{PDOC50237}
{PS50237; HECT}
{BEGIN}
***********************
* HECT domain profile *
***********************

The HECT  (Homologous  to the E6-AP Carboxyl Terminus) domain is an around 350
amino acids  motif  that  has been identified in proteins that all belong to a
particular E3  ubiquitin-protein  ligase  family  [1].  HECT domain containing
proteins accept ubiquitin  from an E2 ubiquitin-conjugating enzyme in the form
of a  thioester and then transfer it to target proteins. The site of ubiquitin
thioester formation  is a conserved cysteine residue located in the last 32-36
aa of the HECT domain [1]. The amino-terminal part of the HECT domain has been
involved in  E2 binding [2]. Once linked to ubiquitin, the target proteins are
degraded in the 26 S proteasome.

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

 - Mammalian  E6-AP  (EC  6.3.2.-).  It  interacts  with the E6 protein of the
   cancer-associated human papillomavirus types16 and 18. The E6/E6-AP complex
   binds to  and  targets  the  p53  tumor-suppressor  protein  for  ubiquitin
   mediated proteolysis.
 - Yeast  RSP5 (EC 6.3.2.-). It is involved in the degradation of several cell
   surface proteins.
 - S.pombe pub1 (EC 6.3.2.-). It regulates ubiquitination of cdc25.
 - Yeast HUL4 and HUL5 (EC 6.3.2.-).
 - Drosophila  hyperplastic  discs  (HYD) protein (EC 6.3.2.-). It is required
   for regulation of cell proliferation in imaginal discs and germ cells.
 - Mammalian  NEDD4  (EC 6.3.2.-). It is involved in the embryonic development
   and differentiation of the central nervous system.
 - Rat  100  kDa  protein  (EC  6.3.2.-).  This  protein  may  be  involved in
   maturation and/or post-transcriptional regulation of mRNA.
 - Rat  UreB1. It contains only a portion of the HECT domain (310 aa), without
   any amino-terminal  extension.  It  could  be a DNA-binding transcriptional
   regulator.
 - Human thyroid receptor interacting protein 12 (TRIP12).

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: December 2001 / First entry.

[ 1] Huibregtse J.M., Scheffner M., Beaudenon S., Howley P.M.
     "A family of proteins structurally and functionally related to the
     E6-AP ubiquitin-protein ligase."
     Proc. Natl. Acad. Sci. U.S.A. 92:2563-2567(1995).
     PubMed=7708685
[ 2] Hatakeyama S., Jensen J.P., Weissman A.M.
     "Subcellular localization and ubiquitin-conjugating enzyme (E2)
     interactions of mammalian HECT family ubiquitin protein ligases."
     J. Biol. Chem. 272:15085-15092(1997).
     PubMed=9182527

--------------------------------------------------------------------------------
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}