Mouse anti-Human sapiens (Human) NMNAT1 Monoclonal Antibody

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). Also acts as a cofactor for glutamate and aspartate ADP-ribosylation by directing PARP1 catalytic activity to glutamate and aspartate residues on histones (By similarity). Fails to cleave phosphorylated dinucleotides NADP(+), NADPH and NaADP(+) (PubMed:17402747). Protects against axonal degeneration following mechanical or toxic insults (By similarity). Neural protection does not correlate with cellular NAD(+) levels but may still require enzyme activity (By similarity)

Subcellular Location

Nucleus

Disease Association

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. [The disease is caused by variants affecting the gene represented in this entry] | 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. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Widely expressed with highest levels in skeletal muscle, heart and kidney. Also expressed in the liver pancreas and placenta. Widely expressed throughout the brain

Subunit

Homohexamer (PubMed:11751893). Interacts with ADPRT/PARP1 (PubMed:11248244)

Pathway

Cofactor biosynthesis; NAD(+) biosynthesis; deamido-NAD(+) from nicotinate D-ribonucleotide: step 1/1

• Schweiger M. et al. Characterization of recombinant human nicotinamide mononucleotide adenylyl transferase (NMNAT), a nuclear enzyme essential for NAD synthesis. — FEBS Lett. (2001)
• Emanuelli M. et al. Molecular cloning, chromosomal localization, tissue mRNA levels, bacterial expression, and enzymatic properties of human NMN adenylyltransferase. — J. Biol. Chem. (2001)
• Fernando F.S. et al. Human homologue of a gene mutated in the slow Wallerian degeneration (C57BL/Wld(s)) mouse. — Gene (2002)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• Gregory S.G. et al. The DNA sequence and biological annotation of human chromosome 1. — Nature (2006)
• Mural R.J. et al. PubMed: CI-56FT96O07V0QG (JUL-)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Zhang X. et al. Structural characterization of a human cytosolic NMN/NaMN adenylyltransferase and implication in human NAD biosynthesis. — J. Biol. Chem. (2003)