The SARAH (for Sav/Rassf/Hpo) domain is a C-terminal eukaryotic module of approximately 50 residues, which is found in three classes of tumor suppressor which have given it its name.

In the Sav and Hpo families, the SARAH domain mediates a heterotypic interaction that relays the signal from Hpo via the scaffolding protein Sav to the downstream component Wts. In addition, SARAH domains also support homotypic interactions, as the human Hpo-ortholog Mst1 has been shown to dimerize via its carboxy-terminal region. The SARAH domain is found associated with other modules, such as the protein kinase domain (see <PDOC00100>), the WW/rsp5/WWP domain (see <PDOC50020>), the C1 domain (see <PDOC00379>), the LIM domain (see <PDOC00382>) or the Ras-associating (RA) domain (see <PDOC50200>) [1].

Secondary structure prediction programs suggest a long α-helix spanning most of the conserved region of the SARAH domain. The carboxy-terminal portion of the SARAH domain is predicted to have a moderate to high coiled-coil propensity. The SARAH domain does not contain any invariant residues, but has several highly conserved positions. While some of the conservation can be explained by generic coiled-coil properties, other residues are specifically conserved in the SARAH family. Regulatory interactions mediated by coiled coils usually involve relatively short helices capable of interacting reversibly in a homotypic and/or heterotypic fashion. As the SARAH domain has coiled-coil characteristics with an unusual heptad arrangement, it is conceivable that SARAH is in fact a trimerization domain [1].

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

• Drosophila melanogaster scaffold protein salvador (Sav).
• Mammalian salvador homolog 1 protein (SAV1).
• Drosophila melanogaster serine/threonine protein kinase hippo (HPO).
• Animal Ras association (RalGDS/AF-6) domain families of proteins (Rassf). These effectors of Ras and Ras-related GTPases are characterized by a RA domain upstream of the SARAH region.

The profile we developed spans the entire SARAH domain.