Glutamine-dependent NAD(+) synthetase (NADSYN1)

The protein contains 706 amino acids for an estimated molecular weight of 79285 Da.

 

Catalyzes the final step of the nicotinamide adenine dinucleotide (NAD) de novo synthesis pathway, the ATP-dependent amidation of deamido-NAD using L-glutamine as a nitrogen source. (updated: Feb. 10, 2021)

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. 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.
  3. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  4. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.

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: 0%
Model score: 67

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VariantDescription
dbSNP:rs2276360
dbSNP:rs7950441
dbSNP:rs7121106
dbSNP:rs35007971
dbSNP:rs12282060
VCRL3; loss of protein expression
VCRL3
VCRL3

No binding partner found

The reference OMIM entry for this protein is 608285

Nad synthetase 1; nadsyn1

DESCRIPTION

Nicotinamide adenine dinucleotide (NAD) is a coenzyme in metabolic redox reactions, a precursor for several cell signaling molecules, and a substrate for protein posttranslational modifications. NAD synthetase (EC 6.3.5.1) catalyzes the final step in the biosynthesis of NAD from nicotinic acid adenine dinucleotide (NaAD) (summary by Hara et al., 2003).

CLONING

By searching EST databases for sequences similar to B. subtilis NAD synthetase, followed by PCR of a fetal brain cDNA library and 5-prime RACE of a myeloid leukemia cell cDNA library, Hara et al. (2003) cloned NADSYN1. The deduced 706-amino acid protein contains an N-terminal carbon-nitrogen hydrolase domain, a P-loop ATP-binding site, and a C-terminal NAD synthase domain. Northern blot analysis detected a 3.1-kb transcript in several mouse tissues, with highest expression in small intestine, kidney, liver, and testis, and weaker expression in skeletal muscle, spleen, lung, heart, and brain. Expression was also detected in human glioma and promyelocytic leukemia cell lines.

GENE FUNCTION

By biochemical assay of recombinant epitope-tagged NADSYN1 expressed in COS-7 cells, Hara et al. (2003) confirmed that NADSYN1 shows NAD synthetase activity. NADSYN1 utilized both glutamine and ammonia as amide donors. Omission of ATP, Mg(2+), or NaAD resulted in complete loss of NAD synthesis. A mutant NADSYN1 in which cys175, corresponding to the catalytic cysteine in nitrilases (see 604618), was replaced with ser did not utilize glutamine. Migration of the active NADSYN1 species on a nonreducing PAGE gel indicated that NADSYN1 forms a homohexamer.

MAPPING

The International Radiation Hybrid Mapping Consortium mapped the NADSYN1 gene to chromosome 11 (TMAP RH71154). ... More on the omim web site

Subscribe to this protein entry history

Feb. 16, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.

June 7, 2019: 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

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 608285 was added.