Reviewed, UniProtKB/Swiss-Prot Q9NWW6 (NRK1_HUMAN)

Names and origin

Protein names

Recommended name:
    Nicotinamide riboside kinase 1
      Short name=NmR-K 1
      Short name=NRK 1
    EC=2.7.1.22
Alternative name(s):
    Ribosylnicotinamide kinase 1
      Short name=RNK 1
    Nicotinic acid riboside kinase 1
    EC=2.7.1.n4
    Ribosylnicotinic acid kinase 1

Gene names

Name:	NRK1
Synonyms:	C9orf95

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	199 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Catalyzes the phosphorylation of nicotinamide riboside (NR) and nicotinic acid riboside (NaR) to form nicotinamide mononucleotide (NMN) and nicotinic acid mononucleotide (NaMN). The enzyme also phosphorylates the antitumor drugs tiazofurin and 3-deazaguanosine. Ref.1
Catalytic activity	ATP + N-ribosylnicotinamide = ADP + nicotinamide ribonucleotide. Ref.1 Ref.6 ATP + D-ribosylnicotinate = ADP + nicotinate D-ribonucleotide. Ref.1 Ref.6
Pathway	Cofactor biosynthesis; NAD(+) biosynthesis.
Subunit structure	Monomer. Ref.6
Sequence similarities	Belongs to the uridine kinase family. NRK subfamily.
Biophysicochemical properties	Kinetic parameters: KM=0.088 mM for nicotinamide riboside (with ATP as cosubstrate) KM=0.068 mM for nicotinamide riboside (with GTP as cosubstrate) KM=0.27 mM for tiazofurin (with ATP as cosubstrate) KM=0.051 mM for nicotinic acid riboside (with ATP as cosubstrate) KM=17 mM for uridine (with ATP as cosubstrate) pH dependence: Optimum pH is 6.5-9.

Ontologies

Keywords
Biological process	Pyridine nucleotide biosynthesis
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Transferase
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	pyridine nucleotide biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW ribosylnicotinamide kinase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9NWW6-1)

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.

Isoform 2 (identifier: Q9NWW6-2)

The sequence of this isoform differs from the canonical sequence as follows:
     106-130: KPLDTIWNRSYFLTIPYEECKRRRS → N

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 199

199

Nicotinamide riboside kinase 1

PRO_0000215891

Regions

Nucleotide binding

10 – 18

9

ATP

Nucleotide binding

172 – 174

3

ATP

Sites

Active site

36

1

Proton acceptor

Metal binding

17

1

Magnesium

Metal binding

36

1

Magnesium

Binding site

56

1

Substrate

Binding site

128

1

ATP

Binding site

129

1

Substrate

Binding site

132

1

ATP

Natural variations

Alternative sequence

106 – 130

25

KPLDT…KRRRS → N in isoform 2.

VSP_012676

Experimental info

Mutagenesis

16

1

K → A: Loss of activity. Ref.8

Mutagenesis

36

1

D → A: Loss of activity. Ref.8 Ref.7

Mutagenesis

56

1

D → A: Loss of activity. Ref.8

Mutagenesis

98

1

E → A: Loss of activity. Ref.7

Mutagenesis

138

1

D → A: Almost no effect. Ref.8

Secondary structure

1

.

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199

Helix Strand Turn

Details...

Beta strand

4 – 11

8

Helix

16 – 24

9

Beta strand

30 – 34

5

Helix

35 – 38

4

Helix

42 – 44

3

Helix

58 – 60

3

Helix

63 – 77

15

Beta strand

94 – 98

5

Helix

106 – 108

3

Turn

109 – 111

3

Beta strand

113 – 119

7

Helix

122 – 131

10

Helix

142 – 145

4

Helix

147 – 157

11

Helix

158 – 160

3

Beta strand

166 – 169

4

Helix

174 – 185

12

Turn

186 – 188

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: 0A0803461F40EA32	FASTA	199	23,193
	10 20 30 40 50 60 MKTFIIGISG VTNSGKTTLA KNLQKHLPNC SVISQDDFFK PESEIETDKN GFLQYDVLEA 70 80 90 100 110 120 LNMEKMMSAI SCWMESARHS VVSTDQESAE EIPILIIEGF LLFNYKPLDT IWNRSYFLTI 130 140 150 160 170 180 PYEECKRRRS TRVYQPPDSP GYFDGHVWPM YLKYRQEMQD ITWEVVYLDG TKSEEDLFLQ 190 VYEDLIQELA KQKCLQVTA
	Isoform 2. Checksum: D197E46A962E45A7	FASTA	175	20,153
	10 20 30 40 50 60 MKTFIIGISG VTNSGKTTLA KNLQKHLPNC SVISQDDFFK PESEIETDKN GFLQYDVLEA 70 80 90 100 110 120 LNMEKMMSAI SCWMESARHS VVSTDQESAE EIPILIIEGF LLFNYNTRVY QPPDSPGYFD 130 140 150 160 170 GHVWPMYLKY RQEMQDITWE VVYLDGTKSE EDLFLQVYED LIQELAKQKC LQVTA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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: 15137942] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY.
[2]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[3]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed: 15164053] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Colon and Hippocampus.
[6]	"Purification and properties of a human nicotinamide ribonucleoside kinase." Sasiak K., Saunders P.P. Arch. Biochem. Biophys. 333:414-418(1996) [PubMed: 8809081] [Abstract] Cited for: CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT. Tissue: Placenta.
[7]	"Nicotinamide riboside kinase structures reveal new pathways to NAD+." Tempel W., Rabeh W.M., Bogan K.L., Belenky P., Wojcik M., Seidle H.F., Nedyalkova L., Yang T., Sauve A.A., Park H.-W., Brenner C. PLoS Biol. 5:2220-2230(2007) [PubMed: 17914902] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.32 ANGSTROMS) OF 2-189 IN COMPLEXES WITH SUBSTRATES, SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF ASP-36 AND GLU-98.
[8]	"Crystal structure of human nicotinamide riboside kinase." Khan J.A., Xiang S., Tong L. Structure 15:1005-1013(2007) [PubMed: 17698003] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) IN COMPLEXES WITH NUCLEOSIDE MONOPHOSPHATE; ADP AND TIAZOFURIN, MUTAGENESIS OF LYS-16; ASP-36; ASP-56 AND ASP-138.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AY611480 mRNA. Translation: AAT11928.1.
AK000566 mRNA. Translation: BAA91259.1.
AL133548 Genomic DNA. Translation: CAH71570.1.
AL133548 Genomic DNA. Translation: CAH71571.1.
CH471089 Genomic DNA. Translation: EAW62568.1.
BC001366 mRNA. Translation: AAH01366.1.
BC036804 mRNA. Translation: AAH36804.1.

IPI

IPI00178946.
IPI00936271.

RefSeq

NP_001121075.1.
NP_060351.1.

UniGene

Hs.494186

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2P0E	X-ray	1.80	A	2-189	[»]
2QG6	X-ray	1.50	A	1-199	[»]
2QL6	X-ray	2.70	A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P	1-199	[»]
2QSY	X-ray	1.95	A	2-189	[»]
2QSZ	X-ray	1.90	A	2-189	[»]
2QT0	X-ray	1.92	A	2-189	[»]
2QT1	X-ray	1.32	A	2-189	[»]

ModBase

Search...

Protein-protein interaction databases

STRING

Q9NWW6.

Proteomic databases

PRIDE

Q9NWW6.

Genome annotation databases

Ensembl

ENST00000361092; ENSP00000354387; ENSG00000106733; Homo sapiens. [Genome view]

GeneID

54981.

KEGG

hsa:54981.

NMPDR

fig|9606.3.peg.31434.

UCSC

uc004ajr.2. human.
uc004ajt.2. human.

Organism-specific databases

CTD

54981.

GeneCards

GC09M076865.

H-InvDB

HIX0008105.

HGNC

HGNC:26057. C9orf95.

MIM

608704. gene.

PharmGKB

PA134946592.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

Q9NWW6.

PhylomeDB

Q9NWW6.

Gene expression databases

ArrayExpress

Q9NWW6.

Bgee

Q9NWW6.

CleanEx

HS_C9orf95.

Genevestigator

Q9NWW6.

GermOnline

ENSG00000106733. Homo sapiens.

Family and domain databases

InterPro

IPR000764. Uridine_kinase.
[Graphical view]

PRINTS

PR00988. URIDINKINASE.

ProtoNet

Search...

Other Resources

NextBio

58250.

SOURCE

Search...

Entry information

Entry name

NRK1_HUMAN

Accession

Primary (citable) accession number: Q9NWW6
Secondary accession number(s): Q5W124, Q8N430

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 19, 2004
Last sequence update:	October 1, 2000
Last modified:	January 19, 2010
This is version 64 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.