Nmnat Nicotinamide mononucleotide adenylyltransferase [Drosophila melanogaster (fruit fly)] - Gene

Summary

Official Symbol: Nmnatprovided by FlyBase
Official Full Name: Nicotinamide mononucleotide adenylyltransferaseprovided by FlyBase
Primary source: FLYBASE:FBgn0039254
Locus tag: Dmel_CG13645
See related: AllianceGenome:FB:FBgn0039254
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Drosophila melanogaster
Lineage: Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota; Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea; Drosophilidae; Drosophila; Sophophora
Also known as: 3R4; AAL90149; CG13645; Dmel\CG13645; DmNmnat; DmNMNAT; dnmnat; dNmnat; nmnat; NMNAT; Nmnat1; NmnatB
Summary: Enables nicotinamide-nucleotide adenylyltransferase activity and unfolded protein binding activity. Involved in dendritic spine maintenance; negative regulation of neuromuscular synaptic transmission; and photoreceptor cell maintenance. Located in several cellular components, including neuromuscular junction; neuronal cell body; and presynaptic active zone. Is expressed in organism. Human ortholog(s) of this gene implicated in Leber congenital amaurosis 9 and spondyloepiphyseal dysplasia, sensorineural hearing loss, intellectual developmental disorder, and Leber congenital amaurosis. Orthologous to several human genes including NMNAT1 (nicotinamide nucleotide adenylyltransferase 1). [provided by Alliance of Genome Resources, Apr 2022]
Orthologs: all
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Genomic context

Location:: 96B11-96B11; 3-86 cM

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
Release 6.54	current	Release 6 plus ISO1 MT (GCF_000001215.4)	3R	NT_033777.3 (24945237..24947400)
Release 5.57	previous assembly	Release 5 (GCF_000001215.2)	3R	NT_033777.2 (20770959..20773122)

Chromosome 3R - NT_033777.3 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Highwire downregulates dNmnat to promote evoked synaptic release, suggesting that Highwire balances the axoprotective and synapse-inhibitory functions of dNmnat.
Title: The E3 ligase Highwire promotes synaptic transmission by targeting the NAD-synthesizing enzyme dNmnat.
On H2O2 challenge tests, Nmnat overexpression was sufficient to increase the survival time and movement capacity of Drosophila, which was probably due to its protection against oxidative stress. On rotenone induced mitochondrial dysfunction, Nmnat overexpression also showed better health span and movement capacity than the control group.
Title: Overexpression of Nmnat improves the adaption of health span in aging Drosophila.
a critical role for nicotinamide mononucleotide adenylyltransferase (Nmnat) in maintaining the integrity and function of peripheral sensory neurons, is reported.
Title: Nmnat mitigates sensory dysfunction in a Drosophila model of paclitaxel-induced peripheral neuropathy.
Thus axon injury seems to both turn on NP, but also dampen it by activating mitochondrial fission. We also identified caspases as negative regulators of axon injury-mediated NP, so mitochondrial fission could control NP through caspase activation. In addition to negative regulators of NP, we found that nicotinamide mononucleotide adenylyltransferase (Nmnat) is absolutely required for this type of NP.
Title: Mitochondria and Caspases Tune Nmnat-Mediated Stabilization to Promote Axon Regeneration.
Nmnat is alternatively spliced into two mRNA variants, RA and RB, which translate to protein isoforms with neuroprotective capacities.
Title: Alternative splicing of Drosophila Nmnat functions as a switch to enhance neuroprotection under stress.
Our studies reveal an essential neuroprotective role for endogenous Nmnat in hypoxia
Title: The role of autophagy in Nmnat-mediated protection against hypoxia-induced dendrite degeneration.
As a neuronal maintenance factor, NMNAT specifically maintains active zone structure by direct protein-protein interaction.
Title: Nicotinamide mononucleotide adenylyltransferase maintains active zone structure by stabilizing Bruchpilot.
An increased level of Nmnat protein in hiw mutants is both required and sufficient to inhibit axonal degeneration.
Title: The Highwire ubiquitin ligase promotes axonal degeneration by tuning levels of Nmnat protein.
These findings demonstrate an essential role of endogenous Nmnat in maintaining axonal integrity that may rely on and function by stabilizing mitochondria.
Title: A novel Drosophila model of nerve injury reveals an essential role of Nmnat in maintaining axonal integrity.
show that overexpression of NMNAT significantly suppresses both behavioral and morphological deficits associated with tauopathy by means of reducing the levels of hyperphosphorylated tau oligomers
Title: NMNAT suppresses tau-induced neurodegeneration by promoting clearance of hyperphosphorylated tau oligomers in a Drosophila model of tauopathy.

Submit: New GeneRIF Correction See all GeneRIFs (14)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Homology

NCBI Orthologs

Orthologs from OrthoDB

Gene Ontology Provided by FlyBase

Function	Evidence Code	Pubs
enables nicotinamide-nucleotide adenylyltransferase activity	IBA Inferred from Biological aspect of Ancestor more info
enables nicotinamide-nucleotide adenylyltransferase activity	IDA Inferred from Direct Assay more info	PubMed
enables nicotinamide-nucleotide adenylyltransferase activity	IEA Inferred from Electronic Annotation more info
enables nicotinate-nucleotide adenylyltransferase activity	IBA Inferred from Biological aspect of Ancestor more info
enables nicotinate-nucleotide adenylyltransferase activity	IEA Inferred from Electronic Annotation more info
enables unfolded protein binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in NAD biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in NAD biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in dendritic spine maintenance	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of neuromuscular synaptic transmission	IDA Inferred from Direct Assay more info	PubMed
involved_in photoreceptor cell maintenance	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in neuromuscular junction	IDA Inferred from Direct Assay more info	PubMed
located_in neuronal cell body	IDA Inferred from Direct Assay more info	PubMed
located_in presynaptic active zone	IMP Inferred from Mutant Phenotype more info	PubMed

General protein information

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Preferred Names: nicotinamide mononucleotide adenylyltransferase

Names: CG13645-PA; CG13645-PB; CG13645-PC; CG13645-PD; Nmnat-PA; Nmnat-PB; Nmnat-PC; Nmnat-PD; adenylyltransferase; nicotinamide mononucleotide; nicotinamide mononucleotide adenyltransferase; nicotinamide mononucleotide adenylyl transferase 1; nicotinamide mononucleotide adenylyltransferase 1; nicotinamide mononucleotide adenylytransferase

NP_001262942.1

EC 2.7.7.-

EC 2.7.7.1

EC 2.7.7.18

NP_001356924.1

EC 2.7.7.-

EC 2.7.7.1

EC 2.7.7.18

NP_651315.2

EC 2.7.7.-

EC 2.7.7.1

EC 2.7.7.18

NP_733064.2

EC 2.7.7.-

EC 2.7.7.1

EC 2.7.7.18

NCBI Reference Sequences (RefSeq)

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Genome Annotation

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference assembly

Genomic

NT_033777.3 Reference assembly

Range

24945237..24947400

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_143058.1 → NP_651315.2 nicotinamide mononucleotide adenylyltransferase, isoform A [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_651315.2

Status: REVIEWED

UniProtKB/TrEMBL

Q9VC03

Related

FBpp0084124, FBtr0084749

Conserved Domains (1) summary

cd09286
Location:46 → 282

NMNAT_Eukarya; Nicotinamide/nicotinate mononucleotide adenylyltransferase, Eukaryotic
NM_170185.1 → NP_733064.2 nicotinamide mononucleotide adenylyltransferase, isoform B [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_733064.2

Status: REVIEWED

UniProtKB/TrEMBL

Q7KS06

Related

FBpp0084125, FBtr0084750

Conserved Domains (1) summary

cd09286
Location:46 → 282

NMNAT_Eukarya; Nicotinamide/nicotinate mononucleotide adenylyltransferase, Eukaryotic
NM_001276013.2 → NP_001262942.1 nicotinamide mononucleotide adenylyltransferase, isoform C [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_001262942.1

Status: REVIEWED

UniProtKB/TrEMBL

A0A0B4KHH7

Conserved Domains (1) summary

cd09286
Location:15 → 251

NMNAT_Eukarya; Nicotinamide/nicotinate mononucleotide adenylyltransferase, Eukaryotic
NM_001369970.1 → NP_001356924.1 nicotinamide mononucleotide adenylyltransferase, isoform D [Drosophila melanogaster]

Status: REVIEWED

UniProtKB/TrEMBL

Q8T405

Conserved Domains (1) summary

cd09286
Location:15 → 251

NMNAT_Eukarya; Nicotinamide/nicotinate mononucleotide adenylyltransferase, Eukaryotic