P22392 (NDKB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	152 AA.
Sequence status	Complete.
Protein existence	Evidence 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.8 Ref.10
Catalytic activity	ATP + nucleoside diphosphate = ADP + nucleoside triphosphate. ATP + protein L-histidine = ADP + protein N-phospho-L-histidine.
Cofactor	Magnesium By similarity.
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. Ref.2 Ref.8
Subcellular location	Cytoplasm. Nucleus. Note: Isoform 2 is mainly cytoplasmic and isoform 1 and isoform 2 are excluded from the nucleolus. Ref.4
Tissue specificity	Ubiquitously expressed. Ref.4
Sequence similarities	Belongs to the NDK family.

Ontologies

Keywords
Biological process	Nucleotide metabolism Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding DNA-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Activator Kinase Transferase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	CTP 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 PubMed 11919189. Source: HGNC negative regulation of apoptotic process Inferred from mutant phenotype PubMed 16862176. Source: HGNC nucleobase-containing small molecule interconversion 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 transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytosol Traceable author statement. Source: Reactome lamellipodium Inferred from direct assay PubMed 11919189. Source: HGNC nucleus Non-traceable author statement. Source: UniProtKB ruffle Inferred from direct assay PubMed 11919189. Source: HGNC
Molecular_function	ATP binding Non-traceable author statement. Source: UniProtKB 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 histidine kinase activity Inferred from electronic annotation. Source: 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
ITGB1BP1	O14713-1	7	EBI-713693,EBI-2127367
NME1	P15531	2	EBI-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.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 152

152

Nucleoside diphosphate kinase B

PRO_0000137117

Regions

Region

1 – 66

66

Interaction with AKAP13

Sites

Active site

118

1

Pros-phosphohistidine intermediate Ref.2

Binding site

12

1

ATP

Binding site

60

1

ATP

Binding site

88

1

ATP

Binding site

94

1

ATP

Binding site

105

1

ATP

Binding site

115

1

ATP

Amino acid modifications

Modified residue

94

1

Phosphothreonine By similarity

Modified residue

128

1

N6-acetyllysine Ref.9

Natural variations

Alternative sequence

1

1

M → MANCERTFIAIKPDGVQRGL VGEIIKRFEQKGFRLVGLKF MQASEDLLKEHYVDLKDRPF FAGLVKYMHSGPVVAMVWEG LNVVKTGRVMLGETNPADSK PGTIRGDFCIQVGRTM in isoform 3.

VSP_036708

Secondary structure

1

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152

Helix Strand Turn

Details...

Beta strand

6 – 11

6

Helix

13 – 17

5

Helix

21 – 31

11

Beta strand

34 – 41

8

Helix

45 – 51

7

Helix

53 – 55

3

Helix

61 – 68

8

Beta strand

73 – 80

8

Helix

83 – 91

9

Helix

96 – 98

3

Helix

104 – 108

5

Helix

112 – 114

3

Beta strand

117 – 119

3

Helix

123 – 133

11

Helix

136 – 138

3

Helix

147 – 150

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (NM23-H2) [UniParc]. Last modified August 1, 1991. Version 1. Checksum: 1A5C3F84D7AD272C	FASTA	152	17,298
	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
	Isoform 3 (NM23-LV) [UniParc]. Checksum: 3AB02272AF24AAC3	FASTA	267	30,137
	10 20 30 40 50 60 MANCERTFIA IKPDGVQRGL VGEIIKRFEQ KGFRLVGLKF MQASEDLLKE HYVDLKDRPF 70 80 90 100 110 120 FAGLVKYMHS GPVVAMVWEG LNVVKTGRVM LGETNPADSK PGTIRGDFCI QVGRTMANLE 130 140 150 160 170 180 RTFIAIKPDG VQRGLVGEII KRFEQKGFRL VAMKFLRASE EHLKQHYIDL KDRPFFPGLV 190 200 210 220 230 240 KYMNSGPVVA MVWEGLNVVK TGRVMLGETN PADSKPGTIR GDFCIQVGRN IIHGSDSVKS 250 260 AEKEISLWFK PEELVDYKSC AHDWVYE

References

	« Hide 'large scale' referencesShow '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. , 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]	"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.
[9]	"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, MASS SPECTROMETRY.
[10]	"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.
[11]	"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].
[12]	"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).
[13]	"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.

IPI

IPI00026260.
IPI00795292.

PIR

A49798.

RefSeq

NP_001018146.1. NM_001018136.2.
NP_001018147.1. NM_001018137.2.
NP_001018148.1. NM_001018138.1.
NP_001018149.1. NM_001018139.2.
NP_002503.1. NM_002512.3.

UniGene

Hs.463456.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1NSK	X-ray	2.80	L/N/O/R/T/U	1-152	[»]
1NUE	X-ray	2.00	A/B/C/D/E/F	2-152	[»]
3BBB	X-ray	1.30	A/B/C/D/E/F	2-152	[»]
3BBC	X-ray	1.70	A/B/C/D/E/F	2-152	[»]
3BBF	X-ray	1.70	A/B/C/D/E/F	2-152	[»]

ProteinModelPortal

P22392.

ModBase

Search...

Protein-protein interaction databases

IntAct

P22392. 13 interactions.

MINT

MINT-1429922.

STRING

9606.ENSP00000376886.

PTM databases

PhosphoSite

P22392.

Polymorphism databases

DMDM

127983.

2D gel databases

DOSAC-COBS-2DPAGE

P22392.

OGP

P22392.

UCD-2DPAGE

P22392.

Proteomic databases

PRIDE

P22392.

Protocols and materials databases

DNASU

4831.
654364.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000393193; ENSP00000376889; ENSG00000011052.
ENST00000393198; ENSP00000376894; ENSG00000011052.

GeneID

4831.
654364.

KEGG

hsa:4831.
hsa:654364.

UCSC

uc002itj.3. human.
uc002itl.3. human.

Organism-specific databases

CTD

4831.
654364.

GeneCards

GC17P049230.
GC17P049242.

HGNC

HGNC:7850. NME2.

HPA

CAB002169.
CAB040571.
HPA008467.
HPA041113.

MIM

156491. gene.

neXtProt

NX_P22392.

PharmGKB

PA162398077.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

HOG000224564.

HOVERGEN

HBG000423.

InParanoid

P22392.

KO

K00940.

OrthoDB

EOG4S1T8G.

PhylomeDB

P22392.

Enzyme and pathway databases

BioCyc

MetaCyc:HS04463-MONOMER.

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

P22392.

Bgee

P22392.

Genevestigator

P22392.

GermOnline

ENSG00000011052. Homo sapiens.

Family and domain databases

Gene3D

3.30.70.141. 1 hit.

InterPro

IPR001564. Nucleoside_diP_kinase.
IPR023005. Nucleoside_diP_kinase_AS.
[Graphical view]

PANTHER

PTHR11349. PTHR11349. 1 hit.

Pfam

PF00334. NDK. 1 hit.
[Graphical view]

PRINTS

PR01243. NUCDPKINASE.

SMART

SM00562. NDK. 1 hit.
[Graphical view]

SUPFAM

SSF54919. NDK. 1 hit.

PROSITE

PS00469. NDP_KINASES. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL2160.

ChiTaRS

NME2. human.

EvolutionaryTrace

P22392.

NextBio

18612.

SOURCE

Search...

Entry information

Entry name

NDKB_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 162 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.