Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Serine/threonine-protein kinase/endoribonuclease IRE1

Gene

Ern1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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).2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.1 Publication

Cofactori

Mg2+1 Publication

Enzyme regulationi

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).1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei599ATPPROSITE-ProRule annotationCombined sources1 Publication1
Active sitei688Proton acceptor; for protein kinase activityPROSITE-ProRule annotationBy similarity1
Binding sitei711ATPCombined sources1 Publication1
Binding sitei892Hydroxy-aryl-aldehyde inhibitor1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi577 – 585ATPPROSITE-ProRule annotationCombined sources1 Publication9
Nucleotide bindingi643 – 645ATPCombined sources1 Publication3
Nucleotide bindingi690 – 693ATPCombined sources1 Publication4

GO - Molecular functioni

  • ADP binding Source: MGI
  • ATP binding Source: UniProtKB
  • endonuclease activity Source: UniProtKB
  • endoribonuclease activity Source: UniProtKB
  • enzyme binding Source: MGI
  • Hsp70 protein binding Source: MGI
  • Hsp90 protein binding Source: MGI
  • identical protein binding Source: MGI
  • magnesium ion binding Source: UniProtKB
  • platelet-derived growth factor receptor binding Source: MGI
  • protein homodimerization activity Source: UniProtKB
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Kinase, Multifunctional enzyme, Serine/threonine-protein kinase, Transferase
Biological processApoptosis, Transcription, Transcription regulation, Unfolded protein response
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-381070 IRE1alpha activates chaperones

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase/endoribonuclease IRE1Curated
Alternative name(s):
Endoplasmic reticulum-to-nucleus signaling 11 Publication
Inositol-requiring protein 11 Publication
Ire1-alpha1 Publication
Short name:
IRE1a1 Publication
Including the following 2 domains:
Serine/threonine-protein kinase (EC:2.7.11.11 Publication)
Endoribonuclease (EC:3.1.26.-2 Publications)
Gene namesi
Name:Ern1Imported
Synonyms:Ire11 Publication
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:1930134 Ern1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini21 – 445LumenalSequence analysisAdd BLAST425
Transmembranei446 – 466HelicalSequence analysisAdd BLAST21
Topological domaini467 – 977CytoplasmicSequence analysisAdd BLAST511

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi889F → A: Abolishes endoribonuclease activity. 1 Publication1
Mutagenesisi892Y → A: Abolishes endoribonuclease activity. 1 Publication1
Mutagenesisi906N → A: Abolishes endoribonuclease activity. 1 Publication1
Mutagenesisi907K → A: Abolishes endoribonuclease activity. 1 Publication1
Mutagenesisi910H → A: Abolishes endoribonuclease activity. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 20Sequence analysisAdd BLAST20
ChainiPRO_000002432821 – 977Serine/threonine-protein kinase/endoribonuclease IRE1Add BLAST957

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi178N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

Autophosphorylated following homodimerization. Autophosphorylation promotes activation of the endoribonuclease domain.1 Publication
ADP-ribosylated by PARP16 upon ER stress, which increases both kinase and endonuclease activities.By similarity

Keywords - PTMi

ADP-ribosylation, Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ9EQY0
PaxDbiQ9EQY0
PRIDEiQ9EQY0

PTM databases

iPTMnetiQ9EQY0
PhosphoSitePlusiQ9EQY0

Expressioni

Tissue specificityi

Ubiquitously expressed. High levels in thymus, liver and lung. In the brain, preferentially expressed in cortical, hippocampal and olfactory neurons.1 Publication

Gene expression databases

BgeeiENSMUSG00000020715
ExpressionAtlasiQ9EQY0 baseline and differential
GenevisibleiQ9EQY0 MM

Interactioni

Subunit structurei

Monomer (By similarity). Homodimer; disulfide-linked; homodimerization takes place in response to endoplasmic reticulum stress and promotes activation of the kinase and endoribonuclease activities (PubMed:25164867). Dimer formation is driven by hydrophobic interactions within the N-terminal luminal domains and stabilized by disulfide bridges (PubMed:25164867). Interacts (via the luminal region) with DNAJB9/ERdj4; interaction takes place in unstressed cells and promotes recruitment of HSPA5/BiP (By similarity). Interacts (via the luminal region) with HSPA5/BiP; HSPA5/BiP is a negative regulator of the unfolded protein response (UPR) that prevents homodimerization of ERN1/IRE1 and subsequent activation of the protein (By similarity). Interacts with PDIA6, a negative regulator of the UPR; the interaction is direct and disrupts homodimerization (By similarity). Interacts with DAB2IP (via PH domain); the interaction occurs in a endoplasmic reticulum stress-induced dependent manner and is required for subsequent recruitment of TRAF2 to ERN1/IRE1 (PubMed:18281285). Interacts with TAOK3 and TRAF2 (By similarity).By similarity2 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi219724, 1 interactor
CORUMiQ9EQY0
IntActiQ9EQY0, 5 interactors
MINTiQ9EQY0
STRINGi10090.ENSMUSP00000001059

Structurei

Secondary structure

1977
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi570 – 579Combined sources10
Beta strandi581 – 583Combined sources3
Beta strandi585 – 594Combined sources10
Beta strandi597 – 601Combined sources5
Turni603 – 605Combined sources3
Beta strandi606 – 608Combined sources3
Helixi610 – 617Combined sources8
Beta strandi628 – 634Combined sources7
Beta strandi637 – 642Combined sources6
Beta strandi646 – 648Combined sources3
Helixi649 – 654Combined sources6
Helixi665 – 680Combined sources16
Turni681 – 683Combined sources3
Helixi691 – 693Combined sources3
Beta strandi694 – 696Combined sources3
Beta strandi707 – 709Combined sources3
Beta strandi713 – 716Combined sources4
Turni735 – 737Combined sources3
Helixi740 – 742Combined sources3
Helixi753 – 768Combined sources16
Turni769 – 771Combined sources3
Turni778 – 780Combined sources3
Helixi781 – 787Combined sources7
Beta strandi797 – 799Combined sources3
Helixi800 – 812Combined sources13
Helixi817 – 819Combined sources3
Helixi823 – 828Combined sources6
Helixi830 – 832Combined sources3
Helixi835 – 849Combined sources15
Beta strandi854 – 856Combined sources3
Helixi857 – 862Combined sources6
Helixi867 – 870Combined sources4
Helixi874 – 877Combined sources4
Helixi880 – 887Combined sources8
Helixi897 – 909Combined sources13
Helixi911 – 913Combined sources3
Helixi916 – 921Combined sources6
Beta strandi924 – 926Combined sources3
Helixi927 – 936Combined sources10
Helixi938 – 947Combined sources10
Helixi948 – 951Combined sources4
Turni954 – 956Combined sources3
Helixi957 – 959Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4PL3X-ray2.90A/B550-977[»]
4PL4X-ray3.00A/B/C/D550-977[»]
4PL5X-ray3.40A/B/C/D550-977[»]
ProteinModelPortaliQ9EQY0
SMRiQ9EQY0
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini571 – 832Protein kinasePROSITE-ProRule annotationAdd BLAST262
Domaini835 – 963KENPROSITE-ProRule annotationAdd BLAST129

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni906 – 907Hydroxy-aryl-aldehyde inhibitor binding1 Publication2

Sequence similaritiesi

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1027 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00390000015684
HOGENOMiHOG000012929
HOVERGENiHBG051506
InParanoidiQ9EQY0
KOiK08852
OMAiMDWRENI
OrthoDBiEOG091G049V
PhylomeDBiQ9EQY0
TreeFamiTF313986

Family and domain databases

Gene3Di1.20.1440.180, 1 hit
2.130.10.10, 1 hit
InterProiView protein in InterPro
IPR010513 KEN_dom
IPR038357 KEN_sf
IPR011009 Kinase-like_dom_sf
IPR018391 PQQ_beta_propeller_repeat
IPR000719 Prot_kinase_dom
IPR018997 PUB_domain
IPR011047 Quinoprotein_ADH-like_supfam
IPR008271 Ser/Thr_kinase_AS
IPR015943 WD40/YVTN_repeat-like_dom_sf
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PF06479 Ribonuc_2-5A, 1 hit
SMARTiView protein in SMART
SM00564 PQQ, 5 hits
SM00580 PUG, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF50998 SSF50998, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS51392 KEN, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 11 Publication (identifier: Q9EQY0-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MPARWLLLLL ALLLPPPGPG SFGRTSTVTL PETLLFVSTL DGSLHAVSKR
60 70 80 90 100
TGSIKWTLKE DPVLQVPTHV EEPAFLPDPN DGSLYTLGGK NNEGLTKLPF
110 120 130 140 150
TIPELVQASP CRSSDGILYM GKKQDIWYVI DLLTGEKQQT LSSAFADSLC
160 170 180 190 200
PSTSLLYLGR TEYTITMYDT KTRELRWNAT YFDYAASLPE DDVDYKMSHF
210 220 230 240 250
VSNGDGLVVT VDSESGDVLW IQNYASPVVA FYVWQGEVLR KVVHINVAVE
260 270 280 290 300
TLRYLTFMSG EVGRITKWKY PFPKETEAKS KLTPTLYVGK YSTSLYASPS
310 320 330 340 350
MVHEGVAVVP RGSTLPLLEG PQTDGVTIGD KGECVITPST DLKFDPGLKG
360 370 380 390 400
KSKLNYLRNY WLLIGHHETP LSASTKMLER FPNNLPKHRE NVIPADSEKR
410 420 430 440 450
SFEEVINIVG QTSDNTPTTV SQDVEEKLAR APAKPEAPVD SMLKDMATII
460 470 480 490 500
LSTFLLVGWV AFIITYPLSV HQQRQLQHQQ FQKELEKIQL LQQQQLPFHP
510 520 530 540 550
HGDLTQDPEF LDSSGPFSES SGTSSPSPSP RASNHSLHPS SSASRAGTSP
560 570 580 590 600
SLEQDDEDEE TRMVIVGKIS FCPKDVLGHG AEGTIVYKGM FDNRDVAVKR
610 620 630 640 650
ILPECFSFAD REVQLLRESD EHPNVIRYFC TEKDRQFQYI AIELCAATLQ
660 670 680 690 700
EYVEQKDFAH LGLEPITLLH QTTSGLAHLH SLNIVHRDLK PHNILLSMPN
710 720 730 740 750
AHGRIKAMIS DFGLCKKLAV GRHSFSRRSG VPGTEGWIAP EMLSEDCKDN
760 770 780 790 800
PTYTVDIFSA GCVFYYVISE GNHPFGKSLQ RQANILLGAC NLDCFHSDKH
810 820 830 840 850
EDVIARELIE KMIAMDPQQR PSAKHVLKHP FFWSLEKQLQ FFQDVSDRIE
860 870 880 890 900
KEALDGPIVR QLERGGRAVV KMDWRENITV PLQTDLRKFR TYKGGSVRDL
910 920 930 940 950
LRAMRNKKHH YRELPVEVQE TLGSIPDDFV RYFTSRFPHL LSHTYQAMEL
960 970
CRHERLFQTY YWHEPTEPQP PVIPYAL
Length:977
Mass (Da):110,185
Last modified:March 1, 2001 - v1
Checksum:i216E3E2FA2FF3F70
GO
Isoform 2Curated (identifier: Q9EQY0-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     406-408: INI → SGK
     409-977: Missing.

Note: No experimental confirmation available.Curated
Show »
Length:408
Mass (Da):45,303
Checksum:i4FF98C4A4EC4D1F3
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_050794406 – 408INI → SGK in isoform 2. 1 Publication3
Alternative sequenceiVSP_050795409 – 977Missing in isoform 2. 1 PublicationAdd BLAST569

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB031332 mRNA Translation: BAB20901.1
AK018505 mRNA Translation: BAB31243.1
CCDSiCCDS25556.1 [Q9EQY0-1]
RefSeqiNP_076402.1, NM_023913.2 [Q9EQY0-1]
UniGeneiMm.340943

Genome annotation databases

EnsembliENSMUST00000001059; ENSMUSP00000001059; ENSMUSG00000020715 [Q9EQY0-1]
ENSMUST00000106801; ENSMUSP00000102413; ENSMUSG00000020715 [Q9EQY0-2]
GeneIDi78943
KEGGimmu:78943
UCSCiuc007lyy.1 mouse [Q9EQY0-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiERN1_MOUSE
AccessioniPrimary (citable) accession number: Q9EQY0
Secondary accession number(s): Q9D340
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 16, 2004
Last sequence update: March 1, 2001
Last modified: March 28, 2018
This is version 152 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health