CALHM1
Domain
A phospholipid-binding pocket is formed between conserved regions of S3 and S4 helices of one subunit and S2 of the adjacent subunit. It may regulate channel assembly and gating.
Function
Pore-forming subunit of gustatory voltage-gated ion channels required for sensory perception of sweet, bitter and umami tastes (By similarity). With CALHM3 forms a fast-activating voltage-gated ATP-release channel in type II taste bud cells, ATP acting as a neurotransmitter to activate afferent neural gustatory pathways (By similarity) (PubMed:23467090). Acts both as a voltage-gated and calcium-activated ion channel: mediates neuronal excitability in response to membrane depolarization and low extracellular Ca(2+) concentration (PubMed:22711817, PubMed:23300080). Has poor ion selectivity and forms a wide pore (around 14 Angstroms) that mediates permeation of small ions including Ca(2+), Na(+), K(+) and Cl(-), as well as larger ions such as ATP(4-) (PubMed:22711817, PubMed:23300080, PubMed:32832629, PubMed:37380652). Mediates Ca(2+) influx and downstream activation of the ERK1 and ERK2 cascade in neurons (PubMed:23345406). Triggers endoplasmic reticulum stress by reducing the Ca(2+) content of the endoplasmic reticulum (PubMed:21574960). May indirectly control amyloid precursor protein (APP) proteolysis and aggregated amyloid-beta (Abeta) peptides levels in a Ca(2+)-dependent manner (PubMed:18585350).
Post-translational modifications
N-glycosylated. Assembly with CALHM3 is associated with N-glycan remodeling and formation of hybrid complex- and high mannose-type glycochains. This N-glycan processing regulates channel trafficking and gating kinetics.
Palmitoylated by ZDHHC3, ZDHHC20 and possibly ZDHHC7. Palmitoylation regulates voltage-dependent gating of the channel by shifting it toward more depolarized potentials.
Sequence Similarities
Belongs to the CALHM family.
Tissue Specificity
Predominantly expressed in adult brain. Detected also in retinoic acid-differentiated SH-SY5Y cells. Specifically expressed in circumvallate taste bud cells.
Cellular localization
- Cell membrane
- Multi-pass membrane protein
- Endoplasmic reticulum membrane
- Multi-pass membrane protein
- Basolateral cell membrane
- Multi-pass membrane protein
- Colocalizes with HSPA5 at the endoplasmic reticulum (PubMed:18585350). Localizes to the basolateral membrane of epithelial cells including taste cells (By similarity).
Alternative names
FAM26C, CALHM1, Calcium homeostasis modulator protein 1, Protein FAM26C