Reviewed, UniProtKB/Swiss-Prot P22392 (NDKB_HUMAN)

Names and origin

Protein names

Recommended name:
    Nucleoside diphosphate kinase B
      Short name=NDP kinase B
      Short name=NDK B
    EC=2.7.4.6
Alternative name(s):
    nm23-H2
    C-myc purine-binding transcription factor PUF

Gene names

Name:	NME2
Synonyms:	NM23B

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	152 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
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 c-Myc gene; binds DNA non-specifically (Ref.3). Ref.8
Catalytic activity	ATP + nucleoside diphosphate = ADP + nucleoside triphosphate.
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.8 Ref.2
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
Post-translational modification	The N-terminus is blocked.
Involvement in disease	This protein is found in reduced amount in tumor cells of high metastatic potential.
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
Disease	Tumor suppressor
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
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. Source: HGNC negative regulation of apoptosis Inferred from mutant phenotype. Source: HGNC negative regulation of cell proliferation Traceable author statement. Source: UniProtKB positive regulation of epithelial cell proliferation Inferred from mutant phenotype. Source: HGNC positive regulation of keratinocyte differentiation Inferred from mutant phenotype. Source: HGNC regulation of transcription, DNA-dependent Ref.3 Traceable author statement. Source: UniProtKB transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell lamellipodium Inferred from direct assay. Source: HGNC nucleus Non-traceable author statement. Source: UniProtKB ruffle Inferred from direct assay. Source: HGNC
Molecular function	ATP binding Non-traceable author statement. Source: UniProtKB magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW nucleoside diphosphate kinase activity Traceable author statement. Source: UniProtKB protein binding Inferred from physical interaction. Source: UniProtKB transcription factor activity Ref.3 Traceable author statement. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
	P01616	1	EBI-713693,EBI-1053880
	Q65ZQ1	1	EBI-713693,EBI-1054063
ACLY	P53396	1	EBI-713693,EBI-1042794
ATIC	P31939	1	EBI-713693,EBI-1048599
DYNC1H1	Q14204	1	EBI-713693,EBI-356015
EPPK1	P58107	1	EBI-713693,EBI-297954
HIST1H2BC	P62807	1	EBI-713693,EBI-354552
HTR1B	P28222	1	EBI-713693,EBI-1056863
ITGB1BP1	O14713-1	3	EBI-713693,EBI-2127367
KIF5B	P33176	1	EBI-713693,EBI-355878
LYZ	P61626	1	EBI-713693,EBI-355360
NME1	P15531	1	EBI-713693,EBI-741141
PDIA6	Q15084	1	EBI-713693,EBI-1043087
POLR2H	P52434	1	EBI-713693,EBI-359505
PPP1R7	Q15435	1	EBI-713693,EBI-1024281
PPP1R8	Q12972	1	EBI-713693,EBI-716633
PSMA2	P25787	1	EBI-713693,EBI-603262
PSMA7	O14818	1	EBI-713693,EBI-603272
RPL38	P63173	1	EBI-713693,EBI-359141
RUVBL2	Q9Y230	1	EBI-713693,EBI-352939
STIP1	P31948	1	EBI-713693,EBI-1054052
YA61	Q9NZ23	1	EBI-713693,EBI-1047727

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

Initiator methionine

1

1

Removed

Chain

2 – 152

151

Nucleoside diphosphate kinase B

PRO_0000137117

Regions

Region

2 – 66

65

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

2

1

N-acetylalanine Ref.10

Modified residue

12

1

N6-acetyllysine Ref.12

Modified residue

49

1

N6-acetyllysine Ref.12

Modified residue

52

1

Phosphotyrosine Ref.11

Modified residue

56

1

N6-acetyllysine Ref.12

Modified residue

85

1

N6-acetyllysine Ref.12

Modified residue

94

1

Phosphothreonine By similarity

Modified residue

100

1

N6-acetyllysine Ref.12

Modified residue

124

1

N6-acetyllysine Ref.12

Modified residue

128

1

N6-acetyllysine Ref.12

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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.

.

.

.

.

.

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.

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.

.

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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 – 69

9

Beta strand

73 – 79

7

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). 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: 1988104] [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: 1851158] [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: 8392752] [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: 16442775] [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: 16625196] [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: 15489334] [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: 7488060] [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: 15249197] [Abstract] Cited for: FUNCTION, INTERACTION WITH AKAP13.
[9]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[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: 19413330] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY.
[11]	"An extensive survey of tyrosine phosphorylation revealing new sites in human mammary epithelial cells." Heibeck T.H., Ding S.-J., Opresko L.K., Zhao R., Schepmoes A.A., Yang F., Tolmachev A.V., Monroe M.E., Camp D.G. II, Smith R.D., Wiley H.S., Qian W.-J. J. Proteome Res. 8:3852-3861(2009) [PubMed: 19534553] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-52, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[12]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-12; LYS-49; LYS-56; LYS-85; LYS-100; LYS-124 AND LYS-128, MASS SPECTROMETRY.
[13]	"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: 7658474] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
[14]	"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: 8747457] [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.
NP_001018147.1.
NP_001018148.1.
NP_001018149.1.
NP_002503.1.

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	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P22392. 55 interactions.

STRING

P22392.

PTM databases

PhosphoSite

P22392.

2-D gel databases

DOSAC-COBS-2DPAGE

P22392.

OGP

P22392.

Proteomic databases

PRIDE

P22392.

Genome annotation databases

Ensembl

ENST00000376392; ENSP00000365572; ENSG00000011052; Homo sapiens. [Genome view]
ENST00000393183; ENSP00000376880; ENSG00000011052; Homo sapiens. [Genome view]
ENST00000393190; ENSP00000376886; ENSG00000243678; Homo sapiens. [Genome view]
ENST00000393191; ENSP00000376887; ENSG00000243678; Homo sapiens. [Genome view]
ENST00000393192; ENSP00000376888; ENSG00000243678; Homo sapiens. [Genome view]
ENST00000393193; ENSP00000376889; ENSG00000243678; Homo sapiens. [Genome view]
ENST00000393194; ENSP00000376890; ENSG00000243678; Homo sapiens. [Genome view]
ENST00000393198; ENSP00000376894; ENSG00000011052; Homo sapiens. [Genome view]
ENST00000393199; ENSP00000376895; ENSG00000011052; Homo sapiens. [Genome view]

GeneID

4831.
654364.

KEGG

hsa:4831.
hsa:654364.

UCSC

uc002itl.1. human.

Organism-specific databases

CTD

4831.
654364.

GeneCards

GC17P046586.
GC17P046598.

H-InvDB

HIX0013992.
HIX0036862.

HGNC

HGNC:7850. NME2.

HPA

CAB002169.

MIM

156491. gene.

PharmGKB

PA250.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P22392.

InParanoid

P22392.

PhylomeDB

P22392.

Enzyme and pathway databases

BioCyc

MetaCyc:ENSG00000121054-MONOMER.

BRENDA

2.7.4.6. 247.

Reactome

REACT_1698. Metabolism of nucleotides.

Gene expression databases

ArrayExpress

P22392.

Bgee

P22392.

Genevestigator

P22392.

GermOnline

ENSG00000011052. Homo sapiens.

Family and domain databases

InterPro

IPR001564. Nuc_diP_kinase_core.
[Graphical view]

Gene3D

G3DSA:3.30.70.141. NDK. 1 hit.

PANTHER

PTHR11349. Nuc_diP_kinase_core. 1 hit.

Pfam

PF00334. NDK. 1 hit.
[Graphical view]

PRINTS

PR01243. NUCDPKINASE.

SMART

SM00562. NDK. 1 hit.
[Graphical view]

PROSITE

PS00469. NDP_KINASES. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

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:	February 9, 2010
This is version 125 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.