LITAF (LPS-induced TNF-activating factor) (also known as SIMPLE; smallintegral membrane protein of the late endosome) is an endosome-associatedintegral membrane protein important for multivesicular body (MVB) sorting. Itis a monotypic membrane protein with both termini exposed to the cytoplasm andis anchored to membranes via an in-plane helical membrane anchor, presentwithin the highly conserved C-terminal region known as the 'LITAF domain' or'SIMPLE-like domain'. The LITAF domain consists of conserved cysteinesseparated by a 22 residue hydrophobic region. LITAF domains are foundthroughout the eukaryotes, suggesting ancient conserved functions, withmultiple instances of expansion, especially in the metazoa [, ].The LITAF domain consists of five β-sheets, three N-terminal and two C-terminal to the predicted hydrophobic anchor region and is stabilized by thecoordination of a zinc atom by two pairs of evolutionarily conserved cysteineresidues. Consistent with a protein domain that resides in close proximity tomembranes, specific residues within the LITAF domain interact withphosphoethanolamine (PE) head groups. The anchoring-region of the LITAF domainis likely to embed into the cytosolic-facing monolayer of the membrane bilayerby adopting an amphipathic character [].
LITAF (LPS-induced TNF-activating factor) (also known as SIMPLE; smallintegral membrane protein of the late endosome) is an endosome-associatedintegral membrane protein important for multivesicular body (MVB) sorting. Itis a monotypic membrane protein with both termini exposed to the cytoplasm andis anchored to membranes via an in-plane helical membrane anchor, presentwithin the highly conserved C-terminal region known as the 'LITAF domain' or'SIMPLE-like domain'. The LITAF domain consists of conserved cysteinesseparated by a 22 residue hydrophobic region. LITAF domains are foundthroughout the eukaryotes, suggesting ancient conserved functions, withmultiple instances of expansion, especially in the metazoa [, ].Proteins containing the LITAF domain include: Vertebrate lipopolysaccharide-induced tumor necrosis factor-alpha factor (LITAF). In human, several mutations in LITAF cause the autosomal dominant inherited peripheral neuropathy, Charcot-Marie-Tooth disease type 1 (CMT1). These mutations map to the LITAF domain [].Eukaryotic cell death-inducing p53-target protein 1 (CDIP1) [].Arabidopsis thaliana GSH-induced LITAF domain protein (GILP), acts as a membrane anchor, bringing other regulators of programmed cell death (PCD) to the plasma membrane [].
