Tchem EIF2AK1 Eukaryotic translation initiation factor 2-alpha kinase 1

Protein Summary

Description

Inhibits protein synthesis at the translation initiation level, in response to various stress conditions, including oxidative stress, heme deficiency, osmotic shock and heat shock. Exerts its function through the phosphorylation of EIF2S1 at 'Ser-48' and 'Ser-51', thus preventing its recycling. Binds hemin forming a 1:1 complex through a cysteine thiolate and histidine nitrogenous coordination. This binding occurs with moderate affinity, allowing it to sense the heme concentration within the cell. Thanks to this unique heme-sensing capacity, plays a crucial role to shut off protein synthesis during acute heme-deficient conditions. In red blood cells (RBCs), controls hemoglobin synthesis ensuring a coordinated regulation of the synthesis of its heme and globin moieties. Thus plays an essential protective role for RBC survival in anemias of iron deficiency. Similarly, in hepatocytes, involved in heme-mediated translational control of CYP2B and CYP3A and possibly other hepatic P450 cytochromes. May also contain ER stress during acute heme-deficient conditions (By similarity). The protein encoded by this gene acts at the level of translation initiation to downregulate protein synthesis in response to stress. The encoded protein is a kinase that can be inactivated by hemin. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

Uniprot Accession IDs

• Q9BQI3
• A8K2R2
• Q549K6
• Q8NBW3
• Q9HC02
• Q9NYE0
• Q9P0V6
• Q9P1J5
• Q9P2H8
• Q9UHG4

Gene Name

• EIF2AK1

Ensembl ID

• ENST00000199389
• ENSP00000199389
• ENSG00000086232

Symbol

• HRI
• KIAA1369
• HCR
• HRI

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
kinase perturbation	0.99
transcription factor perturbation	0.99
molecular function	0.97
disease perturbation	0.95
virus perturbation	0.76

Protein Classes

PANTHER Classes

Protein / Transferase / Kinase / Protein Kinase / Non-receptor Serine/threonine Protein Kinase / Eukaryotic Translation Initiation Factor 2-alpha Kinase 1

DTO Classes

Protein / Kinase / Protein Kinase / Other Group / Pek Family / Eukaryotic Translation Initiation Factor 2-alpha Kinase 1

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: 81.48   (req: < 5)

Gene RIFs: 18   (req: <= 3)

Antibodies: 288   (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: 81.48   (req: >= 5)

Gene RIFs: 18   (req: > 3)

Antibodies: 288   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 16

Tchem

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

Active Ligands: 4

Tclin

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

Active Drug: 0