PROSITE documentation PDOC51392
KEN domain profile


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 [2,3,4].
  • 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.

Last update:

July 2008 / First entry.


Technical section

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

KEN, PS51392; KEN domain profile  (MATRIX)


1AuthorsLee K.P.K. Dey M. Neculai D. Cao C. Dever T.E. Sicheri F.
TitleStructure of the dual enzyme Ire1 reveals the basis for catalysis and regulation in nonconventional RNA splicing.
SourceCell 132:89-100(2008).
PubMed ID18191223

2AuthorsZhou A. Hassel B.A. Silverman R.H.
TitleExpression cloning of 2-5A-dependent RNAase: a uniquely regulated mediator of interferon action.
SourceCell 72:753-765(1993).
PubMed ID7680958

3AuthorsTanaka N. Nakanishi M. Kusakabe Y. Goto Y. Kitade Y. Nakamura K.T.
TitleStructural basis for recognition of 2',5'-linked oligoadenylates by human ribonuclease L.
SourceEMBO J. 23:3929-3938(2004).
PubMed ID15385955

4AuthorsTownsend H.L. Jha B.K. Han J.-Q. Maluf N.K. Silverman R.H. Barton D.J.
TitleA viral RNA competitively inhibits the antiviral endoribonuclease domain of RNase L.
SourceRNA 14:1026-1036(2008).
PubMed ID18426919

5AuthorsTirasophon W. Welihinda A.A. Kaufman R.J.
TitleA stress response pathway from the endoplasmic reticulum to the nucleus requires a novel bifunctional protein kinase/endoribonuclease (Ire1p) in mammalian cells.
SourceGenes Dev. 12:1812-1824(1998).
PubMed ID9637683

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