{PDOC51688}
{PS51688; ICA}
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* Intramolecular chaperone auto-processing (ICA) domain profile *
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The Intramolecular  Chaperone  Auto-processing  (ICA)  [1] domain, also called
Intramolecuar Chaperone   Domain   (ICD)   [2]  or  C-terminal  Intramolecular
Chaperone Domain (CIMCD) [3], is capable of catalyzing trimerization-dependent
auto-proteolysis. The  ICA domain contains two absolutely conserved serine and
lysine residues.  They  form  a  catalytic  dyad that mediates cleavage at the
serine residue.  The  correct  positioning  of these catalytic residues, along
with an  arginine residue that stabilizes the oxyanion during the peptide bond
breakage, is  thought  to  be  achieved  only  upon folding and trimerization,
enabling the  ICA  domain  to  function  as  a  folding sensor. The ICA domain
belongs to peptidase family S74 [E1].

The ICA domain displays an alpha1-beta1-alpha2-beta2-alpha3-beta3-beta4-alpha4
fold (see  <PDB:3GUD>). The ICA domain homotrimer has a jellyfish-like outline
with a  central  threefold symmetry axis and mainly consists of alpha-helices.
It comprises a quite globular core and an extended loop region, reminiscent of
tentacles, protruding  from  the  center.  The  central  part of the core is a
slightly twisted three helix bundle, forming the trimerization interface [3].

Some proteins known to contain an ICA domain are listed below:

 - Animal myelin regulatory factor (MYRF), a key transcriptional regulator for
   of oligodendrocyte   differenciation   and  central  nervous  system  (CNS)
   myelination. The  MYRF  protein  undergoes  an activating cleavage event to
   release the  functional  transcription factor from the transmembrane domain
   that otherwise anchors it to the endoplasmic reticulum [1,2].
 - Tailed  bacteriophage  (Caudovirus)  endosialidases, the tailspike proteins
   essential for   bacteriophages   to   infect   bacteria  encapsulated  with
   polysaccharides.

The profile we developed covers the entire ICA domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: September 2013 / First entry.

[ 1] Li Z., Park Y., Marcotte E.M.
     "A Bacteriophage Tailspike Domain Promotes Self-Cleavage of a Human
     Membrane-Bound Transcription Factor, the Myelin Regulatory Factor
     MYRF."
     PLoS Biol. 11:E1001624-E1001624(2013).
     PubMed=23966832; DOI=10.1371/journal.pbio.1001624
[ 2] Bujalka H., Koenning M., Jackson S., Perreau V.M., Pope B., Hay C.M.,
     Mitew S., Hill A.F., Lu Q.R., Wegner M., Srinivasan R., Svaren J.,
     Willingham M., Barres B.A., Emery B.
     "MYRF Is a Membrane-Associated Transcription Factor That
     Autoproteolytically Cleaves to Directly Activate Myelin Genes."
     PLoS Biol. 11:E1001625-E1001625(2013).
     PubMed=23966833; DOI=10.1371/journal.pbio.1001625
[ 3] Schulz E.C., Dickmanns A., Urlaub H., Schmitt A., Muehlenhoff M.,
     Stummeyer K., Schwarzer D., Gerardy-Schahn R., Ficner R.
     "Crystal structure of an intramolecular chaperone mediating
     triple-beta-helix folding."
     Nat. Struct. Mol. Biol. 17:210-215(2010).
     PubMed=20118935; DOI=10.1038/nsmb.1746
[E1] https://www.ebi.ac.uk/merops/cgi-bin/famsum?family=s74

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