Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 3 (NMNAT3)
The protein contains 252 amino acids for an estimated molecular weight of 28322 Da.
Catalyzes the formation of NAD(+) from nicotinamide mononucleotide (NMN) and ATP. Can also use the deamidated form; nicotinic acid mononucleotide (NaMN) as substrate with the same efficiency. Can use triazofurin monophosphate (TrMP) as substrate. Can also use GTP and ITP as nucleotide donors. Also catalyzes the reverse reaction, i.e. the pyrophosphorolytic cleavage of NAD(+). For the pyrophosphorolytic activity, can use NAD(+), NADH, NaAD, nicotinic acid adenine dinucleotide phosphate (NHD), nicotinamide guanine dinucleotide (NGD) as substrates. Fails to cleave phosphorylated dinucleotides NADP(+), NADPH and NaADP(+). Protects against axonal degeneration following injury. (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- 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.
- 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.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
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.
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Biological Process
'de novo' NAD biosynthetic process from aspartate
NAD biosynthetic process
NAD metabolic process
Nucleotide biosynthetic process
Response to tumor necrosis factor
Response to wounding
Small molecule metabolic process
Vitamin metabolic process
Water-soluble vitamin metabolic process
The reference OMIM entry for this protein is 608702
Nicotinamide nucleotide adenylyltransferase 3; nmnat3
Pyridine nucleotide adenylyltransferase 3; pnat3
DESCRIPTION
The coenzyme NAD and its derivatives are involved in hundreds of metabolic redox reactions and are utilized in protein ADP-ribosylation, histone deacetylation, and in some Ca(2+) signaling pathways. NMNAT (EC 2.7.7.1) is a central enzyme in NAD biosynthesis, catalyzing the condensation of nicotinamide mononucleotide (NMN) or nicotinic acid mononucleotide (NaMN) with the AMP moiety of ATP to form NAD or NaAD (Zhang et al., 2003).CLONING
By searching databases for sequences similar to NMNAT1 (608700) followed by PCR of a brain cDNA library, Zhang et al. (2003) cloned NMNAT3, which they called PNAT3. The deduced 252-amino acid protein contains the signature adenylyltransferase motif. NMNAT3 shares 50% amino acid identity with NMNAT1 and 82% identity with mouse Nmnat3. Northern blot analysis detected a 1.1-kb transcript expressed at high levels in lung and spleen and at lower levels in placenta and kidney. Little to no expression was detected in any other normal tissue examined or in any cancer cell lines examined. Fluorescence-tagged NMNAT3 was expressed in the cytosol of transfected HEK293 and HeLa cells. NMNAT3 was also detected within mitochondria.GENE FUNCTION
Zhang et al. (2003) determined that recombinant NMNAT3 showed a similar rate of adenylyltransferase activity with either NMN or NaMN. The activity of NMNAT3 was low compared with that of NMNAT1, but about 10-fold higher than that of NMNAT2 (608701).BIOCHEMICAL FEATURES
Zhang et al. (2003) solved the crystal structures of NMNAT3 in its apo form and in complexes with its substrates (an ATP analog, NMN, or both the ATP analog and NMN) and with its products (NAD or NaAD). The structure of monomeric NMNAT3 is similar to that of monomeric NMNAT1, with a central parallel 6-stranded beta sheet surrounded by helices. The active site residue arrangement is also similar to that of NMNAT1. The main difference is that NMNAT3 forms a tetramer, while NMNAT1 forms a hexamer.MAPPING
The International Radiation Hybrid Mapping Consortium mapped the NMNAT3 gene to chromosome 3 (TMAP RH65003). ... More on the omim web site
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 608702 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed