NADE_MOUSE
ID NADE_MOUSE Reviewed; 725 AA.
AC Q711T7; Q711P6; Q8CFY6; Q9D280;
DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Glutamine-dependent NAD(+) synthetase;
DE EC=6.3.5.1 {ECO:0000250|UniProtKB:Q6IA69};
DE AltName: Full=NAD(+) synthase [glutamine-hydrolyzing];
DE AltName: Full=NAD(+) synthetase;
DE AltName: Full=NH3-dependent NAD(+) synthetase-like protein;
GN Name=Nadsyn1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RC STRAIN=129/Sv;
RA Engemann S., Stroedicke M., Franck O., Walter J.;
RT "Extended sequence comparison of the BWS syndrome gene cluster on human
RT 11p15.5 and mouse distal chromosome 7.";
RL Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Aorta, Cecum, Thymus, and Vein;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Czech II; TISSUE=Mammary gland;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=12547821; DOI=10.1074/jbc.m209203200;
RA Hara N., Yamada K., Terashima M., Osago H., Shimoyama M., Tsuchiya M.;
RT "Molecular identification of human glutamine- and ammonia-dependent NAD
RT synthetases. Carbon-nitrogen hydrolase domain confers glutamine
RT dependency.";
RL J. Biol. Chem. 278:10914-10921(2003).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, and Liver;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Catalyzes the final step of the nicotinamide adenine
CC dinucleotide (NAD) de novo synthesis pathway, the ATP-dependent
CC amidation of deamido-NAD using L-glutamine as a nitrogen source.
CC {ECO:0000250|UniProtKB:Q6IA69}.
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 PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24385;
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 -!- SUBUNIT: Homohexamer. {ECO:0000250|UniProtKB:Q6IA69}.
CC -!- TISSUE SPECIFICITY: Highly expressed in small intestine, kidney, liver
CC and testis. Weakly expressed in skeletal muscle, spleen, lung, heart
CC and brain. {ECO:0000269|PubMed:12547821}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the NAD synthetase
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAC88023.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AJ305343; CAC83797.1; -; mRNA.
DR EMBL; AJ311612; CAC88023.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AK020264; BAB32048.1; -; mRNA.
DR EMBL; AK041101; BAC30822.1; -; mRNA.
DR EMBL; AK042389; BAC31247.1; -; mRNA.
DR EMBL; BC038016; AAH38016.1; -; mRNA.
DR CCDS; CCDS22047.1; -.
DR RefSeq; NP_001295024.1; NM_001308095.1.
DR RefSeq; NP_084497.1; NM_030221.2.
DR RefSeq; XP_011240323.1; XM_011242021.2.
DR AlphaFoldDB; Q711T7; -.
DR SMR; Q711T7; -.
DR BioGRID; 219702; 2.
DR STRING; 10090.ENSMUSP00000033415; -.
DR iPTMnet; Q711T7; -.
DR PhosphoSitePlus; Q711T7; -.
DR EPD; Q711T7; -.
DR MaxQB; Q711T7; -.
DR PaxDb; Q711T7; -.
DR PeptideAtlas; Q711T7; -.
DR PRIDE; Q711T7; -.
DR ProteomicsDB; 286145; -.
DR Antibodypedia; 30728; 73 antibodies from 18 providers.
DR DNASU; 78914; -.
DR Ensembl; ENSMUST00000033415; ENSMUSP00000033415; ENSMUSG00000031090.
DR GeneID; 78914; -.
DR KEGG; mmu:78914; -.
DR UCSC; uc009kqa.1; mouse.
DR CTD; 55191; -.
DR MGI; MGI:1926164; Nadsyn1.
DR VEuPathDB; HostDB:ENSMUSG00000031090; -.
DR eggNOG; KOG2303; Eukaryota.
DR GeneTree; ENSGT00390000010152; -.
DR HOGENOM; CLU_011884_2_0_1; -.
DR InParanoid; Q711T7; -.
DR OMA; CEDHFYE; -.
DR OrthoDB; 283044at2759; -.
DR PhylomeDB; Q711T7; -.
DR TreeFam; TF351426; -.
DR Reactome; R-MMU-196807; Nicotinate metabolism.
DR UniPathway; UPA00253; UER00334.
DR BioGRID-ORCS; 78914; 1 hit in 59 CRISPR screens.
DR ChiTaRS; Nadsyn1; mouse.
DR PRO; PR:Q711T7; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q711T7; protein.
DR Bgee; ENSMUSG00000031090; Expressed in small intestine Peyer's patch and 202 other tissues.
DR ExpressionAtlas; Q711T7; baseline and differential.
DR Genevisible; Q711T7; MM.
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; ISS:UniProtKB.
DR GO; GO:0008795; F:NAD+ synthase activity; ISO:MGI.
DR GO; GO:0034627; P:'de novo' NAD biosynthetic process; ISS:UniProtKB.
DR GO; GO:0009435; P:NAD biosynthetic process; ISO:MGI.
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; Reference proteome.
FT CHAIN 1..725
FT /note="Glutamine-dependent NAD(+) synthetase"
FT /id="PRO_0000237579"
FT DOMAIN 5..275
FT /note="CN hydrolase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00054"
FT REGION 325..706
FT /note="Ligase"
FT /evidence="ECO:0000250"
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 CONFLICT 186
FT /note="I -> V (in Ref. 3; AAH38016)"
FT /evidence="ECO:0000305"
FT CONFLICT 282
FT /note="K -> R (in Ref. 3; AAH38016)"
FT /evidence="ECO:0000305"
FT CONFLICT 321
FT /note="M -> I (in Ref. 3; AAH38016)"
FT /evidence="ECO:0000305"
FT CONFLICT 461
FT /note="M -> V (in Ref. 3; AAH38016)"
FT /evidence="ECO:0000305"
FT CONFLICT 710
FT /note="F -> L (in Ref. 3; AAH38016)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 725 AA; 81652 MW; C1A79A9AA509B3E4 CRC64;
MGRKVTVATC ALNQWALDFE GNFQRILKSI QIAKGKGARY RLGPELEICG YGCWDHYHES
DTLLHSLQVL AALLDSPVTQ DIICDVGMPI MHRNVRYNCR VIFLNRKILL IRPKMALANE
GNYRELRWFT PWTRSRQTEE YVLPRMLQDL TKQKTVPFGD VVLATQDTCV GSEICEELWT
PRSPHIDMGL DGVEIITNAS GSHHVLRKAH TRVDLVTMAT SKNGGIYLLA NQKGCDGDRL
YYDGCAMIAM NGSIFAQGTQ FSLDDVEVLT ATLDLEDVRS YKAEISSRNL EATRVSPYPR
VTVDFALSVS EDLLEPVSEP MEWTYHRPEE EISLGPACWL WDFLRRSKQA GFFLPLSGGV
DSAASACIVY SMCCLVCDAV KSGNQQVLTD VQNLVDESSY TPQDPRELCG RLLTTCYMAS
ENSSQETHSR ATKLAQLIGS YHINLSIDTA VKAVLGIFSL MTGKLPRFSA HGGSSRENLA
LQNVQARIRM VLAYLFAQLS LWSRGARGSL LVLGSANVDE SLLGYLTKYD CSSADINPIG
GISKTDLRAF VQFCAERFQL PVLQTILSAP ATAELEPLAD GQVSQMDEED MGMTYAELSI
FGRLRKVAKA GPYSMFCKLL NMWRDSYTPT QVAEKVKLFF SKYSMNRHKM TTLTPAYHAE
NYSPDDNRFD LRPFLYNTRW PWQFLCIDNQ VLQLERKASQ TREEQVLEHF KEPSPIWKQL
LPKDP
