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Q9EQY0

- ERN1_MOUSE

UniProt

Q9EQY0 - ERN1_MOUSE

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Protein
Serine/threonine-protein kinase/endoribonuclease IRE1
Gene
Ern1, Ire1
Organism
Mus musculus (Mouse)
Status
Reviewed - 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

Magnesium By similarity.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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei599 – 5991ATP By similarityBy similarity
Active sitei688 – 6881Proton acceptor By similarityBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi577 – 5859ATP By similarityBy similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB
  2. endonuclease activity Source: UniProtKB
  3. endoribonuclease activity Source: MGI
  4. magnesium ion binding Source: UniProtKB
  5. protein binding Source: IntAct
  6. protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  1. HAC1-type intron splice site recognition and cleavage Source: Ensembl
  2. RNA phosphodiester bond hydrolysis, endonucleolytic Source: GOC
  3. activation of signaling protein activity involved in unfolded protein response Source: UniProtKB
  4. cell cycle arrest Source: UniProtKB
  5. endoplasmic reticulum unfolded protein response Source: MGI
  6. intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress Source: MGI
  7. nucleic acid phosphodiester bond hydrolysis Source: GOC
  8. positive regulation of endoplasmic reticulum unfolded protein response Source: Ensembl
  9. protein autophosphorylation Source: MGI
  10. protein phosphorylation Source: UniProtKB
  11. regulation of transcription, DNA-templated Source: UniProtKB-KW
  12. transcription, DNA-templated Source: UniProtKB-KW
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

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:Ern1
Synonyms:Ire1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 11

Organism-specific databases

MGIiMGI:1930134. Ern1.

Subcellular locationi

Endoplasmic reticulum membrane; Single-pass type I membrane protein 1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini21 – 445425Lumenal Reviewed prediction
Add
BLAST
Transmembranei446 – 46621Helical; Reviewed prediction
Add
BLAST
Topological domaini467 – 977511Cytoplasmic Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. endoplasmic reticulum membrane Source: MGI
  2. integral component of endoplasmic reticulum membrane Source: Ensembl
  3. mitochondrion Source: MGI
  4. nuclear inner membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2020 Reviewed prediction
Add
BLAST
Chaini21 – 977957Serine/threonine-protein kinase/endoribonuclease IRE1
PRO_0000024328Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi178 – 1781N-linked (GlcNAc...) Reviewed prediction

Post-translational modificationi

Autophosphorylated By similarity.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

MaxQBiQ9EQY0.
PaxDbiQ9EQY0.
PRIDEiQ9EQY0.

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

ArrayExpressiQ9EQY0.
BgeeiQ9EQY0.
GenevestigatoriQ9EQY0.

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

Protein-protein interaction databases

IntActiQ9EQY0. 4 interactions.
MINTiMINT-2631281.

Structurei

3D structure databases

ProteinModelPortaliQ9EQY0.
SMRiQ9EQY0. Positions 31-370, 561-964.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini571 – 832262Protein kinase
Add
BLAST
Domaini835 – 963129KEN
Add
BLAST

Sequence similaritiesi

Contains 1 KEN domain.

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00390000015684.
HOGENOMiHOG000012929.
HOVERGENiHBG051506.
InParanoidiQ9EQY0.
KOiK08852.
OMAiGLRKVMH.
OrthoDBiEOG7C2R0H.
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.
IPR006567. PUG-dom.
IPR027295. Quinonprotein_ADH-like_fam.
IPR011047. Quinonprotein_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.
[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. Align

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

MPARWLLLLL ALLLPPPGPG SFGRTSTVTL PETLLFVSTL DGSLHAVSKR    50
TGSIKWTLKE DPVLQVPTHV EEPAFLPDPN DGSLYTLGGK NNEGLTKLPF 100
TIPELVQASP CRSSDGILYM GKKQDIWYVI DLLTGEKQQT LSSAFADSLC 150
PSTSLLYLGR TEYTITMYDT KTRELRWNAT YFDYAASLPE DDVDYKMSHF 200
VSNGDGLVVT VDSESGDVLW IQNYASPVVA FYVWQGEVLR KVVHINVAVE 250
TLRYLTFMSG EVGRITKWKY PFPKETEAKS KLTPTLYVGK YSTSLYASPS 300
MVHEGVAVVP RGSTLPLLEG PQTDGVTIGD KGECVITPST DLKFDPGLKG 350
KSKLNYLRNY WLLIGHHETP LSASTKMLER FPNNLPKHRE NVIPADSEKR 400
SFEEVINIVG QTSDNTPTTV SQDVEEKLAR APAKPEAPVD SMLKDMATII 450
LSTFLLVGWV AFIITYPLSV HQQRQLQHQQ FQKELEKIQL LQQQQLPFHP 500
HGDLTQDPEF LDSSGPFSES SGTSSPSPSP RASNHSLHPS SSASRAGTSP 550
SLEQDDEDEE TRMVIVGKIS FCPKDVLGHG AEGTIVYKGM FDNRDVAVKR 600
ILPECFSFAD REVQLLRESD EHPNVIRYFC TEKDRQFQYI AIELCAATLQ 650
EYVEQKDFAH LGLEPITLLH QTTSGLAHLH SLNIVHRDLK PHNILLSMPN 700
AHGRIKAMIS DFGLCKKLAV GRHSFSRRSG VPGTEGWIAP EMLSEDCKDN 750
PTYTVDIFSA GCVFYYVISE GNHPFGKSLQ RQANILLGAC NLDCFHSDKH 800
EDVIARELIE KMIAMDPQQR PSAKHVLKHP FFWSLEKQLQ FFQDVSDRIE 850
KEALDGPIVR QLERGGRAVV KMDWRENITV PLQTDLRKFR TYKGGSVRDL 900
LRAMRNKKHH YRELPVEVQE TLGSIPDDFV RYFTSRFPHL LSHTYQAMEL 950
CRHERLFQTY YWHEPTEPQP PVIPYAL 977
Length:977
Mass (Da):110,185
Last modified:March 1, 2001 - v1
Checksum:i216E3E2FA2FF3F70
GO
Isoform 2 (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.

Show »
Length:408
Mass (Da):45,303
Checksum:i4FF98C4A4EC4D1F3
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei406 – 4083INI → SGK in isoform 2.
VSP_050794
Alternative sequencei409 – 977569Missing in isoform 2.
VSP_050795Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
Links Updated
AB031332 mRNA. Translation: BAB20901.1 .
AK018505 mRNA. Translation: BAB31243.1 .
CCDSi CCDS25556.1. [Q9EQY0-1 ]
RefSeqi NP_076402.1. NM_023913.2. [Q9EQY0-1 ]
UniGenei Mm.340943.

3D structure databases

ProteinModelPortali Q9EQY0.
SMRi Q9EQY0. Positions 31-370, 561-964.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi Q9EQY0. 4 interactions.
MINTi MINT-2631281.

Proteomic databases

MaxQBi Q9EQY0.
PaxDbi Q9EQY0.
PRIDEi Q9EQY0.

Protocols and materials databases

DNASUi 78943.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000001059 ; ENSMUSP00000001059 ; ENSMUSG00000020715 . [Q9EQY0-1 ]
ENSMUST00000106801 ; ENSMUSP00000102413 ; ENSMUSG00000020715 . [Q9EQY0-2 ]
GeneIDi 78943.
KEGGi mmu:78943.
UCSCi uc007lyy.1. mouse. [Q9EQY0-1 ]

Organism-specific databases

CTDi 2081.
MGIi MGI:1930134. Ern1.

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00390000015684.
HOGENOMi HOG000012929.
HOVERGENi HBG051506.
InParanoidi Q9EQY0.
KOi K08852.
OMAi GLRKVMH.
OrthoDBi EOG7C2R0H.
PhylomeDBi Q9EQY0.
TreeFami TF313986.

Miscellaneous databases

NextBioi 349824.
PROi Q9EQY0.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q9EQY0.
Bgeei Q9EQY0.
Genevestigatori Q9EQY0.

Family and domain databases

Gene3Di 2.140.10.10. 2 hits.
InterProi IPR010513. KEN_dom.
IPR011009. Kinase-like_dom.
IPR018391. PQQ_beta_propeller_repeat.
IPR000719. Prot_kinase_dom.
IPR006567. PUG-dom.
IPR027295. Quinonprotein_ADH-like_fam.
IPR011047. Quinonprotein_ADH-like_supfam.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view ]
Pfami PF00069. Pkinase. 1 hit.
PF06479. Ribonuc_2-5A. 1 hit.
[Graphical view ]
SMARTi SM00564. PQQ. 5 hits.
SM00580. PUG. 1 hit.
[Graphical view ]
SUPFAMi SSF50998. SSF50998. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEi PS51392. KEN. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Characterization of mouse Ire1alpha: cloning, mRNA localization in the brain and functional analysis in a neural cell line."
    Miyoshi K., Katayama T., Imaizumi K., Taniguchi M., Mori Y., Hitomi J., Yui D., Manabe T., Gomi F., Yoneda T., Tohyama M.
    Brain Res. Mol. Brain Res. 85:68-76(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
    Strain: C57BL/6.
    Tissue: Brain.
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Strain: C57BL/6J.
    Tissue: Colon.
  3. "IRE1-mediated unconventional mRNA splicing and S2P-mediated ATF6 cleavage merge to regulate XBP1 in signaling the unfolded protein response."
    Lee K., Tirasophon W., Shen X., Michalak M., Prywes R., Okada T., Yoshida H., Mori K., Kaufman R.J.
    Genes Dev. 16:452-466(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.
  4. "AIP1 is critical in transducing IRE1-mediated endoplasmic reticulum stress response."
    Luo D., He Y., Zhang H., Yu L., Chen H., Xu Z., Tang S., Urano F., Min W.
    J. Biol. Chem. 283:11905-11912(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH DAB2IP AND TRAF2.

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: July 9, 2014
This is version 119 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

Complete proteome, Multifunctional enzyme, Reference proteome

Documents

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

External Data

Dasty 3

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