NADR_ECOLI
ID NADR_ECOLI Reviewed; 410 AA.
AC P27278; P76819; Q2M5S7;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 2.
DT 03-AUG-2022, entry version 167.
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 {ECO:0000269|PubMed:10464228};
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; OrderedLocusNames=b4390, JW5800;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=7610040; DOI=10.1093/nar/23.12.2105;
RA Burland V.D., Plunkett G. III, Sofia H.J., Daniels D.L., Blattner F.R.;
RT "Analysis of the Escherichia coli genome VI: DNA sequence of the region
RT from 92.8 through 100 minutes.";
RL Nucleic Acids Res. 23:2105-2119(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-122.
RC STRAIN=K12;
RX PubMed=1327967; DOI=10.1016/0378-1119(92)90002-7;
RA Neuwald A.F., Berg D.E., Stauffer G.V.;
RT "Mutational analysis of the Escherichia coli serB promoter region reveals
RT transcriptional linkage to a downstream gene.";
RL Gene 120:1-9(1992).
RN [5]
RP IDENTIFICATION.
RA Rudd K.E.;
RL Unpublished observations (JUL-1992).
RN [6]
RP FUNCTION AS NMN ADENYLYLTRANSFERASE, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND PATHWAY.
RX PubMed=10464228; DOI=10.1128/jb.181.17.5509-5511.1999;
RA Raffaelli N., Lorenzi T., Mariani P.L., Emanuelli M., Amici A.,
RA Ruggieri S., Magni G.;
RT "The Escherichia coli NadR regulator is endowed with nicotinamide
RT mononucleotide adenylyltransferase activity.";
RL J. Bacteriol. 181:5509-5511(1999).
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:10464228}.
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:10464228};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21361;
CC Evidence={ECO:0000269|PubMed:10464228};
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 -!- 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 (By similarity). {ECO:0000250}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.7 mM for NMN {ECO:0000269|PubMed:10464228};
CC KM=1.7 uM for ATP {ECO:0000269|PubMed:10464228};
CC pH dependence:
CC Optimum pH is 8.6. {ECO:0000269|PubMed:10464228};
CC -!- PATHWAY: Cofactor biosynthesis; NAD(+) biosynthesis [regulation].
CC -!- PATHWAY: Cofactor biosynthesis; NAD(+) biosynthesis; NAD(+) from
CC nicotinamide D-ribonucleotide: step 1/1. {ECO:0000269|PubMed:10464228}.
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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA97286.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; U14003; AAA97286.1; ALT_INIT; Genomic_DNA.
DR EMBL; U00096; AAC77343.2; -; Genomic_DNA.
DR EMBL; AP009048; BAE78379.1; -; Genomic_DNA.
DR EMBL; X63155; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PIR; S56614; S56614.
DR RefSeq; NP_418807.4; NC_000913.3.
DR RefSeq; WP_000093814.1; NZ_LN832404.1.
DR AlphaFoldDB; P27278; -.
DR SMR; P27278; -.
DR BioGRID; 4260800; 3.
DR STRING; 511145.b4390; -.
DR MoonProt; P27278; -.
DR jPOST; P27278; -.
DR PaxDb; P27278; -.
DR PRIDE; P27278; -.
DR EnsemblBacteria; AAC77343; AAC77343; b4390.
DR EnsemblBacteria; BAE78379; BAE78379; BAE78379.
DR GeneID; 948911; -.
DR KEGG; ecj:JW5800; -.
DR KEGG; eco:b4390; -.
DR PATRIC; fig|1411691.4.peg.2295; -.
DR EchoBASE; EB1311; -.
DR eggNOG; COG1056; Bacteria.
DR eggNOG; COG3172; Bacteria.
DR HOGENOM; CLU_052648_0_1_6; -.
DR InParanoid; P27278; -.
DR OMA; QDPFRYW; -.
DR PhylomeDB; P27278; -.
DR BioCyc; EcoCyc:PD04413; -.
DR BioCyc; MetaCyc:PD04413; -.
DR SABIO-RK; P27278; -.
DR UniPathway; UPA00253; -.
DR UniPathway; UPA00253; UER00600.
DR PRO; PR:P27278; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:1902503; C:adenylyltransferase complex; IDA:EcoCyc.
DR GO; GO:1902494; C:catalytic complex; IDA:UniProtKB.
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; IDA:CAFA.
DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; IDA:EcoCyc.
DR GO; GO:0042802; F:identical protein binding; IPI:CAFA.
DR GO; GO:0000287; F:magnesium ion binding; IDA:EcoCyc.
DR GO; GO:0000309; F:nicotinamide-nucleotide adenylyltransferase activity; IDA:EcoCyc.
DR GO; GO:0050262; F:ribosylnicotinamide kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0071248; P:cellular response to metal ion; IDA:CAFA.
DR GO; GO:0009435; P:NAD biosynthetic process; IDA:CAFA.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0010446; P:response to alkaline pH; IDA:CAFA.
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_0000149728"
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"
SQ SEQUENCE 410 AA; 47346 MW; BCBC26CD3ABA2F99 CRC64;
MSSFDYLKTA IKQQGCTLQQ VADASGMTKG YLSQLLNAKI KSPSAQKLEA LHRFLGLEFP
RQKKTIGVVF GKFYPLHTGH IYLIQRACSQ VDELHIIMGF DDTRDRALFE DSAMSQQPTV
PDRLRWLLQT FKYQKNIRIH AFNEEGMEPY PHGWDVWSNG IKKFMAEKGI QPDLIYTSEE
ADAPQYMEHL GIETVLVDPK RTFMSISGAQ IRENPFRYWE YIPTEVKPFF VRTVAILGGE
SSGKSTLVNK LANIFNTTSA WEYGRDYVFS HLGGDEIALQ YSDYDKIALG HAQYIDFAVK
YANKVAFIDT DFVTTQAFCK KYEGREHPFV QALIDEYRFD LVILLENNTP WVADGLRSLG
SSVDRKEFQN LLVEMLEENN IEFVRVEEED YDSRFLRCVE LVREMMGEQR
