Tchem ERN1 Serine/threonine-protein kinase/endoribonuclease IRE1

Protein Summary

Description

Serine/threonine-protein kinase and endoribonuclease that acts as a key sensor for the endoplasmic reticulum unfolded protein response (UPR) (PubMed:11779464, PubMed:11175748, PubMed:12637535, PubMed:9637683, PubMed:21317875). In unstressed cells, the endoplasmic reticulum luminal domain is maintained in its inactive monomeric state by binding to the endoplasmic reticulum chaperone HSPA5/BiP (PubMed:21317875). Accumulation of misfolded protein in the endoplasmic reticulum causes release of HSPA5/BiP, allowing the luminal domain to homodimerize, promoting autophosphorylation of the kinase domain and subsequent activation of the endoribonuclease activity (PubMed:21317875). The endoribonuclease activity is specific for XBP1 mRNA and excises 26 nucleotides from XBP1 mRNA (PubMed:11779464, PubMed:24508390, PubMed:21317875). The resulting spliced transcript of XBP1 encodes a transcriptional activator protein that up-regulates expression of UPR target genes (PubMed:11779464, PubMed:24508390, PubMed:21317875). Acts as an upstream signal for ER stress-induced GORASP2-mediated unconventional (ER/Golgi-independent) trafficking of CFTR to cell membrane by modulating the expression and localization of SEC16A (PubMed:21884936, PubMed:28067262). This gene encodes the transmembrane protein kinase inositol-requiring enzyme 1. The encoded protein contains two functional catalytic domains, a serine/threonine-protein kinase domain and an endoribonuclease domain. This protein functions as a sensor of unfolded proteins in the endoplasmic reticulum (ER) and triggers an intracellular signaling pathway termed the unfolded protein response (UPR). The UPR is an ER stress response that is conserved from yeast to mammals and activates genes involved in degrading misfolded proteins, regulating protein synthesis and activating molecular chaperones. This protein specifically mediates the splicing and activation of the stress response transcription factor X-box binding protein 1. [provided by RefSeq, Aug 2017]

Uniprot Accession IDs

• O75460
• A1L457
• A8K8N8
• A8MXS7
• Q59EE2

Gene Name

• ERN1

Ensembl ID

• ENST00000433197
• ENSP00000401445
• ENSG00000178607
• ENST00000606895
• ENSP00000475519

Symbol

• IRE1
• IRE1
• IRE1P
• IRE1a
• hIRE1p

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
molecular function	1
biological process	0.98
protein domain	0.97
histone modification site profile	0.87
cellular component	0.86

Protein Classes

PANTHER Classes

Protein / Transferase / Kinase / Protein Kinase / Serine/threonine-protein Kinase/endoribonuclease Ire1

DTO Classes

Protein / Kinase / Protein Kinase / Other Group / Ire Family / Serine/threonine-protein Kinase/endoribonuclease Ire1

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: 892.24   (req: < 5)

Gene RIFs: 260   (req: <= 3)

Antibodies: 592   (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: 892.24   (req: >= 5)

Gene RIFs: 260   (req: > 3)

Antibodies: 592   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 33

Tchem

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

Active Ligands: 35

Tclin

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

Active Drug: 0