{PDOC51392}
{PS51392; KEN}
{BEGIN}
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* KEN domain profile *
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The proteins  listed  below  share a common architecture with a protein kinase
homology domain (see <PDOC00100>) followed by an ~135-residue globular kinase-
extension nuclease (KEN) domain made of eight helices (see <PDB:2RIO>) [1]:

 - Mammalian  2-5A-dependent  RNase  or  RNase L (EC 3.1.26.-), an interferon-
   induced enzyme  implicated  in  both the molecular mechanisms of interferon
   action and  the  fundamental control of RNA stability. 2-5A-dependent RNase
   is a  unique  enzyme in that it requires 2-5A, unusual oligoadenylates with
   2',5'-phosphodiester linkages.  RNase  L is catalytically active only after
   binding to an unusual activator molecule containing a 5'-phosphorylated 2',
   5'-linked oligoadenylate  (2-5A),  in the N-terminal half. RNase L consists
   of three   domains,  namely  the  N-terminal  ankyrin  repeat  domain  (see
   <PDOC50088>), the  protein  kinase  homology domain, and the C-terminal KEN
   domain [2-4].
 - Eukaryotic  Ire1/Ern1,  an  ancient  transmembrane  sensor  of  endoplasmic
   reticulum (ER) stress with dual protein kinase and ribonuclease activities.
   In repsonse  to  ER stress Ire1/Ern1 catalyzes the splicing of target mRNAs
   in a  spliceosome-independent  manner.  Ire1/Ern1 is a type 1 transmembrane
   receptor consisting  of  an  N-terminal  ER luminal domain, a transmembrane
   segment and  a  cytoplasmic  region.  The  cytoplasmic region encompasses a
   protein kinase domain followed by a C-terminal KEN domain [1,5].

The dimerization  of  the kinase domain activates the ribonuclease function of
the KEN domain [1].

The profile we developed covers the entire KEN domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: July 2008 / First entry.

[ 1] Lee K.P.K., Dey M., Neculai D., Cao C., Dever T.E., Sicheri F.
     "Structure of the dual enzyme Ire1 reveals the basis for catalysis and
     regulation in nonconventional RNA splicing."
     Cell 132:89-100(2008).
     PubMed=18191223; DOI=10.1016/j.cell.2007.10.057
[ 2] Zhou A., Hassel B.A., Silverman R.H.
     "Expression cloning of 2-5A-dependent RNAase: a uniquely regulated
     mediator of interferon action."
     Cell 72:753-765(1993).
     PubMed=7680958
[ 3] Tanaka N., Nakanishi M., Kusakabe Y., Goto Y., Kitade Y.,
     Nakamura K.T.
     "Structural basis for recognition of 2',5'-linked oligoadenylates by
     human ribonuclease L."
     EMBO J. 23:3929-3938(2004).
     PubMed=15385955; DOI=10.1038/sj.emboj.7600420
[ 4] Townsend H.L., Jha B.K., Han J.-Q., Maluf N.K., Silverman R.H.,
     Barton D.J.
     "A viral RNA competitively inhibits the antiviral endoribonuclease
     domain of RNase L."
     RNA 14:1026-1036(2008).
     PubMed=18426919; DOI=10.1261/rna.958908
[ 5] Tirasophon W., Welihinda A.A., Kaufman R.J.
     "A stress response pathway from the endoplasmic reticulum to the
     nucleus requires a novel bifunctional protein kinase/endoribonuclease
     (Ire1p) in mammalian cells."
     Genes Dev. 12:1812-1824(1998).
     PubMed=9637683

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