Nicotinate phosphoribosyltransferase (NAPRT)

The protein contains 538 amino acids for an estimated molecular weight of 57578 Da.

 

Catalyzes the first step in the biosynthesis of NAD from nicotinic acid, the ATP-dependent synthesis of beta-nicotinate D-ribonucleotide from nicotinate and 5-phospho-D-ribose 1-phosphate (PubMed:17604275, PubMed:21742010, PubMed:26042198). Helps prevent cellular oxidative stress via its role in NAD biosynthesis (PubMed:17604275). (updated: Nov. 7, 2018)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  5. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  6. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

Interpro domains
Total structural coverage: 88%
Model score: 35

(right-click above to access to more options from the contextual menu)

VariantDescription
dbSNP:rs896950

The reference OMIM entry for this protein is 611552

Nicotinate phosphoribosyltransferase domain-containing 1; naprt1
Nicotinic acid phosphoribosyltransferase

DESCRIPTION

Nicotinic acid (NA; niacin) is converted by nicotinic acid phosphoribosyltransferase (NAPRT; EC 2.4.2.11) to NA mononucleotide (NaMN), which is then converted to NA adenine dinucleotide (NaAD), and finally to nicotinamide adenine dinucleotide (NAD), which serves as a coenzyme in cellular redox reactions and is an essential component of a variety of processes in cellular metabolism including response to stress (Hara et al., 2007).

CLONING

Using a candidate sequence of human NAPRT in GenBank (GENBANK AAH06284) and 5-prime and 3-prime RACE, Hara et al. (2007) cloned a full-length human NAPRT cDNA. NAPRT encodes a deduced 538-amino acid protein that is highly conserved. Transfection experiments with recombinant NAPRT in HepG2 cells, which normally lack NAPRT activity, localized the protein in the cytosol at the expected enzymatic activity. Northern blot analysis of mouse tissues showed that NAPRT mRNA is expressed at highest levels in the small intestine, liver, and kidney.

GENE FUNCTION

Hara et al. (2007) found that expression of a tagged recombinant NAPRT demonstrated a 54-kD protein by electrophoresis. The recombinant NAPRT catalyzed the formation of NaMN in the presence of NA, Mg(2+), and PRPP (5-phosphoribosyl 1-pyrophosphate). When NAPRT was purified from nondenaturing gels, the molecular mass was about 110 kD, indicating that the enzyme may exist as a homodimer. In cells expressing endogenous NAPRT, the addition of NA but not nicotinamide (Nam) almost doubled cellular NAD contents and decreased cytotoxicity by hydrogen peroxide. Both effects were reversed by siRNA knockdown of NAPRT expression. The results indicated that NAPRT is essential for NA to increase cellular NAD levels and, thus, to prevent oxidative stress of the cells. Kinetic analyses revealed that NAPRT but not nicotinamide phosphoribosyltransferase (NAMPT; 608764) is insensitive to the physiologic concentration of NAD. Hara et al. (2007) speculated that loss or downregulation of NAPRT and the ensuing inability to make NAD may contribute to some of the clinically observed effects of NA and implies that the vitamin might be used to treat diseases associated with depletion of NAD pools. ... More on the omim web site

Subscribe to this protein entry history

Nov. 16, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

June 20, 2017: Protein entry updated
Automatic update: comparative model was added.

March 25, 2017: Additional information
No protein expression data in P. Mayeux work for NAPRT

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 611552 was added.