Q9EQY0 (ERN1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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:

1. Serine/threonine-protein kinase
   EC=2.7.11.1
2. Endoribonuclease
   EC=3.1.26.-

Gene names

Name:	Ern1
Synonyms:	Ire1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	977 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	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. Ref.3
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. UniProtKB O75460
Cofactor	Magnesium By similarity. UniProtKB O75460
Enzyme regulation	The kinase domain is activated by trans-autophosphorylation. Kinase activity is required for activation of the endoribonuclease domain By similarity. UniProtKB O75460
Subunit structure	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 and TRAF2 By similarity. UniProtKB O75460
Subcellular location	Endoplasmic reticulum membrane; Single-pass type I membrane protein Ref.3.
Tissue specificity	Ubiquitously expressed. High levels in thymus, liver and lung. In the brain, preferentially expressed in cortical, hippocampal and olfactory neurons. Ref.1
Post-translational modification	Autophosphorylated By similarity. UniProtKB O75460 ADP-ribosylated by PARP16 upon ER stress, which increases both kinase and endonuclease activities By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. Contains 1 KEN domain. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Apoptosis Transcription Transcription regulation Unfolded protein response
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Alternative splicing
Domain	Signal Transmembrane Transmembrane helix
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Hydrolase Kinase Serine/threonine-protein kinase Transferase
PTM	ADP-ribosylation Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological_process	activation of signaling protein activity involved in unfolded protein response Inferred from sequence or structural similarity. Source: UniProtKB apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW cell cycle arrest Inferred from direct assay Ref.1. Source: UniProtKB induction of apoptosis Inferred from direct assay Ref.1. Source: UniProtKB mRNA processing Inferred from electronic annotation. Source: InterPro positive regulation of endoplasmic reticulum unfolded protein response Inferred from electronic annotation. Source: Compara protein autophosphorylation Inferred from direct assay PubMed 11430819. Source: MGI regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	endoplasmic reticulum membrane Inferred from direct assay PubMed 9755171. Source: MGI integral to endoplasmic reticulum membrane Inferred from electronic annotation. Source: Compara nuclear inner membrane Inferred from direct assay Ref.3. Source: UniProtKB
Molecular_function	ATP binding Inferred from sequence or structural similarity. Source: UniProtKB endoribonuclease activity Inferred from direct assay PubMed 15601821. Source: MGI magnesium ion binding Inferred from sequence or structural similarity. Source: UniProtKB protein serine/threonine kinase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 Ref.1 (identifier: Q9EQY0-1)

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.

Isoform 2 (identifier: Q9EQY0-2)

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

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 20	20	Potential
	Chain	21 – 977	957	Serine/threonine-protein kinase/endoribonuclease IRE1		PRO_0000024328
Regions
	Topological domain	21 – 445	425	Lumenal Potential
	Transmembrane	446 – 466	21	Helical; Potential
	Topological domain	467 – 977	511	Cytoplasmic Potential
	Domain	571 – 832	262	Protein kinase
	Domain	835 – 963	129	KEN
	Nucleotide binding	577 – 585	9	ATP By similarity UniProtKB P32361
Sites
	Active site	688	1	Proton acceptor By similarity UniProtKB P32361
	Binding site	599	1	ATP By similarity UniProtKB O75460
Amino acid modifications
	Glycosylation	178	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	406 – 408	3	INI → SGK in isoform 2.		VSP_050794
	Alternative sequence	409 – 977	569	Missing in isoform 2.		VSP_050795

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: 216E3E2FA2FF3F70	FASTA	977	110,185
	10 20 30 40 50 60 MPARWLLLLL ALLLPPPGPG SFGRTSTVTL PETLLFVSTL DGSLHAVSKR TGSIKWTLKE 70 80 90 100 110 120 DPVLQVPTHV EEPAFLPDPN DGSLYTLGGK NNEGLTKLPF TIPELVQASP CRSSDGILYM 130 140 150 160 170 180 GKKQDIWYVI DLLTGEKQQT LSSAFADSLC PSTSLLYLGR TEYTITMYDT KTRELRWNAT 190 200 210 220 230 240 YFDYAASLPE DDVDYKMSHF VSNGDGLVVT VDSESGDVLW IQNYASPVVA FYVWQGEVLR 250 260 270 280 290 300 KVVHINVAVE TLRYLTFMSG EVGRITKWKY PFPKETEAKS KLTPTLYVGK YSTSLYASPS 310 320 330 340 350 360 MVHEGVAVVP RGSTLPLLEG PQTDGVTIGD KGECVITPST DLKFDPGLKG KSKLNYLRNY 370 380 390 400 410 420 WLLIGHHETP LSASTKMLER FPNNLPKHRE NVIPADSEKR SFEEVINIVG QTSDNTPTTV 430 440 450 460 470 480 SQDVEEKLAR APAKPEAPVD SMLKDMATII LSTFLLVGWV AFIITYPLSV HQQRQLQHQQ 490 500 510 520 530 540 FQKELEKIQL LQQQQLPFHP HGDLTQDPEF LDSSGPFSES SGTSSPSPSP RASNHSLHPS 550 560 570 580 590 600 SSASRAGTSP SLEQDDEDEE TRMVIVGKIS FCPKDVLGHG AEGTIVYKGM FDNRDVAVKR 610 620 630 640 650 660 ILPECFSFAD REVQLLRESD EHPNVIRYFC TEKDRQFQYI AIELCAATLQ EYVEQKDFAH 670 680 690 700 710 720 LGLEPITLLH QTTSGLAHLH SLNIVHRDLK PHNILLSMPN AHGRIKAMIS DFGLCKKLAV 730 740 750 760 770 780 GRHSFSRRSG VPGTEGWIAP EMLSEDCKDN PTYTVDIFSA GCVFYYVISE GNHPFGKSLQ 790 800 810 820 830 840 RQANILLGAC NLDCFHSDKH EDVIARELIE KMIAMDPQQR PSAKHVLKHP FFWSLEKQLQ 850 860 870 880 890 900 FFQDVSDRIE KEALDGPIVR QLERGGRAVV KMDWRENITV PLQTDLRKFR TYKGGSVRDL 910 920 930 940 950 960 LRAMRNKKHH YRELPVEVQE TLGSIPDDFV RYFTSRFPHL LSHTYQAMEL CRHERLFQTY 970 YWHEPTEPQP PVIPYAL
	Isoform 2 [UniParc]. Checksum: 4FF98C4A4EC4D1F3	FASTA	408	45,303
	10 20 30 40 50 60 MPARWLLLLL ALLLPPPGPG SFGRTSTVTL PETLLFVSTL DGSLHAVSKR TGSIKWTLKE 70 80 90 100 110 120 DPVLQVPTHV EEPAFLPDPN DGSLYTLGGK NNEGLTKLPF TIPELVQASP CRSSDGILYM 130 140 150 160 170 180 GKKQDIWYVI DLLTGEKQQT LSSAFADSLC PSTSLLYLGR TEYTITMYDT KTRELRWNAT 190 200 210 220 230 240 YFDYAASLPE DDVDYKMSHF VSNGDGLVVT VDSESGDVLW IQNYASPVVA FYVWQGEVLR 250 260 270 280 290 300 KVVHINVAVE TLRYLTFMSG EVGRITKWKY PFPKETEAKS KLTPTLYVGK YSTSLYASPS 310 320 330 340 350 360 MVHEGVAVVP RGSTLPLLEG PQTDGVTIGD KGECVITPST DLKFDPGLKG KSKLNYLRNY 370 380 390 400 WLLIGHHETP LSASTKMLER FPNNLPKHRE NVIPADSEKR SFEEVSGK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB031332 mRNA. Translation: BAB20901.1. AK018505 mRNA. Translation: BAB31243.1.
IPI	IPI00111702. IPI00461611.
RefSeq	NP_076402.1. NM_023913.2.
UniGene	Mm.340943.
3D structure databases
ProteinModelPortal	Q9EQY0.
SMR	Q9EQY0. Positions 31-370, 561-964.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9EQY0. 1 interaction.
MINT	MINT-2631281.
Proteomic databases
PaxDb	Q9EQY0.
PRIDE	Q9EQY0.
Protocols and materials databases
DNASU	78943.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000001059; ENSMUSP00000001059; ENSMUSG00000020715. ENSMUST00000106801; ENSMUSP00000102413; ENSMUSG00000020715.
GeneID	78943.
KEGG	mmu:78943.
Organism-specific databases
CTD	2081.
MGI	MGI:1930134. Ern1.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00390000015684.
HOGENOM	HOG000012929.
HOVERGEN	HBG051506.
InParanoid	Q9EQY0.
KO	K08852.
OMA	FRSYKGG.
OrthoDB	EOG42Z4PG.
Gene expression databases
ArrayExpress	Q9EQY0.
Bgee	Q9EQY0.
Genevestigator	Q9EQY0.
GermOnline	ENSMUSG00000020715. Mus musculus.
Family and domain databases
InterPro	IPR010513. KEN_dom. IPR011009. Kinase-like_dom. IPR018391. PQQ_beta_propeller_repeat. IPR000719. Prot_kinase_cat_dom. IPR006567. PUG-dom. IPR011047. Quinonprotein_ADH-like_supfam. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. PF06479. Ribonuc_2-5A. 1 hit. [Graphical view]
SMART	SM00564. PQQ. 5 hits. SM00580. PUG. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit. SSF50998. Quin_alc_DH_like. 1 hit.
PROSITE	PS51392. KEN. 1 hit. PS00107. PROTEIN_KINASE_ATP. False negative. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	349824.
SOURCE	Search...

Entry information

Entry name

ERN1_MOUSE

Accession

Primary (citable) accession number: Q9EQY0
Secondary accession number(s): Q9D340

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 16, 2004
Last sequence update:	March 1, 2001
Last modified:	May 1, 2013
This is version 107 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program