PROSITE documentation PDOC50801

STAS domain profile

The STAS domain is found in the C-terminal cytoplasmic part of anion transporters from eukaryotes and many bacteria, as well as in the bacterial anti-sigma-factor antagonists (ASAs). It was named STAS after sulfate transporters and anti-sigma-factor antagonist [1].

Malfunctions in members of the SLC26A family of anion transporters are involved in three human diseases: diastrophic dysplasia/achondrogenesis type 1B (DTDST), Pendred's syndrome (PDS) and congenital chloride diarrhea (CLD). These proteins contain 12 transmembrane helices followed by a cytoplasmic STAS domain at the C-terminus. The importance of the STAS domain in these transporters is illustrated by the fact that a number of mutations in PDS and DTDST map to it [1].

The activity of bacterial sigma transcription factors is controlled by a regulatory cascade involving an anti-sigma-factor, the ASA and a phosphatase. The antisigma-factor binds to sigma and holds it in an inactive complex. The ASA can also interact with the anti-sigma-factor, allowing the release of the active sigma factor. As the anti-sigma-factor is a protein kinase, it can phosphorylate the anti-sigma antagonist on a conserved serine residue of the STAS domain. This phosphorylation inactivates the ASA that can be reactivated through dephosphorylation by a phosphatase [1,2]. The STAS domain of the ASA SpoIIAA binds GTP and ATP and possesses a weak NTPase activity. Strong sequence conservation suggests that the STAS domain could possess general NTP-binding activity and it has been proposed that the NTPs are likely to elicit specific conformational changes in the STAS domain through binding and/or hydrolysis [1].

Resolution of the solution structure of the ASA SpoIIAA from Bacillus subtilis (see <PDB:1AUZ>) has shown that the STAS domain consists of a four-stranded β-sheet and four α helices. The STAS domain forms a characteristic α-helical handle-like structure [1,3].

Some proteins known to contain a STAS domain are listed below:

• Members of the SLC26 family of anion transporters.
• Anti-sigma-factor antagonists such as Bacillus subtilis SpoIIAA [2].
• Blue-light photoreceptor (Phototropin homolog) from Bacillus subtilis.
• Hypothetical protein K12G11.1 from Caenorhabditis elegans.
• Hypothetical protein SPCC320.05 from fission yeast.

The profile we developed covers the entire STAS domain.