| Primary Identifier | IPR042524 | Type | Homologous_superfamily |
| Short Name | Presenilin_C |
| description | This superfamily represents the C-terminal region of aspartic peptidases belonging to the MEROPS peptidase family A22 (presenilin family), subfamily A22A, the type example being presenilin 1 from Homo sapiens (Human).Presenilins are polytopic transmembrane (TM) proteins, mutations in whichare associated with the occurrence of early-onset familial Alzheimer'sdisease, a rare form of the disease that results from a single-genemutation [, ]. Alzheimer's disease is associated with the formation of extracellular deposits of amyloid, which contain aggregates of the amyloid-beta peptide. The β-peptides are released from the Alzheimer's amyloid precursor protein (APP) by the action of two peptidase activities: "beta-secretase"cleaves at the N terminus of the peptide, and "gamma-secretase"cleaves at the C terminus. The gamma-secretase cleavage occurs in a transmembrane segment of APP. Presenilin, which exists in a complex with nicastrin, APH-1 and PEN-2, has been identified as gamma-secretase from its deficiency []and mutation of its active site residues [], but proteolytic activity has only been directly demonstrated on a peptide derived from APP [].Presenilin-1 is also known to process notch proteins []and syndecan-3 [].Presenilin has nine transmembrane regions with the active site aspartic acid residues located on TM6, within a Tyr-Asp motif, and TM7, within a Gly-Xaa-Gly-Asp motif []. The protein autoprocesses to form an amino-terminal fragment (TMs 1-6) and a C-terminal fragment (TMs 7-9) []. The tertiary structure of the human gamma-sectretase complex has been solved []. Nicastrin is extracellular, whereas presenilin-1, APH-1 and PEN-2 are all transmembrane proteins. The transmembrane regions of all three proteins form a horseshoe shape. |
