Recombinant Human CACHD1 His-tag Protein, CF Summary
| Details of Functionality |
Measured by its binding ability in a functional ELISA. Recombinant Human CACHD1 His-tag (Catalog # 10750-CA) binds Recombinant Human/Mouse Wnt-5a Biotinylated
(Catalog #
BT645). The ED 50 for this effect is 1.25-10.0 μg/mL. |
| Source |
Human embryonic kidney cell, HEK293-derived human CACHD1 protein Glu36-Pro1095, with a C-terminal 6-His tag |
| Accession # |
|
| N-terminal Sequence |
Glu36 |
| Protein/Peptide Type |
Recombinant Proteins |
| Purity |
>95%, by SDS-PAGE visualized with Silver Staining and quantitative densitometry by Coomassie® Blue Staining. |
| Endotoxin Note |
<0.10 EU per 1 μg of the protein by the LAL method. |
Applications/Dilutions
| Dilutions |
|
| Theoretical MW |
119 kDa. Disclaimer note: The observed molecular weight of the protein may vary from the listed predicted molecular weight due to post translational modifications, post translation cleavages, relative charges, and other experimental factors. |
| SDS-PAGE |
113-127 kDa, under reducing conditions |
Packaging, Storage & Formulations
| Storage |
Use a manual defrost freezer and avoid repeated freeze-thaw cycles.- 12 months from date of receipt, -20 to -70 °C as supplied.
- 1 month, 2 to 8 °C under sterile conditions after reconstitution.
- 3 months, -20 to -70 °C under sterile conditions after reconstitution.
|
| Buffer |
Lyophilized from a 0.2 μm filtered solution in PBS with Trehalose. |
| Purity |
>95%, by SDS-PAGE visualized with Silver Staining and quantitative densitometry by Coomassie® Blue Staining. |
| Reconstitution Instructions |
Reconstitute at 500 μg/mL in PBS. |
Notes
This product is produced by and ships from R&D Systems, Inc., a Bio-Techne brand.
Alternate Names for Recombinant Human CACHD1 His-tag Protein, CF
Background
CACHD1 (Ca2+
channel and chemotaxis receptor Domain Containing 1) is a alpha 2δ-Like Protein that
modulates CaV3 voltage-gated calcium channel activity (1, 2). Mature
Human CACHD1 consists of a 1060 amino acid (aa) extracellular domain (ECD), a
21 aa transmembrane segment, and a 158 aa cytoplasmic domain. The ECD contains a
von Willebrand factor A (VWA) domain and two bacterial chemosensory-like cache
domains (1). Within the ECD, human CACHD1 shares 97.5% and 97.7% aa sequence
identity with mouse and rat CACHD1, respectively. Diseases associated with CACHD1 include
Cercarial Dermatitis and Hypertropia. CACHD1 increases the presence of CaV3.1
at the cell surface and causes an increase in channel open probability (2).
CACHD1 is a new activity-modifying protein for voltage-gated calcium channels (2).
Such
physiological actions may have implications in targeting diseases involving
aberrant neuronal firing, as CaV3 channels have been proposed as therapeutic
targets to combat pain and epilepsy (2). CACHD1
and MDGA1 are novel
in vivo substrates for beta-site APP
cleaving enzyme 1 (BACE1), suggesting that cleavage of
both proteins may contribute to the numerous functions of BACE1 in the nervous
system (3). BACE1 inhibition is a major therapeutic approach for Alzheimer
disease (3). CACHD1 closely interacts with voltage-gated calcium channels of
the N-type58 and T-type59 at the cell surface and enhances the densities of their
calcium currents (3). BACE1 cleavage is a mechanism to control CACHD1's
function in calcium signaling and synaptic transmission (3). Expression of CACHD1 increased both CaV2.2 currents and cell
surface trafficking in both cell lines and neurons (4). CACHD1 competed with a2d-1 for binding to
CaV2.2 and for its functional effects and can therefore inhibit responses to
a2d-1 (4). CACHD1
is widely expressed in many tissues, including the brain, lungs, and small
intestine (4). CACHD1 contains a VWA domain that has a disrupted metal
ion-dependent adhesion site (MIDAS)
motif, a sequence that is conserved in the human, rat, mouse, and zebrafish CACHD1
proteins (4). At the Wnt Signaling Gordon Conference in August 2019, Yvonne
Jones (Oxford) presented an unpublished crystal structure of the transmembrane
proteins CACHD1 in a complex between LRP6 and Fz5. Their data suggest that
CACHD1 is an inhibitor of Wnt signaling.
- Cottrell, G.S. et al. (2018) J. Neurosci. 38:9186.
- Stephens, G.J. and G.S. Cottrell (2019) Channels (Austin) 13:120.
- Njavro, J. R. et al. (2020) The FASEB J. 34:2465.
- Dahimene, S. et al. (2018) Cell Reports 25:1610.
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