TM2 domain-containing protein 3 (TM2D3)

TM2 domain-containing protein 3 (TM2D3) is an evolutionarily conserved, integral membrane protein belonging to a three-member TM2D family found in metazoans[1][2][7]. It has a predicted N-terminal signal sequence and two transmembrane domains linked by a short intracellular loop, and is expressed broadly including in the brain and central nervous system[1]. TM2D3 is most clearly implicated in regulation of Notch signaling, acting as a probable positive regulator or modulator, especially at the gamma-secretase cleavage step[2][7]. Its Drosophila ortholog, almondex, is required for embryonic Notch signaling, and knockout causes neurogenic disorders and female sterility due to defective neural progenitor cell development[1]. Functional data in animals and cell lines suggest all three TM2D proteins (TM2D1, TM2D2, TM2D3) may act together, affecting phagocytosis and intracellular trafficking pathways[1]. Rare variants in TM2D3 (such as P155L) are significantly associated with increased risk and earlier onset of late-onset Alzheimer’s disease, possibly by affecting gamma-secretase-mediated Notch signaling or other cell membrane functions relevant to neurodegeneration[1]. Although the protein shares some homology with G protein-coupled receptors (GPCRs) and the beta-amyloid-binding protein BBP, TM2D3 itself does not appear to be a canonical GPCR nor a direct therapeutic drug target; no interacting drugs or drug mechanisms have been firmly established to date[2][3].

Other names

TM2D3BLP2BBP-like protein 2FLJ22604Beta-amyloid-binding protein-like protein 2almondex homolog