PSNPresenilin, signal peptide peptidase, family
|SMART accession number:||SM00730|
|Description:||Presenilin 1 and presenilin 2 are polytopic membrane proteins, whose genes are mutated in some individuals with Alzheimer's disease. Distant homologues, present in eukaryotes and archaea, also contain conserved aspartic acid residues which are predicted to contribute to catalysis. At least one member of this family has been shown to possess signal peptide peptidase activity.|
|Interpro abstract (IPR006639):|
In the MEROPS database peptidases and peptidase homologues are grouped into clans and families. Clans are groups of families for which there is evidence of common ancestry based on a common structural fold:
In many instances the structural protein fold that characterises the clan or family may have lost its catalytic activity, yet retain its function in protein recognition and binding.
Aspartic endopeptidases EC 3.4.23. of vertebrate, fungal and retroviral origin have been characterised [(PUBMED:1455179)]. More recently, aspartic endopeptidases associated with the processing of bacterial type 4 prepilin [(PUBMED:10625704)] and archaean preflagellin have been described [(PUBMED:16983194), (PUBMED:14622420)].
Structurally, aspartic endopeptidases are bilobal enzymes, each lobe contributing a catalytic Asp residue, with an extended active site cleft localised between the two lobes of the molecule. One lobe has probably evolved from the other through a gene duplication event in the distant past. In modern-day enzymes, although the three-dimensional structures are very similar, the amino acid sequences are more divergent, except for the catalytic site motif, which is very conserved. The presence and position of disulphide bridges are other conserved features of aspartic peptidases. All or most aspartate peptidases are endopeptidases. These enzymes have been assigned into clans (proteins which are evolutionary related), and further sub-divided into families, largely on the basis of their tertiary structure.
This group of aspartic peptidases belong to MEROPS peptidase family A22 (presenilin family, clan AD).
SPP and potential eukaryotic homologues represent a family of aspartic proteases that promote intramembrane proteolysis to release biologically important peptides. Signal peptide peptidase (SPP) catalyses intramembrane proteolysis of some signal peptides after they have been cleaved from a preprotein. In humans, SPP activity is required to generate signal sequence-derived human lymphocyte antigen-E epitopes that are recognised by the immune system, and are required in the processing of the hepatitis C virus core protein.
|GO component:||integral to membrane (GO:0016021)|
|GO function:||aspartic-type endopeptidase activity (GO:0004190)|
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