NDKA_DROME
ID NDKA_DROME Reviewed; 153 AA.
AC P08879; Q9V9U5;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 203.
DE RecName: Full=Nucleoside diphosphate kinase;
DE Short=NDK;
DE Short=NDP kinase;
DE EC=2.7.4.6;
DE AltName: Full=Abnormal wing disks protein;
DE AltName: Full=Killer of prune protein;
GN Name=awd; Synonyms=K-pn; ORFNames=CG2210;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=2849580; DOI=10.1101/gad.2.10.1333;
RA Biggs J., Tripoulas N., Hersperger E., Dearolf C., Shearn A.;
RT "Analysis of the lethal interaction between the prune and Killer of prune
RT mutations of Drosophila.";
RL Genes Dev. 2:1333-1343(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Head;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [5]
RP PROTEIN SEQUENCE OF 3-15; 33-35; 47-96 AND 147-153, MASS SPECTROMETRY,
RP BLOCKAGE OF N-TERMINUS, AND ACETYLATION AT ALA-2.
RX PubMed=12099695; DOI=10.1016/s0006-291x(02)00737-4;
RA Stenberg L.M., Stenflo J., Holmgren P., Brown M.A.;
RT "Post-translational processing of Drosophila nucleoside diphosphate
RT kinase.";
RL Biochem. Biophys. Res. Commun. 295:689-694(2002).
RN [6]
RP PROTEIN SEQUENCE OF 90-106.
RC STRAIN=Vallecas; TISSUE=Wing imaginal disk;
RX PubMed=8500545; DOI=10.1006/excr.1993.1141;
RA Santaren J.F., van Damme J., Puype M., Vandekerckhove J.,
RA Garcia-Bellido A.;
RT "Identification of Drosophila wing imaginal disc proteins by two-
RT dimensional gel analysis and microsequencing.";
RL Exp. Cell Res. 206:220-226(1993).
RN [7]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=2175255; DOI=10.1016/0092-8674(90)90496-2;
RA Biggs J., Hersperger E., Steeg P.S., Liotta L.A., Shearn A.;
RT "A Drosophila gene that is homologous to a mammalian gene associated with
RT tumor metastasis codes for a nucleoside diphosphate kinase.";
RL Cell 63:933-940(1990).
RN [8]
RP CATALYTIC ACTIVITY, SUBUNIT, AND MUTAGENESIS OF PRO-97.
RC STRAIN=Canton-S;
RX PubMed=1320004; DOI=10.1016/s0021-9258(18)42343-5;
RA Lascu I., Chaffotte A., Limbourg-Bouchon B., Veron M.;
RT "A Pro/Ser substitution in nucleoside diphosphate kinase of Drosophila
RT melanogaster (mutation killer of prune) affects stability but not catalytic
RT efficiency of the enzyme.";
RL J. Biol. Chem. 267:12775-12781(1992).
RN [9]
RP FUNCTION, AND MUTAGENESIS OF ASP-15; ARG-89; ARG-106; ASP-122 AND GLU-130.
RX PubMed=7559441; DOI=10.1074/jbc.270.39.23021;
RA Timmons L., Xu J., Hersperger G., Deng X.F., Shearn A.;
RT "Point mutations in awdKpn which revert the prune/Killer of prune lethal
RT interaction affect conserved residues that are involved in nucleoside
RT diphosphate kinase substrate binding and catalysis.";
RL J. Biol. Chem. 270:23021-23030(1995).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-126, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RC TISSUE=Embryo;
RX PubMed=18327897; DOI=10.1021/pr700696a;
RA Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL J. Proteome Res. 7:1675-1682(2008).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
RX PubMed=8081741; DOI=10.1016/0969-2126(93)90016-a;
RA Chiadmi M., Morera S., Lascu I., Dumas C., le Bras G., Veron M., Janin J.;
RT "Crystal structure of the Awd nucleotide diphosphate kinase from
RT Drosophila.";
RL Structure 1:283-293(1993).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS), AND COFACTOR.
RX PubMed=7669763; DOI=10.1021/bi00035a011;
RA Morera S., Chiadmi M., Lebras G., Lascu I., Janin J.;
RT "Mechanism of phosphate transfer by nucleoside diphosphate kinase: X-ray
RT structures of the phosphohistidine intermediate of the enzymes from
RT Drosophila and Dictyostelium.";
RL Biochemistry 34:11062-11070(1995).
CC -!- FUNCTION: Major role in the synthesis of nucleoside triphosphates other
CC than ATP. The ATP gamma phosphate is transferred to the NDP beta
CC phosphate via a ping-pong mechanism, using a phosphorylated active-site
CC intermediate. {ECO:0000269|PubMed:2175255, ECO:0000269|PubMed:2849580,
CC ECO:0000269|PubMed:7559441}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 2'-deoxyribonucleoside 5'-diphosphate + ATP = a 2'-
CC deoxyribonucleoside 5'-triphosphate + ADP; Xref=Rhea:RHEA:44640,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61560, ChEBI:CHEBI:73316,
CC ChEBI:CHEBI:456216; EC=2.7.4.6;
CC Evidence={ECO:0000269|PubMed:1320004};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a ribonucleoside 5'-diphosphate + ATP = a ribonucleoside 5'-
CC triphosphate + ADP; Xref=Rhea:RHEA:18113, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:57930, ChEBI:CHEBI:61557, ChEBI:CHEBI:456216; EC=2.7.4.6;
CC Evidence={ECO:0000269|PubMed:1320004};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:7669763};
CC -!- SUBUNIT: Homohexamer. {ECO:0000269|PubMed:1320004}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:2175255}.
CC Cytoplasm, cytoskeleton {ECO:0000269|PubMed:2175255}. Note=Microtubule-
CC associated.
CC -!- MASS SPECTROMETRY: Mass=17082.3; Mass_error=0.6; Method=Electrospray;
CC Note=Acetylated.; Evidence={ECO:0000269|PubMed:12099695};
CC -!- MISCELLANEOUS: Mutations cause abnormal tissue morphology and necrosis
CC and widespread aberrant differentiation.
CC -!- SIMILARITY: Belongs to the NDK family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF57188.3; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; X13107; CAA31500.1; -; mRNA.
DR EMBL; AE014297; AAF57188.3; ALT_INIT; Genomic_DNA.
DR EMBL; AY113576; AAM29581.1; -; mRNA.
DR PIR; S01908; S01908.
DR RefSeq; NP_001287624.1; NM_001300695.1.
DR RefSeq; NP_001287625.1; NM_001300696.1.
DR RefSeq; NP_476761.3; NM_057413.4.
DR PDB; 1NDL; X-ray; 2.40 A; A/B/C=1-153.
DR PDB; 1NSQ; X-ray; 2.18 A; A/B/C=1-153.
DR PDB; 3WX8; X-ray; 1.95 A; A/B/C=1-153.
DR PDBsum; 1NDL; -.
DR PDBsum; 1NSQ; -.
DR PDBsum; 3WX8; -.
DR AlphaFoldDB; P08879; -.
DR SMR; P08879; -.
DR BioGRID; 68580; 117.
DR DIP; DIP-20572N; -.
DR IntAct; P08879; 5.
DR STRING; 7227.FBpp0085223; -.
DR iPTMnet; P08879; -.
DR PaxDb; P08879; -.
DR PRIDE; P08879; -.
DR DNASU; 43739; -.
DR EnsemblMetazoa; FBtr0346611; FBpp0312191; FBgn0000150.
DR GeneID; 43739; -.
DR KEGG; dme:Dmel_CG2210; -.
DR CTD; 43739; -.
DR FlyBase; FBgn0000150; awd.
DR VEuPathDB; VectorBase:FBgn0000150; -.
DR eggNOG; KOG0888; Eukaryota.
DR GeneTree; ENSGT00940000164818; -.
DR HOGENOM; CLU_060216_6_3_1; -.
DR InParanoid; P08879; -.
DR OrthoDB; 1334716at2759; -.
DR PhylomeDB; P08879; -.
DR BRENDA; 2.7.4.6; 1994.
DR Reactome; R-DME-499943; Interconversion of nucleotide di- and triphosphates.
DR Reactome; R-DME-6798695; Neutrophil degranulation.
DR Reactome; R-DME-9748787; Azathioprine ADME.
DR BioGRID-ORCS; 43739; 2 hits in 3 CRISPR screens.
DR ChiTaRS; awd; fly.
DR EvolutionaryTrace; P08879; -.
DR GenomeRNAi; 43739; -.
DR PRO; PR:P08879; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0000150; Expressed in egg cell and 45 other tissues.
DR ExpressionAtlas; P08879; baseline and differential.
DR Genevisible; P08879; DM.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005874; C:microtubule; IDA:FlyBase.
DR GO; GO:0005880; C:nuclear microtubule; IMP:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; HDA:FlyBase.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IDA:FlyBase.
DR GO; GO:0016301; F:kinase activity; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0008017; F:microtubule binding; IDA:FlyBase.
DR GO; GO:0004550; F:nucleoside diphosphate kinase activity; IDA:UniProtKB.
DR GO; GO:0034332; P:adherens junction organization; IMP:FlyBase.
DR GO; GO:0006241; P:CTP biosynthetic process; TAS:UniProtKB.
DR GO; GO:0007427; P:epithelial cell migration, open tracheal system; IMP:FlyBase.
DR GO; GO:0016334; P:establishment or maintenance of polarity of follicular epithelium; IMP:FlyBase.
DR GO; GO:0006183; P:GTP biosynthetic process; TAS:UniProtKB.
DR GO; GO:0007017; P:microtubule-based process; IMP:FlyBase.
DR GO; GO:0000278; P:mitotic cell cycle; IMP:FlyBase.
DR GO; GO:0006165; P:nucleoside diphosphate phosphorylation; IMP:FlyBase.
DR GO; GO:0009117; P:nucleotide metabolic process; TAS:UniProtKB.
DR GO; GO:0007424; P:open tracheal system development; IMP:FlyBase.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:FlyBase.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:FlyBase.
DR GO; GO:0006468; P:protein phosphorylation; IDA:FlyBase.
DR GO; GO:0035152; P:regulation of tube architecture, open tracheal system; IMP:FlyBase.
DR GO; GO:0006228; P:UTP biosynthetic process; TAS:UniProtKB.
DR Gene3D; 3.30.70.141; -; 1.
DR HAMAP; MF_00451; NDP_kinase; 1.
DR InterPro; IPR034907; NDK-like_dom.
DR InterPro; IPR036850; NDK-like_dom_sf.
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; ATP-binding; Cytoplasm; Cytoskeleton;
KW Direct protein sequencing; Kinase; Magnesium; Metal-binding; Microtubule;
KW Nucleotide metabolism; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:12099695"
FT CHAIN 2..153
FT /note="Nucleoside diphosphate kinase"
FT /id="PRO_0000137108"
FT ACT_SITE 119
FT /note="Pros-phosphohistidine intermediate"
FT BINDING 13
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 61
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 89
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 95
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 106
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 116
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|PubMed:12099695"
FT MOD_RES 126
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MUTAGEN 15
FT /note="D->N: In KRm5; lethal due to loss of phosphorylated
FT active site intermediate; when associated with S-97."
FT /evidence="ECO:0000269|PubMed:7559441"
FT MUTAGEN 89
FT /note="R->C: In KRn3; lethal due to loss of phosphorylated
FT active site intermediate; when associated with S-97."
FT /evidence="ECO:0000269|PubMed:7559441"
FT MUTAGEN 97
FT /note="P->S: Killer of prune mutation. Conditionally
FT dominant lethal mutation in individuals with a null
FT mutation in the prune gene."
FT /evidence="ECO:0000269|PubMed:1320004"
FT MUTAGEN 106
FT /note="R->C: In KRm7; lethal due to loss of phosphorylated
FT active site intermediate; when associated with S-97."
FT /evidence="ECO:0000269|PubMed:7559441"
FT MUTAGEN 122
FT /note="D->N: In KRm12; lethal due to lower enzyme activity;
FT when associated with S-97."
FT /evidence="ECO:0000269|PubMed:7559441"
FT MUTAGEN 127
FT /note="A->T: In KRm9; lower enzyme activity; when
FT associated with S-97."
FT MUTAGEN 130
FT /note="E->K: In KRm4; lethal due to loss of catalytic
FT activity; when associated with S-97."
FT /evidence="ECO:0000269|PubMed:7559441"
FT HELIX 3..5
FT /evidence="ECO:0007829|PDB:3WX8"
FT STRAND 7..12
FT /evidence="ECO:0007829|PDB:3WX8"
FT HELIX 14..18
FT /evidence="ECO:0007829|PDB:3WX8"
FT HELIX 22..32
FT /evidence="ECO:0007829|PDB:3WX8"
FT STRAND 35..39
FT /evidence="ECO:0007829|PDB:3WX8"
FT HELIX 46..52
FT /evidence="ECO:0007829|PDB:3WX8"
FT HELIX 54..56
FT /evidence="ECO:0007829|PDB:3WX8"
FT HELIX 62..69
FT /evidence="ECO:0007829|PDB:3WX8"
FT STRAND 74..81
FT /evidence="ECO:0007829|PDB:3WX8"
FT HELIX 84..92
FT /evidence="ECO:0007829|PDB:3WX8"
FT HELIX 97..99
FT /evidence="ECO:0007829|PDB:3WX8"
FT HELIX 105..109
FT /evidence="ECO:0007829|PDB:3WX8"
FT HELIX 113..115
FT /evidence="ECO:0007829|PDB:3WX8"
FT STRAND 118..120
FT /evidence="ECO:0007829|PDB:3WX8"
FT HELIX 124..134
FT /evidence="ECO:0007829|PDB:3WX8"
FT HELIX 137..139
FT /evidence="ECO:0007829|PDB:3WX8"
FT HELIX 148..151
FT /evidence="ECO:0007829|PDB:3WX8"
SQ SEQUENCE 153 AA; 17170 MW; E98765853255445E CRC64;
MAANKERTFI MVKPDGVQRG LVGKIIERFE QKGFKLVALK FTWASKELLE KHYADLSARP
FFPGLVNYMN SGPVVPMVWE GLNVVKTGRQ MLGATNPADS LPGTIRGDFC IQVGRNIIHG
SDAVESAEKE IALWFNEKEL VTWTPAAKDW IYE
