Secreted aspartic endopeptidase (IPR033876)

Short name: SAP-like

Overlapping homologous superfamilies

Domain relationships


SAPs (Secreted aspartic proteinases) are secreted from a group of pathogenic fungi, predominantly Candida species. They are secreted from the pathogen to degrade host proteins. SAP is one of the most significant extracellular hydrolytic enzymes produced by C. albicans. SAP proteins, encoded by a family of 10 SAP genes. All 10 SAP genes of C. albicans encode preproenzymes, approximately 60 amino acid longer than the mature enzyme, which are processed when transported via the secretory pathway. The mature enzymes contain sequence motifs typical for all aspartyl proteinases, including the two conserved aspartate residues other active site and conserved cysteine residues implicated in the maintenance of the three-dimensional structure. Most Sap proteins contain putative N-glycosylation sites, but it remains to be determined which Sap proteins are glycosylated [PMID: 12966142].

A variety of fungal secreted aspartic peptidases are included in this entry:

  • barrierpepsin (MEROPS identifier A01.015)
  • candidapepsin SAP1 (A01.014)
  • candidapepsin SAP2 (A01.060)
  • candidapepsin SAP3 (A01.061)
  • candidapepsin SAP4 (A01.062)
  • candidapepsin SAP5 (A01.063)
  • candidapepsin SAP6 (A01.064)
  • candidapepsin SAP7 (A01.065)
  • candidapepsin SAP8 (A01.066)
  • candidapepsin SAP9 (A01.067)
  • candidapepsin SAP10 (A01.085)
  • candiparapsin (A01.038)
  • canditropsin (A01.037)
  • yapsin-1 (A01.030)
  • yapsin-2 (A01.031)
These are not all products secreted by pathogenic fungi. Barrierpepsin and yapsins are secreted by Sacchomyces cervisiae. Barrierpepsin is secreted by yeasts of mating type a and processes the alpha-mating factor at the Leu-Lys bond, thereby inactivating it. This is mechanism for optimizing the concentration of the mating factor [PMID: 3124102],[PMID: 9249020]. Yapsin-1 releases alpha-mating factor from its precursor [PMID: 8094050].

Aspartyl proteases (APs), also known as acid proteases, (EC:3.4.23.-) are a widely distributed family of proteolytic enzymes [PMID: 6795036, PMID: 2194475, PMID: 1851433, PMID: 15771507, PMID: 24869856, PMID: 1455179] known to exist in vertebrates, fungi, plants, retroviruses and some plant viruses. APs use an Asp dyad to hydrolyze peptide bonds.

APs found in eukaryotic cells are alpha/beta monomers composed of two asymmetric lobes ("bilobed"). Each of the lobes provides a catalytic Asp residue, positioned within the hallmark motif Asp-Thr/Ser-Gly, to the active site. The N- and C-terminal domains, although structurally related by a 2-fold axis, have only limited sequence homology except the vicinity of the active site. This suggests that the enzymes evolved by an ancient duplication event. The enzymes specifically cleave bonds in peptides which have at least six residues in length with hydrophobic residues in both the P1 and P1' positions. The active site is located at the groove formed by the two lobes, with an extended loop projecting over the cleft to form an 11-residue flap, which encloses substrates and inhibitors in the active site. Specificity is determined by nearest-neighbour hydrophobic residues surrounding the catalytic aspartates, and by three residues in the flap. The enzymes are mostly secreted from cells as inactive proenzymes that activate autocatalytically at acidic pH. Eukaryotic APs form peptidase family A1 of clan AA.

GO terms

Biological Process

No terms assigned in this category.

Molecular Function

GO:0004190 aspartic-type endopeptidase activity

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.