NADR_SALTY
ID NADR_SALTY Reviewed; 410 AA.
AC P24518;
DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2002, sequence version 2.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Trifunctional NAD biosynthesis/regulator protein NadR;
DE Includes:
DE RecName: Full=Transcriptional regulator NadR;
DE Includes:
DE RecName: Full=Nicotinamide mononucleotide adenylyltransferase;
DE Short=NMN adenylyltransferase;
DE Short=NMN-AT;
DE Short=NMNAT;
DE EC=2.7.7.1;
DE AltName: Full=Nicotinamide ribonucleotide adenylyltransferase;
DE AltName: Full=Nicotinamide-nucleotide adenylyltransferase;
DE Includes:
DE RecName: Full=Ribosylnicotinamide kinase;
DE Short=RNK;
DE EC=2.7.1.22;
DE AltName: Full=Nicotinamide riboside kinase;
DE Short=NRK;
DE Short=NmR-K;
GN Name=nadR; Synonyms=nadI, pnuA; OrderedLocusNames=STM4580;
OS Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Salmonella.
OX NCBI_TaxID=99287;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=LT2;
RX PubMed=2198247; DOI=10.1128/jb.172.8.4187-4196.1990;
RA Foster J.W., Park Y.K., Penfound T., Fenger T., Spector M.P.;
RT "Regulation of NAD metabolism in Salmonella typhimurium: molecular sequence
RT analysis of the bifunctional nadR regulator and the nadA-pnuC operon.";
RL J. Bacteriol. 172:4187-4196(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=LT2 / SGSC1412 / ATCC 700720;
RX PubMed=11677609; DOI=10.1038/35101614;
RA McClelland M., Sanderson K.E., Spieth J., Clifton S.W., Latreille P.,
RA Courtney L., Porwollik S., Ali J., Dante M., Du F., Hou S., Layman D.,
RA Leonard S., Nguyen C., Scott K., Holmes A., Grewal N., Mulvaney E.,
RA Ryan E., Sun H., Florea L., Miller W., Stoneking T., Nhan M., Waterston R.,
RA Wilson R.K.;
RT "Complete genome sequence of Salmonella enterica serovar Typhimurium LT2.";
RL Nature 413:852-856(2001).
RN [3]
RP CHARACTERIZATION, AND MUTAGENESIS.
RX PubMed=1991723; DOI=10.1128/jb.173.3.1302-1310.1991;
RA Zhu N., Roth J.R.;
RT "The nadI region of Salmonella typhimurium encodes a bifunctional
RT regulatory protein.";
RL J. Bacteriol. 173:1302-1310(1991).
RN [4]
RP MUTAGENESIS OF HIS-77 AND HIS-80.
RX PubMed=12446641; DOI=10.1128/jb.184.24.6906-6917.2002;
RA Kurnasov O.V., Polanuyer B.M., Ananta S., Sloutsky R., Tam A., Gerdes S.Y.,
RA Osterman A.L.;
RT "Ribosylnicotinamide kinase domain of NadR protein: identification and
RT implications in NAD biosynthesis.";
RL J. Bacteriol. 184:6906-6917(2002).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=15805524; DOI=10.1128/jb.187.8.2774-2782.2005;
RA Grose J.H., Bergthorsson U., Roth J.R.;
RT "Regulation of NAD synthesis by the trifunctional NadR protein of
RT Salmonella enterica.";
RL J. Bacteriol. 187:2774-2782(2005).
CC -!- FUNCTION: This enzyme has three activities: DNA binding, nicotinamide
CC mononucleotide (NMN) adenylyltransferase and ribosylnicotinamide (RN)
CC kinase. The DNA-binding domain binds to the nadB operator sequence in
CC an NAD- and ATP-dependent manner. As NAD levels increase within the
CC cell, the affinity of NadR for the nadB operator regions of nadA, nadB,
CC and pncB increases, repressing the transcription of these genes. The RN
CC kinase activity catalyzes the phosphorylation of RN to form
CC nicotinamide ribonucleotide. The NMN adenylyltransferase activity
CC catalyzes the transfer of the AMP moiety of ATP to nicotinamide
CC ribonucleotide to form NAD(+). The NMN adenylyltransferase domain also
CC functions as the NAD and ATP sensor. {ECO:0000269|PubMed:15805524}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + beta-nicotinamide D-ribonucleotide + H(+) = diphosphate
CC + NAD(+); Xref=Rhea:RHEA:21360, ChEBI:CHEBI:14649, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:57540; EC=2.7.7.1;
CC Evidence={ECO:0000269|PubMed:15805524};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + beta-nicotinamide D-riboside = ADP + beta-nicotinamide
CC D-ribonucleotide + H(+); Xref=Rhea:RHEA:14017, ChEBI:CHEBI:14649,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15927, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:456216; EC=2.7.1.22;
CC Evidence={ECO:0000269|PubMed:15805524};
CC -!- ACTIVITY REGULATION: Feed-back regulated by NAD. A high level of NAD
CC causes NadR to lose enzymatic activity and repress several NAD
CC synthetic genes; conversely, a low NAD level activates the assimilatory
CC enzymatic activities and leads to derepression of biosynthetic genes.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.08 mM for ribosylnicotinamide {ECO:0000269|PubMed:15805524};
CC KM=1.2 mM for ATP (with ribosylnicotinamide as cosubstrate)
CC {ECO:0000269|PubMed:15805524};
CC KM=12.8 mM for NMN {ECO:0000269|PubMed:15805524};
CC KM=1.2 uM for ATP (with NMN as cosubstrate)
CC {ECO:0000269|PubMed:15805524};
CC -!- PATHWAY: Cofactor biosynthesis; NAD(+) biosynthesis [regulation].
CC -!- PATHWAY: Cofactor biosynthesis; NAD(+) biosynthesis; NAD(+) from
CC nicotinamide D-ribonucleotide: step 1/1.
CC -!- SUBUNIT: Homotetramer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Peripheral membrane protein.
CC Cytoplasm {ECO:0000250}.
CC -!- SIMILARITY: In the central section; belongs to the bacterial NMN
CC adenylyltransferase family. {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the bacterial RNK
CC family. {ECO:0000305}.
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DR EMBL; M85181; AAA61953.1; -; Genomic_DNA.
DR EMBL; AE006468; AAL23395.1; -; Genomic_DNA.
DR PIR; B37753; B37753.
DR RefSeq; NP_463436.5; NC_003197.2.
DR RefSeq; WP_000093829.1; NC_003197.2.
DR AlphaFoldDB; P24518; -.
DR SMR; P24518; -.
DR STRING; 99287.STM4580; -.
DR TCDB; 4.B.1.1.1; the nicotinamide ribonucleoside (nr) uptake permease (pnuc) family.
DR PaxDb; P24518; -.
DR EnsemblBacteria; AAL23395; AAL23395; STM4580.
DR GeneID; 1256106; -.
DR KEGG; stm:STM4580; -.
DR HOGENOM; CLU_052648_0_1_6; -.
DR OMA; QDPFRYW; -.
DR PhylomeDB; P24518; -.
DR BioCyc; SENT99287:STM4580-MON; -.
DR SABIO-RK; P24518; -.
DR UniPathway; UPA00253; -.
DR UniPathway; UPA00253; UER00600.
DR Proteomes; UP000001014; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0000309; F:nicotinamide-nucleotide adenylyltransferase activity; IBA:GO_Central.
DR GO; GO:0050262; F:ribosylnicotinamide kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0009435; P:NAD biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR CDD; cd00093; HTH_XRE; 1.
DR CDD; cd02167; NMNAT_NadR; 1.
DR Gene3D; 1.10.260.40; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR Gene3D; 3.40.50.620; -; 1.
DR InterPro; IPR001387; Cro/C1-type_HTH.
DR InterPro; IPR004821; Cyt_trans-like.
DR InterPro; IPR010982; Lambda_DNA-bd_dom_sf.
DR InterPro; IPR016429; NAD_NadR.
DR InterPro; IPR038727; NadR/Ttd14_AAA_dom.
DR InterPro; IPR006417; NadR_NMN_Atrans.
DR InterPro; IPR041749; NMNAT_NadR.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR014729; Rossmann-like_a/b/a_fold.
DR Pfam; PF13521; AAA_28; 1.
DR Pfam; PF01381; HTH_3; 1.
DR PIRSF; PIRSF004776; NadR_NMNAT/RNK; 1.
DR SMART; SM00530; HTH_XRE; 1.
DR SUPFAM; SSF47413; SSF47413; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00125; cyt_tran_rel; 1.
DR TIGRFAMs; TIGR01526; nadR_NMN_Atrans; 1.
DR PROSITE; PS50943; HTH_CROC1; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell membrane; Cytoplasm; DNA-binding; Kinase; Membrane;
KW Multifunctional enzyme; NAD; Nucleotide-binding;
KW Pyridine nucleotide biosynthesis; Reference proteome; Repressor;
KW Transcription; Transcription regulation; Transferase.
FT CHAIN 1..410
FT /note="Trifunctional NAD biosynthesis/regulator protein
FT NadR"
FT /id="PRO_0000149729"
FT DOMAIN 7..62
FT /note="HTH cro/C1-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00257"
FT DNA_BIND 18..37
FT /note="H-T-H motif"
FT /evidence="ECO:0000305"
FT REGION 63..229
FT /note="Nicotinamide mononucleotide adenylyltransferase"
FT REGION 230..410
FT /note="Ribosylnicotinamide kinase"
FT BINDING 70..73
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 77
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 104
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 144..157
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 177..179
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 204..206
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 259..261
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 294..297
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT MUTAGEN 21
FT /note="V->M: Loss of DNA binding activity."
FT /evidence="ECO:0000269|PubMed:1991723"
FT MUTAGEN 22
FT /note="A->T: Loss of DNA binding activity."
FT /evidence="ECO:0000269|PubMed:1991723"
FT MUTAGEN 43
FT /note="P->L: Loss of DNA binding activity."
FT /evidence="ECO:0000269|PubMed:1991723"
FT MUTAGEN 77
FT /note="H->A: Complete loss of NMN adenylyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:12446641"
FT MUTAGEN 80
FT /note="H->A: Complete loss of NMN adenylyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:12446641"
FT MUTAGEN 123
FT /note="R->H: No NMN adenylyltransferase activity. Binds DNA
FT independently of NAD; when associated with N-173."
FT /evidence="ECO:0000269|PubMed:1991723"
FT MUTAGEN 173
FT /note="S->N: No NMN adenylyltransferase activity. Binds DNA
FT independently of NAD; when associated with H-123."
FT /evidence="ECO:0000269|PubMed:1991723"
FT MUTAGEN 212
FT /note="R->C: No NMN adenylyltransferase activity. Binds DNA
FT independently of NAD."
FT /evidence="ECO:0000269|PubMed:1991723"
FT MUTAGEN 264
FT /note="G->D: No RN kinase activity."
FT /evidence="ECO:0000269|PubMed:1991723"
FT MUTAGEN 354
FT /note="D->N: Affects RN kinase activity."
FT /evidence="ECO:0000269|PubMed:1991723"
FT CONFLICT 22..24
FT /note="ADA -> LT (in Ref. 1; AAA61953)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 410 AA; 47101 MW; E06B5EFE0E6101C2 CRC64;
MSSFDYLKTA IKQQGCTLQQ VADASGMTKG YLSQLLNAKI KSPSAQKLEA LHRFLGLEFP
RRQKNIGVVF GKFYPLHTGH IYLIQRACSQ VDELHIIMGY DDTRDRGLFE DSAMSQQPTV
SDRLRWLLQT FKYQKNIRIH AFNEEGMEPY PHGWDVWSNG IKAFMAEKGI QPSWIYTSEE
ADAPQYLEHL GIETVLVDPE RTFMNISGAQ IRENPFRYWE YIPTEVKPFF VRTVAILGGE
SSGKSTLVNK LANIFNTTSA WEYGRDYVFS HLGGDEMALQ YSDYDKIALG HAQYIDFAVK
YANKVAFIDT DFVTTQAFCK KYEGREHPFV QALIDEYRFD LVILLENNTP WVADGLRSLG
SSVDRKAFQN LLVEMLKENN IEFVHVKEAD YDGRFLRCVE LVKEMMGEQG
