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Protein

Trifunctional NAD biosynthesis/regulator protein NadR

Gene

nadR

Organism
Escherichia coli (strain K12)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

This enzyme has three activities: DNA binding, nicotinamide mononucleotide (NMN) adenylyltransferase and ribosylnicotinamide (RN) kinase. The DNA-binding domain binds to the nadB operator sequence in an NAD- and ATP-dependent manner. As NAD levels increase within the cell, the affinity of NadR for the nadB operator regions of nadA, nadB, and pncB increases, repressing the transcription of these genes. The RN kinase activity catalyzes the phosphorylation of RN to form nicotinamide ribonucleotide. The NMN adenylyltransferase activity catalyzes the transfer of the AMP moiety of ATP to nicotinamide ribonucleotide to form NAD+. The NMN adenylyltransferase domain also functions as the NAD and ATP sensor.1 Publication

Catalytic activityi

ATP + nicotinamide ribonucleotide = diphosphate + NAD+.
ATP + 1-(beta-D-ribofuranosyl)-nicotinamide = ADP + beta-nicotinamide D-ribonucleotide.

Enzyme regulationi

Feed-back regulated by NAD. A high level of NAD causes NadR to lose enzymatic activity and repress several NAD synthetic genes; conversely, a low NAD level activates the assimilatory enzymatic activities and leads to derepression of biosynthetic genes (By similarity).By similarity

Kineticsi

  1. KM=0.7 mM for NMN1 Publication
  2. KM=1.7 µM for ATP1 Publication

    pH dependencei

    Optimum pH is 8.6.1 Publication

    Pathwayi: NAD(+) biosynthesis

    This protein regulates the pathway NAD(+) biosynthesis, which is part of Cofactor biosynthesis.
    View all proteins of this organism that are known to be involved in the pathway NAD(+) biosynthesis and in Cofactor biosynthesis.

    Pathwayi: NAD(+) biosynthesis

    This protein is involved in step 1 of the subpathway that synthesizes NAD(+) from nicotinamide D-ribonucleotide.
    Proteins known to be involved in this subpathway in this organism are:
    1. Trifunctional NAD biosynthesis/regulator protein NadR (nadR)
    This subpathway is part of the pathway NAD(+) biosynthesis, which is itself part of Cofactor biosynthesis.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes NAD(+) from nicotinamide D-ribonucleotide, the pathway NAD(+) biosynthesis and in Cofactor biosynthesis.

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei77NAD 1By similarity1
    Binding sitei104NAD 1By similarity1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    DNA bindingi18 – 37H-T-H motifCuratedAdd BLAST20
    Nucleotide bindingi70 – 73NAD 1By similarity4
    Nucleotide bindingi144 – 157NAD 1By similarityAdd BLAST14
    Nucleotide bindingi177 – 179NAD 1By similarity3
    Nucleotide bindingi204 – 206NAD 1By similarity3
    Nucleotide bindingi259 – 261NAD 2By similarity3
    Nucleotide bindingi294 – 297NAD 2By similarity4

    GO - Molecular functioni

    • ATP binding Source: CAFA
    • bacterial-type proximal promoter sequence-specific DNA binding Source: EcoCyc
    • magnesium ion binding Source: EcoCyc
    • nicotinamide-nucleotide adenylyltransferase activity Source: EcoCyc
    • ribosylnicotinamide kinase activity Source: UniProtKB-EC

    GO - Biological processi

    • cellular response to metal ion Source: CAFA
    • NAD biosynthetic process Source: CAFA
    • negative regulation of transcription, DNA-templated Source: InterPro
    • protein homotetramerization Source: CAFA
    • response to alkaline pH Source: CAFA
    • transcription, DNA-templated Source: UniProtKB-KW

    Keywordsi

    Molecular functionDNA-binding, Kinase, Multifunctional enzyme, Repressor, Transferase
    Biological processPyridine nucleotide biosynthesis, Transcription, Transcription regulation
    LigandATP-binding, NAD, Nucleotide-binding

    Enzyme and pathway databases

    BioCyciEcoCyc:PD04413
    MetaCyc:PD04413
    SABIO-RKiP27278
    UniPathwayiUPA00253
    UPA00253; UER00600

    Protein family/group databases

    MoonProtiP27278

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Trifunctional NAD biosynthesis/regulator protein NadR
    Including the following 3 domains:
    Transcriptional regulator NadR
    Nicotinamide mononucleotide adenylyltransferase (EC:2.7.7.1)
    Short name:
    NMN adenylyltransferase
    Short name:
    NMN-AT
    Short name:
    NMNAT
    Alternative name(s):
    Nicotinamide ribonucleotide adenylyltransferase
    Nicotinamide-nucleotide adenylyltransferase
    Ribosylnicotinamide kinase (EC:2.7.1.22)
    Short name:
    RNK
    Alternative name(s):
    Nicotinamide riboside kinase
    Short name:
    NRK
    Short name:
    NmR-K
    Gene namesi
    Name:nadR
    Synonyms:nadI
    Ordered Locus Names:b4390, JW5800
    OrganismiEscherichia coli (strain K12)
    Taxonomic identifieri83333 [NCBI]
    Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacteralesEnterobacteriaceaeEscherichia
    Proteomesi
    • UP000000318 Componenti: Chromosome
    • UP000000625 Componenti: Chromosome

    Organism-specific databases

    EcoGeneiEG11335 nadR

    Subcellular locationi

    GO - Cellular componenti

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00001497281 – 410Trifunctional NAD biosynthesis/regulator protein NadRAdd BLAST410

    Proteomic databases

    PaxDbiP27278
    PRIDEiP27278

    Interactioni

    Subunit structurei

    Homotetramer.By similarity

    Protein-protein interaction databases

    BioGridi4260800, 3 interactors
    STRINGi316385.ECDH10B_4548

    Structurei

    3D structure databases

    ProteinModelPortaliP27278
    SMRiP27278
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini7 – 62HTH cro/C1-typePROSITE-ProRule annotationAdd BLAST56

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni63 – 229Nicotinamide mononucleotide adenylyltransferaseAdd BLAST167
    Regioni230 – 410Ribosylnicotinamide kinaseAdd BLAST181

    Sequence similaritiesi

    In the central section; belongs to the bacterial NMN adenylyltransferase family.Curated
    In the C-terminal section; belongs to the bacterial RNK family.Curated

    Phylogenomic databases

    eggNOGiENOG4107VZS Bacteria
    COG1056 LUCA
    COG1396 LUCA
    COG3172 LUCA
    HOGENOMiHOG000127874
    InParanoidiP27278
    KOiK06211
    OMAiKFYPPHA

    Family and domain databases

    CDDicd00093 HTH_XRE, 1 hit
    Gene3Di3.40.50.620, 1 hit
    InterProiView protein in InterPro
    IPR016429 Bifunc_transcrip_reg_NadR
    IPR001387 Cro/C1-type_HTH
    IPR004821 Cyt_trans-like
    IPR010982 Lambda_DNA-bd_dom_sf
    IPR038727 NadR/Ttd14_AAA_dom
    IPR006417 NadR_NMN_Atrans
    IPR027417 P-loop_NTPase
    IPR014729 Rossmann-like_a/b/a_fold
    PfamiView protein in Pfam
    PF13521 AAA_28, 1 hit
    PF01381 HTH_3, 1 hit
    PIRSFiPIRSF004776 NadR_NMNAT/RNK, 1 hit
    SMARTiView protein in SMART
    SM00530 HTH_XRE, 1 hit
    SUPFAMiSSF47413 SSF47413, 1 hit
    SSF52540 SSF52540, 1 hit
    TIGRFAMsiTIGR00125 cyt_tran_rel, 1 hit
    TIGR01526 nadR_NMN_Atrans, 1 hit
    PROSITEiView protein in PROSITE
    PS50943 HTH_CROC1, 1 hit

    Sequencei

    Sequence statusi: Complete.

    P27278-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MSSFDYLKTA IKQQGCTLQQ VADASGMTKG YLSQLLNAKI KSPSAQKLEA
    60 70 80 90 100
    LHRFLGLEFP RQKKTIGVVF GKFYPLHTGH IYLIQRACSQ VDELHIIMGF
    110 120 130 140 150
    DDTRDRALFE DSAMSQQPTV PDRLRWLLQT FKYQKNIRIH AFNEEGMEPY
    160 170 180 190 200
    PHGWDVWSNG IKKFMAEKGI QPDLIYTSEE ADAPQYMEHL GIETVLVDPK
    210 220 230 240 250
    RTFMSISGAQ IRENPFRYWE YIPTEVKPFF VRTVAILGGE SSGKSTLVNK
    260 270 280 290 300
    LANIFNTTSA WEYGRDYVFS HLGGDEIALQ YSDYDKIALG HAQYIDFAVK
    310 320 330 340 350
    YANKVAFIDT DFVTTQAFCK KYEGREHPFV QALIDEYRFD LVILLENNTP
    360 370 380 390 400
    WVADGLRSLG SSVDRKEFQN LLVEMLEENN IEFVRVEEED YDSRFLRCVE
    410
    LVREMMGEQR
    Length:410
    Mass (Da):47,346
    Last modified:February 1, 1995 - v2
    Checksum:iBCBC26CD3ABA2F99
    GO

    Sequence cautioni

    The sequence AAA97286 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U14003 Genomic DNA Translation: AAA97286.1 Different initiation.
    U00096 Genomic DNA Translation: AAC77343.2
    AP009048 Genomic DNA Translation: BAE78379.1
    X63155 Genomic DNA No translation available.
    PIRiS56614
    RefSeqiNP_418807.4, NC_000913.3
    WP_000093814.1, NZ_LN832404.1

    Genome annotation databases

    EnsemblBacteriaiAAC77343; AAC77343; b4390
    BAE78379; BAE78379; BAE78379
    GeneIDi948911
    KEGGiecj:JW5800
    eco:b4390
    PATRICifig|1411691.4.peg.2295

    Similar proteinsi

    Entry informationi

    Entry nameiNADR_ECOLI
    AccessioniPrimary (citable) accession number: P27278
    Secondary accession number(s): P76819, Q2M5S7
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1992
    Last sequence update: February 1, 1995
    Last modified: April 25, 2018
    This is version 146 of the entry and version 2 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Escherichia coli
      Escherichia coli (strain K12): entries and cross-references to EcoGene
    2. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    3. SIMILARITY comments
      Index of protein domains and families

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