NMNAT1

This gene encodes an enzyme which catalyzes a key step in the biosynthesis of nicotinamide adenine dinucleotide (NAD). The encoded enzyme is one of several nicotinamide nucleotide adenylyltransferases, and is specifically localized to the cell nucleus. Activity of this protein leads to the activation of a nuclear deacetylase that functions in the protection of damaged neurons. Mutations in this gene have been associated with Leber congenital amaurosis 9. Alternative splicing results in multiple transcript variants. Pseudogenes of this gene are located on chromosomes 1, 3, 4, 14, and 15. [provided by RefSeq, Jul 2014]

Full Name

Nicotinamide Nucleotide Adenylyltransferase 1

Function

Catalyzes the formation of NAD+ from nicotinamide mononucleotide (NMN) and ATP (PubMed:17402747).
Can also use the deamidated form; nicotinic acid mononucleotide (NaMN) as substrate with the same efficiency (PubMed:17402747).
Can use triazofurin monophosphate (TrMP) as substrate (PubMed:17402747).
Also catalyzes the reverse reaction, i.e. the pyrophosphorolytic cleavage of NAD+ (PubMed:17402747).
For the pyrophosphorolytic activity, prefers NAD+ and NaAD as substrates and degrades NADH, nicotinic acid adenine dinucleotide phosphate (NHD) and nicotinamide guanine dinucleotide (NGD) less effectively (PubMed:17402747).
Involved in the synthesis of ATP in the nucleus, together with PARP1, PARG and NUDT5 (PubMed:27257257).
Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming (PubMed:27257257).
Fails to cleave phosphorylated dinucleotides NADP+, NADPH and NaADP+ (PubMed:17402747).
Protects against axonal degeneration following mechanical or toxic insults (By similarity).

Biological Process

ATP generation from poly-ADP-D-riboseManual Assertion Based On ExperimentIDA:UniProtKB
NAD biosynthetic processManual Assertion Based On ExperimentIBA:GO_Central
Negative regulation of neuron deathIEA:Ensembl
Nucleotide biosynthetic process1 PublicationIC:UniProtKB
Response to woundingIEA:Ensembl

Cellular Location

Nucleus

Involvement in disease

Leber congenital amaurosis 9 (LCA9):
A severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus.
Spondyloepiphyseal dysplasia, sensorineural hearing loss, impaired intellectual development, and Leber congenital amaurosis (SHILCA):
An autosomal recessive disorder characterized by early-onset retinal degeneration, sensorineural hearing loss, short stature due to spondyloepiphyseal dysplasia, and motor and intellectual delay. Brain imaging shows abnormalities including delayed myelination, leukoencephalopathy, and cerebellar hypoplasia.