PUBLICATION
Evolution of Vertebrate Immunity: Sequence and Functional Analysis of the SEFIR Domain Family Member Act1
- Authors
- Ryzhakov, G., Blazek, K., and Udalova, I.A.
- ID
- ZDB-PUB-110613-10
- Date
- 2011
- Source
- Journal of molecular evolution 72(5-6): 521-30 (Journal)
- Registered Authors
- Keywords
- Act1/CIKS, SEFIR, NF-κB, TRAF6, IL-17
- MeSH Terms
-
- Amino Acid Motifs/genetics
- Amino Acid Sequence
- Animals
- Evolution, Molecular*
- Gene Expression Regulation
- HEK293 Cells
- Humans
- Models, Biological
- Molecular Sequence Data
- Protein Binding/genetics
- Receptors, Interleukin-17/genetics
- Receptors, Interleukin-17/metabolism
- Sequence Alignment
- Signal Transduction
- Species Specificity
- TNF Receptor-Associated Factor 6/metabolism
- Tumor Necrosis Factor Receptor-Associated Peptides and Proteins/chemistry*
- Tumor Necrosis Factor Receptor-Associated Peptides and Proteins/genetics
- Tumor Necrosis Factor Receptor-Associated Peptides and Proteins/metabolism*
- Vertebrates/genetics
- Vertebrates/immunology*
- Vertebrates/metabolism
- PubMed
- 21643828 Full text @ J. Mol. Evol.
Citation
Ryzhakov, G., Blazek, K., and Udalova, I.A. (2011) Evolution of Vertebrate Immunity: Sequence and Functional Analysis of the SEFIR Domain Family Member Act1. Journal of molecular evolution. 72(5-6):521-30.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping