Motif corresponding to a short interface helix parallel to the membrane planes and found across more than 80 different protein families. For a complete list of Pfam CLAN categories see below.

Structural description: The short helix lies almost parallel to the membrane planes at the membrane-water interface region close to the extracellular side. Besdies the hydrogen bond pattern i,i+4 of a regular alpha-heilx, the motif shows also the pattern between main chain atoms in positions i,i+3, typical of an irregular 3₁₀ helix. The backbone torsion angle pattern associated to the motif is illustrated below.

Functional annotation: The motif hits 3002 transmembrane proteins in the Swiss-Prot database, but it has a relatively high false positive rate of 57%. The Swiss-Prot ids of the proteins carrying the motif are listed below. The GO terms associated to the motif are the following: oxidoreductase activity; iron ion binding; electron transport; mitochondrion; metal ion binding; mitochondrial electron transport chain; transport.

The motif is potentially an interesting case of convergent evolution motif as it has been dervied from proteins with totally different sequence and structure but that seem to share a common functional feature/mechanism. In the aspartate symporter (2nwl, chain B) the motif is found in correspondence of one of the two helical hairpins which is thought to act as a gate, adopting a open conformation and allowing the aspartate to reach the binding site from the extracellular solution (PMID: 17230192). Also according to our SCOPPI and protein-ligand interaction analysis, the motif residues Thr352, Ala353, Gly354 and Val355 (2nwl, chain B) non-covalently bind the aspartate molecule. In the serine protease(2ic8, chain A) the structural motif is part of a long membrane-embedded loop between the first two transmembrane helices which also acts as a gate which changes conformation when the substrate enters (PMID: 1726495). For the cytochrome b (1kb9, chain C) there is no evidence in literature that the motif can be associated to a gating function, but, from our SCOPPI analysis is evident that some motif's residues bind stimmatellin A, a Q₀ inhibitor. It can be postulated that, also in this third case the motif is involved in conformational changes upon substrate binding.