archaeosortase archaeosortase an archaeosortase is a protein that occurs in the cell membranes of some archaea. archaeosortases recognize and remove carboxyl-terminal protein sorting signals about 25 amino acids long from secreted proteins. a genome that encodes one archaeosortase may encode over fifty target proteins. the best characterized archaeosortase target is the haloferax volcanii s-layer glycoprotein, an extensively modified protein with o-linked glycosylations, n-linked glycosylations, and a large prenyl-derived lipid modification toward the c-terminus. knockout of the archaeosortase a (arta) gene, or permutation of the motif pro-gly-phe (pgf) to pro-phe-gly in the s-layer glycoprotein, blocks attachment of the lipid moiety as well as blocking removal of the pgf-cterm protein-sorting domain. thus archaeosortase appears to be a transpeptidase, like sortase, rather than a simple protease. archaeosortases are related to exosortases, their uncharacterized counterparts in gram-negative bacteria. the names of both families of proteins reflect roles analogous to sortases in gram-positive bacteria, with which they share no sequence homology. the sequences of archaeosortases and exosortases consists mostly of hydrophobic transmembrane helices, which sortases lack. archaeosortases fall into a number of distinct subtypes, each responsible for recognizing sorting signals with a different signature motif. archaeosortase a (arta) recognizes the pgf-cterm signal, artb recognizes vpxxxp-cterm, atrc recognizes pef-cterm, and so on; one archaeal genome may encode two different archaeosortase systems. invariant residues shared by all archaeosortases and exosortases include a cys and an arg. replacement of either destroys catalytic activity, suggesting convergent evolution of the active site with the sortases. in the archaeal model species haloferax volcanii, archaeosortase a belongs to a fairly large collection of identified membrane-associated proteases, but apparently also to the smaller set of intramembrane cleaving proteases, along with the rhomboid protease rhoii, and in contrast to bacterial sortases.