Fraternal twins: Swiprosin-1/EFhd2 and Swiprosin-2/EFhd1, two homologous EF-hand containing calcium binding adaptor proteins with distinct functions

Dütting, Sebastian; Brachs, Sebastian; Mielenz, Dirk

doi:10.1186/1478-811x-9-2

Cited by 70 publications

(83 citation statements)

References 109 publications

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“…EF-hand domain-containing protein D2 (EFHD2), also known as Swiprosin-1 (SWS1), which is most abundant in brain, regulates spontaneous apoptosis through the regulation of Bcl-xS abundance (Dütting et al, 2011). EFHD2 is associated with pathological forms of tau proteins in the tauopathy mouse model JNPL3, which expresses the human tau (P301L) mutant, and co-localizes with aggregated tau proteins and formed granular structures (Ferrer-Acosta et al, 2013).…”

Section: Apoptosismentioning

confidence: 99%

The influence of chronic ibuprofen treatment on proteins expressed in the mouse hippocampus

Matsuura

Otani

Takano

et al. 2015

European Journal of Pharmacology

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Section: Apoptosismentioning

confidence: 99%

The influence of chronic ibuprofen treatment on proteins expressed in the mouse hippocampus

Matsuura

Otani

Takano

et al. 2015

European Journal of Pharmacology

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“…As calmodulin, EF-hand domain-containing protein D1 (EFHD1) (spot # 3; supplemental Table S1; supplemental (Table I). mitochondria (27), and it has been speculated to be involved in protecting cells from oxidative stress (28). There is no report on the biological relationship between EFHD1 and estrogen.…”

Section: Strategy For Identifying Er␣-associatedmentioning

confidence: 99%

Estrogen Receptor Alpha Interacts with Mitochondrial Protein HADHB and Affects Beta-Oxidation Activity

Zhou

2012

Molecular & Cellular Proteomics

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It is known that estrogen receptors can function as nuclear receptors and transcription factors in the nucleus and as signaling molecules in the plasma membrane. In addition, the localization of the receptors in mitochondria suggests that they may play important roles in mitochondria. In order to identify novel proteins that are involved in ER␣-mediated actions of estrogens, we used a proteomic method that integrated affinity purification, two-dimensional gel electrophoresis, and mass spectrometry to isolate and identify cellular proteins that interact with ER␣. One of the proteins identified was trifunctional protein ␤-subunit (HADHB), a mitochondrial protein that is required for ␤-oxidation of fatty acids in mitochondria. We have verified the interaction between ER␣ and HADHB by coimmunoprecipitation and established that ER␣ directly binds to HADHB by performing an in vitro binding assay. In addition, we have shown that ER␣ colocalizes with HADHB in the mitochondria by confocal microscopy, and the two proteins interact with each other within mitochondria by performing coimmunoprecipitation using purified mitochondria as starting materials. We have demonstrated that the expression of ER␣ affects HADHB activity, and a combination of 17␤-estrodiol and tamoxifen affects the activity of HADHB prepared from human breast cancer cells that express ER␣ but not from the cells that are ER␣ deficient. Furthermore, we have demonstrated that 17␤-estrodiol plus tamoxifen affects the association of ER␣ with HADHB in human cell extract. Our results suggest that HADHB is a functional molecular target of ER␣ in the mitochondria, and the interaction may play an important role in the estrogen-mediated lipid metabolism in animals and humans. Molecular & Cellular Proteomics 11: 10.1074/mcp.M111.011056, 1-12, 2012.The biological activities of steroid hormone estrogens are mediated by two estrogen receptors (ERs), 1 ER␣ and ER␤, which are widely distributed in different tissues (1). Traditionally, ERs are considered nuclear receptors and classical transcription factors (2). Upon binding to estrogen, ERs undergo a conformational change, translocate to the nucleus, and regulate the expression of estrogen responsive genes through binding to estrogen response elements residing in those genes (3). Since its cloning in the 1980s (4), this classical mechanism has been studied extensively, and a large group of nuclear proteins called co-activators and co-repressors, which interact with ER␣, has been identified (5). Much less is known about the relatively newly cloned ER␤ (6). Like the majority of other nuclear receptors, ER␣ and ER␤ contain two activation domains, AF1 near the N terminus and AF2 in the ligand binding domain (7). The interactions between ER␣/ER␤ and co-activators/co-repressors are normally mediated by the binding of the AF2 domain of ER␣/ER␤ to one or more conserved pentapeptide LXXLL motifs (where X is any amino acid) in co-activators/co-repressors (5). In addition to the nucleus, ER␣ and ER␤ are also found to be localized in...

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“…(1,2) EFhd1 and EFhd2 share a high degree of sequence identity and homology, suggesting at least partially redundant functions. (1) Both proteins bind Ca 2 + .…”

Section: Introductionmentioning

confidence: 97%

“…(1,2) EFhd1 and EFhd2 share a high degree of sequence identity and homology, suggesting at least partially redundant functions. (1) Both proteins bind Ca 2 + . (2)(3)(4) EFhd2 is highly expressed in the brain, (5) has been proposed to be a calcium sensor protein, (3) and is putatively linked to neurodegenerative diseases (see review (1) ).…”

Section: Introductionmentioning

confidence: 97%

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Monoclonal Antibodies to Discriminate the EF Hand Containing Calcium Binding Adaptor Proteins EFhd1 and EFhd2

Brachs

Lang

Buslei

et al. 2013

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy

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Small Ca(2+) binding adaptor proteins of the EF hand family play important roles in neuronal and immune cell Ca(2+) signaling. Swiprosin-1/EFhd2 (EFhd2) and Swiprosin-2/EFhd1 (EFhd1) are conserved and very homologous Ca(2+) binding adaptor proteins of the EF hand family, with possibly redundant functions. In particular, EFhd2 has been proposed to be involved in B cell signaling and neuropathological disorders. Little is known thus far about the expression of EFhd2 on the single cell level in tissue sections or blood cells. Here we describe the generation of four specific anti-EFhd2 monoclonal antibodies. These recognize murine and human EFhd2, but not murine EFhd1, and their binding site maps to a region in the N-terminal part of EFhd2, where EFhd2 and EFhd1 differ most. Moreover, to detect EFhd1 specifically, we also generated anti-EFhd1 polyclonal antibodies, making use of a singular peptide of the N-terminal part of the protein. Using anti-EFhd2 MAb, we reveal two EFhd2 pools in B cells, one at the membrane and one cytoplasmic pool. Staining of human peripheral blood mononuclear cells shows EFhd2 expression in B cells but a ∼5 fold higher expression in monocytes. Taken together, EFhd2 monoclonal antibodies will be valuable to assess the real subcellular localization and expression level of EFhd2 in healthy and diseased primary cells and tissues.

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Fraternal twins: Swiprosin-1/EFhd2 and Swiprosin-2/EFhd1, two homologous EF-hand containing calcium binding adaptor proteins with distinct functions

Cited by 70 publications

References 109 publications

The influence of chronic ibuprofen treatment on proteins expressed in the mouse hippocampus

The influence of chronic ibuprofen treatment on proteins expressed in the mouse hippocampus

Estrogen Receptor Alpha Interacts with Mitochondrial Protein HADHB and Affects Beta-Oxidation Activity

Monoclonal Antibodies to Discriminate the EF Hand Containing Calcium Binding Adaptor Proteins EFhd1 and EFhd2

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