PROSITE documentation PDOC00373
Gram-positive cocci surface proteins LPxTG motif profile


Surface proteins from Gram-positive cocci are covalently linked to the bacterial cell wall by sortase, a membrane-anchored transpeptidase that cleaves proteins between the threonine and the glycine of a conserved LPxTG motif, with the formation of a thioester between the conserved cysteine of sortase and the threonine carboxyl group. The newly liberated C-terminus of the threonine is transferred via an amide bond exchange to the amino group of the pentaglycine wall crossbridge, thereby tethering the C-terminus end of the surface protein to the bacterial peptidoglycan [1,2,3].

Surface proteins from Gram-positive cocci contain an N-terminal signal peptide and a C-terminal sorting signal. The 35-residue sorting signal is composed of a conserved LPxTG motif, a hydrophobic domain, and a tail of positively charged residues. This structure is represented in the following schematic representation:

                                           +-- sorting signal ---+
                                           |                     |
  |Signal|                                 |LPxTG| Hydrophobic |+|
  'Signal': signal peptide;
  'Hydrophobic': hydrophobic domain;
  '+': positive charged tail.

In the case of immunoglobulin A1 proteases, the typical gram-positive cell wall anchor motif LPxTG is located in their N-terminal regions, in contrast with other known streptococcal and staphylococcal proteins [4].

Some proteins known to contain LPxTG motif containing sorting signal are listed below:

  • Aggregation substance from streptococcus faecalis (asa1).
  • C5a peptidase from Streptococcus pyogenes (scpA).
  • C protein α-antigen from Streptococcus agalactiae (bca).
  • Cell surface antigen I/II (PAC) from Streptococcus mutans.
  • Dextranase from Streptococcus downei (dex).
  • Fibronectin-binding protein from Staphylococcus aureus (fnbA).
  • Fimbrial subunits from Actinomyces naeslundii and viscosus.
  • IgA binding protein from Streptococcus pyogenes (arp4).
  • IgA binding protein (B antigen) from Streptococcus agalactiae (bag).
  • IgG binding proteins from Streptococci and Staphylococcus aureus.
  • Internalin A from Listeria monocytogenes (inlA).
  • M proteins from streptococci.
  • Muramidase-released protein from Streptococcus suis (mrp).
  • Nisin leader peptide processing protease from Lactococcus lactis (nisP).
  • Protein A from Staphylococcus aureus.
  • Trypsin-resistant surface T protein from streptococci.
  • Wall-associated protein from Streptococcus mutans (wapA).
  • Wall-associated serine proteinases from Lactococcus lactis.

The profile we developed covers the LPxTG motif, the hydrophobic stretch and the positively charged region.


This profile replaces a pattern whose specificity was inadequate.

Last update:

July 2018 / Profile revised.


Technical section

PROSITE method (with tools and information) covered by this documentation:

GRAM_POS_ANCHORING, PS50847; Gram-positive cocci surface proteins LPxTG motif profile  (MATRIX)


1AuthorsMazmanian S.K. Liu G. Ton-That H. Schneewind O.
TitleStaphylococcus aureus sortase, an enzyme that anchors surface proteins to the cell wall.
SourceScience 285:760-763(1999).
PubMed ID10427003

2AuthorsTon-That H. Liu G. Mazmanian S.K. Faull K.F. Schneewind O.
SourceProc. Natl. Acad. Sci. U.S.A. 96:12424-12429(1999).

3AuthorsPerry A.M. Ton-That H. Mazmanian S.K. Schneewind O.
TitleAnchoring of surface proteins to the cell wall of Staphylococcus aureus. III. Lipid II is an in vivo peptidoglycan substrate for sortase-catalyzed surface protein anchoring.
SourceJ. Biol. Chem. 277:16241-16248(2002).
PubMed ID11856734

4AuthorsPoulsen K. Reinholdt J. Jespersgaard C. Boye K. Brown T.A. Hauge M. Kilian M.
TitleA comprehensive genetic study of streptococcal immunoglobulin A1 proteases: evidence for recombination within and between species.
SourceInfect. Immun. 66:181-190(1998).
PubMed ID9423856

PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see prosite_license.html.


View entry in original PROSITE document format
View entry in raw text format (no links)