PROSITE documentation PDOC51392KEN domain profile
Description
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.
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Technical section
PROSITE method (with tools and information) covered by this documentation:
References
| 1 | Authors | Lee K.P.K. Dey M. Neculai D. Cao C. Dever T.E. Sicheri F. |
| Title | Structure of the dual enzyme Ire1 reveals the basis for catalysis and regulation in nonconventional RNA splicing. | |
| Source | Cell 132:89-100(2008). | |
| PubMed ID | 18191223 | |
| DOI | 10.1016/j.cell.2007.10.057 |
| 2 | Authors | Zhou A. Hassel B.A. Silverman R.H. |
| Title | Expression cloning of 2-5A-dependent RNAase: a uniquely regulated mediator of interferon action. | |
| Source | Cell 72:753-765(1993). | |
| PubMed ID | 7680958 |
| 3 | Authors | Tanaka N. Nakanishi M. Kusakabe Y. Goto Y. Kitade Y. Nakamura K.T. |
| Title | Structural basis for recognition of 2',5'-linked oligoadenylates by human ribonuclease L. | |
| Source | EMBO J. 23:3929-3938(2004). | |
| PubMed ID | 15385955 | |
| DOI | 10.1038/sj.emboj.7600420 |
| 4 | Authors | Townsend H.L. Jha B.K. Han J.-Q. Maluf N.K. Silverman R.H. Barton D.J. |
| Title | A viral RNA competitively inhibits the antiviral endoribonuclease domain of RNase L. | |
| Source | RNA 14:1026-1036(2008). | |
| PubMed ID | 18426919 | |
| DOI | 10.1261/rna.958908 |
| 5 | Authors | Tirasophon W. Welihinda A.A. Kaufman R.J. |
| Title | A stress response pathway from the endoplasmic reticulum to the nucleus requires a novel bifunctional protein kinase/endoribonuclease (Ire1p) in mammalian cells. | |
| Source | Genes Dev. 12:1812-1824(1998). | |
| PubMed ID | 9637683 |
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