PROSITE documentation PDOC51837
LITAF domain profile


LITAF (LPS-induced TNF-activating factor) (also known as SIMPLE; small integral membrane protein of the late endosome) is an endosome-associated integral membrane protein important for multivesicular body (MVB) sorting. It is a monotypic membrane protein with both termini exposed to the cytoplasm and is anchored to membranes via an in-plane helical membrane anchor, present within the highly conserved C-terminal region known as the 'LITAF domain' or 'SIMPLE-like domain'. The LITAF domain consists of conserved cysteines separated by a 22 residue hydrophobic region. LITAF domains are found throughout the eukaryotes, suggesting ancient conserved functions, with multiple instances of expansion, especially in the metazoa [1,2].

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 the coordination of a zinc atom by two pairs of evolutionarily conserved cysteine residues. Consistent with a protein domain that resides in close proximity to membranes, specific residues within the LITAF domain interact with phosphoethanolamine (PE) head groups. The anchoring-region of the LITAF domain is likely to embed into the cytosolic-facing monolayer of the membrane bilayer by adopting an amphipathic character [2].

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

  • Vertebrate Lipopolysaccharide-induced tumor necrosis factor-α 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.

The profile we developed covers the entire LITAF domain.

Last update:

June 2017 / First entry.


Technical section

PROSITE method (with tools and information) covered by this documentation:

LITAF, PS51837; LITAF domain profile  (MATRIX)


1AuthorsQin W. Wunderley L. Barrett A.L. High S. Woodman P.G.
TitleThe Charcot Marie Tooth disease protein LITAF is a zinc-binding monotopic membrane protein.
SourceBiochem. J. 473:3965-3978(2016).
PubMed ID27582497

2AuthorsHo A.K. Wagstaff J.L. Manna P.T. Wartosch L. Qamar S. Garman E.F. Freund S.M.V. Roberts R.C.
TitleThe topology, structure and PE interaction of LITAF underpin a Charcot-Marie-Tooth disease type 1C.
SourceBMC Biol. 14:109-109(2016).
PubMed ID27927196

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