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Protein

Nicotinamide riboside kinase 2

Gene

NMRK2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Catalyzes the phosphorylation of nicotinamide riboside (NR) and nicotinic acid riboside (NaR) to form nicotinamide mononucleotide (NMN) and nicotinic acid mononucleotide (NaMN). Reduces laminin matrix deposition and cell adhesion to laminin, but not to fibronectin. Involved in the regulation of PXN at the protein level and of PXN tyrosine phosphorylation. May play a role in the regulation of terminal myogenesis.2 Publications

Catalytic activityi

ATP + 1-(beta-D-ribofuranosyl)-nicotinamide = ADP + beta-nicotinamide D-ribonucleotide.1 Publication
ATP + beta-D-ribosylnicotinate = ADP + nicotinate beta-D-ribonucleotide.1 Publication

Kineticsi

  1. KM=0.19 mM for nicotinamide riboside (with ATP as cosubstrate)1 Publication
  2. KM=30 mM for nicotinamide riboside (with GTP as cosubstrate)1 Publication
  3. KM=0.11 mM for tiazofurin (with ATP as cosubstrate)1 Publication
  4. KM=0.063 mM for nicotinic acid riboside (with ATP as cosubstrate)1 Publication
  5. KM=1.3 mM for uridine (with ATP as cosubstrate)1 Publication

    Pathwayi: NAD(+) biosynthesis

    This protein is involved in the pathway NAD(+) biosynthesis, which is part of Cofactor biosynthesis.1 Publication
    View all proteins of this organism that are known to be involved in the pathway NAD(+) biosynthesis and in Cofactor biosynthesis.

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Metal bindingi16MagnesiumBy similarity1
    Active sitei35Proton acceptorBy similarity1
    Metal bindingi35MagnesiumBy similarity1
    Binding sitei130ATPBy similarity1
    Binding sitei131SubstrateBy similarity1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi9 – 17ATPBy similarity9
    Nucleotide bindingi134 – 136ATPBy similarity3
    Nucleotide bindingi174 – 176ATPBy similarity3

    GO - Molecular functioni

    GO - Biological processi

    Keywordsi

    Molecular functionKinase, Transferase
    Biological processPyridine nucleotide biosynthesis
    LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.1.173 2681
    ReactomeiR-HSA-196807 Nicotinate metabolism
    UniPathwayiUPA00253

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Nicotinamide riboside kinase 2 (EC:2.7.1.221 Publication)
    Short name:
    NRK 2
    Short name:
    NmR-K 2
    Alternative name(s):
    Integrin beta-1-binding protein 3
    Muscle integrin-binding protein
    Short name:
    MIBP
    Nicotinic acid riboside kinase 2 (EC:2.7.1.1731 Publication)
    Ribosylnicotinamide kinase 2
    Short name:
    RNK 2
    Ribosylnicotinic acid kinase 2
    Gene namesi
    Name:NMRK2
    Synonyms:ITGB1BP3, NRK2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 19

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000077009.13
    HGNCiHGNC:17871 NMRK2
    MIMi608705 gene
    neXtProtiNX_Q9NPI5

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi35D → A: Loss of activity. 1 Publication1
    Mutagenesisi100E → A: Loss of activity. 1 Publication1

    Organism-specific databases

    OpenTargetsiENSG00000077009
    PharmGKBiPA134938442

    Polymorphism and mutation databases

    BioMutaiNMRK2
    DMDMi50401178

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00002158941 – 230Nicotinamide riboside kinase 2Add BLAST230

    Proteomic databases

    EPDiQ9NPI5
    PaxDbiQ9NPI5
    PeptideAtlasiQ9NPI5
    PRIDEiQ9NPI5
    ProteomicsDBi82019

    PTM databases

    iPTMnetiQ9NPI5
    PhosphoSitePlusiQ9NPI5

    Expressioni

    Tissue specificityi

    Predominantly expressed in skeletal muscle and, at a much lower level, in the heart (at protein level). No expression in brain, kidney, liver, lung, pancreas nor placenta.1 Publication

    Inductioni

    Down-regulated during myoblast differentiation.By similarity

    Gene expression databases

    BgeeiENSG00000077009
    CleanExiHS_ITGB1BP3
    ExpressionAtlasiQ9NPI5 baseline and differential
    GenevisibleiQ9NPI5 HS

    Organism-specific databases

    HPAiHPA049909
    HPA054792
    HPA072450

    Interactioni

    Subunit structurei

    Monomer (By similarity). Interacts with ITGB1 alone or when associated with alpha-7, but not with alpha-5.By similarity2 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    LRP12Q9Y5612EBI-514059,EBI-296693

    Protein-protein interaction databases

    BioGridi118080, 3 interactors
    CORUMiQ9NPI5
    IntActiQ9NPI5, 4 interactors
    MINTiQ9NPI5
    STRINGi9606.ENSP00000168977

    Structurei

    3D structure databases

    ProteinModelPortaliQ9NPI5
    SMRiQ9NPI5
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni35 – 38Substrate bindingBy similarity4
    Regioni54 – 55Substrate bindingBy similarity2
    Regioni136 – 137Substrate bindingBy similarity2

    Sequence similaritiesi

    Belongs to the uridine kinase family. NRK subfamily.Curated

    Phylogenomic databases

    eggNOGiKOG3308 Eukaryota
    COG0572 LUCA
    GeneTreeiENSGT00510000046782
    HOGENOMiHOG000043899
    HOVERGENiHBG052669
    InParanoidiQ9NPI5
    KOiK10524
    OMAiPQKFARA
    OrthoDBiEOG091G0JV5
    PhylomeDBiQ9NPI5
    TreeFamiTF105395

    Family and domain databases

    InterProiView protein in InterPro
    IPR027417 P-loop_NTPase
    SUPFAMiSSF52540 SSF52540, 1 hit

    Sequences (2)i

    Sequence statusi: Complete.

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

    Isoform 1 (identifier: Q9NPI5-1) [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
    MKLIVGIGGM TNGGKTTLTN SLLRALPNCC VIHQDDFFKP QDQIAVGEDG
    60 70 80 90 100
    FKQWDVLESL DMEAMLDTVQ AWLSSPQKFA RAHGVSVQPE ASDTHILLLE
    110 120 130 140 150
    GFLLYSYKPL VDLYSRRYFL TVPYEECKWR RSTRNYTVPD PPGLFDGHVW
    160 170 180 190 200
    PMYQKYRQEM EANGVEVVYL DGMKSREELF REVLEDIQNS LLNRSQESAP
    210 220 230
    SPARPARTQG PGRGCGHRTA RPAASQQDSM
    Length:230
    Mass (Da):26,046
    Last modified:October 1, 2000 - v1
    Checksum:i27F8275A596758E7
    GO
    Isoform 2 (identifier: Q9NPI5-3) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         39-39: K → KAPLFQ

    Note: No experimental confirmation available.
    Show »
    Length:235
    Mass (Da):26,602
    Checksum:i20A4D09E207DB3A8
    GO

    Sequence cautioni

    The sequence AAF26711 differs from that shown. Aberrant splicing.Curated

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_024549178E → K. Corresponds to variant dbSNP:rs16992131Ensembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_05433239K → KAPLFQ in isoform 2. 1 Publication1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF190819 mRNA Translation: AAF26711.1 Sequence problems.
    AY611481 mRNA Translation: AAT11929.1
    AL365377 mRNA Translation: CAB96949.1
    AK001663 mRNA Translation: BAA91820.1
    AK022514 mRNA Translation: BAB14071.1
    AC011488 Genomic DNA No translation available.
    BC093637 mRNA Translation: AAH93637.1
    BC101575 mRNA Translation: AAI01576.1
    BC143329 mRNA Translation: AAI43330.1
    CCDSiCCDS12115.1 [Q9NPI5-1]
    CCDS74259.1 [Q9NPI5-3]
    RefSeqiNP_001276046.1, NM_001289117.1 [Q9NPI5-3]
    NP_733778.1, NM_170678.2 [Q9NPI5-1]
    UniGeneiHs.135458

    Genome annotation databases

    EnsembliENST00000168977; ENSP00000168977; ENSG00000077009 [Q9NPI5-1]
    ENST00000593949; ENSP00000472581; ENSG00000077009 [Q9NPI5-3]
    ENST00000616156; ENSP00000480091; ENSG00000077009 [Q9NPI5-3]
    GeneIDi27231
    KEGGihsa:27231
    UCSCiuc002lyz.4 human [Q9NPI5-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Similar proteinsi

    Entry informationi

    Entry nameiNRK2_HUMAN
    AccessioniPrimary (citable) accession number: Q9NPI5
    Secondary accession number(s): B7ZKR3, Q52M81, Q9NZK3
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 19, 2004
    Last sequence update: October 1, 2000
    Last modified: June 20, 2018
    This is version 125 of the entry and version 1 of the sequence. See 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

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