Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

EIF2AK3 (Q9NZJ5) - Overview - Molecular Target Synopsis

Protein


EIF2AK3, Eukaryotic translation initiation factor 2-alpha kinase 3
Enzyme Classification 2.7.11.1
UniProt Q9NZJ5

Also Known as E2AK3_HUMAN, EIF2AK3, PEK, PERK

Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2-alpha/EIF2S1) on 'Ser-52' during the unfolded protein response (UPR) and in response to low amino acid availability. Converts phosphorylated eIF-2-alpha/EIF2S1 either in a global protein synthesis inhibitor, leading to a reduced overall utilization of amino acids, or to a translation initiation activator of specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion. Serves as a critical effector of unfolded protein response (UPR)-induced G1 growth arrest due to the loss of cyclin-D1 (CCND1). Involved in control of mitochondrial morphology and function. Forms dimers with HSPA5/BIP in resting cells (By similarity). Oligomerizes in ER-stressed cells (By similarity). Interacts with DNAJC3 and MFN2 (By similarity). Interacts with TMEM33 (PubMed:26268696). Interacts with PDIA6 (PubMed:24508390).

5SV7
THE CRYSTAL STRUCTURE OF A CHAPERONE
RCSB/PDB
Inspect Structure
See all 3D Structures for EIF2AK3

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: EIF2AK3 is active in the following subcellular-locations: endoplasmic reticulum membrane.
GO terms: EIF2AK3 is active in the following subcellular-locations: cytoplasm, cytosolic ribosome, endoplasmic reticulum, endoplasmic reticulum membrane, integral component of endoplasmic reticulum membrane, membrane, perinuclear region of cytoplasm.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project EIF2AK3 has gain in 2 cell-lines, loss in 0 cell-lines and no signal in 1002 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: MALME_3M, MDA_N, SK_MEL_28

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: SK-MM-2, NCI-H929, LP-1

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: CD20-positive B cell, MCF-7, SK-N-SH

(see details)

RNA Interference


EIF2AK3 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: TOV112D, KPD. (see details)

3D Structures


For EIF2AK3 there are:
11 structures (15 chains) solved
9 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


EIF2AK3 has been screened with 163 compounds (301 bioactivities), 83 compounds have bioactivities that show binding affinity of <= 500nM (152 bioactivities). (see details)