The CRAL-TRIO domain is a structurally conserved element of about 170 amino acids, which constitute a hydrophobic lipid binding pocket. The CRAL-TRIO domain is found in GTPase-activating proteins (GAPs), guanine nucleotide exchange factors (GEFs) and a family of hydrophobic ligand binding proteins, including the yeast SEC14 protein and mammalian retinaldehyde- and α-tocopherol-binding proteins. The CRAL-TRIO domain may either constitute all of the protein or only part of it [1,2,3,4,5].

The resolution of the crystal structure of SEC14 has revealed the structure of the CRAL-TRIO lipid binding domain (see <PDB:1AUA>). The CRAL-TRIO lipid binding domain is an α/β domain, which forms a large hydrophobic pocket. The pocket floor is constituted by six β-strands and the sides of the cavity are formed by α-helices [3].

Some proteins known to contain a CRAL-TRIO domain are listed below:

• Yeast phosphatidylinositol-transfer protein (SEC14). It is required for transport of secretory proteins from the golgi complex in vivo and it catalyzes the transfer of phosphatidylinositol and phosphatidylcholine between membranes in vitro.
• Animal retinal-binding protein.
• Animal neurofibromin (protein NF-1). In human, defects in NF-1 are the cause of type 1 neurofibromatosis (NF-1), one of the most frequent autosomal dominant diseases.
• Mammalian BCL2/adenovirus E1B 19 kDa protein-interacting protein 2 (NIP2). NIP2 is an apoptosis regulator.
• Mammalian guanine nucleotide exchange factor DBS (DBL's big sister).
• Mammalian cellular retinol retinaldehyde-binding protein (CRALBP). It carries 11-cis-retinol and 11-cis-retinaldehyde as endogenous ligands and may be a functional component of the visual cycle.
• Mammalian α-tocopherol transfer protein (α-TTP). It binds α- tocopherol and enhances its transfer between separate membranes.
• Mammalian α-tocopherol-associated protein (TAP).

The profile we developed covers the entire CRAL-TRIO domain.