Tchem EIF2AK3 Eukaryotic translation initiation factor 2-alpha kinase 3

Protein Summary

Description

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. The protein encoded by this gene phosphorylates the alpha subunit of eukaryotic translation-initiation factor 2, leading to its inactivation, and thus to a rapid reduction of translational initiation and repression of global protein synthesis. This protein is thought to modulate mitochondrial function. It is a type I membrane protein located in the endoplasmic reticulum (ER), where it is induced by ER stress caused by malfolded proteins. Mutations in this gene are associated with Wolcott-Rallison syndrome. [provided by RefSeq, Sep 2015]

Uniprot Accession IDs

• Q9NZJ5
• A0AVH1
• A0AVH2
• B2RCU9
• O95846
• Q53QY0
• Q53SB1

Gene Name

• EIF2AK3

Ensembl ID

• ENST00000303236
• ENSP00000307235
• ENSG00000172071

Symbol

• PEK
• PERK
• PEK
• WRS
• PERK

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
molecular function	0.96
chemical	0.92
transcription factor binding site profile	0.91
protein domain	0.85

Protein Classes

PANTHER Classes

Protein / Transferase / Kinase / Protein Kinase / Non-receptor Serine/threonine Protein Kinase / Eukaryotic Translation Initiation Factor 2-alpha Kinase 3

DTO Classes

Protein / Kinase / Protein Kinase / Other Group / Pek Family / Pek Subfamily / Eukaryotic Translation Initiation Factor 2-alpha Kinase 3

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 2031.15   (req: < 5)

Gene RIFs: 187   (req: <= 3)

Antibodies: 570   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 2031.15   (req: >= 5)

Gene RIFs: 187   (req: > 3)

Antibodies: 570   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 42

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 79

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0