Peptidase family A1 domain
IPR033121
Definition
This entry represents domain found in the peptidase A1 family. This entry also includes a probable inactive secreted aspartyl protease from Malassezia globosa, which may promote an inflammatory immune response in the host when the host skin barrier is breached PMID:37748748. It has no detectable protease activity in vitro that could be due to the active site motif diverging from the canonical Asp-X-Gly-X motif (where X is Thr or Ser) to containing a Tyr residue (Asp-Ser-Gly-Tyr) PMID:37748748. Aspartyl proteases (APs), also known as acid proteases, ([ec:3.4.23.-]) are a widely distributed family of proteolytic enzymes [[cite:PMID:6795036], [cite:PMID:2194475], [cite:PMID:1851433], [cite:PMID:15771507], [cite:PMID:24869856], [cite: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 α/β 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.
10 human proteins with this domain
Each is a reviewed human protein in the Seroatlas serome and a potential autoantibody target; this domain groups them into one antibody-relevant category. Every entry links to its own record.
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