ERN1
entrez
2081
canonical
uniprot
O75460
canonical
ensembl
ENSG00000178607
resolver
ensp
ENSP00000401445
resolver
genesymbol
ERN1
resolver
genesymbol_syn
IRE1
resolver
hgnc
HGNC:3449
resolver
uniprot
A1L457
resolver
uniprot
A8K8N8
resolver
uniprot
A8MXS7
resolver
uniprot
Q59EE2
resolver
uniprot_entry
ERN1_HUMAN
resolver
uniprot_sec
A1L457
resolver
uniprot_sec
A8K8N8
resolver
uniprot_sec
A8MXS7
resolver
uniprot_sec
Q59EE2
resolver
activity_regulation
ACTIVITY REGULATION: The kinase domain is activated by trans-autophosphorylation following homodimerization (PubMed:12637535, PubMed:9637683). Kinase activity is required for activation of the endoribonuclease domain (PubMed:12637535, PubMed:9637683). Endoribonuclease activity is specifically inhibited by hydroxy-aryl-aldehydes (HAA) (By similarity). {ECO:0000250|UniProtKB:Q9EQY0, ECO:0000269|PubMed:12637535, ECO:0000269|PubMed:9637683}.
uniprot
proteins
amino_acid_sequence
MPARRLLLLLTLLLPGLGIFGSTSTVTLPETLLFVSTLDGSLHAVSKRTGSIKWTLKEDPVLQVPTHVEEPAFLPDPNDGSLYTLGSKNNEGLTKLPFTIPELVQASPCRSSDGILYMGKKQDIWYVIDLLTGEKQQTLSSAFADSLCPSTSLLYLGRTEYTITMYDTKTRELRWNATYFDYAASLPEDDVDYKMSHFVSNGDGLVVTVDSESGDVLWIQNYASPVVAFYVWQREGLRKVMHINVAVETLRYLTFMSGEVGRITKWKYPFPKETEAKSKLTPTLYVGKYSTSLYASPSMVHEGVAVVPRGSTLPLLEGPQTDGVTIGDKGECVITPSTDVKFDPGLKSKNKLNYLRNYWLLIGHHETPLSASTKMLERFPNNLPKHRENVIPADSEKKSFEEVINLVDQTSENAPTTVSRDVEEKPAHAPARPEAPVDSMLKDMATIILSTFLLIGWVAFIITYPLSMHQQQQLQHQQFQKELEKIQLLQQQQQQLPFHPPGDTAQDGELLDTSGPYSESSGTSSPSTSPRASNHSLCSGSSASKAGSSPSLEQDDGDEETSVVIVGKISFCPKDVLGHGAEGTIVYRGMFDNRDVAVKRILPECFSFADREVQLLRESDEHPNVIRYFCTEKDRQFQYIAIELCAATLQEYVEQKDFAHLGLEPITLLQQTTSGLAHLHSLNIVHRDLKPHNILISMPNAHGKIKAMISDFGLCKKLAVGRHSFSRRSGVPGTEGWIAPEMLSEDCKENPTYTVDIFSAGCVFYYVISEGSHPFGKSLQRQANILLGACSLDCLHPEKHEDVIARELIEKMIAMDPQKRPSAKHVLKHPFFWSLEKQLQFFQDVSDRIEKESLDGPIVKQLERGGRAVVKMDWRENITVPLQTDLRKFRTYKGGSVRDLLRAMRNKKHHYRELPAEVRETLGSLPDDFVCYFTSRFPHLLAHTYRAMELCSHERLFQPYYFHEPPEPQPPVTPDAL
uniprot
proteins
ec_number
2.7.11.1
uniprot
proteins
ec_number
3.1.26.-
uniprot
proteins
function
FUNCTION: Serine/threonine-protein kinase and endoribonuclease that acts as a key sensor for the endoplasmic reticulum unfolded protein response (UPR) (PubMed:11175748, PubMed:11779464, PubMed:12637535, PubMed:19328063, PubMed:21317875, PubMed:28128204, PubMed:30118681, PubMed:36739529, PubMed:9637683). 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 proteins 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:21317875, PubMed:24508390). The resulting spliced transcript of XBP1 encodes a transcriptional activator protein that up-regulates expression of UPR target genes (PubMed:11779464, PubMed:21317875, PubMed:24508390). 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). {ECO:0000269|PubMed:11175748, ECO:0000269|PubMed:11779464, ECO:0000269|PubMed:12637535, ECO:0000269|PubMed:19328063, ECO:0000269|PubMed:21317875, ECO:0000269|PubMed:21884936, ECO:0000269|PubMed:28067262, ECO:0000269|PubMed:28128204, ECO:0000269|PubMed:30118681, ECO:0000269|PubMed:36739529, ECO:0000269|PubMed:9637683, ECO:0000305|PubMed:24508390}.
uniprot
proteins
mass_dalton
109735
uniprot
proteins
mutagenesis
MUTAGEN 105; /note="Q->E: Impaired ability to homodimerize."; /evidence="ECO:0000269|PubMed:16973740"; MUTAGEN 109; /note="C->S: No effect on dimerization. No effect on interaction with P4HB; when associated with S-148 and S-332."; /evidence="ECO:0000269|PubMed:12637535, ECO:0000269|PubMed:32149426"; MUTAGEN 123; /note="D->P: Abolishes ability to homodimerize."; /evidence="ECO:0000269|PubMed:16973740"; MUTAGEN 125; /note="W->A: Abolishes ability to homodimerize."; /evidence="ECO:0000269|PubMed:16973740"; MUTAGEN 148; /note="C->S: No effect on dimerization. Weakens dimer; when associated with S-332. Abolishes interaction with PDIA6. Prolonged splicing of XBP1, probably due to prolonged activation of PDIA6. Inhibits formation of oxidized multimeric forms of ERN1 in response to ER stress. No effect on interaction with P4HB; when associated with S-109 and S-332."; /evidence="ECO:0000269|PubMed:12637535, ECO:0000269|PubMed:24508390, ECO:0000269|PubMed:32149426"; MUTAGEN 332; /note="C->S: No effect on dimerization. Weakens dimer; when associated with S-148. No effect on interaction with P4HB; when associated with S-109 and S-148."; /evidence="ECO:0000269|PubMed:12637535, ECO:0000269|PubMed:32149426"; MUTAGEN 599; /note="K->A: Loss of autophosphorylation and of endoribonuclease activity. Inhibition of growth arrest."; /evidence="ECO:0000269|PubMed:11175748, ECO:0000269|PubMed:9637683
uniprot
proteins
post_translational_modification
PTM: Autophosphorylated following homodimerization. Autophosphorylation promotes activation of the endoribonuclease domain (PubMed:12637535, PubMed:21317875, PubMed:28128204, PubMed:9637683). In response to ER stress, phosphorylated at Ser-724, Ser-729 and possibly Ser-726; phosphorylation promotes oligomerization and endoribonuclease activity (PubMed:30118681). Dephosphorylated at Ser-724, Ser-729 and possibly Ser-726 by RPAP2 to abort failed ER-stress adaptation and trigger apoptosis (PubMed:30118681). Phosphorylated at Ser-724; in response to the ER stressor tunicamycin (PubMed:36739529). {ECO:0000269|PubMed:12637535, ECO:0000269|PubMed:21317875, ECO:0000269|PubMed:28128204, ECO:0000269|PubMed:30118681, ECO:0000269|PubMed:36739529, ECO:0000269|PubMed:9637683}.; PTM: ADP-ribosylated by PARP16 upon ER stress, which increases both kinase and endonuclease activities. {ECO:0000269|PubMed:23103912}.
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
Ser/Thr protein kinase family
uniprot
proteins
pubmed
11175748
uniprot
proteins
pubmed
11278723
uniprot
proteins
pubmed
11779464
uniprot
proteins
pubmed
12637535
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16625196
uniprot
proteins
pubmed
16973740
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
19328063
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21317875
uniprot
proteins
pubmed
21884936
uniprot
proteins
pubmed
23103912
uniprot
proteins
pubmed
23378536
uniprot
proteins
pubmed
24508390
uniprot
proteins
pubmed
28067262
uniprot
proteins
pubmed
28128204
uniprot
proteins
pubmed
29198525
uniprot
proteins
pubmed
30118681
uniprot
proteins
pubmed
31875558
uniprot
proteins
pubmed
32149426
uniprot
proteins
pubmed
36739529
uniprot
proteins
pubmed
9637683
uniprot
proteins
sequence_length
977
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000269|PubMed:9637683}; Single-pass type I membrane protein {ECO:0000269|PubMed:9637683}.
uniprot
proteins
transmembrane_region
TRANSMEM 444..464; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins