Switch-associated protein 70 (SWAP70)
The protein contains 585 amino acids for an estimated molecular weight of 68998 Da.
Phosphatidylinositol 3,4,5-trisphosphate-dependent guanine nucleotide exchange factor (GEF) which, independently of RAS, transduces signals from tyrosine kinase receptors to RAC. It also mediates signaling of membrane ruffling. Regulates the actin cytoskeleton as an effector or adapter protein in response to agonist stimulated phosphatidylinositol (3,4)-bisphosphate production and cell protrusion (By similarity). (updated: Feb. 4, 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.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
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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| Variant | Description |
|---|---|
| dbSNP:rs397686 | |
| dbSNP:rs415895 |
Biological Process
Actin filament bundle assembly
Isotype switching
Negative regulation of actin filament depolymerization
Negative regulation of cell-cell adhesion mediated by integrin
Negative regulation of peptidyl-serine dephosphorylation
Positive regulation of actin filament bundle assembly
Positive regulation of cytosolic calcium ion concentration
Positive regulation of mast cell chemotaxis
Regulation of protein localization
Cellular Component
Actin cytoskeleton
Cytoplasm
Cytoskeleton
Lamellipodium
Nucleus
Obsolete cell
Plasma membrane
The reference OMIM entry for this protein is 604762
Switch-associated protein 70
Swap70
CLONING
The B-cell receptor is composed of the immunoglobulin (Ig) heavy and light chains and the covalently bound accessory molecules Ig-alpha (CD79A; 112205) and Ig-beta (CD79B; 147245). Crosslinking of the B-cell receptor by antigens stimulates the activation of intracellular protein kinases. B-cell activation leads to hypermutation of the Ig variable regions and to heavy chain class switching, in which the Ig constant region of mu (IgM; see 147020) is replaced by that of another class: gamma (IgG; see 147100), alpha (IgA; see 146900), or epsilon (IgE; see 147180). Class switching is achieved by a looping out and deletion mechanism between the switch region of mu and the switch region of the isotope that is to be expressed. Masat et al. (2000) explored the possibility that switch-associated protein-70 (SWAP70) acts as a link between the recognition of specific switch regions and causation of a DNA break. Swap70 had been isolated in the mouse as part of a complex that is able to promote recombination between 2 switch regions in vitro (Borggrefe et al., 1998; Borggrefe et al., 1999). By screening a human lymphoma cDNA library using mouse Swap70 sequences as the probe, Masat et al. (2000) isolated a cDNA encoding SWAP70. Although the 585-amino acid SWAP70 protein contains 3 nuclear localization signals, SWAP70 was found mainly in the cytoplasm in small resting B cells. On stimulation, SWAP70 translocated to the nucleus. In activated, class-switching B cell cultures, it was associated with membrane IgG, but not IgM. Masat et al. (2000) suggested that SWAP70 is involved not only in nuclear events but also in signaling in B-cell activation.GENE FUNCTION
Shinohara et al. (2002) demonstrated that SWAP70 specifically binds phosphatidylinositol-3,4,5-triphosphate. On stimulation by growth factors, cytoplasmic SWAP70, which is dependent on phosphoinositide-3-hydroxykinase but independent of Ras (see 190020), moved to cell membrane rearrangements known as ruffles. However, mutant SWAP70 lacking the ability to bind phosphatidylinositol-3,4,5-triphosphate blocked membrane ruffling induced by epidermal growth factor (EGF; 131530) or platelet-derived growth factor (see 173430). SWAP70 shows low homology with Rac-guanine nucleotide exchange factors, and catalyzes phosphatidylinositol-3,4,5-triphosphate-dependent guanine nucleotide exchange to Rac (see 602048). SWAP70-deficient fibroblasts showed impaired membrane ruffling after stimulation with EGF, and failed to activate Rac fully. Shinohara et al. (2002) concluded that SWAP70 is a different type of Rac-GEF which, independently of Ras, transduces signals from tyrosine kinase receptors to Rac.MAPPING
By FISH, Masat et al. (2000) mapped the human SWAP70 gene to 11p15 in a region that shows homology of synteny to mouse chromosome 7. They used linkage analysis and FISH on metaphase chromosomes to map the mouse Swap70 gene to mid-chromosome 7.ANIMAL MODEL
B cells migrate directly from the blood stream to secondary lymphoid organs and lymph nodes. Before diapedesis, these cells roll in an L-selectin (SELE; 153240)-dependent manner, receive signals through CCR7 (600242) and CXCR4 (162643), and adhere to high endothelial venules (HEVs) via integrin alpha-L (ITGAL; 153370)/beta-2 (ITGB2; 600065). Pearce et al. (2006) observed reduced lymph node swelling in Swap70 -/- mice, with reduced accumulation of B cells, particularly of the B2 subset, following footpad imm ... More on the omim web site
May 12, 2019: Protein entry updated
Automatic update: model status changed
Nov. 17, 2018: Protein entry updated
Automatic update: model status changed
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Oct. 27, 2017: Protein entry updated
Automatic update: model status changed
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 604762 was added.
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed