CACHD1 Products

Description

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 At the Wnt Signaling Gordon Conference in August 2019, Yvonne Jones (Oxford) presented an unpublished crystal structure of the transmembrane proteins CACHD1 in a complex between LRP6 and Fz5.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.

Bioinformatics

Uniprot	Q5VU97.2
Product By Gene ID	57685
Alternate Names	CACHD1 cache domain containing 1 Cache domain-containing protein 1 KIAA1573VWFA and cache domain-containing protein 1 RP4-655E10.1 von Willebrand factor type A and cache domain containing 1 VWCD1