»]
ProteinModelPortaliP15531.
SMRiP15531.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP15531.

Family & Domainsi

Sequence similaritiesi

Belongs to the NDK family.Curated

Phylogenomic databases

eggNOGiKOG0888. Eukaryota.
COG0105. LUCA.
GeneTreeiENSGT00760000119146.
HOGENOMiHOG000224564.
HOVERGENiHBG000423.
InParanoidiP15531.
KOiK00940.
OMAiVERFFME.
OrthoDBiEOG091G0PLD.
PhylomeDBiP15531.
TreeFamiTF106373.

Family and domain databases

HAMAPiMF_00451. NDP_kinase. 1 hit.
InterProiIPR001564. Nucleoside_diP_kinase.
IPR023005. Nucleoside_diP_kinase_AS.
[Graphical view]
PfamiPF00334. NDK. 1 hit.
[Graphical view]
PRINTSiPR01243. NUCDPKINASE.
SMARTiSM00562. NDK. 1 hit.
[Graphical view]
PROSITEiPS00469. NDP_KINASES. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P15531-1) [UniParc]FASTAAdd to basket
Also known as: NM23-H1A

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

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

YE
Length:152
Mass (Da):17,149
Last modified:April 1, 1990 - v1
Checksum:iAAE9C0DF63CB70A1
GO
Isoform 2 (identifier: P15531-2) [UniParc]FASTAAdd to basket
Also known as: NM23-H1B

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MVLLSTLGIVFQGEGPPISSCDTGTM

Show »
Length:177
Mass (Da):19,654
Checksum:iDEA9961E992D0378
GO
Isoform 3 (identifier: P22392-2) [UniParc]FASTAAdd to basket
Also known as: NM23-LV
The sequence of this isoform can be found in the external entry P22392.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Note: Based on a naturally occurring readthrough transcript which produces an NME1-NME2 fusion protein.
Length:267
Mass (Da):30,137
GO

Sequence cautioni

The sequence CAA35621 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_004625120S → G in a neuroblastoma sample; increased motility of carcinoma cells. 1 PublicationCorresponds to variant rs121917887dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0367071M → MVLLSTLGIVFQGEGPPISS CDTGTM in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X17620 mRNA. Translation: CAA35621.1. Different initiation.
X73066 mRNA. Translation: CAA51527.1.
X75598 Genomic DNA. Translation: CAA53270.1.
AF487339 mRNA. Translation: AAO85436.1.
AK291105 mRNA. Translation: BAF83794.1.
CR542104 mRNA. Translation: CAG46901.1.
CR542115 mRNA. Translation: CAG46912.1.
AC005839 Genomic DNA. No translation available.
CH471109 Genomic DNA. Translation: EAW94568.1.
BC000293 mRNA. Translation: AAH00293.1.
BC018994 mRNA. Translation: AAH18994.1.
CCDSiCCDS11578.1. [P15531-2]
CCDS11579.1. [P15531-1]
PIRiA33386.
RefSeqiNP_000260.1. NM_000269.2. [P15531-1]
NP_937818.1. NM_198175.1. [P15531-2]
UniGeneiHs.463456.

Genome annotation databases

EnsembliENST00000013034; ENSP00000013034; ENSG00000239672. [P15531-2]
ENST00000336097; ENSP00000337060; ENSG00000239672. [P15531-2]
ENST00000393196; ENSP00000376892; ENSG00000239672. [P15531-1]
GeneIDi4830.
KEGGihsa:4830.
UCSCiuc002ith.3. human. [P15531-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X17620 mRNA. Translation: CAA35621.1. Different initiation.
X73066 mRNA. Translation: CAA51527.1.
X75598 Genomic DNA. Translation: CAA53270.1.
AF487339 mRNA. Translation: AAO85436.1.
AK291105 mRNA. Translation: BAF83794.1.
CR542104 mRNA. Translation: CAG46901.1.
CR542115 mRNA. Translation: CAG46912.1.
AC005839 Genomic DNA. No translation available.
CH471109 Genomic DNA. Translation: EAW94568.1.
BC000293 mRNA. Translation: AAH00293.1.
BC018994 mRNA. Translation: AAH18994.1.
CCDSiCCDS11578.1. [P15531-2]
CCDS11579.1. [P15531-1]
PIRiA33386.
RefSeqiNP_000260.1. NM_000269.2. [P15531-1]
NP_937818.1. NM_198175.1. [P15531-2]
UniGeneiHs.463456.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1JXVX-ray2.20A/B/C/D/E/F1-152[»]
1UCNX-ray2.00A/B/C1-152[»]
2HVDX-ray2.15A/B/C1-152[»]
2HVEX-ray2.40A/B/C1-152[»]
3L7UX-ray2.10A/B/C1-152[»]
4ENOX-ray2.80A/B1-152[»]
ProteinModelPortaliP15531.
SMRiP15531.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110894. 58 interactors.
DIPiDIP-39164N.
IntActiP15531. 28 interactors.
MINTiMINT-221462.
STRINGi9606.ENSP00000013034.

Chemistry databases

ChEMBLiCHEMBL2159.
DrugBankiDB00718. Adefovir Dipivoxil.
DB00709. Lamivudine.
DB00300. Tenofovir.

PTM databases

iPTMnetiP15531.
PhosphoSitePlusiP15531.
SwissPalmiP15531.

Polymorphism and mutation databases

BioMutaiNME1.
DMDMi127981.

2D gel databases

DOSAC-COBS-2DPAGEP15531.
OGPiP15531.

Proteomic databases

EPDiP15531.
PaxDbiP15531.
PeptideAtlasiP15531.
PRIDEiP15531.
TopDownProteomicsiP15531-1. [P15531-1]

Protocols and materials databases

DNASUi4830.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000013034; ENSP00000013034; ENSG00000239672. [P15531-2]
ENST00000336097; ENSP00000337060; ENSG00000239672. [P15531-2]
ENST00000393196; ENSP00000376892; ENSG00000239672. [P15531-1]
GeneIDi4830.
KEGGihsa:4830.
UCSCiuc002ith.3. human. [P15531-1]

Organism-specific databases

CTDi4830.
DisGeNETi4830.
GeneCardsiNME1.
HGNCiHGNC:7849. NME1.
HPAiCAB040571.
HPA008467.
HPA041113.
MalaCardsiNME1.
MIMi156490. gene.
neXtProtiNX_P15531.
OpenTargetsiENSG00000239672.
PharmGKBiPA249.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0888. Eukaryota.
COG0105. LUCA.
GeneTreeiENSGT00760000119146.
HOGENOMiHOG000224564.
HOVERGENiHBG000423.
InParanoidiP15531.
KOiK00940.
OMAiVERFFME.
OrthoDBiEOG091G0PLD.
PhylomeDBiP15531.
TreeFamiTF106373.

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000011052-MONOMER.
ZFISH:ENSG00000011052-MONOMER.
BRENDAi2.7.4.6. 2681.
ReactomeiR-HSA-499943. Synthesis and interconversion of nucleotide di- and triphosphates.
SIGNORiP15531.

Miscellaneous databases

ChiTaRSiNME1. human.
EvolutionaryTraceiP15531.
GeneWikiiNME1.
GenomeRNAii4830.
PROiP15531.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000239672.
CleanExiHS_NME1.
ExpressionAtlasiP15531. baseline and differential.
GenevisibleiP15531. HS.

Family and domain databases

HAMAPiMF_00451. NDP_kinase. 1 hit.
InterProiIPR001564. Nucleoside_diP_kinase.
IPR023005. Nucleoside_diP_kinase_AS.
[Graphical view]
PfamiPF00334. NDK. 1 hit.
[Graphical view]
PRINTSiPR01243. NUCDPKINASE.
SMARTiSM00562. NDK. 1 hit.
[Graphical view]
PROSITEiPS00469. NDP_KINASES. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNDKA_HUMAN
AccessioniPrimary (citable) accession number: P15531
Secondary accession number(s): Q6FGK3, Q86XQ2, Q9UDJ6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 1, 1990
Last modified: November 30, 2016
This is version 196 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

The role of this protein in tumor development and progression is uncertain. This protein is found in reduced amount in some tumor cells of high metastatic potential. However, increased NME1 levels correlate with aggressive tumor features in neuroblastoma. May have distinct if not opposite roles in different tumors.

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.