9.B.297.  The Archaeosortase (Art) Family 

Integral membrane archaeosortases recognize and remove carboxyl-terminal protein targetting signals about 25 amino acids long from secreted proteins (Haft et al. 2012). A genome that encodes one archaeosortase may encode over fifty target proteins. The best characterized archaeosortase target is the Halofax volcanii S-layer glycoprotein, an extensively modified protein withO- and N-linked glycosylations as well as a large prenyl-derived lipid modification toward the C-terminus (Abdul Halim et al. 2013). 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 (Abdul Halim et al. 2015). 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 lack significant sequence similarity. The sequences of archaeosortases and exosortases consists mostly of hydrophobic transmembrane helices, which sortases lack (Abdul Halim et al. 2018). 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, ArtC recognizes PEF-CTERM, and so on; one archaeal genome may encode two different archaeosortase systems (Giménez et al. 2015).

This family belongs to the .



Abdul Halim, M.F., F. Pfeiffer, J. Zou, A. Frisch, D. Haft, S. Wu, N. Tolić, H. Brewer, S.H. Payne, L. Paša-Tolić, and M. Pohlschroder. (2013). Haloferax volcanii archaeosortase is required for motility, mating, and C-terminal processing of the S-layer glycoprotein. Mol. Microbiol. 88: 1164-1175.

Abdul Halim, M.F., K.R. Karch, Y. Zhou, D.H. Haft, B.A. Garcia, and M. Pohlschroder. (2015). Permuting the PGF Signature Motif Blocks both Archaeosortase-Dependent C-Terminal Cleavage and Prenyl Lipid Attachment for the Haloferax volcanii S-Layer Glycoprotein. J. Bacteriol. 198: 808-815.

Abdul Halim, M.F., R. Rodriguez, J.D. Stoltzfus, I.G. Duggin, and M. Pohlschroder. (2018). Conserved residues are critical for Haloferax volcanii archaeosortase catalytic activity: Implications for convergent evolution of the catalytic mechanisms of non-homologous sortases from archaea and bacteria. Mol. Microbiol. 108: 276-287.

Giménez, M.I., M. Cerletti, and R.E. De Castro. (2015). Archaeal membrane-associated proteases: insights on Haloferax volcanii and other haloarchaea. Front Microbiol 6: 39.

Haft, D.H., S.H. Payne, and J.D. Selengut. (2012). Archaeosortases and exosortases are widely distributed systems linking membrane transit with posttranslational modification. J. Bacteriol. 194: 36-48.


TC#NameOrganismal TypeExample

Archaeosortase A of 303 aas and 7 or 8 TMSs, probably in a 4 + 4 TMS arrangement.

ArtA of Haloferax volcanii


TC#NameOrganismal TypeExample

Exosortase/archaeosortase family protein, EpsH, of 199 aas and 4 TMSs in a 1 + 3 TMS arrangement.

Exosortase, EpsH, of Tamlana sedimentorum


Transmembrane exosortase of 291 aas and 5 TMSs.

Exosortase of Lokiarchaeum sp. GC14_75


Uncharacterized protein of 252 aas and 5 TMSs.

UP of Candidatus Lokiarchaeota archaeon CR_4 (sediment metagenome)