Ern1
entrez
78943
canonical
uniprot
Q9EQY0
canonical
ensembl
ENSMUSG00000020715
resolver
ensp
ENSMUSP00000001059
resolver
genesymbol
Ern1
resolver
genesymbol_syn
Ire1
resolver
uniprot
Q9D340
resolver
uniprot_entry
ERN1_MOUSE
resolver
uniprot_sec
Q9D340
resolver
activity_regulation
ACTIVITY REGULATION: The kinase domain is activated by trans-autophosphorylation following homodimerization. Kinase activity is required for activation of the endoribonuclease domain (PubMed:25164867). Endoribonuclease activity is specifically inhibited by hydroxy-aryl-aldehydes (HAA) MKC9989, OICR464 and OICR573 (PubMed:25164867). {ECO:0000269|PubMed:25164867}.
uniprot
proteins
amino_acid_sequence
MPARWLLLLLALLLPPPGPGSFGRTSTVTLPETLLFVSTLDGSLHAVSKRTGSIKWTLKEDPVLQVPTHVEEPAFLPDPNDGSLYTLGGKNNEGLTKLPFTIPELVQASPCRSSDGILYMGKKQDIWYVIDLLTGEKQQTLSSAFADSLCPSTSLLYLGRTEYTITMYDTKTRELRWNATYFDYAASLPEDDVDYKMSHFVSNGDGLVVTVDSESGDVLWIQNYASPVVAFYVWQGEVLRKVVHINVAVETLRYLTFMSGEVGRITKWKYPFPKETEAKSKLTPTLYVGKYSTSLYASPSMVHEGVAVVPRGSTLPLLEGPQTDGVTIGDKGECVITPSTDLKFDPGLKGKSKLNYLRNYWLLIGHHETPLSASTKMLERFPNNLPKHRENVIPADSEKRSFEEVINIVGQTSDNTPTTVSQDVEEKLARAPAKPEAPVDSMLKDMATIILSTFLLVGWVAFIITYPLSVHQQRQLQHQQFQKELEKIQLLQQQQLPFHPHGDLTQDPEFLDSSGPFSESSGTSSPSPSPRASNHSLHPSSSASRAGTSPSLEQDDEDEETRMVIVGKISFCPKDVLGHGAEGTIVYKGMFDNRDVAVKRILPECFSFADREVQLLRESDEHPNVIRYFCTEKDRQFQYIAIELCAATLQEYVEQKDFAHLGLEPITLLHQTTSGLAHLHSLNIVHRDLKPHNILLSMPNAHGRIKAMISDFGLCKKLAVGRHSFSRRSGVPGTEGWIAPEMLSEDCKDNPTYTVDIFSAGCVFYYVISEGNHPFGKSLQRQANILLGACNLDCFHSDKHEDVIARELIEKMIAMDPQQRPSAKHVLKHPFFWSLEKQLQFFQDVSDRIEKEALDGPIVRQLERGGRAVVKMDWRENITVPLQTDLRKFRTYKGGSVRDLLRAMRNKKHHYRELPVEVQETLGSIPDDFVRYFTSRFPHLLSHTYQAMELCRHERLFQTYYWHEPTEPQPPVIPYAL
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:11850408, PubMed:25164867). In unstressed cells, the endoplasmic reticulum luminal domain is maintained in its inactive monomeric state by binding to the endoplasmic reticulum chaperone HSPA5/BiP. 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:25164867). The endoribonuclease activity is specific for XBP1 mRNA and excises 26 nucleotides from XBP1 mRNA (PubMed:11850408, PubMed:25164867). The resulting spliced transcript of XBP1 encodes a transcriptional activator protein that up-regulates expression of UPR target genes (PubMed:11850408, PubMed:25164867). 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 (By similarity). {ECO:0000250|UniProtKB:O75460, ECO:0000269|PubMed:11850408, ECO:0000269|PubMed:25164867}.
uniprot
proteins
mass_dalton
110185
uniprot
proteins
mutagenesis
MUTAGEN 889; /note="F->A: Abolishes endoribonuclease activity."; /evidence="ECO:0000269|PubMed:25164867"; MUTAGEN 892; /note="Y->A: Abolishes endoribonuclease activity."; /evidence="ECO:0000269|PubMed:25164867"; MUTAGEN 906; /note="N->A: Abolishes endoribonuclease activity."; /evidence="ECO:0000269|PubMed:25164867"; MUTAGEN 907; /note="K->A: Abolishes endoribonuclease activity."; /evidence="ECO:0000269|PubMed:25164867"; MUTAGEN 910; /note="H->A: Abolishes endoribonuclease activity."; /evidence="ECO:0000269|PubMed:25164867
uniprot
proteins
post_translational_modification
PTM: Autophosphorylated following homodimerization. Autophosphorylation promotes activation of the endoribonuclease domain (PubMed:25164867). 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 (By similarity). Phosphorylated at Ser-724; in response to the ER stressor tunicamycin (PubMed:36739529). {ECO:0000250|UniProtKB:O75460, ECO:0000269|PubMed:25164867, ECO:0000269|PubMed:30118681, ECO:0000269|PubMed:36739529}.; PTM: ADP-ribosylated by PARP16 upon ER stress, which increases both kinase and endonuclease activities. {ECO:0000250|UniProtKB:O75460}.
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
Ser/Thr protein kinase family
uniprot
proteins
pubmed
11146108
uniprot
proteins
pubmed
11780124
uniprot
proteins
pubmed
11850408
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
18281285
uniprot
proteins
pubmed
25164867
uniprot
proteins
pubmed
30118681
uniprot
proteins
pubmed
35975910
uniprot
proteins
pubmed
36739529
uniprot
proteins
sequence_length
977
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000269|PubMed:11850408}; Single-pass type I membrane protein {ECO:0000269|PubMed:11850408}.
uniprot
proteins
transmembrane_region
TRANSMEM 446..466; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins