Alpha-soluble NSF attachment protein (NAPA)
The protein contains 295 amino acids for an estimated molecular weight of 33233 Da.
Required for vesicular transport between the endoplasmic reticulum and the Golgi apparatus (Probable). Together with GNA12 promotes CDH5 localization to plasma membrane (PubMed:15980433). (updated: Jan. 31, 2018)
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.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
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, is annotated as membranous in UniProt.
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Biological Process
Apical protein localization
Brain development
COPII vesicle coating
Endoplasmic reticulum to Golgi vesicle-mediated transport
Intra-Golgi vesicle-mediated transport
Intracellular protein transport
Membrane fusion
Membrane organization
Neuron differentiation
Positive regulation of ATPase activity
Post-Golgi vesicle-mediated transport
Regulation of synaptic vesicle priming
Retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum
SNARE complex disassembly
Synaptic transmission, glutamatergic
Synaptic vesicle priming
The reference OMIM entry for this protein is 603215
N-ethylmaleimide-sensitive factor attachment protein, alpha; napa
Soluble nsf-attachment protein, alpha; snapa
Snap, alpha
CLONING
Whiteheart et al. (1993) cloned bovine cDNAs encoding alpha-, beta-, and gamma-SNAP (see 603216). They reported that alpha- and gamma-SNAP are found in a wide range of tissues and act synergistically in intra-Golgi transport. By PCR using degenerate primers based on regions of alpha-SNAP conserved between several species, Lemons et al. (1997) isolated a human megakaryocyte cell cDNA encoding alpha-SNAP. The sequence of the predicted 295-amino acid human protein shares 37%, 60%, and 67% identity with the sequences of yeast, Drosophila, and squid alpha-SNAP, respectively.GENE FUNCTION
The 'SNARE hypothesis' is a model explaining the process of docking and fusion of vesicles to their target membranes. According to this model, membrane proteins from the vesicle (v-SNAREs) and proteins from the target membrane (t-SNAREs) govern the specificity of vesicle targeting and docking through mutual recognition. Once the 2 classes of SNAREs bind to each other, they form a complex that recruits the general elements of the fusion apparatus, namely NSF (N-ethylmaleimide-sensitive factor; 601633) and SNAPs (soluble NSF-attachment proteins), to the site of membrane fusion, thereby forming the 20S fusion complex. Lemons et al. (1997) found that platelets contain some of the same proteins, including NSF, p115/TAP (603344), alpha-SNAP, gamma-SNAP, and the t-SNAREs syntaxin-2 and syntaxin-4 (186591), that are used in many vesicular transport processes in other cell types. They concluded that platelet exocytosis uses a molecular mechanism similar to that used by other secretory cells, such as neurons, although the proteins used by the platelet and their modes of regulation may be quite different. By yeast 2-hybrid analysis of a testis cDNA library, Andreeva et al. (2005) identified alpha-SNAP as an interacting partner of G-alpha-12 (GNA12; 604394). Protein pull-down assays confirmed that G-alpha-12 interacted directly with alpha-SNAP in COS-7 and human umbilical vein endothelial cells (HUVECs). Domain-swapping experiments and mutation analysis showed that the first 37 N-terminal amino acids of G-alpha-12 and the convex surface of alpha-SNAP were necessary for the interaction. Cotransfection of HUVECs with G-alpha-12 and alpha-SNAP stabilized VE-cadherin (CDH5; 601120) at the plasma membrane, whereas downregulation of alpha-SNAP with small interfering RNA resulted in loss of VE-cadherin from the cell surface. Downregulation of alpha-SNAP in conjunction with G-alpha-12 overexpression decreased HUVEC endothelial barrier function.MAPPING
Chae et al. (2002) noted that homology maps between human chromosome 19 and mouse chromosome 7, where the hyh gene (see later) maps, show gene content and order within the hyh candidate interval to be preserved between mouse and human. They placed the human homolog, SNAPA, on chromosome 19q13.3.ANIMAL MODEL
The 'hyh' (hydrocephalus with hop gait) mouse shows a markedly small cerebral cortex at birth and dies postnatally from progressive enlargement of the ventricular system (Bronson and Lane, 1990). Chae et al. (2002) mapped the hyh phenotype to a region on mouse chromosome 7 containing 5 genes. Mutation was found only in the gene encoding alpha-Snap (Napa); sequence analysis showed a G-to-A transition in exon 4 that resulted in the amino acid substitution M105I. Chae et al. (2004) showed that the small hyh cortex reflects altered cell fate. Neural progenitor cells withdraw pr ... More on the omim web site
Feb. 5, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 603215 was added.