Anti-CALHM3 Antibody

Calcium homeostasis has major roles in different extra and intra cellular processes and is therefore crucial for cell physiology¹.

The calcium homeostasis modulator 3 (CalHM3 or protein FAM26A) belongs to a family of six calcium modulating genes mapped to chromosomes 10 and 6. All CALHM genes are present in vertebrates but they lack sequence homology to other known genes.

The most researched member of this family is CALHM1 (FAM26C). CALHM1 is a monomer comprised of four transmembrane helices with both the amino and carboxyl termini located in the cytoplasm. Interestingly, this structure is shared with connexins, pannexins and innexins.

CALHM channel gating is regulated allosterically by both voltage and Ca²⁺ concentration. Low concentrations of Ca²⁺ and depolarization cause channel activation. The molecular basis for voltage-dependent gating remains unknown. CALHM3 channels do not have canonical voltage sensors as found in other channels. CALHM channels poorly discriminate cations and anions enabling signaling molecules such as Ca²⁺ and ATP to permeate to its pore. This suggests a non-discriminatory ion selectivity filter or a wide ion conduction pore. Recent studies have shown that it is the latter and not the former that accounts for weak ion selectivity².

CALHM3 are specifically expressed in taste buds and localized to TRPM5 cells. Changes in calcium homeostasis have been associated with Alzheimer’s disease development. CALHM3 polymorphism can modulate the age for disease onset. In addition, several SNPs within the CALHM3 gene were found to be associated with Creutzfeldt-Jakob disease pathophysiology³.