{PDOC51837}
{PS51837; LITAF}
{BEGIN}
************************
* 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 beta-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-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.

The profile we developed covers the entire LITAF domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: June 2017 / First entry.

[ 1] Qin W., Wunderley L., Barrett A.L., High S., Woodman P.G.
     "The Charcot Marie Tooth disease protein LITAF is a zinc-binding
     monotopic membrane protein."
     Biochem. J. 473:3965-3978(2016).
     PubMed=27582497; DOI=10.1042/BCJ20160657
[ 2] Ho A.K., Wagstaff J.L., Manna P.T., Wartosch L., Qamar S.,
     Garman E.F., Freund S.M.V., Roberts R.C.
     "The topology, structure and PE interaction of LITAF underpin a
     Charcot-Marie-Tooth disease type 1C."
     BMC Biol. 14:109-109(2016).
     PubMed=27927196; DOI=10.1186/s12915-016-0332-8

--------------------------------------------------------------------------------
PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and
distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives
(CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html
--------------------------------------------------------------------------------

{END}