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Q9EPA7

- NMNA1_MOUSE

UniProt

Q9EPA7 - NMNA1_MOUSE

Protein

Nicotinamide mononucleotide adenylyltransferase 1

Gene

Nmnat1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 105 (01 Oct 2014)
      Sequence version 2 (09 May 2003)
      Previous versions | rss
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    Functioni

    Catalyzes the formation of NAD+ from nicotinamide mononucleotide (NMN) and ATP. Can also use the deamidated form; nicotinic acid mononucleotide (NaMN) as substrate with the same efficiency. Can use triazofurin monophosphate (TrMP) as substrate. Also catalyzes the reverse reaction, i.e. the pyrophosphorolytic cleavage of NAD+. For the pyrophosphorolytic activity, prefers NAD+ and NAAD as substrates and degrades NADH, nicotinic acid adenine dinucleotide phosphate (NHD) and nicotinamide guanine dinucleotide (NGD) less effectively. Fails to cleave phosphorylated dinucleotides NADP+, NADPH and NAADP+ By similarity. Protects against axonal degeneration following mechanical or toxic insults. Delays axonal degeneration after axotomy. Results in a >10-fold increase in intact neurites 72 hours after injury.By similarity2 Publications

    Catalytic activityi

    ATP + nicotinamide ribonucleotide = diphosphate + NAD+.By similarity
    ATP + beta-nicotinate-D-ribonucleotide = diphosphate + deamido-NAD+.

    Cofactori

    Divalent metal cations. Zinc confers higher activity than magnesium By similarity.By similarity

    Enzyme regulationi

    Activity is strongly inhibited by galotannin. Inhibited by P1-(adenosine-5')-P4-(nicotinic-acid-riboside-5')-tetraphosphate (Nap4AD) By similarity.By similarity

    Kineticsi

    1. KM=20.1 µM for nicotinamide mononucleotide (NMN)1 Publication

    Vmax=34.1 µmol/min/mg enzyme1 Publication

    Pathwayi

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei16 – 161SubstrateBy similarity
    Binding sitei55 – 551SubstrateBy similarity
    Binding sitei159 – 1591SubstrateBy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi15 – 2410ATPSequence Analysis
    Nucleotide bindingi223 – 2286ATPSequence Analysis

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. nicotinamide-nucleotide adenylyltransferase activity Source: UniProtKB
    3. nicotinate-nucleotide adenylyltransferase activity Source: UniProtKB-EC

    GO - Biological processi

    1. NAD biosynthetic process Source: UniProtKB-UniPathway

    Keywords - Molecular functioni

    Nucleotidyltransferase, Transferase

    Keywords - Biological processi

    Pyridine nucleotide biosynthesis

    Keywords - Ligandi

    ATP-binding, Magnesium, NAD, Nucleotide-binding, Zinc

    Enzyme and pathway databases

    BRENDAi2.7.7.1. 3474.
    ReactomeiREACT_209575. Nicotinate metabolism.
    SABIO-RKQ9EPA7.
    UniPathwayiUPA00253; UER00600.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Nicotinamide mononucleotide adenylyltransferase 1 (EC:2.7.7.1)
    Short name:
    NMN adenylyltransferase 1
    Alternative name(s):
    Nicotinate-nucleotide adenylyltransferase 1 (EC:2.7.7.18)
    Short name:
    NaMN adenylyltransferase 1
    Gene namesi
    Name:Nmnat1
    Synonyms:D4Cole1e, Nmnat
    OrganismiMus musculus (Mouse)Imported
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 4

    Organism-specific databases

    MGIiMGI:1913704. Nmnat1.

    Subcellular locationi

    Nucleus 1 Publication

    GO - Cellular componenti

    1. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi125 – 1284RKRK → AAAA: Locates to the cytoplasm. Has no affect on enzyme activity or axonal protection. 1 Publication
    Mutagenesisi170 – 1701W → A: Decrease in enzyme activity. Has no axonal protective effect. 2 Publications

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 285285Nicotinamide mononucleotide adenylyltransferase 1PRO_0000135013Add
    BLAST

    Post-translational modificationi

    Phosphorylated.By similarity

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiQ9EPA7.
    PaxDbiQ9EPA7.
    PRIDEiQ9EPA7.

    PTM databases

    PhosphoSiteiQ9EPA7.

    Expressioni

    Developmental stagei

    Expressed throughout development and in adulthood.1 Publication

    Inductioni

    By neuronal injury.

    Gene expression databases

    ArrayExpressiQ9EPA7.
    BgeeiQ9EPA7.
    CleanExiMM_NMNAT1.
    GenevestigatoriQ9EPA7.

    Interactioni

    Subunit structurei

    Homohexamer. Interacts with ADPRT/PARP1 By similarity.By similarity

    Protein-protein interaction databases

    STRINGi10090.ENSMUSP00000030845.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9EPA7.
    SMRiQ9EPA7. Positions 6-276.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi123 – 1297Nuclear localization signalSequence Analysis

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiCOG1057.
    GeneTreeiENSGT00530000063189.
    HOGENOMiHOG000216047.
    HOVERGENiHBG052640.
    InParanoidiQ9EPA7.
    KOiK06210.
    OMAiHRVAMCQ.
    PhylomeDBiQ9EPA7.
    TreeFamiTF315035.

    Family and domain databases

    Gene3Di3.40.50.620. 1 hit.
    InterProiIPR004821. Cyt_trans-like.
    IPR005248. NAMN_adtrnsfrase.
    IPR014729. Rossmann-like_a/b/a_fold.
    [Graphical view]
    PANTHERiPTHR12039. PTHR12039. 1 hit.
    PfamiPF01467. CTP_transf_2. 1 hit.
    [Graphical view]
    TIGRFAMsiTIGR00482. TIGR00482. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    Q9EPA7-1 [UniParc]FASTAAdd to Basket

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    MDSSKKTEVV LLACGSFNPI TNMHLRLFEL AKDYMHATGK YSVIKGIISP    50
    VGDAYKKKGL IPAHHRIIMA ELATKNSHWV EVDTWESLQK EWVETVKVLR 100
    YHQEKLATGS CSYPQSSPAL EKPGRKRKWA DQKQDSSPQK PQEPKPTGVP 150
    KVKLLCGADL LESFSVPNLW KMEDITQIVA NFGLICITRA GSDAQKFIYE 200
    SDVLWRHQSN IHLVNEWITN DISSTKIRRA LRRGQSIRYL VPDLVQEYIE 250
    KHELYNTESE GRNAGVTLAP LQRNAAEAKH NHSTL 285
    Length:285
    Mass (Da):32,355
    Last modified:May 9, 2003 - v2
    Checksum:i2769D42E894EB84F
    GO

    Sequence cautioni

    The sequence AAG17285.1 differs from that shown. Reason: Erroneous initiation.
    The sequence AAG17286.1 differs from that shown. Reason: Erroneous initiation.
    The sequence AAG38490.1 differs from that shown. Reason: Erroneous initiation.

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF260924 mRNA. Translation: AAG17285.1. Different initiation.
    AF260925 mRNA. Translation: AAG17286.1. Different initiation.
    AF260927 Genomic DNA. Translation: AAG38490.1. Different initiation.
    AY679721 mRNA. Translation: AAT76443.1.
    CCDSiCCDS18960.1.
    RefSeqiNP_597679.1. NM_133435.1.
    XP_006539168.1. XM_006539105.1.
    UniGeneiMm.76062.

    Genome annotation databases

    EnsembliENSMUST00000030845; ENSMUSP00000030845; ENSMUSG00000028992.
    ENSMUST00000105693; ENSMUSP00000101318; ENSMUSG00000028992.
    GeneIDi66454.
    KEGGimmu:66454.
    UCSCiuc008vwj.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF260924 mRNA. Translation: AAG17285.1 . Different initiation.
    AF260925 mRNA. Translation: AAG17286.1 . Different initiation.
    AF260927 Genomic DNA. Translation: AAG38490.1 . Different initiation.
    AY679721 mRNA. Translation: AAT76443.1 .
    CCDSi CCDS18960.1.
    RefSeqi NP_597679.1. NM_133435.1.
    XP_006539168.1. XM_006539105.1.
    UniGenei Mm.76062.

    3D structure databases

    ProteinModelPortali Q9EPA7.
    SMRi Q9EPA7. Positions 6-276.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 10090.ENSMUSP00000030845.

    PTM databases

    PhosphoSitei Q9EPA7.

    Proteomic databases

    MaxQBi Q9EPA7.
    PaxDbi Q9EPA7.
    PRIDEi Q9EPA7.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000030845 ; ENSMUSP00000030845 ; ENSMUSG00000028992 .
    ENSMUST00000105693 ; ENSMUSP00000101318 ; ENSMUSG00000028992 .
    GeneIDi 66454.
    KEGGi mmu:66454.
    UCSCi uc008vwj.1. mouse.

    Organism-specific databases

    CTDi 64802.
    MGIi MGI:1913704. Nmnat1.

    Phylogenomic databases

    eggNOGi COG1057.
    GeneTreei ENSGT00530000063189.
    HOGENOMi HOG000216047.
    HOVERGENi HBG052640.
    InParanoidi Q9EPA7.
    KOi K06210.
    OMAi HRVAMCQ.
    PhylomeDBi Q9EPA7.
    TreeFami TF315035.

    Enzyme and pathway databases

    UniPathwayi UPA00253 ; UER00600 .
    BRENDAi 2.7.7.1. 3474.
    Reactomei REACT_209575. Nicotinate metabolism.
    SABIO-RK Q9EPA7.

    Miscellaneous databases

    ChiTaRSi NMNAT1. mouse.
    NextBioi 321736.
    PROi Q9EPA7.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9EPA7.
    Bgeei Q9EPA7.
    CleanExi MM_NMNAT1.
    Genevestigatori Q9EPA7.

    Family and domain databases

    Gene3Di 3.40.50.620. 1 hit.
    InterProi IPR004821. Cyt_trans-like.
    IPR005248. NAMN_adtrnsfrase.
    IPR014729. Rossmann-like_a/b/a_fold.
    [Graphical view ]
    PANTHERi PTHR12039. PTHR12039. 1 hit.
    Pfami PF01467. CTP_transf_2. 1 hit.
    [Graphical view ]
    TIGRFAMsi TIGR00482. TIGR00482. 1 hit.
    ProtoNeti Search...

    Publicationsi

    1. "A Ufd2/D4Cole1e chimeric protein and overexpression of Rbp7 in the slow Wallerian degeneration (WldS) mouse."
      Conforti L., Tarlton A., Mack T.G.A., Mi W., Buckmaster E.A., Wagner D., Perry V.H., Coleman M.P.
      Proc. Natl. Acad. Sci. U.S.A. 97:11377-11382(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
      Strain: 129, C57BL/6J and C57BL/Ola.
    2. "The NAD biosynthesis pathway mediated by nicotinamide phosphoribosyltransferase regulates Sir2 activity in mammalian cells."
      Revollo J.R., Grimm A.A., Imai S.
      J. Biol. Chem. 279:50754-50763(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], BIOPHYSICOCHEMICAL PROPERTIES.
      Strain: BALB/c.
      Tissue: Liver.
    3. "Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration."
      Araki T., Sasaki Y., Milbrandt J.
      Science 305:1010-1013(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, MUTAGENESIS OF TRP-170.
    4. "Stimulation of nicotinamide adenine dinucleotide biosynthetic pathways delays axonal degeneration after axotomy."
      Sasaki Y., Araki T., Milbrandt J.
      J. Neurosci. 26:8484-8491(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, MUTAGENESIS OF 125-ARG--LYS-128.

    Entry informationi

    Entry nameiNMNA1_MOUSE
    AccessioniPrimary (citable) accession number: Q9EPA7
    Secondary accession number(s): Q6B504
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 9, 2003
    Last sequence update: May 9, 2003
    Last modified: October 1, 2014
    This is version 105 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    In strain C57BL/Ola, an 85 kb region on chromosome 4 containing Nmnat1 and Ube4b is triplicated. The N-terminal 70 residues of Ube4b becomes linked to the complete Nmnat1 protein and encodes a fusion protein located in the nucleus which is responsible for the Wallerian degeneration slow (Wlds) phenotype characterized by delayed Wallerian degeneration of injured axons.

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3