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Protein

Nicotinamide riboside kinase 2

Gene

NMRK2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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.
ATP + beta-D-ribosylnicotinate = ADP + nicotinate beta-D-ribonucleotide.

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

    Pathway:iNAD(+) biosynthesis

    This protein is involved in 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.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi16 – 161MagnesiumBy similarity
    Active sitei35 – 351Proton acceptorBy similarity
    Metal bindingi35 – 351MagnesiumBy similarity
    Binding sitei55 – 551SubstrateBy similarity
    Binding sitei130 – 1301ATPBy similarity
    Binding sitei131 – 1311SubstrateBy similarity
    Binding sitei134 – 1341ATPBy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi9 – 179ATPBy similarity

    GO - Molecular functioni

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Kinase, Transferase

    Keywords - Biological processi

    Pyridine nucleotide biosynthesis

    Keywords - Ligandi

    ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.1.173. 2681.
    UniPathwayiUPA00253.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Nicotinamide riboside kinase 2 (EC:2.7.1.22)
    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:2.7.1.173)
    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
    ProteomesiUP000005640 Componenti: Chromosome 19

    Organism-specific databases

    HGNCiHGNC:17871. NMRK2.

    Subcellular locationi

    GO - Cellular componenti

    Complete GO annotation...

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi35 – 351D → A: Loss of activity. 1 Publication
    Mutagenesisi100 – 1001E → A: Loss of activity. 1 Publication

    Organism-specific databases

    PharmGKBiPA134938442.

    Polymorphism and mutation databases

    BioMutaiNMRK2.
    DMDMi50401178.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 230230Nicotinamide riboside kinase 2PRO_0000215894Add
    BLAST

    Proteomic databases

    PaxDbiQ9NPI5.
    PRIDEiQ9NPI5.

    PTM databases

    PhosphoSiteiQ9NPI5.

    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

    BgeeiQ9NPI5.
    CleanExiHS_ITGB1BP3.
    ExpressionAtlasiQ9NPI5. baseline and differential.
    GenevisibleiQ9NPI5. HS.

    Organism-specific databases

    HPAiHPA049909.

    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. 4 interactions.
    IntActiQ9NPI5. 4 interactions.
    MINTiMINT-1401053.
    STRINGi9606.ENSP00000168977.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9NPI5.
    SMRiQ9NPI5. Positions 3-191.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the uridine kinase family. NRK subfamily.Curated

    Phylogenomic databases

    eggNOGiCOG0572.
    GeneTreeiENSGT00510000046782.
    HOGENOMiHOG000043899.
    HOVERGENiHBG052669.
    InParanoidiQ9NPI5.
    KOiK10524.
    OMAiHRKQMED.
    OrthoDBiEOG7JQBPF.
    PhylomeDBiQ9NPI5.
    TreeFamiTF105395.

    Family and domain databases

    Gene3Di3.40.50.300. 1 hit.
    InterProiIPR027417. P-loop_NTPase.
    [Graphical view]
    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 AAF26711.1 differs from that shown.Aberrant splicing.Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti178 – 1781E → K.
    Corresponds to variant rs16992131 [ dbSNP | Ensembl ].
    VAR_024549

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei39 – 391K → KAPLFQ in isoform 2. 1 PublicationVSP_054332

    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.
    ENST00000593949; ENSP00000472581; ENSG00000077009. [Q9NPI5-3]
    ENST00000616156; ENSP00000480091; ENSG00000077009. [Q9NPI5-3]
    GeneIDi27231.
    KEGGihsa:27231.
    UCSCiuc002lyz.4. human. [Q9NPI5-1]
    uc010xia.2. human.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    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.

    3D structure databases

    ProteinModelPortaliQ9NPI5.
    SMRiQ9NPI5. Positions 3-191.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi118080. 4 interactions.
    IntActiQ9NPI5. 4 interactions.
    MINTiMINT-1401053.
    STRINGi9606.ENSP00000168977.

    PTM databases

    PhosphoSiteiQ9NPI5.

    Polymorphism and mutation databases

    BioMutaiNMRK2.
    DMDMi50401178.

    Proteomic databases

    PaxDbiQ9NPI5.
    PRIDEiQ9NPI5.

    Protocols and materials databases

    DNASUi27231.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000168977; ENSP00000168977; ENSG00000077009.
    ENST00000593949; ENSP00000472581; ENSG00000077009. [Q9NPI5-3]
    ENST00000616156; ENSP00000480091; ENSG00000077009. [Q9NPI5-3]
    GeneIDi27231.
    KEGGihsa:27231.
    UCSCiuc002lyz.4. human. [Q9NPI5-1]
    uc010xia.2. human.

    Organism-specific databases

    CTDi27231.
    GeneCardsiGC19P003933.
    HGNCiHGNC:17871. NMRK2.
    HPAiHPA049909.
    MIMi608705. gene.
    neXtProtiNX_Q9NPI5.
    PharmGKBiPA134938442.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiCOG0572.
    GeneTreeiENSGT00510000046782.
    HOGENOMiHOG000043899.
    HOVERGENiHBG052669.
    InParanoidiQ9NPI5.
    KOiK10524.
    OMAiHRKQMED.
    OrthoDBiEOG7JQBPF.
    PhylomeDBiQ9NPI5.
    TreeFamiTF105395.

    Enzyme and pathway databases

    UniPathwayiUPA00253.
    BRENDAi2.7.1.173. 2681.

    Miscellaneous databases

    GeneWikiiITGB1BP3.
    GenomeRNAii27231.
    NextBioi35481178.
    PROiQ9NPI5.
    SOURCEiSearch...

    Gene expression databases

    BgeeiQ9NPI5.
    CleanExiHS_ITGB1BP3.
    ExpressionAtlasiQ9NPI5. baseline and differential.
    GenevisibleiQ9NPI5. HS.

    Family and domain databases

    Gene3Di3.40.50.300. 1 hit.
    InterProiIPR027417. P-loop_NTPase.
    [Graphical view]
    SUPFAMiSSF52540. SSF52540. 1 hit.
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "A novel muscle-specific beta 1 integrin binding protein (MIBP) that modulates myogenic differentiation."
      Li J., Mayne R., Wu C.
      J. Cell Biol. 147:1391-1398(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH ITGB1.
      Tissue: Heart.
    2. "Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes establish a Preiss-Handler independent route to NAD+ in fungi and humans."
      Bieganowski P., Brenner C.
      Cell 117:495-502(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION.
    3. The European IMAGE consortium
      Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    4. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Teratocarcinoma.
    5. "The DNA sequence and biology of human chromosome 19."
      Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V.
      , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
      Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. "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] (ISOFORMS 1 AND 2).
      Tissue: Liver.
    7. "The muscle integrin binding protein (MIBP) interacts with alpha7beta1 integrin and regulates cell adhesion and laminin matrix deposition."
      Li J., Rao H., Burkin D., Kaufman S.J., Wu C.
      Dev. Biol. 261:209-219(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH INTEGRIN ALPHA-7/BETA-1.
    8. Cited for: SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF ASP-35 AND GLU-100.

    Entry informationi

    Entry nameiNRK2_HUMAN
    AccessioniPrimary (citable) accession number: Q9NPI5
    Secondary accession number(s): B7ZKR3, Q52M81, Q9NZK3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 19, 2004
    Last sequence update: October 1, 2000
    Last modified: July 22, 2015
    This is version 107 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 19
      Human chromosome 19: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3

    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 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.