Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Ensembl
	HGNC	UniGene	Nucleotide	OMIM	UCSC

Home Page

FLASH GENE

Symbol

NMNAT2

contributors: mct - updated : 05-10-2016

HGNC name	nicotinamide nucleotide adenylyltransferase 2
HGNC id	16789

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart       highly Homo sapiens Endocrine pancreas         Homo sapiens Hearing/Equilibrium ear inner cochlea     Nervous brain diencephalon amygdala   specific Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum skeletal     Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Endocrine islet cell (alpha,beta...) Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

mono polymer

homomer , tetramer

HOMOLOGY

intraspecies

homolog to NMNAT2

Homologene

FAMILY

nicotinamide mononucleotide adenylyltransferase (NMNAT) enzyme family

CATEGORY

chaperone/stress , enzyme

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,Golgi
	intracellular,cytoplasm,organelle,endosome
text	NMNAT2 is localized to the Golgi complex

basic FUNCTION	catalyzing an essential step in NAD (NADP) biosynthetic pathway
	brain-specific NMNAT2 delays injury-induced axon degeneration dependent on its NAD synthesis activity
	endogenous NMNAT2 prevents spontaneous degeneration of healthy axons
	NMNAT1, NMNAT2, NMNAT3 catalyzes the formation of nicotinamide adenine dinucleotide
	is a neuronal protein peripherally attached to membranes via palmitoylation, suggesting that NMNAT2 is transported to synaptic terminals via an endosomal pathway
	NMNAT2 activity supports axon survival through a site of action distinct from NMNAT2 transport vesicles and protein stability, a key determinant of axon protection, is enhanced by mutations that disrupt palmitoylation and dissociate NMNAT2 from these vesicles
	is a critical survival factor for axons
	NMNAT2 localisation and turnover are a valuable target for modulating axon degeneration
	requirement for NMNAT2 in axon maintenance even during development
	important functional role of NMNAT2 in TP53-mediated signaling
	is a critical survival factor for axons and its constant supply from neuronal cell bodies into axons is required for axon extension
	having a chaperone function, independent from its enzymatic activity
	exerts its chaperone or enzymatic function in a context-dependent manner to maintain neuronal health
	acts not only as a NAD synthase involved in axonal maintenance but as a molecular chaperone helping neurons to overcome protein unfolding and protein aggregation

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

cofactor

signaling

NAD (NADP) biosynthetic pathway

a component

INTERACTION

DNA

RNA

small molecule

protein	NMNAT2 affects MAPT phosphorylation by regulating PPP2CA activity
	NMNAT2, a NAD(+) synthetase, is a novel downstream target gene of TP53
	NMNAT2 is a substrate for cytosolic thioesterases LYPLA1 and LYPLA2 and palmitoylation/depalmitoylation dynamics are on a time scale similar to its short half-life
	absence of SARM1 rescues development and survival of NMNAT2-deficient axons
	NMNAT2 complexes with heat shock protein 90 (HSP90AA1) to refold aggregated protein substrates
	role for SKP1 as an auxiliary component of the target recognition module that enhances binding of FBXO45 to NMNAT2

cell & other

REGULATION

Other

palmitoylation is necessary to target NMNAT2 to post-Golgi vesicles, thereby influencing its protein turnover and axon protective capacity

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --low   may contribute to axon degeneration in a variety of neurodegenerative disorders constitutional     --low   during cardiac hypertrophy

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed neurology neurodegenerative   endogenous NMNAT2 represents an exciting new therapeutic target for axonal disorders cardiovascular cardiomyopathy   modulation of NMNAT2 activity may be beneficial in cardiac hypertrophy

ANIMAL & CELL MODELS