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Protein

Nucleoside diphosphate kinase A

Gene

NME1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

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.

Catalytic activityi

ATP + nucleoside diphosphate = ADP + nucleoside triphosphate.

Cofactori

Activity 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

GO - Biological processi

Keywordsi

Molecular functionKinase, Transferase
Biological processDifferentiation, Endocytosis, Neurogenesis, Nucleotide metabolism
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000011052-MONOMER
BRENDAi2.7.4.6 2681
ReactomeiR-HSA-499943 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

EuPathDBiHostDB:ENSG00000239672.7
HGNCiHGNC:7849 NME1
MIMi156490 gene
neXtProtiNX_P15531

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
DrugBankiDB03491 2'-Deoxyguanosine-5'-Diphosphate
DB02181 2'-Deoxyguanosine-5'-Triphosphate
DB04542 3'-Azido-3'-Deoxythymidine-5'-Diphosphate
DB04366 3'-Deoxy 3'-Amino Adenosine-5'-Diphosphate
DB00718 Adefovir Dipivoxil
DB02607 Adenosine Phosphonoacetic Acid
DB04068 Fudp
DB04315 Guanosine-5'-Diphosphate
DB00709 Lamivudine
DB02345 Selenocysteine
DB00300 Tenofovir
DB03103 Thymidine-5'- Diphosphate

Polymorphism and mutation databases

BioMutaiNME1
DMDMi127981

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001371141 – 152Nucleoside diphosphate kinase AAdd BLAST152

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
MaxQBiP15531
PaxDbiP15531
PeptideAtlasiP15531
PRIDEiP15531
ProteomicsDBi53183
53184 [P15531-2]
TopDownProteomicsiP15531-1 [P15531-1]

2D gel databases

DOSAC-COBS-2DPAGEiP15531
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 Expressed in 111 organ(s), highest expression level in left adrenal gland
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 PRUNE1. 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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi110894, 72 interactors
CORUMiP15531
DIPiDIP-39164N
IntActiP15531, 33 interactors
MINTiP15531
STRINGi9606.ENSP00000013034

Structurei

Secondary structure

1152
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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
OMAiKIVAMKM
OrthoDBiEOG091G0PLD
PhylomeDBiP15531
TreeFamiTF106373

Family and domain databases

Gene3Di3.30.70.141, 1 hit
HAMAPiMF_00451 NDP_kinase, 1 hit
InterProiView protein in InterPro
IPR034907 NDK-like_dom
IPR036850 NDK-like_dom_sf
IPR001564 Nucleoside_diP_kinase
IPR023005 Nucleoside_diP_kinase_AS
PfamiView protein in Pfam
PF00334 NDK, 1 hit
PRINTSiPR01243 NUCDPKINASE
SMARTiView protein in SMART
SM00562 NDK, 1 hit
SUPFAMiSSF54919 SSF54919, 1 hit
PROSITEiView protein in PROSITE
PS00469 NDP_KINASES, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

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

This entry has 3 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E7ERL0E7ERL0_HUMAN
Nucleoside diphosphate kinase A
NME1
139Annotation score:
E5RHP0E5RHP0_HUMAN
Nucleoside diphosphate kinase A
NME1
82Annotation score:
C9K028C9K028_HUMAN
Nucleoside diphosphate kinase A
NME1
60Annotation score:

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 dbSNP:rs121917887Ensembl.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

Similar proteinsi

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[»]
5UI4X-ray2.75A/B/C/D/E/F1-152[»]
ProteinModelPortaliP15531
SMRiP15531
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110894, 72 interactors
CORUMiP15531
DIPiDIP-39164N
IntActiP15531, 33 interactors
MINTiP15531
STRINGi9606.ENSP00000013034

Chemistry databases

ChEMBLiCHEMBL2159
DrugBankiDB03491 2'-Deoxyguanosine-5'-Diphosphate
DB02181 2'-Deoxyguanosine-5'-Triphosphate
DB04542 3'-Azido-3'-Deoxythymidine-5'-Diphosphate
DB04366 3'-Deoxy 3'-Amino Adenosine-5'-Diphosphate
DB00718 Adefovir Dipivoxil
DB02607 Adenosine Phosphonoacetic Acid
DB04068 Fudp
DB04315 Guanosine-5'-Diphosphate
DB00709 Lamivudine
DB02345 Selenocysteine
DB00300 Tenofovir
DB03103 Thymidine-5'- Diphosphate

PTM databases

iPTMnetiP15531
PhosphoSitePlusiP15531
SwissPalmiP15531

Polymorphism and mutation databases

BioMutaiNME1
DMDMi127981

2D gel databases

DOSAC-COBS-2DPAGEiP15531
OGPiP15531

Proteomic databases

EPDiP15531
MaxQBiP15531
PaxDbiP15531
PeptideAtlasiP15531
PRIDEiP15531
ProteomicsDBi53183
53184 [P15531-2]
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
EuPathDBiHostDB:ENSG00000239672.7
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
OMAiKIVAMKM
OrthoDBiEOG091G0PLD
PhylomeDBiP15531
TreeFamiTF106373

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiNME1 human
EvolutionaryTraceiP15531
GeneWikiiNME1
GenomeRNAii4830
PROiPR:P15531
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000239672 Expressed in 111 organ(s), highest expression level in left adrenal gland
CleanExiHS_NME1
ExpressionAtlasiP15531 baseline and differential
GenevisibleiP15531 HS

Family and domain databases

Gene3Di3.30.70.141, 1 hit
HAMAPiMF_00451 NDP_kinase, 1 hit
InterProiView protein in InterPro
IPR034907 NDK-like_dom
IPR036850 NDK-like_dom_sf
IPR001564 Nucleoside_diP_kinase
IPR023005 Nucleoside_diP_kinase_AS
PfamiView protein in Pfam
PF00334 NDK, 1 hit
PRINTSiPR01243 NUCDPKINASE
SMARTiView protein in SMART
SM00562 NDK, 1 hit
SUPFAMiSSF54919 SSF54919, 1 hit
PROSITEiView protein in PROSITE
PS00469 NDP_KINASES, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiNDKA_HUMAN
AccessioniPrimary (citable) accession number: P15531
Secondary accession number(s): Q6FGK3, Q86XQ2, Q9UDJ6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 1, 1990
Last modified: November 7, 2018
This is version 215 of the entry and version 1 of the sequence. See 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

Keywords - Technical termi

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

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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