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Protein

Nucleoside diphosphate kinase A

Gene

Nme1

Organism
Rattus norvegicus (Rat)
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 (By similarity).By similarity

Catalytic activityi

ATP + nucleoside diphosphate = ADP + nucleoside triphosphate.

Cofactori

Mg2+By similarity

Enzyme regulationi

Autophosphorylation at His-118 increases serine/threonine protein kinase activity of the enzyme. Interaction with the SET complex inhibits exonuclease activity (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei12ATPBy similarity1
Binding sitei60ATPBy similarity1
Binding sitei88ATPBy similarity1
Binding sitei94ATPBy similarity1
Binding sitei105ATPBy similarity1
Binding sitei115ATPBy similarity1
Active sitei118Pros-phosphohistidine intermediateBy similarity1

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • deoxyribonuclease activity Source: Ensembl
  • enzyme binding Source: RGD
  • gamma-tubulin binding Source: RGD
  • GTP binding Source: Ensembl
  • identical protein binding Source: Ensembl
  • intermediate filament binding Source: RGD
  • magnesium ion binding Source: Ensembl
  • nucleoside diphosphate kinase activity Source: RGD
  • protein kinase binding Source: RGD
  • ribosomal small subunit binding Source: Ensembl
  • RNA binding Source: Ensembl
  • RNA polymerase II regulatory region sequence-specific DNA binding Source: RGD
  • single-stranded DNA binding Source: RGD

GO - Biological processi

  • cellular response to drug Source: RGD
  • cellular response to fatty acid Source: RGD
  • cellular response to glucose stimulus Source: RGD
  • CTP biosynthetic process Source: InterPro
  • endocytosis Source: UniProtKB-KW
  • GTP biosynthetic process Source: InterPro
  • hippocampus development Source: RGD
  • negative regulation of gene expression Source: RGD
  • negative regulation of myeloid leukocyte differentiation Source: RGD
  • nucleoside diphosphate phosphorylation Source: RGD
  • positive regulation of DNA binding Source: Ensembl
  • positive regulation of epithelial cell proliferation Source: Ensembl
  • positive regulation of neuron projection development Source: RGD
  • regulation of apoptotic process Source: GO_Central
  • response to amine Source: RGD
  • response to cAMP Source: RGD
  • response to drug Source: RGD
  • response to testosterone Source: RGD
  • UTP biosynthetic process Source: InterPro

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-RNO-499943. Interconversion of nucleotide di- and triphosphates.
SABIO-RKiQ05982.

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):
Metastasis inhibition factor NM23
Tumor metastatic process-associated protein
Gene namesi
Name:Nme1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 10

Organism-specific databases

RGDi70497. Nme1.

Subcellular locationi

GO - Cellular componenti

  • centrosome Source: RGD
  • cytosol Source: RGD
  • extracellular exosome Source: Ensembl
  • membrane Source: RGD
  • mitochondrial outer membrane Source: CACAO
  • nucleus Source: UniProtKB-SubCell
  • perinuclear region of cytoplasm Source: RGD
  • ruffle membrane Source: Ensembl

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

This protein is found in reduced amount in tumor cells of high metastatic potential.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00001371162 – 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)By similarity
Modified residuei120PhosphoserineBy similarity1
Modified residuei122PhosphoserineBy similarity1
Modified residuei125PhosphoserineBy similarity1

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ05982.
PRIDEiQ05982.

PTM databases

iPTMnetiQ05982.
PhosphoSitePlusiQ05982.

Expressioni

Gene expression databases

BgeeiENSRNOG00000002693.
GenevisibleiQ05982. RN.

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.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
MEN1O00255-25EBI-1165329,EBI-9869387From a different organism.

GO - Molecular functioni

  • enzyme binding Source: RGD
  • gamma-tubulin binding Source: RGD
  • identical protein binding Source: Ensembl
  • intermediate filament binding Source: RGD
  • protein kinase binding Source: RGD

Protein-protein interaction databases

BioGridi251322. 1 interactor.
IntActiQ05982. 1 interactor.
STRINGi10116.ENSRNOP00000003658.

Structurei

3D structure databases

ProteinModelPortaliQ05982.
SMRiQ05982.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the NDK family.Curated

Phylogenomic databases

eggNOGiKOG0888. Eukaryota.
COG0105. LUCA.
GeneTreeiENSGT00760000119146.
HOGENOMiHOG000224564.
HOVERGENiHBG000423.
InParanoidiQ05982.
KOiK00940.
OMAiKIVAMKM.
OrthoDBiEOG091G0PLD.
PhylomeDBiQ05982.
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.
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.

Sequencei

Sequence statusi: Complete.

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

Q05982-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MANSERTFIA IKPDGVQRGL VGEIIKRFEQ KGFRLVGLKF IQASEDLLKE
60 70 80 90 100
HYIDLKDRPF FSGLVKYMHS GPVVAMVWEG LNVVKTGRVM LGETNPADSK
110 120 130 140 150
PGTIRGDFCI QVGRNIIHGS DSVESAEKEI SLWFQPEELV DYKSCAQNWI

YE
Length:152
Mass (Da):17,193
Last modified:February 1, 1994 - v1
Checksum:i32C49E6271195C3B
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D13374 mRNA. Translation: BAA02635.1.
PIRiA45208.
RefSeqiNP_612557.1. NM_138548.2.
XP_017452467.1. XM_017596978.1.
XP_017452468.1. XM_017596979.1.
UniGeneiRn.6236.

Genome annotation databases

EnsembliENSRNOT00000003658; ENSRNOP00000003658; ENSRNOG00000002693.
GeneIDi191575.
KEGGirno:191575.

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.

Entry informationi

Entry nameiNDKA_RAT
AccessioniPrimary (citable) accession number: Q05982
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: February 1, 1994
Last modified: July 5, 2017
This is version 147 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families