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P22392 (NDKB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 175. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Nucleoside diphosphate kinase B

Short name=NDK B
Short name=NDP kinase B
EC=2.7.4.6
Alternative name(s):
C-myc purine-binding transcription factor PUF
Histidine protein kinase NDKB
EC=2.7.13.3
nm23-H2
Gene names
Name:NME2
Synonyms:NM23B
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length152 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Major role in the synthesis of nucleoside triphosphates other than ATP. Negatively regulates Rho activity by interacting with AKAP13/LBC. Acts as a transcriptional activator of the MYC gene; binds DNA non-specifically (Ref.3). Exhibits histidine protein kinase activity. Ref.9 Ref.12

Catalytic activity

ATP + nucleoside diphosphate = ADP + nucleoside triphosphate. HAMAP-Rule MF_00451

ATP + protein L-histidine = ADP + protein N-phospho-L-histidine. HAMAP-Rule MF_00451

Cofactor

Magnesium By similarity. HAMAP-Rule MF_00451

Subunit structure

Hexamer of two different chains: A and B (A6, A5B, A4B2, A3B3, A2B4, AB5, B6). Interacts with CAPN8 By similarity. Interacts with AKAP13. Interacts ITGB1BP1 (via C-terminal domain region). Ref.2 Ref.8 Ref.9

Subcellular location

Cytoplasm. Nucleus. Cell projectionlamellipodium. Cell projectionruffle. Note: Isoform 2is mainly cytoplasmic and isoform 1 and isoform 2are excluded from the nucleolus. Colocalizes with ITGB1 and ITGB1BP1 at the edge or peripheral ruffles and lamellipodia during the early stages of cell spreading on fibronectin or collagen but not on vitronectin or laminin substrates. Ref.4 Ref.8

Tissue specificity

Ubiquitously expressed. Ref.4

Sequence similarities

Belongs to the NDK family.

Ontologies

Keywords
   Biological processNucleotide metabolism
Transcription
Transcription regulation
   Cellular componentCell projection
Cytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
   LigandATP-binding
DNA-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionActivator
Kinase
Transferase
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processCTP biosynthetic process

Inferred from electronic annotation. Source: InterPro

GTP biosynthetic process

Inferred from electronic annotation. Source: InterPro

UTP biosynthetic process

Inferred from electronic annotation. Source: InterPro

cell adhesion

Traceable author statement Ref.8. Source: HGNC

integrin-mediated signaling pathway

Inferred from direct assay Ref.8. Source: UniProtKB

negative regulation of apoptotic process

Inferred from mutant phenotype PubMed 16862176. Source: HGNC

nucleobase-containing small molecule interconversion

Traceable author statement. Source: Reactome

nucleobase-containing small molecule metabolic process

Traceable author statement. Source: Reactome

nucleoside triphosphate biosynthetic process

Inferred from direct assay Ref.2. Source: UniProtKB

positive regulation of epithelial cell proliferation

Inferred from mutant phenotype PubMed 16862176. Source: HGNC

positive regulation of keratinocyte differentiation

Inferred from mutant phenotype PubMed 16862176. Source: HGNC

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 15703214. Source: UniProtKB

regulation of epidermis development

Inferred from mutant phenotype PubMed 16862176. Source: HGNC

regulation of transcription, DNA-templated

Traceable author statement Ref.3. Source: UniProtKB

small molecule metabolic process

Traceable author statement. Source: Reactome

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcell periphery

Inferred from direct assay Ref.8. Source: UniProtKB

cytoplasm

Inferred from direct assay PubMed 15703214. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

extracellular vesicular exosome

Inferred from direct assay PubMed 19199708PubMed 20458337. Source: UniProt

lamellipodium

Inferred from direct assay Ref.8. Source: HGNC

nucleus

Inferred from direct assay PubMed 21630459. Source: UniProt

ruffle

Inferred from direct assay Ref.8. Source: HGNC

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

DNA binding

Inferred from electronic annotation. Source: UniProtKB-KW

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

nucleoside diphosphate kinase activity

Inferred from direct assay Ref.2. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.8. Source: UniProtKB

protein histidine kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

sequence-specific DNA binding transcription factor activity

Traceable author statement Ref.3. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

ITGB1BP1O14713-17EBI-713693,EBI-2127367
NME1P155312EBI-713693,EBI-741141

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P22392-1)

Also known as: NM23-H2;

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.
Isoform 3 (identifier: P22392-2)

Also known as: NM23-LV;

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MANCERTFIA...DFCIQVGRTM
Note: Based on a naturally occurring readthrough transcript which produces an NME1-NME2 fusion protein. Initiator Met-1 is removed (By similarity). Contains a N-acetylalanine at position 2 (By similarity).

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.10
Chain2 – 152151Nucleoside diphosphate kinase B HAMAP-Rule MF_00451
PRO_0000137117

Regions

Region2 – 6665Interaction with AKAP13 HAMAP-Rule MF_00451

Sites

Active site1181Pros-phosphohistidine intermediate Ref.2
Binding site121ATP
Binding site601ATP
Binding site881ATP
Binding site941ATP
Binding site1051ATP
Binding site1151ATP

Amino acid modifications

Modified residue21N-acetylalanine Ref.10
Modified residue1281N6-acetyllysine Ref.11

Natural variations

Alternative sequence11M → MANCERTFIAIKPDGVQRGL VGEIIKRFEQKGFRLVGLKF MQASEDLLKEHYVDLKDRPF FAGLVKYMHSGPVVAMVWEG LNVVKTGRVMLGETNPADSK PGTIRGDFCIQVGRTM in isoform 3.
VSP_036708

Secondary structure

................................. 152
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (NM23-H2) [UniParc].

Last modified August 1, 1991. Version 1.
Checksum: 1A5C3F84D7AD272C

FASTA15217,298
        10         20         30         40         50         60 
MANLERTFIA IKPDGVQRGL VGEIIKRFEQ KGFRLVAMKF LRASEEHLKQ HYIDLKDRPF 

        70         80         90        100        110        120 
FPGLVKYMNS GPVVAMVWEG LNVVKTGRVM LGETNPADSK PGTIRGDFCI QVGRNIIHGS 

       130        140        150 
DSVKSAEKEI SLWFKPEELV DYKSCAHDWV YE 

« Hide

Isoform 3 (NM23-LV) [UniParc].

Checksum: 3AB02272AF24AAC3
Show »

FASTA26730,137

References

« Hide 'large scale' references
[1]"Identification of a second human nm23 gene, nm23-H2."
Stahl J.A., Leone A., Rosengard A.M., Porter L., Liotta L.A., Steeg P.S., King C.R.
Cancer Res. 51:445-449(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Nucleoside diphosphate kinase from human erythrocytes. Structural characterization of the two polypeptide chains responsible for heterogeneity of the hexameric enzyme."
Gilles A.-M., Presecan E., Vonica A., Lascu I.
J. Biol. Chem. 266:8784-8789(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE (ISOFORM 1), SUBUNIT, ACTIVE SITE.
[3]"Human c-myc transcription factor PuF identified as nm23-H2 nucleoside diphosphate kinase, a candidate suppressor of tumor metastasis."
Postel E.H., Berberich S.J., Flint S.J., Ferrone C.A.
Science 261:478-480(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]"Read-through transcript from NM23-H1 into the neighboring NM23-H2 gene encodes a novel protein, NM23-LV."
Valentijn L.J., Koster J., Versteeg R.
Genomics 87:483-489(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
Tissue: Neuroblastoma.
[5]"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. expand/collapse author list , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
Tissue: Eye.
[7]"Characterization of the human nm23-H2 promoter region and localization of the microsatellite D17S396."
Seifert M., Seib T., Engel M., Dooley S., Welter C.
Biochem. Biophys. Res. Commun. 215:910-914(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-18.
[8]"Integrin cytoplasmic domain-associated protein 1alpha (ICAP-1alpha) interacts directly with the metastasis suppressor nm23-H2, and both proteins are targeted to newly formed cell adhesion sites upon integrin engagement."
Fournier H.N., Dupe-Manet S., Bouvard D., Lacombe M.L., Marie C., Block M.R., Albiges-Rizo C.
J. Biol. Chem. 277:20895-20902(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ITGB1BP1, SUBCELLULAR LOCATION.
[9]"Lbc proto-oncogene product binds to and could be negatively regulated by metastasis suppressor nm23-H2."
Iwashita S., Fujii M., Mukai H., Ono Y., Miyamoto M.
Biochem. Biophys. Res. Commun. 320:1063-1068(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH AKAP13.
[10]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[11]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-128, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"Reversible histidine phosphorylation in mammalian cells: a teeter-totter formed by nucleoside diphosphate kinase and protein histidine phosphatase 1."
Wieland T., Hippe H.J., Ludwig K., Zhou X.B., Korth M., Klumpp S.
Methods Enzymol. 471:379-402(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS HISTIDINE PROTEIN KINASE.
[13]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]"The crystal structure of a human nucleoside diphosphate kinase, NM23-H2."
Webb P.A., Perisic O., Mendola C.E., Backer J.M., Williams R.L.
J. Mol. Biol. 251:574-587(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
[15]"X-ray structure of human nucleoside diphosphate kinase B complexed with GDP at 2-A resolution."
Morera S., Lacombe M.-L., Xu Y., Lebras G., Janin J.
Structure 3:1307-1314(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2 ANGSTROMS).
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X58965 mRNA. Translation: CAB37870.1.
M36981 mRNA. Translation: AAA36369.1.
L16785 mRNA. Translation: AAA60228.1.
DQ109675 mRNA. Translation: AAZ82097.1.
AC005839 Genomic DNA. No translation available.
BC002476 mRNA. Translation: AAH02476.1.
BC133029 mRNA. Translation: AAI33030.1.
BC133031 mRNA. Translation: AAI33032.1.
U29200 Genomic DNA. Translation: AAA86745.1.
CCDSCCDS11580.1. [P22392-1]
PIRA49798.
RefSeqNP_001018146.1. NM_001018136.2. [P22392-2]
NP_001018147.1. NM_001018137.2. [P22392-1]
NP_001018148.1. NM_001018138.1. [P22392-1]
NP_001018149.1. NM_001018139.2. [P22392-1]
NP_002503.1. NM_002512.3. [P22392-1]
UniGeneHs.463456.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1NSKX-ray2.80L/N/O/R/T/U1-152[»]
1NUEX-ray2.00A/B/C/D/E/F2-152[»]
3BBBX-ray1.30A/B/C/D/E/F2-152[»]
3BBCX-ray1.70A/B/C/D/E/F2-152[»]
3BBFX-ray1.70A/B/C/D/E/F2-152[»]
ProteinModelPortalP22392.
SMRP22392. Positions 2-152.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110895. 41 interactions.
576341. 8 interactions.
IntActP22392. 17 interactions.
MINTMINT-1429922.
STRING9606.ENSP00000376886.

Chemistry

ChEMBLCHEMBL2160.

PTM databases

PhosphoSiteP22392.

Polymorphism databases

DMDM127983.

2D gel databases

DOSAC-COBS-2DPAGEP22392.
OGPP22392.
UCD-2DPAGEP22392.

Proteomic databases

MaxQBP22392.
PRIDEP22392.

Protocols and materials databases

DNASU4831.
654364.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000393193; ENSP00000376889; ENSG00000011052. [P22392-2]
GeneID4831.
654364.
KEGGhsa:4831.
hsa:654364.
UCSCuc002itj.3. human. [P22392-2]
uc002itl.3. human. [P22392-1]

Organism-specific databases

CTD4831.
654364.
GeneCardsGC17P049242.
HGNCHGNC:7850. NME2.
HPACAB002169.
CAB040571.
HPA008467.
HPA041113.
MIM156491. gene.
neXtProtNX_P22392.
PharmGKBPA162398077.
GenAtlasSearch...

Phylogenomic databases

HOGENOMHOG000224564.
HOVERGENHBG000423.
InParanoidP22392.
KOK00940.
OrthoDBEOG7GJ6FG.
PhylomeDBP22392.
TreeFamTF106373.

Enzyme and pathway databases

BioCycMetaCyc:HS04463-MONOMER.
ReactomeREACT_111217. Metabolism.
SignaLinkP22392.

Gene expression databases

BgeeP22392.
GenevestigatorP22392.

Family and domain databases

Gene3D3.30.70.141. 1 hit.
HAMAPMF_00451. NDP_kinase.
InterProIPR001564. Nucleoside_diP_kinase.
IPR023005. Nucleoside_diP_kinase_AS.
[Graphical view]
PfamPF00334. NDK. 1 hit.
[Graphical view]
PRINTSPR01243. NUCDPKINASE.
SMARTSM00562. NDK. 1 hit.
[Graphical view]
SUPFAMSSF54919. SSF54919. 1 hit.
PROSITEPS00469. NDP_KINASES. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSNME2. human.
EvolutionaryTraceP22392.
GeneWikiNME1-NME2.
NME2.
NextBio18612.
PROP22392.
SOURCESearch...

Entry information

Entry nameNDKB_HUMAN
AccessionPrimary (citable) accession number: P22392
Secondary accession number(s): A8MWA3, Q1WM23, Q6LCT6
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: August 1, 1991
Last modified: July 9, 2014
This is version 175 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM