NRK2_HUMAN
ID NRK2_HUMAN Reviewed; 230 AA.
AC Q9NPI5; B7ZKR3; Q52M81; Q9NZK3;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Nicotinamide riboside kinase 2;
DE Short=NRK 2;
DE Short=NmR-K 2;
DE EC=2.7.1.22 {ECO:0000269|PubMed:17914902};
DE AltName: Full=Integrin beta-1-binding protein 3;
DE AltName: Full=Muscle integrin-binding protein;
DE Short=MIBP;
DE AltName: Full=Nicotinic acid riboside kinase 2;
DE EC=2.7.1.173 {ECO:0000269|PubMed:17914902};
DE AltName: Full=Ribosylnicotinamide kinase 2;
DE Short=RNK 2;
DE AltName: Full=Ribosylnicotinic acid kinase 2;
GN Name=NMRK2; Synonyms=ITGB1BP3, NRK2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, AND
RP INTERACTION WITH ITGB1.
RC TISSUE=Heart;
RX PubMed=10613898; DOI=10.1083/jcb.147.7.1391;
RA Li J., Mayne R., Wu C.;
RT "A novel muscle-specific beta 1 integrin binding protein (MIBP) that
RT modulates myogenic differentiation.";
RL J. Cell Biol. 147:1391-1398(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION.
RX PubMed=15137942; DOI=10.1016/s0092-8674(04)00416-7;
RA Bieganowski P., Brenner C.;
RT "Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes
RT establish a Preiss-Handler independent route to NAD+ in fungi and humans.";
RL Cell 117:495-502(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RG The European IMAGE consortium;
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Teratocarcinoma;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Liver;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP INTERACTION WITH INTEGRIN ALPHA-7/BETA-1.
RX PubMed=12941630; DOI=10.1016/s0012-1606(03)00304-x;
RA Li J., Rao H., Burkin D., Kaufman S.J., Wu C.;
RT "The muscle integrin binding protein (MIBP) interacts with alpha7beta1
RT integrin and regulates cell adhesion and laminin matrix deposition.";
RL Dev. Biol. 261:209-219(2003).
RN [8]
RP SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES, CATALYTIC ACTIVITY,
RP AND MUTAGENESIS OF ASP-35 AND GLU-100.
RX PubMed=17914902; DOI=10.1371/journal.pbio.0050263;
RA Tempel W., Rabeh W.M., Bogan K.L., Belenky P., Wojcik M., Seidle H.F.,
RA Nedyalkova L., Yang T., Sauve A.A., Park H.-W., Brenner C.;
RT "Nicotinamide riboside kinase structures reveal new pathways to NAD+.";
RL PLoS Biol. 5:2220-2230(2007).
CC -!- FUNCTION: Catalyzes the phosphorylation of nicotinamide riboside (NR)
CC and nicotinic acid riboside (NaR) to form nicotinamide mononucleotide
CC (NMN) and nicotinic acid mononucleotide (NaMN). Reduces laminin matrix
CC deposition and cell adhesion to laminin, but not to fibronectin.
CC Involved in the regulation of PXN at the protein level and of PXN
CC tyrosine phosphorylation. May play a role in the regulation of terminal
CC myogenesis. {ECO:0000269|PubMed:10613898, ECO:0000269|PubMed:15137942}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + beta-nicotinamide D-riboside = ADP + beta-nicotinamide
CC D-ribonucleotide + H(+); Xref=Rhea:RHEA:14017, ChEBI:CHEBI:14649,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15927, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:456216; EC=2.7.1.22;
CC Evidence={ECO:0000269|PubMed:17914902};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + beta-D-ribosylnicotinate = ADP + H(+) + nicotinate beta-
CC D-ribonucleotide; Xref=Rhea:RHEA:25568, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:57502, ChEBI:CHEBI:58527,
CC ChEBI:CHEBI:456216; EC=2.7.1.173;
CC Evidence={ECO:0000269|PubMed:17914902};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.19 mM for nicotinamide riboside (with ATP as cosubstrate)
CC {ECO:0000269|PubMed:17914902};
CC KM=30 mM for nicotinamide riboside (with GTP as cosubstrate)
CC {ECO:0000269|PubMed:17914902};
CC KM=0.11 mM for tiazofurin (with ATP as cosubstrate)
CC {ECO:0000269|PubMed:17914902};
CC KM=0.063 mM for nicotinic acid riboside (with ATP as cosubstrate)
CC {ECO:0000269|PubMed:17914902};
CC KM=1.3 mM for uridine (with ATP as cosubstrate)
CC {ECO:0000269|PubMed:17914902};
CC -!- PATHWAY: Cofactor biosynthesis; NAD(+) biosynthesis.
CC {ECO:0000305|PubMed:17914902}.
CC -!- SUBUNIT: Monomer (By similarity). Interacts with ITGB1 alone or when
CC associated with alpha-7, but not with alpha-5. {ECO:0000250,
CC ECO:0000269|PubMed:10613898, ECO:0000269|PubMed:12941630}.
CC -!- INTERACTION:
CC Q9NPI5; Q9Y561: LRP12; NbExp=2; IntAct=EBI-514059, EBI-296693;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9NPI5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NPI5-3; Sequence=VSP_054332;
CC -!- TISSUE SPECIFICITY: Predominantly expressed in skeletal muscle and, at
CC a much lower level, in the heart (at protein level). No expression in
CC brain, kidney, liver, lung, pancreas nor placenta.
CC {ECO:0000269|PubMed:10613898}.
CC -!- INDUCTION: Down-regulated during myoblast differentiation.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the uridine kinase family. NRK subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF26711.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305};
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DR EMBL; AF190819; AAF26711.1; ALT_SEQ; mRNA.
DR EMBL; AY611481; AAT11929.1; -; mRNA.
DR EMBL; AL365377; CAB96949.1; -; mRNA.
DR EMBL; AK001663; BAA91820.1; -; mRNA.
DR EMBL; AK022514; BAB14071.1; -; mRNA.
DR EMBL; AC011488; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC093637; AAH93637.1; -; mRNA.
DR EMBL; BC101575; AAI01576.1; -; mRNA.
DR EMBL; BC143329; AAI43330.1; -; mRNA.
DR CCDS; CCDS12115.1; -. [Q9NPI5-1]
DR CCDS; CCDS74259.1; -. [Q9NPI5-3]
DR RefSeq; NP_001276046.1; NM_001289117.1. [Q9NPI5-3]
DR RefSeq; NP_733778.1; NM_170678.2. [Q9NPI5-1]
DR AlphaFoldDB; Q9NPI5; -.
DR SMR; Q9NPI5; -.
DR BioGRID; 118080; 5.
DR CORUM; Q9NPI5; -.
DR IntAct; Q9NPI5; 4.
DR MINT; Q9NPI5; -.
DR STRING; 9606.ENSP00000480091; -.
DR iPTMnet; Q9NPI5; -.
DR PhosphoSitePlus; Q9NPI5; -.
DR BioMuta; NMRK2; -.
DR DMDM; 50401178; -.
DR EPD; Q9NPI5; -.
DR MassIVE; Q9NPI5; -.
DR PaxDb; Q9NPI5; -.
DR PeptideAtlas; Q9NPI5; -.
DR PRIDE; Q9NPI5; -.
DR ProteomicsDB; 82019; -. [Q9NPI5-1]
DR Antibodypedia; 23411; 107 antibodies from 20 providers.
DR DNASU; 27231; -.
DR Ensembl; ENST00000168977.7; ENSP00000168977.1; ENSG00000077009.14. [Q9NPI5-1]
DR Ensembl; ENST00000593949.1; ENSP00000472581.1; ENSG00000077009.14. [Q9NPI5-3]
DR Ensembl; ENST00000616156.4; ENSP00000480091.1; ENSG00000077009.14. [Q9NPI5-3]
DR GeneID; 27231; -.
DR KEGG; hsa:27231; -.
DR MANE-Select; ENST00000168977.7; ENSP00000168977.1; NM_170678.3; NP_733778.1.
DR UCSC; uc002lyz.4; human. [Q9NPI5-1]
DR CTD; 27231; -.
DR DisGeNET; 27231; -.
DR GeneCards; NMRK2; -.
DR HGNC; HGNC:17871; NMRK2.
DR HPA; ENSG00000077009; Group enriched (heart muscle, skeletal muscle, tongue).
DR MIM; 608705; gene.
DR neXtProt; NX_Q9NPI5; -.
DR OpenTargets; ENSG00000077009; -.
DR PharmGKB; PA134938442; -.
DR VEuPathDB; HostDB:ENSG00000077009; -.
DR eggNOG; KOG3308; Eukaryota.
DR GeneTree; ENSGT00940000159842; -.
DR HOGENOM; CLU_058668_0_0_1; -.
DR InParanoid; Q9NPI5; -.
DR OMA; YQKYRRE; -.
DR OrthoDB; 1230625at2759; -.
DR PhylomeDB; Q9NPI5; -.
DR TreeFam; TF105395; -.
DR BRENDA; 2.7.1.173; 2681.
DR BRENDA; 2.7.1.22; 2681.
DR PathwayCommons; Q9NPI5; -.
DR Reactome; R-HSA-196807; Nicotinate metabolism.
DR SignaLink; Q9NPI5; -.
DR UniPathway; UPA00253; -.
DR BioGRID-ORCS; 27231; 10 hits in 1066 CRISPR screens.
DR ChiTaRS; NMRK2; human.
DR GeneWiki; ITGB1BP3; -.
DR GenomeRNAi; 27231; -.
DR Pharos; Q9NPI5; Tbio.
DR PRO; PR:Q9NPI5; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9NPI5; protein.
DR Bgee; ENSG00000077009; Expressed in apex of heart and 126 other tissues.
DR ExpressionAtlas; Q9NPI5; baseline and differential.
DR Genevisible; Q9NPI5; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0050262; F:ribosylnicotinamide kinase activity; EXP:Reactome.
DR GO; GO:0061769; F:ribosylnicotinate kinase activity; EXP:Reactome.
DR GO; GO:0009435; P:NAD biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0019674; P:NAD metabolic process; TAS:Reactome.
DR GO; GO:0045662; P:negative regulation of myoblast differentiation; IEA:Ensembl.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR SUPFAM; SSF52540; SSF52540; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Kinase; Magnesium; Metal-binding;
KW Nucleotide-binding; Pyridine nucleotide biosynthesis; Reference proteome;
KW Transferase.
FT CHAIN 1..230
FT /note="Nicotinamide riboside kinase 2"
FT /id="PRO_0000215894"
FT REGION 191..230
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 35
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q9NWW6"
FT BINDING 9..17
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9NWW6"
FT BINDING 16
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q9NWW6"
FT BINDING 35..38
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9NWW6"
FT BINDING 35
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q9NWW6"
FT BINDING 54..55
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9NWW6"
FT BINDING 130
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9NWW6"
FT BINDING 131
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9NWW6"
FT BINDING 134..136
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9NWW6"
FT BINDING 136..137
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9NWW6"
FT BINDING 174..176
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9NWW6"
FT VAR_SEQ 39
FT /note="K -> KAPLFQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_054332"
FT VARIANT 178
FT /note="E -> K (in dbSNP:rs16992131)"
FT /id="VAR_024549"
FT MUTAGEN 35
FT /note="D->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:17914902"
FT MUTAGEN 100
FT /note="E->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:17914902"
SQ SEQUENCE 230 AA; 26046 MW; 27F8275A596758E7 CRC64;
MKLIVGIGGM TNGGKTTLTN SLLRALPNCC VIHQDDFFKP QDQIAVGEDG FKQWDVLESL
DMEAMLDTVQ AWLSSPQKFA RAHGVSVQPE ASDTHILLLE GFLLYSYKPL VDLYSRRYFL
TVPYEECKWR RSTRNYTVPD PPGLFDGHVW PMYQKYRQEM EANGVEVVYL DGMKSREELF
REVLEDIQNS LLNRSQESAP SPARPARTQG PGRGCGHRTA RPAASQQDSM
