CRAL-TRIO lipid binding domain superfamily
IPR036865
Definition
The CRAL-TRIO domain is a protein structural domain that binds small lipophilic molecules PMID:12767229. The domain is named after cellular retinaldehyde-binding protein (CRALBP) and TRIO guanine exchange factor. 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 alpha-tocopherol-binding proteins. The domain may either constitute all of the protein or only part of it [[cite:PMID:2198263], [cite:PMID:8349655], [cite:PMID:9461221], [cite:PMID:10829015]]. This domain is also found in Phosphatidylinositol transfer protein SFH5. Phosphatidylinositol transfer protein SFH5 is a non-classical member of the PITP family that functions in lipid transport and signalling at cellular membranes. Unlike canonical PITPs, which typically bind and transfer both phosphatidylinositol (PtdIns) and phosphatidylcholine (PtdCho), SFH5 exhibits selective PtdIns-binding and transfer activity while lacking detectable PtdCho-binding capacity. This functional distinction places SFH5 in a unique subset of lipid transfer proteins with specialised roles in membrane lipid dynamics. A primary function of SFH5 is the regulation of PtdIns(4,5)P2 homeostasis at the plasma membrane, a critical phosphoinositide involved in numerous signalling cascades, cytoskeletal organisation, and membrane trafficking events. Additionally, SFH5 possesses heme-binding capability, suggesting a secondary role in cellular responses to organic oxidant-induced stress. This dual functionality, combining lipid transfer with potential redox sensing, highlights SFH5 as a multifunctional protein that integrates membrane lipid regulation with stress response pathways [[cite:PMID:10848624], [cite:PMID:12869188], [cite:PMID:16709158]]. The structure of the domain in SEC14 proteins has been determined PMID:9461221. The structure contains several α helices as well as a β sheet composed of 6 strands. Strands 2, 3, 4 and 5 form a parallel β-sheet, with strands 1 and 6 being anti-parallel. The structure also identified a hydrophobic binding pocket for lipid binding.
26 human proteins with this domain
Each is a reviewed human protein in the Seroatlas serome and a potential autoantibody target; this domain groups them into one antibody-relevant category. Every entry links to its own record.
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