W2 | |||||||||
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![]() crystal structure of the catalytic fragment of eukaryotic initiation factor 2b epsilon | |||||||||
Identifiers | |||||||||
Symbol | W2 | ||||||||
Pfam | PF02020 | ||||||||
Pfam clan | CL0020 | ||||||||
InterPro | IPR003307 | ||||||||
SCOP2 | 1paq / SCOPe / SUPFAM | ||||||||
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In molecular biology, the protein domain eIF4-gamma/eIF5/eIF2-epsilon is a family of evolutionarily related proteins. This domain is found at the C-terminus of several translation Initiation factors.[1] It was first detected at the very C-termini of the yeast protein GCD6, eIF-2B epsilon, and two other eukaryotic translation initiation factors, eIF-4 gamma and eIF-5 and it may be involved in the interaction of eIF-2B, eIF-4 gamma, and eIF-5 with eIF-2.[1]
In molecular biology, the eIF-W2 domain functions as the binding site for Mnk eIF4E kinase,[2] an enzyme that phosphorylates eukaryotic initiation factor 4E (eIF4E). For eIF2B-epsilon, the W2 C-terminal domain functions in guanine nucleotide exchange on eIF2. For eIF5, the W2 domain functions in mediating the multifactor complex (MFC) formation with eIF1, eIF2-GTP, eIF3 and Met-tRNAiMet. The eIF5 W2 C-terminal domain and the adjacent N-terminal linker region is responsible for the GDI activity against eIF2-GDP.[3]
The W2 domain has a globular fold and is exclusively composed out of alpha-helices.[4][5][6] The structure can be divided into a structural C-terminal core onto which the two N-terminal helices are attached. The core contains two aromatic/acidic residue-rich regions (AA boxes), which are important for mediating protein-protein interactions.
This entry covers the entire W2 domain, which is part of the TPR clan.
Translation initiation is a well regulated and highly coordinated cellular process in eukaryotes, in which at least 11 eukaryotic initiation factors (eIFs) are included.[7] These factors come together to form the pre-initiation complex.
The W2 domain (two invariant tryptophans) is a region of approximately 165 amino acids which is found in the C-terminus of the following eukaryotic initiation factors(eIFs):
Genes encoding proteins containing this domain include AAG1, BZW1, BZW2, EIF2B5, EIF4G1, EIF4G2, EIF4G3, and EIF5.