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Presenilin 1 of the γ-secretase (GS) complex.  Substrate proteins are recognized by their transmembrane domains, and nicastrin actively excludes larger substrates through steric hindrance, thus serving as a molecular gatekeeper for substrate binding and catalysis (Bolduc et al. 2015). γ-secretase interacts with the myoinositol transporter (TC#2.A.1.1.25), and this interaction regulates the activity of γ-secretase in its production of Abeta (Teranishi et al. 2015). See family description for more details. gamma-Secretase promotes membrane insertion of the human papillomavirus L2 capsid protein during viral infection (Inoue et al. 2018).
   Anterior pharynx-defective 1A (APH-1A) is a seven transmembrane component of gamma-secretase (GS), an aspartyl protease enzyme involved in the production of toxic amyloid-beta peptides in Alzheimer's disease patients. Cryo-EM structures of the enzyme complex revealed a central cavity in its APH-1A component, similar to water-containing cavities in G-protein coupled receptors (GPCRs). Aguayo-Ortiz and Dominguez 2019 performed molecular dynamics and umbrella sampling simulations to understand the role of the APH-1A cavity in the GS complex. APH-1A is able to store water molecules in its inner cavity and transport some of them between cell spaces. This allows the influx of extracellular cations into a central hydrophilic cavity but cannot transport them into the intracellular space. This may be an alternative APH-1A function besides its complex stabilization role (Aguayo-Ortiz and Dominguez 2019).

The γ-secretin complex of Mus musculus
Presenilin (Q9DCZ9)
γ-secretin subunit, Nicastrin (P57716)
γ-secretin subunit, Aph-1A (Q8BVF7)
γ-secretin subunit, Pen-2 (Q9CQR7) 

Presenilin homologue of 238 aas and 7 TMSs

Presenilin of Volvox carteri (Green alga)

Prresenilin of 283 aas and 7 TMSs.

Presenilin of Chlorella variabilis (Green alga)

Uncharacterized protein of 247 aas and 7 TMSs

UP of Phytophthora sojae (Soybean stem and root rot agent) (Phytophthora megasperma)

Uncharacterized protein of 514 aas and 7 TMSs

UP of Trypanosoma vivax

Uncharacterized protein of 449 aas and 7 TMSs

UP of Leishmania mexicana

Uncharacterized protein of 794 aas and 7 C-terminal TMSs with a large N-terminal hydrophilic domain of unknown function.

UP of Thalassiosira oceanica (Marine diatom)