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 02-SEP-2026, entry version 219. 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; Altocrustacea; Allotriocarida; OC Hexapoda; Insecta; Pterygota; Neoptera; Eumetabola; Endopterygota; OC Aparaglossata; Panorpida; 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 AlphaFoldDB; P08879; -. DR MDposit; P08879; -. DR SMR; P08879; -. DR BioGRID; 68580; 120. DR DIP; DIP-20572N; -. DR FunCoup; P08879; 1472. DR IntAct; P08879; 189. DR STRING; 7227.FBpp0311978; -. DR iPTMnet; P08879; -. DR PaxDb; 7227-FBpp0311978; -. DR PeptideAtlas; P08879; -. DR DNASU; 43739; -. DR EnsemblMetazoa; FBtr0346611; FBpp0312191; FBgn0000150. DR GeneID; 43739; -. DR KEGG; dme:Dmel_CG2210; -. DR AGR; FB:FBgn0000150; -. DR CTD; 43739; -. DR FlyBase; FBgn0000150; awd. DR VEuPathDB; VectorBase:FBgn0000150; -. DR eggNOG; KOG0888; Eukaryota. DR HOGENOM; CLU_060216_6_3_1; -. DR InParanoid; P08879; -. DR OrthoDB; 2162449at2759; -. 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 Reactome; R-DME-9755088; Ribavirin ADME. DR BioGRID-ORCS; 43739; 2 hits in 3 CRISPR screens. DR EvolutionaryTrace; P08879; -. DR GenomeRNAi; 43739; -. DR PRO; PR:P08879; -. DR Proteomes; UP000000803; Chromosome 3R. DR Bgee; FBgn0000150; Expressed in egg cell and 303 other cell types or tissues. DR ExpressionAtlas; P08879; baseline and differential. DR GO; GO:0005874; C:microtubule; IDA:FlyBase. DR GO; GO:0005739; C:mitochondrion; ISS: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:0009202; P:deoxyribonucleoside triphosphate biosynthetic process; IDA: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:0009142; P:nucleoside triphosphate biosynthetic process; IBA:GO_Central. DR GO; GO:0009117; P:nucleotide metabolic process; TAS:UniProtKB. DR GO; GO:0007424; P:open tracheal system development; IMP:FlyBase. DR GO; GO:0035152; P:regulation of tube architecture, open tracheal system; IMP:FlyBase. DR GO; GO:0009201; P:ribonucleoside triphosphate biosynthetic process; IDA:UniProtKB. DR GO; GO:0006228; P:UTP biosynthetic process; TAS:UniProtKB. DR CDD; cd04413; NDPk_I; 1. DR FunFam; 3.30.70.141:FF:000039; Nucleoside diphosphate kinase B; 1. DR Gene3D; 3.30.70.141; Nucleoside diphosphate kinase-like domain; 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 NCBIfam; NF001908; PRK00668.1; 1. DR PANTHER; PTHR11349; NUCLEOSIDE DIPHOSPHATE KINASE; 1. DR Pfam; PF00334; NDK; 1. DR PRINTS; PR01243; NUCDPKINASE. DR SMART; SM00562; NDK; 1. DR SUPFAM; SSF54919; Nucleoside diphosphate kinase, NDK; 1. DR PROSITE; PS00469; NDPK; 1. DR PROSITE; PS51374; NDPK_LIKE; 1. DR PDBsum; 1NDL; -. DR PDBsum; 1NSQ; -. DR PDBsum; 3WX8; -. 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 //