EF-hand domain-containing protein D2 (EFHD2)
The protein contains 240 amino acids for an estimated molecular weight of 26697 Da.
May regulate B-cell receptor (BCR)-induced immature and primary B-cell apoptosis. Plays a role as negative regulator of the canonical NF-kappa-B-activating branch. Controls spontaneous apoptosis through the regulation of BCL2L1 abundance. (updated: March 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.
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.
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Biological Process
The reference OMIM entry for this protein is 616450
Ef-hand domain family, member d2; efhd2
Swiprosin 1; sws1
DESCRIPTION
EFHD2 is a calcium-binding adaptor protein associated with pathologically aggregated tau (MAPT; 157140) in Alzheimer disease (AD; 104300) brain and in a mouse model of frontotemporal dementia (FTD; 600274). EFHD2 has cell type-specific functions, including modulation of intracellular calcium responses, actin dynamics, and microtubule transport (summary by Borger et al., 2014).CLONING
Using 2-dimensional gel electrophoresis followed by mass spectrometric analysis, Vuadens et al. (2004) identified EFHD2, which they called swiprosin-1, as a CD8 (see 186910)-positive lymphocyte-specific protein. The predicted protein contains 240 amino acids and has 2 potential EF-hand domains. RT-PCR and Northern blot analysis confirmed that swiprosin-1 was preferentially expressed in CD8-positive T cells compared with CD4 (186940)-positive T cells and CD19 (107265)-positive B cells. Avramidou et al. (2007) reported that human SWS1 shares 91% amino acid identity with its mouse ortholog. SWS1 contains 4 myristoylation sites, 3 binding sites for SH3 domain proteins, 2 EF-hand domains, and a C-terminal coiled-coil domain. Northern blot analysis of mouse tissues revealed highest expression in brain, followed by spleen, lung, and liver, with low expression in kidney and thymus. RT-PCR analysis detected expression throughout mouse B-cell differentiation.GENE FUNCTION
Avramidou et al. (2007) found that Sws1 expression induced and was required for apoptosis elicited by B-cell receptor (BCR) engagement in mouse WEHI231 immature B cells. Decreased Sws1 expression promoted survival of WEHI231 cells. Abundance of Sws1 regulated Bclxl (600039) amounts reciprocally at the transcriptional level. Activation of Nfkb (see 164011) counteracted Sws1-induced apoptosis in WEHI231 cells. Avramidou et al. (2007) concluded that SWS1 determines B-cell life span and sets the threshold for BCR signaling in immature B cells. Thylur et al. (2009) found that SWS1 was expressed in human mast cells and was upregulated in vitro after mitogen stimulation and in vivo in mouse models of passive cutaneous anaphylaxis and atopic dermatitis. Targeting of specific protein kinase C isotypes by small interfering RNA (siRNA) revealed PKCB1 (PRKCB1; 176970) and PKC-eta (PRKCH; 605437) as the most active forms involved in mitogen-induced SWS1 expression in mast cells. Targeting SWS1 with siRNA inhibited expression of IL3 (147740) and IL8 (146930). Thylur et al. (2009) concluded that SWS1 is a regulator for the positive-feedback activation of mast cells. Kwon et al. (2013) reported that human SWS1 localized to microvilli-like membrane protrusions and lamellipodia and exhibited actin-binding activity. SWS1 overexpression enhanced lamellipodia formation and cell spreading. SWS1 induced actin bundling in the presence of calcium, and mutation analysis indicated that bundling was partly dependent on the EF-hand motifs. SWS1 dimerized in a calcium-dependent manner via its coiled-coil domain. A lys-rich region in the coiled-coil domain was essential for regulating actin bundling. Mutations in the EF-hand motif and coiled-coil domain significantly reduced cell spreading and lamellipodia formation. Kwon et al. (2013) concluded that SWS1 binds actin and modulates actin bundling. Huh et al. (2013) found that human SWS1 increased lamellipodia formation in mouse melanoma cells by regulating the accessibility of filamentous (F)-actin (see 102610) to cofilin (CFL1; 60144 ... 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. 10, 2018: Protein entry updated
Automatic update: OMIM entry 616450 was added.
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
Oct. 27, 2017: Protein entry updated
Automatic update: model status changed
Feb. 25, 2016: Protein entry updated
Automatic update: model status changed
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed