Vesicle-fusing ATPase (NSF)
The protein contains 744 amino acids for an estimated molecular weight of 82594 Da.
Required for vesicle-mediated transport. Catalyzes the fusion of transport vesicles within the Golgi cisternae. Is also required for transport from the endoplasmic reticulum to the Golgi stack. Seems to function as a fusion protein required for the delivery of cargo proteins to all compartments of the Golgi stack independent of vesicle origin. Interaction with AMPAR subunit GRIA2 leads to influence GRIA2 membrane cycling (By similarity). (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology.
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| Variant | Description |
|---|---|
| dbSNP:rs155733 |
Biological Process
Chemical synaptic transmission
COPII vesicle coating
Endoplasmic reticulum to Golgi vesicle-mediated transport
Exocytosis
Golgi to plasma membrane protein transport
Golgi vesicle docking
Intra-Golgi vesicle-mediated transport
Intracellular protein transport
Metabolic process
Plasma membrane fusion
Positive regulation of protein catabolic process
Positive regulation of receptor recycling
Potassium ion transport
Regulation of exocytosis
Retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum
SNARE complex disassembly
Vesicle-mediated transport
The reference OMIM entry for this protein is 601633
N-ethylmaleimide-sensitive factor; nsf
CLONING
Mammalian N-ethylmaleimide-sensitive protein was first described by Glick and Rothman (1987) as the protein that restored the ability of Golgi membranes that had been inactivated with the reagent N-ethylmaleimide to re-engage in vesicular transport. The NSF gene was subsequently cloned from Chinese hamster cells by Block et al. (1988) and Wilson et al. (1989). NSF is a member of the AAA (ATPases associated with diverse cellular activities) gene family. Hoyle et al. (1996) stated that the genes are most related throughout the approximately 200-amino acid domain (the AAA domain) that binds ATP; however, the family is notable not only for its conservation but also for diverse functions of its proteins in eukaryotic cells. The family can be subdivided into those with either 1 or 2 ATP-binding domains. NSF is a 2-domain member of the AAA family. Valosin-containing protein (601023), which is also involved in membrane fusion, is another 2-AAA domain protein.GENE FUNCTION
The process of vesicle targeting and fusion in the secretory and endocytic pathways has been described by the SNAREs hypothesis (Rothman, 1994). This proposes that vesicles dock with specific target membranes by binding to membrane-specific SNAREs (soluble N-ethylmaleimide-sensitive factors attachment protein receptors) (see 604026). Hoyle et al. (1996) noted that targeting specificity is also affected by the Rabs, a group of small soluble GTPases. After the vesicle has bound to the target membrane, the SNARE multimer is joined by the soluble SNAP proteins and N-ethylmaleimide-sensitive factor (NSF). The resulting large complex is thought to allow membrane fusion and the ATPase activity of the NSF appears to be essential for the process. Hoyle et al. (1996) stated that while many of different SNAREs, Rabs, and SNAPs are involved in membrane fusion, there is only 1 NSF, and the SNARE hypothesis describes NSF-dependent fusion. By use of microarray expression profiling of prefrontal cortex from matched pairs of patients with schizophrenia (181500) and control subjects and hierarchical data analysis, Mirnics et al. (2000) found that transcripts encoding proteins involved in the regulation of presynaptic function were decreased in all subjects with schizophrenia. Genes of presynaptic function showed a different combination of decreased expression across subjects. Over 250 other gene groups did not show altered expression. Selected presynaptic function gene microarray observations were verified by in situ hybridization. Two of the most consistently changed transcripts in the presynaptic functional gene group, N-ethylmaleimide-sensitive factor and synapsin-2 (600755), were decreased in 10 of 10 and 9 of 10 subjects with schizophrenia, respectively. The combined data suggested that subjects with schizophrenia share a common abnormality in presynaptic function.MAPPING
By PCR amplification in a human monochromosomal somatic cell hybrid mapping panel, Hoyle et al. (1996) mapped the NSF gene to human chromosome 17. To determine a regional mapping position for NSF and to confirm their cell hybrid results, they isolated NSF-containing human cosmids for fluorescence in situ hybridization (FISH) mapping. The results showed that the gene mapped to 17q21-q22. They mapped the mouse homolog, Nsf, to mouse chromosome 11 by analysis of DNA from interspecific backcrosses. Hoyle et al. (1996) noted that there are neurologic disorders mapping in that region o ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 601633 was added.