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Protein

Serine/threonine-protein kinase/endoribonuclease IRE1

Gene

Ern1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Senses unfolded proteins in the lumen of the endoplasmic reticulum via its N-terminal domain which leads to enzyme auto-activation. The active endoribonuclease domain splices XBP1 mRNA to generate a new C-terminus, converting it into a potent unfolded-protein response transcriptional activator and triggering growth arrest and apoptosis.1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.By similarity

Cofactori

Mg2+By similarity

Enzyme regulationi

The kinase domain is activated by trans-autophosphorylation. Kinase activity is required for activation of the endoribonuclease domain (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei599ATPPROSITE-ProRule annotationBy similarity1
Active sitei688Proton acceptorPROSITE-ProRule annotationBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi577 – 585ATPPROSITE-ProRule annotationBy similarity9

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Apoptosis, Transcription, Transcription regulation, Unfolded protein response

Keywords - Ligandi

ATP-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 IRE1
Alternative name(s):
Endoplasmic reticulum-to-nucleus signaling 1
Inositol-requiring protein 1
Ire1-alpha
Short name:
IRE1a
Including the following 2 domains:
Gene namesi
Name:Ern1Imported
Synonyms:Ire1By similarity
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:1930134. Ern1.

Subcellular locationi

Topology

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

GO - Cellular componenti

  • AIP1-IRE1 complex Source: ParkinsonsUK-UCL
  • cytoplasm Source: MGI
  • endoplasmic reticulum Source: MGI
  • endoplasmic reticulum membrane Source: MGI
  • integral component of endoplasmic reticulum membrane Source: MGI
  • IRE1-RACK1-PP2A complex Source: MGI
  • IRE1-TRAF2-ASK1 complex Source: MGI
  • mitochondrion Source: MGI
  • nuclear inner membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

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...)Sequence analysis1

Post-translational modificationi

Autophosphorylated.By similarity
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

Homodimer; disulfide-linked. Dimer formation is driven by hydrophobic interactions within the N-terminal luminal domains and stabilized by disulfide bridges. Also binds HSPA5, a negative regulator of the unfolded protein response. This interaction may disrupt homodimerization and prevent activation of ERN1 (By similarity). Interacts with TAOK3 (By similarity). Interacts with DAB2IP (via PH domain); the interaction occurs in a ER stress-induced dependent manner and is required for subsequent recruitment of TRAF2 to ERN1. Interacts with TRAF2.By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
Tnfrsf1aP251182EBI-5480799,EBI-518014
Traf6P701966EBI-5480799,EBI-448028

GO - Molecular functioni

Protein-protein interaction databases

BioGridi219724. 1 interactor.
IntActiQ9EQY0. 5 interactors.
MINTiMINT-2631281.
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

Sequence similaritiesi

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.PROSITE-ProRule annotation
Contains 1 KEN domain.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

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

Family and domain databases

Gene3Di2.140.10.10. 2 hits.
InterProiIPR010513. KEN_dom.
IPR011009. Kinase-like_dom.
IPR018391. PQQ_beta_propeller_repeat.
IPR000719. Prot_kinase_dom.
IPR018997. PUB_domain.
IPR027295. Quinoprotein_ADH-like_fam.
IPR011047. Quinoprotein_ADH-like_supfam.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
PF06479. Ribonuc_2-5A. 1 hit.
[Graphical view]
SMARTiSM00564. PQQ. 5 hits.
SM00580. PUG. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF50998. SSF50998. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS51392. KEN. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

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

Cross-referencesi

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.

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...

Protein-protein interaction databases

BioGridi219724. 1 interactor.
IntActiQ9EQY0. 5 interactors.
MINTiMINT-2631281.
STRINGi10090.ENSMUSP00000001059.

PTM databases

iPTMnetiQ9EQY0.
PhosphoSitePlusiQ9EQY0.

Proteomic databases

EPDiQ9EQY0.
PaxDbiQ9EQY0.
PRIDEiQ9EQY0.

Protocols and materials databases

DNASUi78943.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi2081.
MGIiMGI:1930134. Ern1.

Phylogenomic databases

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

Enzyme and pathway databases

ReactomeiR-MMU-381070. IRE1alpha activates chaperones.

Miscellaneous databases

PROiQ9EQY0.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000020715.
ExpressionAtlasiQ9EQY0. baseline and differential.
GenevisibleiQ9EQY0. MM.

Family and domain databases

Gene3Di2.140.10.10. 2 hits.
InterProiIPR010513. KEN_dom.
IPR011009. Kinase-like_dom.
IPR018391. PQQ_beta_propeller_repeat.
IPR000719. Prot_kinase_dom.
IPR018997. PUB_domain.
IPR027295. Quinoprotein_ADH-like_fam.
IPR011047. Quinoprotein_ADH-like_supfam.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
PF06479. Ribonuc_2-5A. 1 hit.
[Graphical view]
SMARTiSM00564. PQQ. 5 hits.
SM00580. PUG. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF50998. SSF50998. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS51392. KEN. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiERN1_MOUSE
AccessioniPrimary (citable) accession number: Q9EQY0
Secondary accession number(s): Q9D340
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 16, 2004
Last sequence update: March 1, 2001
Last modified: November 30, 2016
This is version 141 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Multifunctional enzyme, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.