InterPro domain: IPR037519

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 [ 1 , 2 ].

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 [ 3 ].
• Eukaryotic cell death-inducing p53-target protein 1 (CDIP1) [ 4 ].
• 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 [ 5 ].

1. The Charcot Marie Tooth disease protein LITAF is a zinc-binding monotopic membrane protein. Biochem. J. 473, 3965-3978
2. The topology, structure and PE interaction of LITAF underpin a Charcot-Marie-Tooth disease type 1C. BMC Biol. 14, 109
3. SIMPLE mutations in Charcot-Marie-Tooth disease and the potential role of its protein product in protein degradation. Hum. Mutat. 25, 372-83
4. CDIP, a novel pro-apoptotic gene, regulates TNFalpha-mediated apoptosis in a p53-dependent manner. EMBO J. 26, 3410-22
5. The LSD1-interacting protein GILP is a LITAF domain protein that negatively regulates hypersensitive cell death in Arabidopsis. PLoS ONE 6, e18750