caa a22 4500 445821329 CHVBK 20180317145245.0 cr unu---uuuuu 170323e20110601xx s 000 0 eng 10.1007/s00239-011-9450-7 doi (NATIONALLICENCE)springer-10.1007/s00239-011-9450-7 Evolution of Vertebrate Immunity: Sequence and Functional Analysis of the SEFIR Domain Family Member Act1 [Elektronische Daten] [Grigory Ryzhakov, Katrina Blazek, Irina Udalova] SEF/IL-17R/CIKS/ACT1 homology (SEFIR) domain containing proteins, which include the IL-17 receptors and an adaptor protein Act1, have essential roles in vertebrate immunity. However, the molecular mechanisms of Act1 function remain largely unexplored. In this article, we employed an evolutionary analysis to discover novel structural and functional properties of Act1. Firstly, we have found that the previously identified helix-loop-helix and Ufd2-box domains in human Act1 have relatively recent evolutionary origins in higher vertebrates. Zebrafish Act1, which lacks these domains, is unable to induce JNK phosphorylation and activate cytokine expression when expressed in human cells. Secondly, we have established that Act1-like proteins contain DEATH-domains in basal animals, such as Hydra and primitive chordates, but lack this domain in vertebrates. Finally, we have shown that Act1-TRAF6 interactions are conserved throughout vertebrate evolution: Act1 derived from zebrafish can bind to TRAF6 and activate NF-κB in human cells. Moreover, we have identified a novel highly conserved motif at the amino-terminus of Act1, which is critical for binding to TRAF6 and activating NF-κB-dependent gene expression. We propose a model of evolutionary changes in Act1-mediated signalling, which contributes to a better understanding of evolution of the vertebrate immunity. Springer Science+Business Media, LLC, 2011 Act1/CIKS nationallicence SEFIR nationallicence NF-κB nationallicence TRAF6 nationallicence IL-17 nationallicence Ryzhakov Grigory Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College of Science, Technology and Medicine, 65 Aspenlea Road, Hammersmith, W6 8LH, London, UK aut Blazek Katrina Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College of Science, Technology and Medicine, 65 Aspenlea Road, Hammersmith, W6 8LH, London, UK aut Udalova Irina Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College of Science, Technology and Medicine, 65 Aspenlea Road, Hammersmith, W6 8LH, London, UK aut Journal of Molecular Evolution Springer-Verlag 72/5-6(2011-06-01), 521-530 0022-2844 72:5-6<521 2011 72 239 https://doi.org/10.1007/s00239-011-9450-7 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00239-011-9450-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ryzhakov Grigory Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College of Science, Technology and Medicine, 65 Aspenlea Road, Hammersmith, W6 8LH, London, UK aut NATIONALLICENCE 700 1- Blazek Katrina Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College of Science, Technology and Medicine, 65 Aspenlea Road, Hammersmith, W6 8LH, London, UK aut NATIONALLICENCE 700 1- Udalova Irina Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College of Science, Technology and Medicine, 65 Aspenlea Road, Hammersmith, W6 8LH, London, UK aut NATIONALLICENCE 773 0- Journal of Molecular Evolution Springer-Verlag 72/5-6(2011-06-01), 521-530 0022-2844 72:5-6<521 2011 72 239 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer