Peptidase A22A, presenilin 2 (IPR001493)
Short name: Pept_A22A_PS2
Overlapping homologous superfamilies
This group of aspartic peptidases belong to MEROPS peptidase family A22 (presenilin family, clan AD): subfamily A22A, the type example being presenilin 1 from Homo sapiens (Human).
Presenilins are polytopic transmembrane (TM) proteins, mutations in which are associated with the occurrence of early-onset familial Alzheimer's disease, a rare form of the disease that results from a single-gene mutation [PMID: 9791530, PMID: 9521418]. The physiological functions of presenilins are unknown, but they may be related to developmental signalling, apoptotic signal transduction, or processing of selected proteins, such as the beta-amyloid precursor protein(beta-APP). There are a number of subtypes which belong to this presenilin family. That presenilin homologues have been identified in species that do not have an Alzhemier's disease correlate suggests that they may have functions unrelated to the disease, homologues having been identified in mouse, Drosophila melanogaster, Caenorhabditis elegans [PMID: 7566091] and other members of the eukarya including plants.
In humans, there are two presenilin genes (PS1 and PS2)that share 67% amino acid identity, the greatest divergence between the two falling in the N terminus and in the large hydrophilic loop towards the C terminus of each molecule. Six to nine TM domains are predicted for each, and biochemical analysis has demonstrated that their C-termini are cytoplasmic; but the orientation of their N-termini and large hydrophilic loops remains to be resolved. They are expressed in almost all tissues, including the brain and, at a cellular level, they have been localised to the nuclear envelope, endoplasmic reticulum and Golgi apparatus.
The signature defines vertebrate presenilin 2 (MEROPS identifier A22.002), which unlike presenilin 1 has been found to have pro-apoptotic actions, which are enhanced by the mutations that have been characterised in this protein; however, when compared to PS1 gene mutations, they are thought to be responsible for only a small percentage of early-onset familial Alzheimer's disease cases (ca. 1%) [PMID: 9791533].
- PR01074 (PRESENILIN2)