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Q9BZQ4

- NMNA2_HUMAN

UniProt

Q9BZQ4 - NMNA2_HUMAN

Protein

Nicotinamide mononucleotide adenylyltransferase 2

Gene

NMNAT2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 109 (01 Oct 2014)
      Sequence version 1 (01 Jun 2001)
      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 but with a lower efficiency. Cannot use triazofurin monophosphate (TrMP) as substrate. Also catalyzes the reverse reaction, i.e. the pyrophosphorolytic cleavage of NAD+. For the pyrophosphorolytic activity prefers NAD+, NADH and NAAD as substrates and degrades nicotinic acid adenine dinucleotide phosphate (NHD) less effectively. Fails to cleave phosphorylated dinucleotides NADP+, NADPH and NAADP+.2 Publications

    Catalytic activityi

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

    Cofactori

    Divalent metal cations. Magnesium confers the highest activity.3 Publications

    Enzyme regulationi

    Inhibited by P1-(adenosine-5')-P3-(nicotinamide-riboside-5')-triphosphate (Np3AD) and P1-(adenosine-5')-P4-(nicotinamide-riboside-5')-tetraphosphate (Np4AD).1 Publication

    Kineticsi

    KM is >100 µM for triazofurin monophosphate.

    1. KM=32 µM for NMN2 Publications
    2. KM=70 µM for NAD+2 Publications
    3. KM=204 µM for ATP2 Publications
    4. KM=1119 µM for PPi2 Publications
    5. KM=14.5 µM for NaMN2 Publications
    6. KM=304 µM for NMNH2 Publications

    Vmax=1.1 µmol/min/mg enzyme for NAD synthesis2 Publications

    Vmax=3 µmol/min/mg enzyme for pyrophosphorolytic NAD+ cleavage2 Publications

    Vmax=7 µmol/min/mg enzyme for pyrophosphorolytic NADH cleavage2 Publications

    pH dependencei

    Optimum pH is 6.0-9.0.3 Publications

    Pathwayi

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei16 – 161SubstrateBy similarity
    Binding sitei55 – 551SubstrateBy similarity
    Binding sitei202 – 2021SubstrateBy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi15 – 2410ATPSequence Analysis
    Nucleotide bindingi269 – 2746ATPSequence Analysis

    GO - Molecular functioni

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

    GO - Biological processi

    1. NAD biosynthetic process Source: UniProtKB
    2. NAD metabolic process Source: Reactome
    3. small molecule metabolic process Source: Reactome
    4. vitamin metabolic process Source: Reactome
    5. water-soluble vitamin metabolic process Source: Reactome

    Keywords - Molecular functioni

    Nucleotidyltransferase, Transferase

    Keywords - Biological processi

    Pyridine nucleotide biosynthesis

    Keywords - Ligandi

    ATP-binding, Magnesium, NAD, Nucleotide-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:HS08173-MONOMER.
    BRENDAi2.7.7.1. 2681.
    ReactomeiREACT_11088. Nicotinate metabolism.
    SABIO-RKQ9BZQ4.
    UniPathwayiUPA00253; UER00600.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Nicotinamide mononucleotide adenylyltransferase 2 (EC:2.7.7.1)
    Short name:
    NMN adenylyltransferase 2
    Alternative name(s):
    Nicotinate-nucleotide adenylyltransferase 2 (EC:2.7.7.18)
    Short name:
    NaMN adenylyltransferase 2
    Gene namesi
    Name:NMNAT2
    Synonyms:C1orf15, KIAA0479
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 1

    Organism-specific databases

    HGNCiHGNC:16789. NMNAT2.

    Subcellular locationi

    Cytoplasm 1 Publication. Golgi apparatus 1 Publication

    GO - Cellular componenti

    1. Golgi apparatus Source: UniProtKB
    2. Golgi membrane Source: Reactome
    3. late endosome Source: Ensembl
    4. synapse Source: Ensembl
    5. trans-Golgi network Source: Ensembl

    Keywords - Cellular componenti

    Cytoplasm, Golgi apparatus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi24 – 241H → A: Reduces activity by 95%. 1 Publication
    Mutagenesisi92 – 921W → G: Reduces activity by 95%. 1 Publication

    Organism-specific databases

    PharmGKBiPA25604.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 307307Nicotinamide mononucleotide adenylyltransferase 2PRO_0000135014Add
    BLAST

    Proteomic databases

    PaxDbiQ9BZQ4.
    PRIDEiQ9BZQ4.

    PTM databases

    PhosphoSiteiQ9BZQ4.

    Expressioni

    Tissue specificityi

    Highly expressed in brain, in particular in cerebrum, cerebellum, occipital lobe, frontal lobe, temporal lobe and putamen. Also found in the heart, skeletal muscle, pancreas and islets of Langerhans.3 Publications

    Gene expression databases

    BgeeiQ9BZQ4.
    CleanExiHS_NMNAT2.
    GenevestigatoriQ9BZQ4.

    Organism-specific databases

    HPAiHPA015240.

    Interactioni

    Subunit structurei

    Monomer.1 Publication

    Protein-protein interaction databases

    BioGridi116693. 1 interaction.
    DIPiDIP-60169N.
    STRINGi9606.ENSP00000287713.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9BZQ4.
    SMRiQ9BZQ4. Positions 9-109, 197-302.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiCOG1057.
    HOGENOMiHOG000216047.
    HOVERGENiHBG052640.
    InParanoidiQ9BZQ4.
    KOiK06210.
    OMAiPMERFTF.
    OrthoDBiEOG7PVWPQ.
    PhylomeDBiQ9BZQ4.
    TreeFamiTF315035.

    Family and domain databases

    Gene3Di3.40.50.620. 2 hits.
    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]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q9BZQ4-1) [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

    MTETTKTHVI LLACGSFNPI TKGHIQMFER ARDYLHKTGR FIVIGGIVSP    50
    VHDSYGKQGL VSSRHRLIMC QLAVQNSDWI RVDPWECYQD TWQTTCSVLE 100
    HHRDLMKRVT GCILSNVNTP SMTPVIGQPQ NETPQPIYQN SNVATKPTAA 150
    KILGKVGESL SRICCVRPPV ERFTFVDENA NLGTVMRYEE IELRILLLCG 200
    SDLLESFCIP GLWNEADMEV IVGDFGIVVV PRDAADTDRI MNHSSILRKY 250
    KNNIMVVKDD INHPMSVVSS TKSRLALQHG DGHVVDYLSQ PVIDYILKSQ 300
    LYINASG 307
    Length:307
    Mass (Da):34,439
    Last modified:June 1, 2001 - v1
    Checksum:i702F1C74B38ECECB
    GO
    Isoform 2 (identifier: Q9BZQ4-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-28: MTETTKTHVILLACGSFNPITKGHIQMF → MEIQELEEIQACQGLWEVFVTLS

    Note: No experimental confirmation available.

    Show »
    Length:302
    Mass (Da):34,015
    Checksum:i782C9FB1D5B0E153
    GO

    Sequence cautioni

    The sequence BAA32324.1 differs from that shown. Reason: Erroneous initiation.

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 2828MTETT…HIQMF → MEIQELEEIQACQGLWEVFV TLS in isoform 2. 1 PublicationVSP_015571Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF288395 mRNA. Translation: AAG60615.1.
    AB007948 mRNA. Translation: BAA32324.1. Different initiation.
    AL354953, AL356981 Genomic DNA. Translation: CAH70979.1.
    AL354953, AL356981, AL449223 Genomic DNA. Translation: CAH70982.1.
    AL356981, AL354953 Genomic DNA. Translation: CAI15467.1.
    AL356981, AL354953, AL449223 Genomic DNA. Translation: CAI15468.1.
    AL449223, AL354953, AL356981 Genomic DNA. Translation: CAI16624.1.
    BC020998 mRNA. Translation: AAH20998.1.
    CCDSiCCDS1353.1. [Q9BZQ4-1]
    CCDS1354.1. [Q9BZQ4-2]
    RefSeqiNP_055854.1. NM_015039.3. [Q9BZQ4-1]
    NP_733820.1. NM_170706.3. [Q9BZQ4-2]
    UniGeneiHs.497123.

    Genome annotation databases

    EnsembliENST00000287713; ENSP00000287713; ENSG00000157064. [Q9BZQ4-1]
    ENST00000294868; ENSP00000294868; ENSG00000157064. [Q9BZQ4-2]
    GeneIDi23057.
    KEGGihsa:23057.
    UCSCiuc001gqb.2. human. [Q9BZQ4-2]
    uc001gqc.2. human. [Q9BZQ4-1]

    Polymorphism databases

    DMDMi30580486.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF288395 mRNA. Translation: AAG60615.1 .
    AB007948 mRNA. Translation: BAA32324.1 . Different initiation.
    AL354953 , AL356981 Genomic DNA. Translation: CAH70979.1 .
    AL354953 , AL356981 , AL449223 Genomic DNA. Translation: CAH70982.1 .
    AL356981 , AL354953 Genomic DNA. Translation: CAI15467.1 .
    AL356981 , AL354953 , AL449223 Genomic DNA. Translation: CAI15468.1 .
    AL449223 , AL354953 , AL356981 Genomic DNA. Translation: CAI16624.1 .
    BC020998 mRNA. Translation: AAH20998.1 .
    CCDSi CCDS1353.1. [Q9BZQ4-1 ]
    CCDS1354.1. [Q9BZQ4-2 ]
    RefSeqi NP_055854.1. NM_015039.3. [Q9BZQ4-1 ]
    NP_733820.1. NM_170706.3. [Q9BZQ4-2 ]
    UniGenei Hs.497123.

    3D structure databases

    ProteinModelPortali Q9BZQ4.
    SMRi Q9BZQ4. Positions 9-109, 197-302.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 116693. 1 interaction.
    DIPi DIP-60169N.
    STRINGi 9606.ENSP00000287713.

    PTM databases

    PhosphoSitei Q9BZQ4.

    Polymorphism databases

    DMDMi 30580486.

    Proteomic databases

    PaxDbi Q9BZQ4.
    PRIDEi Q9BZQ4.

    Protocols and materials databases

    DNASUi 23057.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000287713 ; ENSP00000287713 ; ENSG00000157064 . [Q9BZQ4-1 ]
    ENST00000294868 ; ENSP00000294868 ; ENSG00000157064 . [Q9BZQ4-2 ]
    GeneIDi 23057.
    KEGGi hsa:23057.
    UCSCi uc001gqb.2. human. [Q9BZQ4-2 ]
    uc001gqc.2. human. [Q9BZQ4-1 ]

    Organism-specific databases

    CTDi 23057.
    GeneCardsi GC01M183217.
    HGNCi HGNC:16789. NMNAT2.
    HPAi HPA015240.
    MIMi 608701. gene.
    neXtProti NX_Q9BZQ4.
    PharmGKBi PA25604.
    HUGEi Search...
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG1057.
    HOGENOMi HOG000216047.
    HOVERGENi HBG052640.
    InParanoidi Q9BZQ4.
    KOi K06210.
    OMAi PMERFTF.
    OrthoDBi EOG7PVWPQ.
    PhylomeDBi Q9BZQ4.
    TreeFami TF315035.

    Enzyme and pathway databases

    UniPathwayi UPA00253 ; UER00600 .
    BioCyci MetaCyc:HS08173-MONOMER.
    BRENDAi 2.7.7.1. 2681.
    Reactomei REACT_11088. Nicotinate metabolism.
    SABIO-RK Q9BZQ4.

    Miscellaneous databases

    ChiTaRSi NMNAT2. human.
    GeneWikii NMNAT2.
    GenomeRNAii 23057.
    NextBioi 44115.
    PROi Q9BZQ4.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q9BZQ4.
    CleanExi HS_NMNAT2.
    Genevestigatori Q9BZQ4.

    Family and domain databases

    Gene3Di 3.40.50.620. 2 hits.
    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 ]
    ProtoNeti Search...

    Publicationsi

    1. "Cloning and characterization of 13 novel transcripts and the human RGS8 gene from the 1q25 region encompassing the hereditary prostate cancer (HPC1) locus."
      Sood R., Bonner T.I., Malakowska I., Stephan D.A., Robbins C.M., Connors T.D., Morgenbesser S.D., Su K., Faruque M.U., Pinkett H., Graham C., Baxevanis A.D., Klinger K.W., Landes G.M., Trent J.M., Carpten J.D.
      Genomics 73:211-222(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    2. "Characterization of cDNA clones in size-fractionated cDNA libraries from human brain."
      Seki N., Ohira M., Nagase T., Ishikawa K., Miyajima N., Nakajima D., Nomura N., Ohara O.
      DNA Res. 4:345-349(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Brain.
    3. "The DNA sequence and biological annotation of human chromosome 1."
      Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
      , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
      Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
      Tissue: Lung carcinoma.
    5. "Identification of a novel human nicotinamide mononucleotide adenylyltransferase."
      Raffaelli N., Sorci L., Amici A., Emanuelli M., Mazzola F., Magni G.
      Biochem. Biophys. Res. Commun. 297:835-840(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBUNIT, COFACTOR, TISSUE SPECIFICITY, PH DEPENDENCE.
    6. "Characterization of human brain nicotinamide 5'-mononucleotide adenylyltransferase-2 and expression in human pancreas."
      Yalowitz J.A., Xiao S., Biju M.P., Antony A.C., Cummings O.W., Deeg M.A., Jayaram H.N.
      Biochem. J. 377:317-326(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS OF HIS-24 AND TRP-92, COFACTOR, TISSUE SPECIFICITY.
    7. "Subcellular compartmentation and differential catalytic properties of the three human nicotinamide mononucleotide adenylyltransferase isoforms."
      Berger F., Lau C., Dahlmann M., Ziegler M.
      J. Biol. Chem. 280:36334-36341(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE SPECIFICITY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    8. "Initial-rate kinetics of human NMN-adenylyltransferases: substrate and metal ion specificity, inhibition by products and multisubstrate analogues, and isozyme contributions to NAD+ biosynthesis."
      Sorci L., Cimadamore F., Scotti S., Petrelli R., Cappellacci L., Franchetti P., Orsomando G., Magni G.
      Biochemistry 46:4912-4922(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION, COFACTOR.

    Entry informationi

    Entry nameiNMNA2_HUMAN
    AccessioniPrimary (citable) accession number: Q9BZQ4
    Secondary accession number(s): O75067
    , Q5T1Q3, Q8WU99, Q96QW1
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 9, 2003
    Last sequence update: June 1, 2001
    Last modified: October 1, 2014
    This is version 109 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 1
      Human chromosome 1: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3