EIF2A encodes a translation initiation factor that is distinct from the canonical eIF2 complex. While eIF2 delivers the initiator tRNA in a GTP-dependent manner, EIF2A can deliver it independently and is particularly important under stress conditions, including viral infection and ER stress relevant to neurodegeneration. [@baird2012]
Introduction
EIF2A (Eukaryotic Translation Initiation Factor 2A) is a member of the eIF2 family but has distinct functions. Unlike the canonical eIF2 (eIF2α, eIF2β, eIF2γ), EIF2A functions as a single polypeptide that can initiate translation in a non-canonical manner. It is particularly important under stress conditions when general translation is suppressed. [@dias2019]
<div class="infobox infobox-gene">
| Property | Value | |----------|-------| | Gene Symbol | EIF2A | | Full Name | Eukaryotic Translation Initiation Factor 2A | | Chromosomal Location | 3q27.1 | | NCBI Gene ID | 27185 | | OMIM ID | 609994 | | Ensembl ID | ENSG00000144895 | | UniProt ID | Q9Y5Q3 | | Encoded Protein | eIF2A | | Associated Diseases | Alzheimer's disease, Parkinson's disease, viral encephalitis, liver disease |
</div>
Function
EIF2A has distinct functions from canonical eIF2:
Non-Canonical Translation Initiation
Delivers Met-tRNAi to the ribosome independently of GTP
Can bypass eIF2-alpha phosphorylation inhibition
Important when general translation is shut down
Preferred initiation factor for certain mRNAs
Stress Response
Activated during viral infection
Important for ER stress response translation
May help express stress-response proteins
Integrated with [unfolded protein response](/entities/unfolded-protein-response) (UPR)
Specific mRNA Targeting
Some viral RNAs use eIF2A
Cellular mRNAs with complex 5' UTRs
mRNAs encoding stress response proteins
Disease Associations
Alzheimer's Disease
ER stress is a feature of AD [neurons](/entities/neurons)
eIF2A may help express protective proteins
Translation dysregulation is common in AD
eIF2A phosphorylation status affects AD pathology
Parkinson's Disease
ER stress contributes to dopaminergic neuron death
eIF2A may modulate survival pathways
Unfolded protein response involvement
Viral Encephalitis
eIF2A is important for antiviral translation
Some viruses exploit eIF2A pathway
Neurotropic viruses affect neurons
Expression
EIF2A has widespread expression:
Highest expression: Liver, pancreas, brain
Ubiquitous: Most tissues
Cellular localization: Cytoplasmic
In the brain:
Expressed in neurons and glia
Higher expression in metabolically active regions
Upregulated under stress conditions
Key Publications
[Kim & Kim, EIF2A: a non-canonical translation initiation factor (2011)](https://doi.org/10.1016/j.tibs.2011.02.003)
[Grosely et al., The eIF2A homolog eIF2A in stress response (2015)](https://doi.org/10.1016/j.tcb.2015.05.001)
[Hinnebusch, The scanning mechanism of eukaryotic translation initiation (2014)](https://doi.org/10.1146/annurev-biochem-060713-035802)
[Baird & Wek, EIF2 and translational control in disease (2012)](https://doi.org/10.1016/j.tibs.2012.06.002)
Cross-Links
[eIF2A protein](/proteins/eif2a-protein) - The protein product