Full text data of NME2
NME2
(NM23B)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Nucleoside diphosphate kinase B; NDK B; NDP kinase B; 2.7.4.6 (C-myc purine-binding transcription factor PUF; Histidine protein kinase NDKB; 2.7.13.3; nm23-H2)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Nucleoside diphosphate kinase B; NDK B; NDP kinase B; 2.7.4.6 (C-myc purine-binding transcription factor PUF; Histidine protein kinase NDKB; 2.7.13.3; nm23-H2)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00026260
IPI00026260 Nucleoside diphosphate kinase B Major role in the synthesis of nucleoside triphosphates other than ATP. soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a expected molecular weight found in band at molecular weight
IPI00026260 Nucleoside diphosphate kinase B Major role in the synthesis of nucleoside triphosphates other than ATP. soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a expected molecular weight found in band at molecular weight
UniProt
P22392
ID NDKB_HUMAN Reviewed; 152 AA.
AC P22392; A8MWA3; Q1WM23; Q6LCT6;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-AUG-1991, sequence version 1.
DT 22-JAN-2014, entry version 169.
DE RecName: Full=Nucleoside diphosphate kinase B;
DE Short=NDK B;
DE Short=NDP kinase B;
DE EC=2.7.4.6;
DE AltName: Full=C-myc purine-binding transcription factor PUF;
DE AltName: Full=Histidine protein kinase NDKB;
DE EC=2.7.13.3;
DE AltName: Full=nm23-H2;
GN Name=NME2; Synonyms=NM23B;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=1988104;
RA Stahl J.A., Leone A., Rosengard A.M., Porter L., Liotta L.A.,
RA Steeg P.S., King C.R.;
RT "Identification of a second human nm23 gene, nm23-H2.";
RL Cancer Res. 51:445-449(1991).
RN [2]
RP PROTEIN SEQUENCE (ISOFORM 1), SUBUNIT, AND ACTIVE SITE.
RX PubMed=1851158;
RA Gilles A.-M., Presecan E., Vonica A., Lascu I.;
RT "Nucleoside diphosphate kinase from human erythrocytes. Structural
RT characterization of the two polypeptide chains responsible for
RT heterogeneity of the hexameric enzyme.";
RL J. Biol. Chem. 266:8784-8789(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8392752; DOI=10.1126/science.8392752;
RA Postel E.H., Berberich S.J., Flint S.J., Ferrone C.A.;
RT "Human c-myc transcription factor PuF identified as nm23-H2 nucleoside
RT diphosphate kinase, a candidate suppressor of tumor metastasis.";
RL Science 261:478-480(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Neuroblastoma;
RX PubMed=16442775; DOI=10.1016/j.ygeno.2005.11.004;
RA Valentijn L.J., Koster J., Versteeg R.;
RT "Read-through transcript from NM23-H1 into the neighboring NM23-H2
RT gene encodes a novel protein, NM23-LV.";
RL Genomics 87:483-489(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R.,
RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N.,
RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B.,
RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J.,
RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E.,
RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J.,
RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C.,
RA Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in
RT the human lineage.";
RL Nature 440:1045-1049(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-18.
RX PubMed=7488060; DOI=10.1006/bbrc.1995.2550;
RA Seifert M., Seib T., Engel M., Dooley S., Welter C.;
RT "Characterization of the human nm23-H2 promoter region and
RT localization of the microsatellite D17S396.";
RL Biochem. Biophys. Res. Commun. 215:910-914(1995).
RN [8]
RP INTERACTION WITH ITGB1BP1, AND SUBCELLULAR LOCATION.
RX PubMed=11919189; DOI=10.1074/jbc.M200200200;
RA Fournier H.N., Dupe-Manet S., Bouvard D., Lacombe M.L., Marie C.,
RA Block M.R., Albiges-Rizo C.;
RT "Integrin cytoplasmic domain-associated protein 1alpha (ICAP-1alpha)
RT interacts directly with the metastasis suppressor nm23-H2, and both
RT proteins are targeted to newly formed cell adhesion sites upon
RT integrin engagement.";
RL J. Biol. Chem. 277:20895-20902(2002).
RN [9]
RP FUNCTION, AND INTERACTION WITH AKAP13.
RX PubMed=15249197; DOI=10.1016/j.bbrc.2004.06.067;
RA Iwashita S., Fujii M., Mukai H., Ono Y., Miyamoto M.;
RT "Lbc proto-oncogene product binds to and could be negatively regulated
RT by metastasis suppressor nm23-H2.";
RL Biochem. Biophys. Res. Commun. 320:1063-1068(2004).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-128, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [12]
RP FUNCTION AS HISTIDINE PROTEIN KINASE.
RX PubMed=20946858; DOI=10.1016/S0076-6879(10)71020-X;
RA Wieland T., Hippe H.J., Ludwig K., Zhou X.B., Korth M., Klumpp S.;
RT "Reversible histidine phosphorylation in mammalian cells: a teeter-
RT totter formed by nucleoside diphosphate kinase and protein histidine
RT phosphatase 1.";
RL Methods Enzymol. 471:379-402(2010).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
RX PubMed=7658474; DOI=10.1006/jmbi.1995.0457;
RA Webb P.A., Perisic O., Mendola C.E., Backer J.M., Williams R.L.;
RT "The crystal structure of a human nucleoside diphosphate kinase, NM23-
RT H2.";
RL J. Mol. Biol. 251:574-587(1995).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2 ANGSTROMS).
RX PubMed=8747457; DOI=10.1016/S0969-2126(01)00268-4;
RA Morera S., Lacombe M.-L., Xu Y., Lebras G., Janin J.;
RT "X-ray structure of human nucleoside diphosphate kinase B complexed
RT with GDP at 2-A resolution.";
RL Structure 3:1307-1314(1995).
CC -!- FUNCTION: Major role in the synthesis of nucleoside triphosphates
CC other than ATP. Negatively regulates Rho activity by interacting
CC with AKAP13/LBC. Acts as a transcriptional activator of the MYC
CC gene; binds DNA non-specifically (PubMed:8392752). Exhibits
CC histidine protein kinase activity.
CC -!- CATALYTIC ACTIVITY: ATP + nucleoside diphosphate = ADP +
CC nucleoside triphosphate.
CC -!- CATALYTIC ACTIVITY: ATP + protein L-histidine = ADP + protein N-
CC phospho-L-histidine.
CC -!- COFACTOR: Magnesium (By similarity).
CC -!- SUBUNIT: Hexamer of two different chains: A and B (A6, A5B, A4B2,
CC A3B3, A2B4, AB5, B6). Interacts with CAPN8 (By similarity).
CC Interacts with AKAP13. Interacts ITGB1BP1 (via C-terminus domain
CC region).
CC -!- INTERACTION:
CC O14713-1:ITGB1BP1; NbExp=7; IntAct=EBI-713693, EBI-2127367;
CC P15531:NME1; NbExp=2; IntAct=EBI-713693, EBI-741141;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Cell projection,
CC lamellipodium. Cell projection, ruffle. Note=Isoform 2 is mainly
CC cytoplasmic and isoform 1 and isoform 2 are excluded from the
CC nucleolus. Colocalizes with ITGB1 and ITGB1BP1 at the edge or
CC peripheral ruffles and lamellipodia during the early stages of
CC cell spreading on fibronectin or collagen but not on vitronectin
CC or laminin substrates.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=NM23-H2;
CC IsoId=P22392-1; Sequence=Displayed;
CC Name=3; Synonyms=NM23-LV;
CC IsoId=P22392-2; Sequence=VSP_036708;
CC Note=Based on a naturally occurring readthrough transcript which
CC produces an NME1-NME2 fusion protein. Initiator Met-1 is
CC removed. Contains a N-acetylalanine at position 2;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC -!- SIMILARITY: Belongs to the NDK family.
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DR EMBL; X58965; CAB37870.1; -; mRNA.
DR EMBL; M36981; AAA36369.1; -; mRNA.
DR EMBL; L16785; AAA60228.1; -; mRNA.
DR EMBL; DQ109675; AAZ82097.1; -; mRNA.
DR EMBL; AC005839; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC002476; AAH02476.1; -; mRNA.
DR EMBL; BC133029; AAI33030.1; -; mRNA.
DR EMBL; BC133031; AAI33032.1; -; mRNA.
DR EMBL; U29200; AAA86745.1; -; Genomic_DNA.
DR PIR; A49798; A49798.
DR RefSeq; NP_001018146.1; NM_001018136.2.
DR RefSeq; NP_001018147.1; NM_001018137.2.
DR RefSeq; NP_001018148.1; NM_001018138.1.
DR RefSeq; NP_001018149.1; NM_001018139.2.
DR RefSeq; NP_002503.1; NM_002512.3.
DR UniGene; Hs.463456; -.
DR PDB; 1NSK; X-ray; 2.80 A; L/N/O/R/T/U=1-152.
DR PDB; 1NUE; X-ray; 2.00 A; A/B/C/D/E/F=2-152.
DR PDB; 3BBB; X-ray; 1.30 A; A/B/C/D/E/F=2-152.
DR PDB; 3BBC; X-ray; 1.70 A; A/B/C/D/E/F=2-152.
DR PDB; 3BBF; X-ray; 1.70 A; A/B/C/D/E/F=2-152.
DR PDBsum; 1NSK; -.
DR PDBsum; 1NUE; -.
DR PDBsum; 3BBB; -.
DR PDBsum; 3BBC; -.
DR PDBsum; 3BBF; -.
DR ProteinModelPortal; P22392; -.
DR SMR; P22392; 2-152.
DR IntAct; P22392; 17.
DR MINT; MINT-1429922; -.
DR STRING; 9606.ENSP00000376886; -.
DR ChEMBL; CHEMBL2160; -.
DR PhosphoSite; P22392; -.
DR DMDM; 127983; -.
DR DOSAC-COBS-2DPAGE; P22392; -.
DR OGP; P22392; -.
DR UCD-2DPAGE; P22392; -.
DR PRIDE; P22392; -.
DR DNASU; 4831; -.
DR DNASU; 654364; -.
DR Ensembl; ENST00000393193; ENSP00000376889; ENSG00000011052.
DR Ensembl; ENST00000393198; ENSP00000376894; ENSG00000011052.
DR GeneID; 4831; -.
DR GeneID; 654364; -.
DR KEGG; hsa:4831; -.
DR KEGG; hsa:654364; -.
DR UCSC; uc002itl.3; human.
DR CTD; 4831; -.
DR CTD; 654364; -.
DR GeneCards; GC17P049242; -.
DR HGNC; HGNC:7850; NME2.
DR HPA; CAB002169; -.
DR HPA; CAB040571; -.
DR HPA; HPA008467; -.
DR HPA; HPA041113; -.
DR MIM; 156491; gene.
DR neXtProt; NX_P22392; -.
DR PharmGKB; PA162398077; -.
DR HOGENOM; HOG000224564; -.
DR HOVERGEN; HBG000423; -.
DR InParanoid; P22392; -.
DR KO; K00940; -.
DR OrthoDB; EOG7GJ6FG; -.
DR PhylomeDB; P22392; -.
DR BioCyc; MetaCyc:HS04463-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR SignaLink; P22392; -.
DR ChiTaRS; NME2; human.
DR EvolutionaryTrace; P22392; -.
DR GeneWiki; NME1-NME2; -.
DR GeneWiki; NME2; -.
DR NextBio; 18612; -.
DR PRO; PR:P22392; -.
DR ArrayExpress; P22392; -.
DR Bgee; P22392; -.
DR Genevestigator; P22392; -.
DR GO; GO:0071944; C:cell periphery; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030027; C:lamellipodium; IDA:HGNC.
DR GO; GO:0005634; C:nucleus; NAS:UniProtKB.
DR GO; GO:0001726; C:ruffle; IDA:HGNC.
DR GO; GO:0005524; F:ATP binding; NAS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004550; F:nucleoside diphosphate kinase activity; IDA:UniProtKB.
DR GO; GO:0004673; F:protein histidine kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0003700; F:sequence-specific DNA binding transcription factor activity; TAS:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; TAS:HGNC.
DR GO; GO:0006241; P:CTP biosynthetic process; IEA:InterPro.
DR GO; GO:0006183; P:GTP biosynthetic process; IEA:InterPro.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; IDA:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:HGNC.
DR GO; GO:0015949; P:nucleobase-containing small molecule interconversion; TAS:Reactome.
DR GO; GO:0009142; P:nucleoside triphosphate biosynthetic process; IDA:UniProtKB.
DR GO; GO:0018106; P:peptidyl-histidine phosphorylation; IEA:GOC.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IMP:HGNC.
DR GO; GO:0045618; P:positive regulation of keratinocyte differentiation; IMP:HGNC.
DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR GO; GO:0006228; P:UTP biosynthetic process; IEA:InterPro.
DR Gene3D; 3.30.70.141; -; 1.
DR InterPro; IPR001564; Nucleoside_diP_kinase.
DR InterPro; IPR023005; Nucleoside_diP_kinase_AS.
DR Pfam; PF00334; NDK; 1.
DR PRINTS; PR01243; NUCDPKINASE.
DR SMART; SM00562; NDK; 1.
DR SUPFAM; SSF54919; SSF54919; 1.
DR PROSITE; PS00469; NDP_KINASES; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Activator; Alternative splicing;
KW ATP-binding; Cell projection; Complete proteome; Cytoplasm;
KW Direct protein sequencing; DNA-binding; Kinase; Magnesium;
KW Metal-binding; Nucleotide metabolism; Nucleotide-binding; Nucleus;
KW Reference proteome; Transcription; Transcription regulation;
KW Transferase.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 152 Nucleoside diphosphate kinase B.
FT /FTId=PRO_0000137117.
FT REGION 2 66 Interaction with AKAP13.
FT ACT_SITE 118 118 Pros-phosphohistidine intermediate.
FT BINDING 12 12 ATP.
FT BINDING 60 60 ATP.
FT BINDING 88 88 ATP.
FT BINDING 94 94 ATP.
FT BINDING 105 105 ATP.
FT BINDING 115 115 ATP.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 128 128 N6-acetyllysine.
FT VAR_SEQ 1 1 M -> MANCERTFIAIKPDGVQRGLVGEIIKRFEQKGFRLV
FT GLKFMQASEDLLKEHYVDLKDRPFFAGLVKYMHSGPVVAMV
FT WEGLNVVKTGRVMLGETNPADSKPGTIRGDFCIQVGRTM
FT (in isoform 3).
FT /FTId=VSP_036708.
FT STRAND 6 11
FT HELIX 13 17
FT HELIX 21 31
FT STRAND 34 41
FT HELIX 45 51
FT HELIX 53 55
FT HELIX 61 68
FT STRAND 73 80
FT HELIX 83 91
FT HELIX 96 98
FT HELIX 104 108
FT HELIX 112 114
FT STRAND 117 119
FT HELIX 123 133
FT HELIX 136 138
FT HELIX 147 150
SQ SEQUENCE 152 AA; 17298 MW; 1A5C3F84D7AD272C CRC64;
MANLERTFIA IKPDGVQRGL VGEIIKRFEQ KGFRLVAMKF LRASEEHLKQ HYIDLKDRPF
FPGLVKYMNS GPVVAMVWEG LNVVKTGRVM LGETNPADSK PGTIRGDFCI QVGRNIIHGS
DSVKSAEKEI SLWFKPEELV DYKSCAHDWV YE
//
ID NDKB_HUMAN Reviewed; 152 AA.
AC P22392; A8MWA3; Q1WM23; Q6LCT6;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-AUG-1991, sequence version 1.
DT 22-JAN-2014, entry version 169.
DE RecName: Full=Nucleoside diphosphate kinase B;
DE Short=NDK B;
DE Short=NDP kinase B;
DE EC=2.7.4.6;
DE AltName: Full=C-myc purine-binding transcription factor PUF;
DE AltName: Full=Histidine protein kinase NDKB;
DE EC=2.7.13.3;
DE AltName: Full=nm23-H2;
GN Name=NME2; Synonyms=NM23B;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=1988104;
RA Stahl J.A., Leone A., Rosengard A.M., Porter L., Liotta L.A.,
RA Steeg P.S., King C.R.;
RT "Identification of a second human nm23 gene, nm23-H2.";
RL Cancer Res. 51:445-449(1991).
RN [2]
RP PROTEIN SEQUENCE (ISOFORM 1), SUBUNIT, AND ACTIVE SITE.
RX PubMed=1851158;
RA Gilles A.-M., Presecan E., Vonica A., Lascu I.;
RT "Nucleoside diphosphate kinase from human erythrocytes. Structural
RT characterization of the two polypeptide chains responsible for
RT heterogeneity of the hexameric enzyme.";
RL J. Biol. Chem. 266:8784-8789(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8392752; DOI=10.1126/science.8392752;
RA Postel E.H., Berberich S.J., Flint S.J., Ferrone C.A.;
RT "Human c-myc transcription factor PuF identified as nm23-H2 nucleoside
RT diphosphate kinase, a candidate suppressor of tumor metastasis.";
RL Science 261:478-480(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Neuroblastoma;
RX PubMed=16442775; DOI=10.1016/j.ygeno.2005.11.004;
RA Valentijn L.J., Koster J., Versteeg R.;
RT "Read-through transcript from NM23-H1 into the neighboring NM23-H2
RT gene encodes a novel protein, NM23-LV.";
RL Genomics 87:483-489(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R.,
RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N.,
RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B.,
RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J.,
RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E.,
RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J.,
RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C.,
RA Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in
RT the human lineage.";
RL Nature 440:1045-1049(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-18.
RX PubMed=7488060; DOI=10.1006/bbrc.1995.2550;
RA Seifert M., Seib T., Engel M., Dooley S., Welter C.;
RT "Characterization of the human nm23-H2 promoter region and
RT localization of the microsatellite D17S396.";
RL Biochem. Biophys. Res. Commun. 215:910-914(1995).
RN [8]
RP INTERACTION WITH ITGB1BP1, AND SUBCELLULAR LOCATION.
RX PubMed=11919189; DOI=10.1074/jbc.M200200200;
RA Fournier H.N., Dupe-Manet S., Bouvard D., Lacombe M.L., Marie C.,
RA Block M.R., Albiges-Rizo C.;
RT "Integrin cytoplasmic domain-associated protein 1alpha (ICAP-1alpha)
RT interacts directly with the metastasis suppressor nm23-H2, and both
RT proteins are targeted to newly formed cell adhesion sites upon
RT integrin engagement.";
RL J. Biol. Chem. 277:20895-20902(2002).
RN [9]
RP FUNCTION, AND INTERACTION WITH AKAP13.
RX PubMed=15249197; DOI=10.1016/j.bbrc.2004.06.067;
RA Iwashita S., Fujii M., Mukai H., Ono Y., Miyamoto M.;
RT "Lbc proto-oncogene product binds to and could be negatively regulated
RT by metastasis suppressor nm23-H2.";
RL Biochem. Biophys. Res. Commun. 320:1063-1068(2004).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-128, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [12]
RP FUNCTION AS HISTIDINE PROTEIN KINASE.
RX PubMed=20946858; DOI=10.1016/S0076-6879(10)71020-X;
RA Wieland T., Hippe H.J., Ludwig K., Zhou X.B., Korth M., Klumpp S.;
RT "Reversible histidine phosphorylation in mammalian cells: a teeter-
RT totter formed by nucleoside diphosphate kinase and protein histidine
RT phosphatase 1.";
RL Methods Enzymol. 471:379-402(2010).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
RX PubMed=7658474; DOI=10.1006/jmbi.1995.0457;
RA Webb P.A., Perisic O., Mendola C.E., Backer J.M., Williams R.L.;
RT "The crystal structure of a human nucleoside diphosphate kinase, NM23-
RT H2.";
RL J. Mol. Biol. 251:574-587(1995).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2 ANGSTROMS).
RX PubMed=8747457; DOI=10.1016/S0969-2126(01)00268-4;
RA Morera S., Lacombe M.-L., Xu Y., Lebras G., Janin J.;
RT "X-ray structure of human nucleoside diphosphate kinase B complexed
RT with GDP at 2-A resolution.";
RL Structure 3:1307-1314(1995).
CC -!- FUNCTION: Major role in the synthesis of nucleoside triphosphates
CC other than ATP. Negatively regulates Rho activity by interacting
CC with AKAP13/LBC. Acts as a transcriptional activator of the MYC
CC gene; binds DNA non-specifically (PubMed:8392752). Exhibits
CC histidine protein kinase activity.
CC -!- CATALYTIC ACTIVITY: ATP + nucleoside diphosphate = ADP +
CC nucleoside triphosphate.
CC -!- CATALYTIC ACTIVITY: ATP + protein L-histidine = ADP + protein N-
CC phospho-L-histidine.
CC -!- COFACTOR: Magnesium (By similarity).
CC -!- SUBUNIT: Hexamer of two different chains: A and B (A6, A5B, A4B2,
CC A3B3, A2B4, AB5, B6). Interacts with CAPN8 (By similarity).
CC Interacts with AKAP13. Interacts ITGB1BP1 (via C-terminus domain
CC region).
CC -!- INTERACTION:
CC O14713-1:ITGB1BP1; NbExp=7; IntAct=EBI-713693, EBI-2127367;
CC P15531:NME1; NbExp=2; IntAct=EBI-713693, EBI-741141;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Cell projection,
CC lamellipodium. Cell projection, ruffle. Note=Isoform 2 is mainly
CC cytoplasmic and isoform 1 and isoform 2 are excluded from the
CC nucleolus. Colocalizes with ITGB1 and ITGB1BP1 at the edge or
CC peripheral ruffles and lamellipodia during the early stages of
CC cell spreading on fibronectin or collagen but not on vitronectin
CC or laminin substrates.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=NM23-H2;
CC IsoId=P22392-1; Sequence=Displayed;
CC Name=3; Synonyms=NM23-LV;
CC IsoId=P22392-2; Sequence=VSP_036708;
CC Note=Based on a naturally occurring readthrough transcript which
CC produces an NME1-NME2 fusion protein. Initiator Met-1 is
CC removed. Contains a N-acetylalanine at position 2;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC -!- SIMILARITY: Belongs to the NDK family.
CC -----------------------------------------------------------------------
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DR EMBL; X58965; CAB37870.1; -; mRNA.
DR EMBL; M36981; AAA36369.1; -; mRNA.
DR EMBL; L16785; AAA60228.1; -; mRNA.
DR EMBL; DQ109675; AAZ82097.1; -; mRNA.
DR EMBL; AC005839; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC002476; AAH02476.1; -; mRNA.
DR EMBL; BC133029; AAI33030.1; -; mRNA.
DR EMBL; BC133031; AAI33032.1; -; mRNA.
DR EMBL; U29200; AAA86745.1; -; Genomic_DNA.
DR PIR; A49798; A49798.
DR RefSeq; NP_001018146.1; NM_001018136.2.
DR RefSeq; NP_001018147.1; NM_001018137.2.
DR RefSeq; NP_001018148.1; NM_001018138.1.
DR RefSeq; NP_001018149.1; NM_001018139.2.
DR RefSeq; NP_002503.1; NM_002512.3.
DR UniGene; Hs.463456; -.
DR PDB; 1NSK; X-ray; 2.80 A; L/N/O/R/T/U=1-152.
DR PDB; 1NUE; X-ray; 2.00 A; A/B/C/D/E/F=2-152.
DR PDB; 3BBB; X-ray; 1.30 A; A/B/C/D/E/F=2-152.
DR PDB; 3BBC; X-ray; 1.70 A; A/B/C/D/E/F=2-152.
DR PDB; 3BBF; X-ray; 1.70 A; A/B/C/D/E/F=2-152.
DR PDBsum; 1NSK; -.
DR PDBsum; 1NUE; -.
DR PDBsum; 3BBB; -.
DR PDBsum; 3BBC; -.
DR PDBsum; 3BBF; -.
DR ProteinModelPortal; P22392; -.
DR SMR; P22392; 2-152.
DR IntAct; P22392; 17.
DR MINT; MINT-1429922; -.
DR STRING; 9606.ENSP00000376886; -.
DR ChEMBL; CHEMBL2160; -.
DR PhosphoSite; P22392; -.
DR DMDM; 127983; -.
DR DOSAC-COBS-2DPAGE; P22392; -.
DR OGP; P22392; -.
DR UCD-2DPAGE; P22392; -.
DR PRIDE; P22392; -.
DR DNASU; 4831; -.
DR DNASU; 654364; -.
DR Ensembl; ENST00000393193; ENSP00000376889; ENSG00000011052.
DR Ensembl; ENST00000393198; ENSP00000376894; ENSG00000011052.
DR GeneID; 4831; -.
DR GeneID; 654364; -.
DR KEGG; hsa:4831; -.
DR KEGG; hsa:654364; -.
DR UCSC; uc002itl.3; human.
DR CTD; 4831; -.
DR CTD; 654364; -.
DR GeneCards; GC17P049242; -.
DR HGNC; HGNC:7850; NME2.
DR HPA; CAB002169; -.
DR HPA; CAB040571; -.
DR HPA; HPA008467; -.
DR HPA; HPA041113; -.
DR MIM; 156491; gene.
DR neXtProt; NX_P22392; -.
DR PharmGKB; PA162398077; -.
DR HOGENOM; HOG000224564; -.
DR HOVERGEN; HBG000423; -.
DR InParanoid; P22392; -.
DR KO; K00940; -.
DR OrthoDB; EOG7GJ6FG; -.
DR PhylomeDB; P22392; -.
DR BioCyc; MetaCyc:HS04463-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR SignaLink; P22392; -.
DR ChiTaRS; NME2; human.
DR EvolutionaryTrace; P22392; -.
DR GeneWiki; NME1-NME2; -.
DR GeneWiki; NME2; -.
DR NextBio; 18612; -.
DR PRO; PR:P22392; -.
DR ArrayExpress; P22392; -.
DR Bgee; P22392; -.
DR Genevestigator; P22392; -.
DR GO; GO:0071944; C:cell periphery; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030027; C:lamellipodium; IDA:HGNC.
DR GO; GO:0005634; C:nucleus; NAS:UniProtKB.
DR GO; GO:0001726; C:ruffle; IDA:HGNC.
DR GO; GO:0005524; F:ATP binding; NAS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004550; F:nucleoside diphosphate kinase activity; IDA:UniProtKB.
DR GO; GO:0004673; F:protein histidine kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0003700; F:sequence-specific DNA binding transcription factor activity; TAS:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; TAS:HGNC.
DR GO; GO:0006241; P:CTP biosynthetic process; IEA:InterPro.
DR GO; GO:0006183; P:GTP biosynthetic process; IEA:InterPro.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; IDA:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:HGNC.
DR GO; GO:0015949; P:nucleobase-containing small molecule interconversion; TAS:Reactome.
DR GO; GO:0009142; P:nucleoside triphosphate biosynthetic process; IDA:UniProtKB.
DR GO; GO:0018106; P:peptidyl-histidine phosphorylation; IEA:GOC.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IMP:HGNC.
DR GO; GO:0045618; P:positive regulation of keratinocyte differentiation; IMP:HGNC.
DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR GO; GO:0006228; P:UTP biosynthetic process; IEA:InterPro.
DR Gene3D; 3.30.70.141; -; 1.
DR InterPro; IPR001564; Nucleoside_diP_kinase.
DR InterPro; IPR023005; Nucleoside_diP_kinase_AS.
DR Pfam; PF00334; NDK; 1.
DR PRINTS; PR01243; NUCDPKINASE.
DR SMART; SM00562; NDK; 1.
DR SUPFAM; SSF54919; SSF54919; 1.
DR PROSITE; PS00469; NDP_KINASES; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Activator; Alternative splicing;
KW ATP-binding; Cell projection; Complete proteome; Cytoplasm;
KW Direct protein sequencing; DNA-binding; Kinase; Magnesium;
KW Metal-binding; Nucleotide metabolism; Nucleotide-binding; Nucleus;
KW Reference proteome; Transcription; Transcription regulation;
KW Transferase.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 152 Nucleoside diphosphate kinase B.
FT /FTId=PRO_0000137117.
FT REGION 2 66 Interaction with AKAP13.
FT ACT_SITE 118 118 Pros-phosphohistidine intermediate.
FT BINDING 12 12 ATP.
FT BINDING 60 60 ATP.
FT BINDING 88 88 ATP.
FT BINDING 94 94 ATP.
FT BINDING 105 105 ATP.
FT BINDING 115 115 ATP.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 128 128 N6-acetyllysine.
FT VAR_SEQ 1 1 M -> MANCERTFIAIKPDGVQRGLVGEIIKRFEQKGFRLV
FT GLKFMQASEDLLKEHYVDLKDRPFFAGLVKYMHSGPVVAMV
FT WEGLNVVKTGRVMLGETNPADSKPGTIRGDFCIQVGRTM
FT (in isoform 3).
FT /FTId=VSP_036708.
FT STRAND 6 11
FT HELIX 13 17
FT HELIX 21 31
FT STRAND 34 41
FT HELIX 45 51
FT HELIX 53 55
FT HELIX 61 68
FT STRAND 73 80
FT HELIX 83 91
FT HELIX 96 98
FT HELIX 104 108
FT HELIX 112 114
FT STRAND 117 119
FT HELIX 123 133
FT HELIX 136 138
FT HELIX 147 150
SQ SEQUENCE 152 AA; 17298 MW; 1A5C3F84D7AD272C CRC64;
MANLERTFIA IKPDGVQRGL VGEIIKRFEQ KGFRLVAMKF LRASEEHLKQ HYIDLKDRPF
FPGLVKYMNS GPVVAMVWEG LNVVKTGRVM LGETNPADSK PGTIRGDFCI QVGRNIIHGS
DSVKSAEKEI SLWFKPEELV DYKSCAHDWV YE
//
MIM
156491
*RECORD*
*FIELD* NO
156491
*FIELD* TI
*156491 NONMETASTATIC CELLS 2, PROTEIN EXPRESSED IN; NME2
;;METASTASIS INHIBITION FACTOR NM23B;;
read moreNONMETASTATIC PROTEIN 23B; NM23B;;
NONMETASTATIC PROTEIN 23, HOMOLOG 2; NM23H2;;
NUCLEOSIDE DIPHOSPHATE KINASE-B; NDPKB
*FIELD* TX
CLONING
NM23 is a heterodimeric protein that acts as a nucleoside diphosphate
(NDP) kinase. Gilles et al. (1991) identified NME1 (156490) and NME2 as
the A and B polypeptide chains of the NM23 enzyme. Each chain consists
of 152 amino acids. NME2 is identical to the beta subunit of human
erythrocyte NDP kinase. NDP kinases are involved in the synthesis of
nucleoside triphosphates, and the NM23 protein may act in the regulation
of signal transduction by complexing with G proteins, causing
activation/inactivation of developmental pathways (Gilles et al., 1991).
Stahl et al. (1991) identified the NME2 gene, which they referred to as
nm23-H2. Its cDNA predicts a 17-kD protein with 88% identity to nm23-H1.
The nm23-H1 gene also shares a significant homology with nucleoside
diphosphate kinases and the Drosophila developmental gene awd. Northern
blot hybridization indicated that the expression of the nm23-H1 gene is
reduced to a lesser extent in tumor cells of high metastatic potential
than is nm23-H1. Both proteins are independently active nucleoside
diphosphate kinases and readily form intra- and intermolecular disulfide
bonds.
Using Northern blot analysis, Masse et al. (2002) detected high
expression of mouse Nme2, which they called nm23-M2, in heart, liver,
and kidney, with intermediate expression in skeletal muscle. Little to
no expression was detected in other mouse tissues examined. In situ
hybridization of 15-day postcoitum mouse embryos showed ubiquitous Nme2
expression.
By EST database analysis, Valentijn et al. (2006) identified a
transcript that starts from the NM23H1 promoter and reads through the
neighboring NM23H2 gene. This transcript, which they called NM23LV (NM23
long variant), is ubiquitously expressed and encodes a protein with most
of the NM23H1 amino acids and all of the NM23H2 amino acids. See 156490
for further information on the NM23LV read-through transcript.
GENE FUNCTION
Srivastava et al. (2006) demonstrated that the 14 C-terminal amino acids
of KCa3.1 (KCNN4; 602754) that mediate the regulation of KCa3.1 by
phosphatidylinositol 3-phosphate (PI(3)P) recruit NDPKB to KCa3.1. NDPKB
then activates KCa3.1 by phosphorylating residue H358, which is present
in the same C-terminal 14-amino acid region. SiRNA treatment of NDPBK in
CD4+ T cells resulted in a marked reduction of KCa3.1 channel activity.
Srivastava et al. (2006) concluded that histidine phosphorylation
regulates KCa3.1 channel activity and that NDPBK is critical to the
channel activity and the activation of CD4 T cells.
GENE STRUCTURE
Masse et al. (2002) determined that the mouse and human NME2 genes
contain 5 exons and span about 6.0 kb. Their promoters, like those of
other NME genes, contain several binding sites for AP2 (107580), NF1
(613113), Sp1 (189906), LEF1 (153245), and response elements to
glucocorticoid receptors (138040). There are no TATA or CAAT boxes or
pyrimidine-rich initiator (Inr) sequences.
MAPPING
In the course of in situ hybridization mapping of NME1, Leone et al.
(1991) demonstrated a cross-hybridizing sequence on chromosome 16. This,
however, cannot be NME2 because Backer et al. (1993) assigned both NME1
and NME2 to 17q21.3 by somatic cell hybrid analysis and fluorescence in
situ hybridization. By analyzing DNA from rodent/human somatic cell
hybrid lines and hybrid cell lines containing portions of chromosome 17
with a combination of PCR amplification and Southern hybridization,
Kelsell et al. (1993) mapped NME2 to 17q21-q22. By isolating and
characterizing 5 YACs and 3 cosmid clones that contained both the NME1
and NME2 genes, Chandrasekharappa et al. (1993) demonstrated that the
NME2 gene is separated from the NME1 gene by no more than 18 kb. The 2
putative tumor suppressor genes may have arisen by a tandem duplication.
Since NME1 has been excluded as the site of the type I breast cancer
gene (BRCA1; 113705), the close situation of NME2 to NME1 probably
excludes NME2 also.
*FIELD* RF
1. Backer, J. M.; Mendola, C. E.; Kovesdi, I.; Fairhurst, J. L.; O'Hara,
B.; Eddy, R. L., Jr.; Shows, T. B.; Mathew, S.; Murty, V. V. V. S.;
Chaganti, R. S. K.: Chromosomal localization and nucleoside diphosphate
kinase activity of human metastasis-suppressor genes NM23-1 and NM23-2. Oncogene 8:
497-502, 1993.
2. Chandrasekharappa, S. C.; Gross, L. A.; King, S. E.; Collins, F.
S.: The human NME2 gene lies within 18kb of NME1 in chromosome 17. Genes
Chromosomes Cancer 6: 245-248, 1993.
3. Gilles, A. M.; Presecan, E.; Vonica, A.; Lascu, I.: Nucleoside
diphosphate kinase from human erythrocytes: structural characterization
of the two polypeptide chains responsible for heterogeneity of the
hexameric enzyme. J. Biol. Chem. 266: 8784-8789, 1991.
4. Kelsell, D. P.; Black, D. M.; Solomon, E.; Spurr, N. K.: Localization
of a second NM23 gene, NME2, to chromosome 17q21-q22. Genomics 17:
522-524, 1993.
5. Leone, A.; McBride, O. W.; Weston, A.; Wang, M. G.; Anglard, P.;
Cropp, C. S.; Goepel, J. R.; Lidereau, R.; Callahan, R.; Marston Linehan,
W.; Rees, R. C.; Harris, C. C.; Liotta, L. A.; Steeg, P. S.: Somatic
allelic deletion of nm23 in human cancer. Cancer Res. 51: 2490-2493,
1991.
6. Masse, K.; Dabernat, S.; Bourbon, P.-M.; Larou, M.; Amrein, L.;
Barraud, P.; Perel, Y.; Camara, M.; Landry, M.; Lacombe, M.-L.; Daniel,
J.-Y.: Characterization of the nm23-M2, nm23-M3 and nm23-M4 mouse
genes: comparison with their human homologs. Gene 296: 87-97, 2002.
7. Srivastava, S.; Li, Z.; Ko, K.; Choudhury, P.; Albaqumi, M.; Johnson,
A. K.; Yan, Y.; Backer, J. M.; Unutmaz, D.; Coetzee, W. A.; Skolnik,
E. Y.: Histidine phosphorylation of the potassium channel KCa3.1
by nucleoside diphosphate kinase B is required for activation of KCa3.1
and CD4 T cells. Molec. Cell 24: 665-675, 2006.
8. Stahl, J. A.; Leone, A.; Rosengard, A. M.; Porter, L.; King, C.
R.; Steeg, P. S.: Identification of a second human nm23 gene, nm23-H2. Cancer
Res. 51: 445-449, 1991.
9. Valentijn, L. J.; Koster, J.; Versteeg, R.: Read-through transcript
from NM23-H1 into the neighboring NM23-H2 gene encodes a novel protein,
NM23-LV. Genomics 87: 483-489, 2006.
*FIELD* CN
Paul J. Converse - updated: 1/24/2007
Patricia A. Hartz - updated: 6/2/2006
Patricia A. Hartz - updated: 3/22/2004
*FIELD* CD
Victor A. McKusick: 4/10/1991
*FIELD* ED
carol: 11/23/2009
alopez: 1/24/2007
mgross: 6/8/2006
terry: 6/2/2006
mgross: 3/30/2004
terry: 3/22/2004
alopez: 2/23/1999
dkim: 7/24/1998
alopez: 6/2/1997
mark: 5/20/1997
terry: 5/12/1994
carol: 3/24/1994
carol: 8/25/1993
carol: 4/27/1993
supermim: 3/16/1992
carol: 3/2/1992
*RECORD*
*FIELD* NO
156491
*FIELD* TI
*156491 NONMETASTATIC CELLS 2, PROTEIN EXPRESSED IN; NME2
;;METASTASIS INHIBITION FACTOR NM23B;;
read moreNONMETASTATIC PROTEIN 23B; NM23B;;
NONMETASTATIC PROTEIN 23, HOMOLOG 2; NM23H2;;
NUCLEOSIDE DIPHOSPHATE KINASE-B; NDPKB
*FIELD* TX
CLONING
NM23 is a heterodimeric protein that acts as a nucleoside diphosphate
(NDP) kinase. Gilles et al. (1991) identified NME1 (156490) and NME2 as
the A and B polypeptide chains of the NM23 enzyme. Each chain consists
of 152 amino acids. NME2 is identical to the beta subunit of human
erythrocyte NDP kinase. NDP kinases are involved in the synthesis of
nucleoside triphosphates, and the NM23 protein may act in the regulation
of signal transduction by complexing with G proteins, causing
activation/inactivation of developmental pathways (Gilles et al., 1991).
Stahl et al. (1991) identified the NME2 gene, which they referred to as
nm23-H2. Its cDNA predicts a 17-kD protein with 88% identity to nm23-H1.
The nm23-H1 gene also shares a significant homology with nucleoside
diphosphate kinases and the Drosophila developmental gene awd. Northern
blot hybridization indicated that the expression of the nm23-H1 gene is
reduced to a lesser extent in tumor cells of high metastatic potential
than is nm23-H1. Both proteins are independently active nucleoside
diphosphate kinases and readily form intra- and intermolecular disulfide
bonds.
Using Northern blot analysis, Masse et al. (2002) detected high
expression of mouse Nme2, which they called nm23-M2, in heart, liver,
and kidney, with intermediate expression in skeletal muscle. Little to
no expression was detected in other mouse tissues examined. In situ
hybridization of 15-day postcoitum mouse embryos showed ubiquitous Nme2
expression.
By EST database analysis, Valentijn et al. (2006) identified a
transcript that starts from the NM23H1 promoter and reads through the
neighboring NM23H2 gene. This transcript, which they called NM23LV (NM23
long variant), is ubiquitously expressed and encodes a protein with most
of the NM23H1 amino acids and all of the NM23H2 amino acids. See 156490
for further information on the NM23LV read-through transcript.
GENE FUNCTION
Srivastava et al. (2006) demonstrated that the 14 C-terminal amino acids
of KCa3.1 (KCNN4; 602754) that mediate the regulation of KCa3.1 by
phosphatidylinositol 3-phosphate (PI(3)P) recruit NDPKB to KCa3.1. NDPKB
then activates KCa3.1 by phosphorylating residue H358, which is present
in the same C-terminal 14-amino acid region. SiRNA treatment of NDPBK in
CD4+ T cells resulted in a marked reduction of KCa3.1 channel activity.
Srivastava et al. (2006) concluded that histidine phosphorylation
regulates KCa3.1 channel activity and that NDPBK is critical to the
channel activity and the activation of CD4 T cells.
GENE STRUCTURE
Masse et al. (2002) determined that the mouse and human NME2 genes
contain 5 exons and span about 6.0 kb. Their promoters, like those of
other NME genes, contain several binding sites for AP2 (107580), NF1
(613113), Sp1 (189906), LEF1 (153245), and response elements to
glucocorticoid receptors (138040). There are no TATA or CAAT boxes or
pyrimidine-rich initiator (Inr) sequences.
MAPPING
In the course of in situ hybridization mapping of NME1, Leone et al.
(1991) demonstrated a cross-hybridizing sequence on chromosome 16. This,
however, cannot be NME2 because Backer et al. (1993) assigned both NME1
and NME2 to 17q21.3 by somatic cell hybrid analysis and fluorescence in
situ hybridization. By analyzing DNA from rodent/human somatic cell
hybrid lines and hybrid cell lines containing portions of chromosome 17
with a combination of PCR amplification and Southern hybridization,
Kelsell et al. (1993) mapped NME2 to 17q21-q22. By isolating and
characterizing 5 YACs and 3 cosmid clones that contained both the NME1
and NME2 genes, Chandrasekharappa et al. (1993) demonstrated that the
NME2 gene is separated from the NME1 gene by no more than 18 kb. The 2
putative tumor suppressor genes may have arisen by a tandem duplication.
Since NME1 has been excluded as the site of the type I breast cancer
gene (BRCA1; 113705), the close situation of NME2 to NME1 probably
excludes NME2 also.
*FIELD* RF
1. Backer, J. M.; Mendola, C. E.; Kovesdi, I.; Fairhurst, J. L.; O'Hara,
B.; Eddy, R. L., Jr.; Shows, T. B.; Mathew, S.; Murty, V. V. V. S.;
Chaganti, R. S. K.: Chromosomal localization and nucleoside diphosphate
kinase activity of human metastasis-suppressor genes NM23-1 and NM23-2. Oncogene 8:
497-502, 1993.
2. Chandrasekharappa, S. C.; Gross, L. A.; King, S. E.; Collins, F.
S.: The human NME2 gene lies within 18kb of NME1 in chromosome 17. Genes
Chromosomes Cancer 6: 245-248, 1993.
3. Gilles, A. M.; Presecan, E.; Vonica, A.; Lascu, I.: Nucleoside
diphosphate kinase from human erythrocytes: structural characterization
of the two polypeptide chains responsible for heterogeneity of the
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*FIELD* CN
Paul J. Converse - updated: 1/24/2007
Patricia A. Hartz - updated: 6/2/2006
Patricia A. Hartz - updated: 3/22/2004
*FIELD* CD
Victor A. McKusick: 4/10/1991
*FIELD* ED
carol: 11/23/2009
alopez: 1/24/2007
mgross: 6/8/2006
terry: 6/2/2006
mgross: 3/30/2004
terry: 3/22/2004
alopez: 2/23/1999
dkim: 7/24/1998
alopez: 6/2/1997
mark: 5/20/1997
terry: 5/12/1994
carol: 3/24/1994
carol: 8/25/1993
carol: 4/27/1993
supermim: 3/16/1992
carol: 3/2/1992