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Protein

Bifunctional NAD biosynthesis protein NadR

Gene

nadR

Organism
Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

This enzyme has two activities: nicotinamide mononucleotide (NMN) adenylyltransferase and ribosylnicotinamide (RN) kinase. 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+.1 Publication

Catalytic activityi

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

Enzyme regulationi

Feed-back regulated by NAD. At high levels of NAD the RN kinase activity is inhibited.

Kineticsi

  1. KM=0.14 mM for NMN1 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. Bifunctional NAD biosynthesis 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 sitei71NAD 11 Publication1
    Binding sitei98NAD 11 Publication1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi64 – 67NAD 11 Publication4
    Nucleotide bindingi139 – 152NAD 11 PublicationAdd BLAST14
    Nucleotide bindingi172 – 174NAD 11 Publication3
    Nucleotide bindingi199 – 201NAD 11 Publication3
    Nucleotide bindingi254 – 256NAD 21 Publication3
    Nucleotide bindingi289 – 292NAD 21 Publication4

    GO - Molecular functioni

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Kinase, Transferase

    Keywords - Biological processi

    Pyridine nucleotide biosynthesis

    Keywords - Ligandi

    ATP-binding, NAD, Nucleotide-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:MONOMER-8322.
    UniPathwayiUPA00253; UER00600.
    UPA00253.

    Protein family/group databases

    TCDBi4.B.1.1.2. the nicotinamide ribonucleoside (nr) uptake permease (pnuc) family.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Bifunctional NAD biosynthesis protein NadR
    Including the following 2 domains:
    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
    Ordered Locus Names:HI_0763
    OrganismiHaemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
    Taxonomic identifieri71421 [NCBI]
    Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaPasteurellalesPasteurellaceaeHaemophilus
    Proteomesi
    • UP000000579 Componenti: Chromosome

    Subcellular locationi

    • Cell membrane 1 Publication; Peripheral membrane protein 1 Publication
    • Cytoplasm 1 Publication

    • Note: Found as a soluble cytoplasmic protein as well as a membrane-associated protein. In combination with corepressor (NAD), the cytoplasmic form of NadR would be capable of acting as a transcriptional repressor.

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi126K → A or T: Significant reduction of RNK activity, also NMN adenylyltransferase activity is impaired. 1 Publication1
    Mutagenesisi238G → N or S: Complete loss of RNK activity, no effect on NMN adenylyltransferase activity. 1 Publication1
    Mutagenesisi256W → F: No effect on enzyme activities, but NAD feedback inhibition is almost lost. 1 Publication1
    Mutagenesisi292Y → I: Almost no effect. 1 Publication1
    Mutagenesisi304D → C, N or S: Complete loss of RNK activity, no effect on NMN adenylyltransferase activity. 1 Publication1
    Mutagenesisi352R → A, C, M or N: Complete loss of RNK activity, no effect on NMN adenylyltransferase activity. 1 Publication1

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00000966891 – 421Bifunctional NAD biosynthesis protein NadRAdd BLAST421

    Interactioni

    Subunit structurei

    Homotetramer.1 Publication

    Protein-protein interaction databases

    STRINGi71421.HI0763.

    Structurei

    Secondary structure

    1421
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi60 – 65Combined sources6
    Helixi72 – 82Combined sources11
    Beta strandi86 – 94Combined sources9
    Helixi96 – 105Combined sources10
    Helixi114 – 124Combined sources11
    Turni127 – 131Combined sources5
    Beta strandi132 – 138Combined sources7
    Beta strandi140 – 142Combined sources3
    Helixi149 – 162Combined sources14
    Beta strandi168 – 171Combined sources4
    Helixi175 – 177Combined sources3
    Helixi178 – 184Combined sources7
    Beta strandi188 – 190Combined sources3
    Helixi203 – 208Combined sources6
    Helixi210 – 216Combined sources7
    Turni219 – 221Combined sources3
    Helixi222 – 224Combined sources3
    Beta strandi227 – 232Combined sources6
    Helixi238 – 249Combined sources12
    Beta strandi253 – 255Combined sources3
    Helixi260 – 265Combined sources6
    Beta strandi266 – 269Combined sources4
    Turni276 – 278Combined sources3
    Helixi279 – 296Combined sources18
    Beta strandi298 – 305Combined sources8
    Helixi307 – 318Combined sources12
    Helixi323 – 331Combined sources9
    Beta strandi335 – 341Combined sources7
    Helixi360 – 372Combined sources13
    Helixi373 – 375Combined sources3
    Beta strandi379 – 382Combined sources4
    Helixi386 – 400Combined sources15

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1LW7X-ray2.90A57-421[»]
    ProteinModelPortaliP44308.
    SMRiP44308.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP44308.

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni57 – 224Nicotinamide mononucleotide adenylyltransferaseAdd BLAST168
    Regioni225 – 421Ribosylnicotinamide kinaseAdd BLAST197

    Sequence similaritiesi

    In the N-terminal 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.
    COG3172. LUCA.
    KOiK06211.
    OMAiTAIRQKG.
    PhylomeDBiP44308.

    Family and domain databases

    Gene3Di3.40.50.300. 1 hit.
    3.40.50.620. 1 hit.
    InterProiIPR016429. Bifunc_transcrip_reg_NadR.
    IPR004821. Cyt_trans-like.
    IPR006417. NadR_NMN_Atrans.
    IPR027417. P-loop_NTPase.
    IPR014729. Rossmann-like_a/b/a_fold.
    [Graphical view]
    PfamiPF01467. CTP_transf_like. 1 hit.
    [Graphical view]
    PIRSFiPIRSF004776. NadR_NMNAT/RNK. 1 hit.
    SUPFAMiSSF52540. SSF52540. 1 hit.
    TIGRFAMsiTIGR00125. cyt_tran_rel. 1 hit.
    TIGR01526. nadR_NMN_Atrans. 1 hit.

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative initiation. AlignAdd to basket

    Isoform Long (identifier: P44308-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MGFTTGREFH PALRMRAKYN AKYLGTKSER EKYFHLAYNK HTQFLRYQEQ
    60 70 80 90 100
    IMSKTKEKKV GVIFGKFYPV HTGHINMIYE AFSKVDELHV IVCSDTVRDL
    110 120 130 140 150
    KLFYDSKMKR MPTVQDRLRW MQQIFKYQKN QIFIHHLVED GIPSYPNGWQ
    160 170 180 190 200
    SWSEAVKTLF HEKHFEPSIV FSSEPQDKAP YEKYLGLEVS LVDPDRTFFN
    210 220 230 240 250
    VSATKIRTTP FQYWKFIPKE ARPFFAKTVA ILGGESSGKS VLVNKLAAVF
    260 270 280 290 300
    NTTSAWEYGR EFVFEKLGGD EQAMQYSDYP QMALGHQRYI DYAVRHSHKI
    310 320 330 340 350
    AFIDTDFITT QAFCIQYEGK AHPFLDSMIK EYPFDVTILL KNNTEWVDDG
    360 370 380 390 400
    LRSLGSQKQR QQFQQLLKKL LDKYKVPYIE IESPSYLDRY NQVKAVIEKV
    410 420
    LNEEEISELQ NTTFPIKGTS Q
    Length:421
    Mass (Da):49,432
    Last modified:November 1, 1995 - v1
    Checksum:iD9A4FD4970A6E7E8
    GO
    Isoform Short (identifier: P44308-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-51: Missing.

    Note: Shows the same catalytic activity as isoform Long.
    Show »
    Length:370
    Mass (Da):43,192
    Checksum:i6F99B0CA15ABBB59
    GO

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0400711 – 51Missing in isoform Short. CuratedAdd BLAST51

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    L42023 Genomic DNA. Translation: AAC22421.1.
    PIRiD64091.
    RefSeqiNP_438922.1. NC_000907.1. [P44308-1]
    WP_005690353.1. NC_000907.1.

    Genome annotation databases

    EnsemblBacteriaiAAC22421; AAC22421; HI_0763.
    GeneIDi950800.
    KEGGihin:HI0763.
    PATRICi20190177. VBIHaeInf48452_0802.

    Keywords - Coding sequence diversityi

    Alternative initiation

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    L42023 Genomic DNA. Translation: AAC22421.1.
    PIRiD64091.
    RefSeqiNP_438922.1. NC_000907.1. [P44308-1]
    WP_005690353.1. NC_000907.1.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1LW7X-ray2.90A57-421[»]
    ProteinModelPortaliP44308.
    SMRiP44308.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi71421.HI0763.

    Protein family/group databases

    TCDBi4.B.1.1.2. the nicotinamide ribonucleoside (nr) uptake permease (pnuc) family.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblBacteriaiAAC22421; AAC22421; HI_0763.
    GeneIDi950800.
    KEGGihin:HI0763.
    PATRICi20190177. VBIHaeInf48452_0802.

    Phylogenomic databases

    eggNOGiENOG4107VZS. Bacteria.
    COG1056. LUCA.
    COG3172. LUCA.
    KOiK06211.
    OMAiTAIRQKG.
    PhylomeDBiP44308.

    Enzyme and pathway databases

    UniPathwayiUPA00253; UER00600.
    UPA00253.
    BioCyciMetaCyc:MONOMER-8322.

    Miscellaneous databases

    EvolutionaryTraceiP44308.

    Family and domain databases

    Gene3Di3.40.50.300. 1 hit.
    3.40.50.620. 1 hit.
    InterProiIPR016429. Bifunc_transcrip_reg_NadR.
    IPR004821. Cyt_trans-like.
    IPR006417. NadR_NMN_Atrans.
    IPR027417. P-loop_NTPase.
    IPR014729. Rossmann-like_a/b/a_fold.
    [Graphical view]
    PfamiPF01467. CTP_transf_like. 1 hit.
    [Graphical view]
    PIRSFiPIRSF004776. NadR_NMNAT/RNK. 1 hit.
    SUPFAMiSSF52540. SSF52540. 1 hit.
    TIGRFAMsiTIGR00125. cyt_tran_rel. 1 hit.
    TIGR01526. nadR_NMN_Atrans. 1 hit.
    ProtoNetiSearch...

    Entry informationi

    Entry nameiNADR_HAEIN
    AccessioniPrimary (citable) accession number: P44308
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1995
    Last sequence update: November 1, 1995
    Last modified: November 2, 2016
    This is version 116 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Multifunctional enzyme, Reference proteome

    Documents

    1. Haemophilus influenzae
      Haemophilus influenzae (strain Rd): entries and gene names
    2. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.