NADE_DROME
ID NADE_DROME Reviewed; 787 AA.
AC Q9VYA0; A4V4E7; Q8IH17;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Glutamine-dependent NAD(+) synthetase;
DE EC=6.3.5.1 {ECO:0000250|UniProtKB:Q6IA69};
DE AltName: Full=NAD(+) synthase [glutamine-hydrolyzing];
GN Name=Nadsyn {ECO:0000312|FlyBase:FBgn0030512};
GN ORFNames=CG9940 {ECO:0000312|FlyBase:FBgn0030512};
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 [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 [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Embryo;
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 [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-703, 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 [5]
RP FUNCTION.
RX PubMed=27448710; DOI=10.1016/j.exger.2016.07.006;
RA Wen D.T., Zheng L., Ni L., Wang H., Feng Y., Zhang M.;
RT "The expression of CG9940 affects the adaptation of cardiac function,
RT mobility, and lifespan to exercise in aging Drosophila.";
RL Exp. Gerontol. 83:6-14(2016).
CC -!- FUNCTION: Catalyzes the ATP-dependent amidation of deamido-NAD to form
CC NAD. Uses L-glutamine as a nitrogen source (By similarity). Because of
CC its role in energy metabolism, involved in the modulation of aged-
CC related cardiac function, mobility, and lifespan (PubMed:27448710).
CC {ECO:0000250|UniProtKB:Q6IA69, ECO:0000269|PubMed:27448710}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + deamido-NAD(+) + H2O + L-glutamine = AMP + diphosphate +
CC H(+) + L-glutamate + NAD(+); Xref=Rhea:RHEA:24384, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29985, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57540, ChEBI:CHEBI:58359,
CC ChEBI:CHEBI:58437, ChEBI:CHEBI:456215; EC=6.3.5.1;
CC Evidence={ECO:0000250|UniProtKB:Q6IA69};
CC -!- PATHWAY: Cofactor biosynthesis; NAD(+) biosynthesis; NAD(+) from
CC deamido-NAD(+) (L-Gln route): step 1/1. {ECO:0000250|UniProtKB:Q6IA69}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the NAD synthetase
CC family. {ECO:0000305}.
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DR EMBL; AE014298; AAF48303.1; -; Genomic_DNA.
DR EMBL; AE014298; AAN09333.1; -; Genomic_DNA.
DR EMBL; BT001474; AAN71229.1; -; mRNA.
DR RefSeq; NP_001285224.1; NM_001298295.1.
DR RefSeq; NP_572913.1; NM_132685.2.
DR RefSeq; NP_727727.1; NM_167378.2.
DR AlphaFoldDB; Q9VYA0; -.
DR SMR; Q9VYA0; -.
DR BioGRID; 58705; 1.
DR IntAct; Q9VYA0; 1.
DR STRING; 7227.FBpp0073675; -.
DR iPTMnet; Q9VYA0; -.
DR PaxDb; Q9VYA0; -.
DR PRIDE; Q9VYA0; -.
DR DNASU; 32328; -.
DR EnsemblMetazoa; FBtr0073844; FBpp0073675; FBgn0030512.
DR EnsemblMetazoa; FBtr0073845; FBpp0073676; FBgn0030512.
DR EnsemblMetazoa; FBtr0343352; FBpp0310009; FBgn0030512.
DR GeneID; 32328; -.
DR KEGG; dme:Dmel_CG9940; -.
DR UCSC; CG9940-RA; d. melanogaster.
DR CTD; 32328; -.
DR FlyBase; FBgn0030512; Nadsyn.
DR VEuPathDB; VectorBase:FBgn0030512; -.
DR eggNOG; KOG2303; Eukaryota.
DR GeneTree; ENSGT00390000010152; -.
DR HOGENOM; CLU_011884_2_0_1; -.
DR InParanoid; Q9VYA0; -.
DR OMA; CEDHFYE; -.
DR OrthoDB; 283044at2759; -.
DR PhylomeDB; Q9VYA0; -.
DR Reactome; R-DME-196807; Nicotinate metabolism.
DR UniPathway; UPA00253; UER00334.
DR BioGRID-ORCS; 32328; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 32328; -.
DR PRO; PR:Q9VYA0; -.
DR Proteomes; UP000000803; Chromosome X.
DR Bgee; FBgn0030512; Expressed in adult Malpighian tubule (Drosophila) and 22 other tissues.
DR ExpressionAtlas; Q9VYA0; baseline and differential.
DR Genevisible; Q9VYA0; DM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004359; F:glutaminase activity; IBA:GO_Central.
DR GO; GO:0003952; F:NAD+ synthase (glutamine-hydrolyzing) activity; IBA:GO_Central.
DR GO; GO:0009435; P:NAD biosynthetic process; IBA:GO_Central.
DR GO; GO:1900074; P:negative regulation of neuromuscular synaptic transmission; IMP:FlyBase.
DR CDD; cd00553; NAD_synthase; 1.
DR Gene3D; 3.40.50.620; -; 1.
DR Gene3D; 3.60.110.10; -; 1.
DR HAMAP; MF_02090; NadE_glutamine_dep; 1.
DR InterPro; IPR003010; C-N_Hydrolase.
DR InterPro; IPR036526; C-N_Hydrolase_sf.
DR InterPro; IPR014445; Gln-dep_NAD_synthase.
DR InterPro; IPR022310; NAD/GMP_synthase.
DR InterPro; IPR003694; NAD_synthase.
DR InterPro; IPR014729; Rossmann-like_a/b/a_fold.
DR PANTHER; PTHR23090; PTHR23090; 1.
DR Pfam; PF00795; CN_hydrolase; 1.
DR Pfam; PF02540; NAD_synthase; 1.
DR PIRSF; PIRSF006630; NADS_GAT; 1.
DR SUPFAM; SSF56317; SSF56317; 1.
DR TIGRFAMs; TIGR00552; nadE; 1.
DR PROSITE; PS50263; CN_HYDROLASE; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Ligase; NAD; Nucleotide-binding; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..787
FT /note="Glutamine-dependent NAD(+) synthetase"
FT /id="PRO_0000152249"
FT DOMAIN 5..275
FT /note="CN hydrolase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00054"
FT REGION 325..787
FT /note="Ligase"
FT ACT_SITE 45
FT /note="Proton acceptor; for glutaminase activity"
FT /evidence="ECO:0000250|UniProtKB:P9WJJ3"
FT ACT_SITE 114
FT /note="For glutaminase activity"
FT /evidence="ECO:0000250|UniProtKB:P9WJJ3"
FT ACT_SITE 175
FT /note="Nucleophile; for glutaminase activity"
FT /evidence="ECO:0000250|UniProtKB:P9WJJ3"
FT ACT_SITE 357
FT /evidence="ECO:0000250"
FT BINDING 355..362
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT MOD_RES 703
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT CONFLICT 247
FT /note="A -> V (in Ref. 3; AAN71229)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 787 AA; 87615 MW; 0B2B6106E327F0C5 CRC64;
MGRKVTVAVS TLNQWALDFE GNMVRILQSI LEAKDMGASY RTGPELEVCG YSCEDHFREP
DTFLHSWEVL LEVMMSPMCE NMLVDVGMPV MHRNVAYNCR VAFFNRQILL IRPKMAMCDD
GNYRESRWFT AWTKALQTEE YVLPRMIAQH TGQQTVPFGD AVIATRDTCL GYEICEELWN
VRSKHIEMSL AGVELIVNSS GSYMELRKAH ITSDLIRNAS FKAGGAYLFS NLRGCDGQRV
YFNGCSAIAL NGEILARSQQ FALQDVEVTL ATIDLEEIRA YRVSLRSRCT AAASAAEYPR
IHCDFEMSTH SDIFKTSTPP LNWPMHTPEE EIALGPACWL WDYLRRSGQG GFFLPLSGGV
DSSSSATIVH SMCRQIVQAV QQGDAQVLHD IRQLLADSDY TPDNAAGLCN RLLVTCYMGS
VNSSKETRRR AAQLANQLGS YHIEISIDSA VNALLSIFNA VTGLTPRFRT QGGCARQNLA
LQNMQSRIRM VLAYIFAQLT LWVRNRPGGL LVLGSANVDE SLRGYLTKYD CSSADINPIG
GISKMDLRRF LTYAKDKFNL PVLESIIDAP PTAELEPLQE NGELQQTDEA DMGMTYAELS
QFGRLRKQSF CGPYSMFCHL VATWKSDLSP KEVAEKVKHF FLCYAINRHK MTVLTPSVHA
ESYSPDDNRF DHRPFLYRPN WSWQFKAIDD EAEKLQPIYT PSSAQLRPSS EDLLISTQRS
SHLDDSKHSS PLSSASASAS IDVGISTAAV PLPGAAAPGG LSKKPSGYSK VHVNVLGKIK
DRTGIPV
