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PROSITE documentation PDOC51036Zinc finger A20-type profile
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PURL: https://purl.expasy.org/prosite/documentation/PDOC51036
NF-kappaB transcription factors mediate the effects of pro-inflammatory cytokines such as TNF-α and interleukin-1 β. Failure to downregulate NF-kappaB transcriptional activity results in chronic inflammation and cell death [1]. It has been shown that A20 protein can downregulates NF-kappaB signaling by targeting receptor interacting protein (RIP), an essential mediator of the proximal TNF receptor 1 (TNFR1) signalling complex, to the proteasome [2].
The C-terminal region of A20, is composed of seven C4-type zinc fingers, that function as a ubiquitin ligase by polyubiquitinating RIP with Lys-48-linked ubiquitin chains, thereby targeting RIP for proteasomal degradation [2].
A20-type zinc fingers are found in all eukaryotes and form fusions with a variety of domains involved in ubiquitin signaling pathways.
The profile we developed covers the whole A20-type zinc finger.
Last update:November 2004 / First entry.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Dixit V. Mak T.W. |
| Title | NF-kappaB signaling. Many roads lead to madrid. | |
| Source | Cell 111:615-619(2002). | |
| PubMed ID | 12464174 |
| 2 | Authors | Wertz I.E. O'Rourke K.M. Zhou H. Eby M. Aravind L. Seshagiri S. Wu P. Wiesmann C. Baker R. Boone D.L. Ma A. Koonin E.V. Dixit V.M. |
| Title | De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-kappaB signalling. | |
| Source | Nature 430:694-699(2004). | |
| PubMed ID | 15258597 | |
| DOI | 10.1038/nature02794 |
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