<p>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:</p><ul> <li>Each clan is identified with two letters, the first representing the catalytic type of the families included in the clan (with the letter 'P' being used for a clan containing families of more than one of the catalytic types serine, threonine and cysteine). Some families cannot yet be assigned to clans, and when a formal assignment is required, such a family is described as belonging to clan A-, C-, M-, N-, S-, T- or U-, according to the catalytic type. Some clans are divided into subclans because there is evidence of a very ancient divergence within the clan, for example MA(E), the gluzincins, and MA(M), the metzincins.</li><li>Peptidase families are grouped by their catalytic type, the first character representing the catalytic type: A, aspartic; C, cysteine; G, glutamic acid; M, metallo; N, asparagine; S, serine; T, threonine; and U, unknown. The serine, threonine and cysteine peptidases utilise the amino acid as a nucleophile and form an acyl intermediate - these peptidases can also readily act as transferases. In the case of aspartic, glutamic and metallopeptidases, the nucleophile is an activated water molecule. In the case of the asparagine endopeptidases, the nucleophile is asparagine and all are self-processing endopeptidases. </li></ul><p>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. </p><p>Aspartic endopeptidases <db_xref db="EC" dbkey="3.4.23."/> of vertebrate, fungal and retroviral origin have been characterised [<cite idref="PUB00006548"/>]. More recently, aspartic endopeptidases associated with the processing of bacterial type 4 prepilin [<cite idref="PUB00020023"/>] and archaean preflagellin have been described [<cite idref="PUB00035904"/>, <cite idref="PUB00014343"/>].</p><p>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.</p><p>This group of aspartic peptidases belong to MEROPS peptidase family A22 (presenilin family, clan AD).</p><p>SPP and potential eukaryotic homologs 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.</p>