N-ethylmaleimide sensitive fusion protein

NSF
Identifiers
Aliases	NSF, SKD2, N-ethylmaleimide sensitive factor, N-ethylmaleimide sensitive factor, vesicle fusing ATPase, SEC18, DEE96
External IDs	OMIM: 601633 MGI: 104560 HomoloGene: 4502 GeneCards: NSF
Gene location (Human) Chr. Chromosome 17 (human) Band 17q21.31 Start 46,590,669 bp End 46,757,464 bp
Gene location (Mouse) Chr. Chromosome 11 (mouse) Band 11 E1|11 67.54 cM Start 103,712,608 bp End 103,844,882 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in superior frontal gyrus prefrontal cortex Brodmann area 9 cerebellar cortex cerebellar hemisphere nucleus accumbens hypothalamus islet of Langerhans hippocampus proper caudate nucleus Top expressed in pontine nuclei subiculum medial dorsal nucleus medial vestibular nucleus dorsal tegmental nucleus superior colliculus medial geniculate nucleus ventral tegmental area dorsomedial hypothalamic nucleus piriform cortex More reference expression data BioGPS n/a
Gene ontology Molecular function nucleotide binding PDZ domain binding syntaxin-1 binding metal ion binding protein binding syntaxin binding hydrolase activity ATP binding protein kinase binding SNARE binding protein-containing complex binding ionotropic glutamate receptor binding ATPase activity Cellular component postsynaptic density myelin sheath plasma membrane dendritic shaft lysosomal membrane extracellular exosome Golgi membrane cytoplasm cytosol Golgi stack Biological process plasma membrane fusion positive regulation of protein catabolic process regulation of exocytosis potassium ion transport endoplasmic reticulum to Golgi vesicle-mediated transport COPII vesicle coating protein transport intracellular protein transport vesicle-mediated transport positive regulation of receptor recycling exocytosis retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum SNARE complex disassembly transport Golgi to plasma membrane protein transport Golgi vesicle docking Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4905 18195 Ensembl ENSG00000073969 ENSG00000278174 ENSG00000276262 ENSMUSG00000034187 UniProt P46459 P46460 RefSeq (mRNA) NM_006178 NM_008740 RefSeq (protein) NP_006169 NP_032766 Location (UCSC) Chr 17: 46.59 – 46.76 Mb Chr 11: 103.71 – 103.84 Mb PubMed search
Wikidata
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N-ethylmaleimide-sensitive factor, also known as NSF or N-ethylmaleimide sensitive fusion proteins, is an enzyme which in humans is encoded by the NSF gene.

Function

NSF is a homohexameric AAA ATPase involved in membrane fusion. NSF is ubiquitously found in the membrane of eukaryotic cells. It is a central component of the cellular machinery in the transfer of membrane vesicles from one membrane compartment to another. During this process, SNARE proteins on two joining membranes (usually a vesicle and a target membrane such as the plasma membrane) form a complex, with the α-helical domains of the SNAREs coiling around each other and forming a very stable four-helix bundle. As SNAREs intertwine, they pull the vesicle towards the target membrane, excluding water and promoting fusion of the vesicle with the target membrane. NSF unravels SNARE complexes once membrane fusion has occurred, using the hydrolysis of ATP as an energy source, allowing the dissociated SNAREs to be recycled for reuse in further rounds of membrane fusion. This proposal remains controversial, however. Recent work indicates that the ATPase function of NSF does not function in recycling of vesicles but rather functions in the act of fusing vesicles with the plasma membrane.

SNARE hypothesis

Because neuronal function depends on the release of neurotransmitters at a synapse — a process in which synaptic vesicles fuse with the presynaptic membrane — NSF is a key synaptic component. Thus, conditional temperature-sensitive mutations in the Drosophila melanogaster gene for NSF lead to a comatose behaviour at the restrictive temperature (and hence the gene is called comatose), presumably because neuronal functions are blocked. In Dictyostelium discoideum amoebae, similar mutations lead to a cessation of cell movement at the restrictive temperature, indicating a role for intracellular membrane transport in migration. Another neuronal role for NSF is indicated by its direct binding to the GluR2 subunit of AMPA type glutamate receptors (which detect the neurotransmitter glutamate). This gives NSF a putative role in delivery and expression of AMPA receptors at the synapse.

NSF was discovered by James Rothman and colleagues in 1987 while at Stanford University; they identified NSF after observing that a cytoplasmic factor, required for membrane fusions, was inactivated by treatment with N-ethylmaleimide. This assay enabled them to purify NSF.

Interactions

N-ethylmaleimide sensitive fusion protein has been shown to interact with NAPA.

Further reading