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Protein

Serine/threonine-protein kinase/endoribonuclease IRE1

Gene

ERN1

Organism
Homo sapiens (Human)
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.By similarity3 Publications

Catalytic activityi

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

Cofactori

Enzyme regulationi

The kinase domain is activated by trans-autophosphorylation. Kinase activity is required for activation of the endoribonuclease domain.2 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei599 – 5991ATPPROSITE-ProRule annotation1 Publication
Active sitei688 – 6881Proton acceptorPROSITE-ProRule annotationBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi577 – 5859ATPPROSITE-ProRule annotationBy similarity

GO - Molecular functioni

  • ADP binding Source: ParkinsonsUK-UCL
  • ATP binding Source: UniProtKB
  • endoribonuclease activity Source: UniProtKB
  • enzyme binding Source: UniProtKB
  • Hsp70 protein binding Source: ParkinsonsUK-UCL
  • Hsp90 protein binding Source: ParkinsonsUK-UCL
  • identical protein binding Source: IntAct
  • magnesium ion binding Source: UniProtKB
  • protein homodimerization activity Source: ParkinsonsUK-UCL
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  • activation of JUN kinase activity Source: ParkinsonsUK-UCL
  • activation of signaling protein activity involved in unfolded protein response Source: UniProtKB
  • cell cycle arrest Source: UniProtKB
  • cellular protein metabolic process Source: Reactome
  • cellular response to glucose stimulus Source: ParkinsonsUK-UCL
  • cellular response to vascular endothelial growth factor stimulus Source: UniProtKB
  • endoplasmic reticulum unfolded protein response Source: Reactome
  • endothelial cell proliferation Source: UniProtKB
  • HAC1-type intron splice site recognition and cleavage Source: WormBase
  • insulin metabolic process Source: ParkinsonsUK-UCL
  • intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress Source: Ensembl
  • IRE1-mediated unfolded protein response Source: ParkinsonsUK-UCL
  • mRNA catabolic process Source: ParkinsonsUK-UCL
  • mRNA cleavage Source: ParkinsonsUK-UCL
  • mRNA splicing, via endonucleolytic cleavage and ligation Source: UniProtKB
  • peptidyl-serine autophosphorylation Source: ParkinsonsUK-UCL
  • peptidyl-serine trans-autophosphorylation Source: ParkinsonsUK-UCL
  • positive regulation of endoplasmic reticulum unfolded protein response Source: UniProtKB
  • positive regulation of RNA splicing Source: UniProtKB
  • protein autophosphorylation Source: ParkinsonsUK-UCL
  • protein phosphorylation Source: UniProtKB
  • regulation of macroautophagy Source: ParkinsonsUK-UCL
  • regulation of transcription, DNA-templated Source: UniProtKB-KW
  • response to endoplasmic reticulum stress Source: ParkinsonsUK-UCL
  • RNA phosphodiester bond hydrolysis, endonucleolytic Source: GOC
  • transcription, DNA-templated Source: UniProtKB-KW
  • UFP-specific transcription factor mRNA processing involved in endoplasmic reticulum unfolded protein response Source: ParkinsonsUK-UCL
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

ReactomeiREACT_18368. IRE1alpha activates chaperones.
SignaLinkiO75460.

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
Short name:
hIRE1p
Ire1-alpha
Short name:
IRE1a
Including the following 2 domains:
Gene namesi
Name:ERN1Imported
Synonyms:IRE1Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:3449. ERN1.

Subcellular locationi

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

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini19 – 443425LumenalSequence AnalysisAdd
BLAST
Transmembranei444 – 46421HelicalSequence AnalysisAdd
BLAST
Topological domaini465 – 977513CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  • AIP1-IRE1 complex Source: Ensembl
  • cytoplasm Source: UniProtKB
  • endoplasmic reticulum Source: UniProtKB
  • endoplasmic reticulum membrane Source: Reactome
  • integral component of endoplasmic reticulum membrane Source: UniProtKB
  • Ire1 complex Source: ParkinsonsUK-UCL
  • IRE1-RACK1-PP2A complex Source: ParkinsonsUK-UCL
  • IRE1-TRAF2-ASK1 complex Source: ParkinsonsUK-UCL
  • mitochondrion Source: Ensembl
  • nuclear inner membrane Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi109 – 1091C → S: No effect on dimerization. 1 Publication
Mutagenesisi148 – 1481C → S: No effect on dimerization. Weakens dimer; when associated with S-148. 1 Publication
Mutagenesisi332 – 3321C → S: No effect on dimerization. Weakens dimer; when associated with S-332. 1 Publication
Mutagenesisi599 – 5991K → A: Loss of autophosphorylation and of endoribonuclease activity. Inhibition of growth arrest. 2 Publications

Organism-specific databases

PharmGKBiPA27861.

Polymorphism and mutation databases

BioMutaiERN1.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1818Sequence AnalysisAdd
BLAST
Chaini19 – 977959Serine/threonine-protein kinase/endoribonuclease IRE1PRO_0000024327Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi176 – 1761N-linked (GlcNAc...)Sequence Analysis
Modified residuei973 – 9731Phosphothreonine1 Publication

Post-translational modificationi

Autophosphorylated.1 Publication
ADP-ribosylated by PARP16 upon ER stress, which increases both kinase and endonuclease activities.

Keywords - PTMi

ADP-ribosylation, Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiO75460.
PaxDbiO75460.
PRIDEiO75460.

PTM databases

PhosphoSiteiO75460.

Expressioni

Tissue specificityi

Ubiquitously expressed. High levels observed in pancreatic tissue.1 Publication

Gene expression databases

BgeeiO75460.
CleanExiHS_ERN1.
GenevisibleiO75460. HS.

Organism-specific databases

HPAiCAB009495.
HPA027730.

Interactioni

Subunit structurei

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 (By similarity). 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. Interacts with TAOK3 and TRAF2.By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself2EBI-371750,EBI-371750
Bak1O087342EBI-371750,EBI-822441From a different organism.
BAXQ078122EBI-371750,EBI-516580
BaxQ078132EBI-371750,EBI-700711From a different organism.
Hspa5P200292EBI-371750,EBI-772325From a different organism.
SYVN1Q86TM62EBI-371750,EBI-947849
TAOK3Q9H2K83EBI-371750,EBI-1384100
TRAF2Q129333EBI-371750,EBI-355744

Protein-protein interaction databases

BioGridi108391. 21 interactions.
DIPiDIP-31711N.
IntActiO75460. 11 interactions.
MINTiMINT-3001268.
STRINGi9606.ENSP00000401445.

Structurei

Secondary structure

1
977
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi32 – 376Combined sources
Beta strandi40 – 467Combined sources
Turni47 – 493Combined sources
Beta strandi52 – 576Combined sources
Beta strandi73 – 753Combined sources
Turni77 – 793Combined sources
Beta strandi82 – 843Combined sources
Beta strandi93 – 953Combined sources
Helixi100 – 1045Combined sources
Beta strandi120 – 1289Combined sources
Beta strandi154 – 16411Combined sources
Beta strandi168 – 1725Combined sources
Beta strandi176 – 1827Combined sources
Beta strandi197 – 2015Combined sources
Beta strandi205 – 2095Combined sources
Turni211 – 2133Combined sources
Beta strandi216 – 2216Combined sources
Beta strandi226 – 2316Combined sources
Beta strandi238 – 2403Combined sources
Beta strandi243 – 2464Combined sources
Helixi247 – 26418Combined sources
Helixi273 – 2797Combined sources
Beta strandi280 – 2845Combined sources
Beta strandi286 – 2883Combined sources
Beta strandi297 – 3004Combined sources
Turni359 – 3613Combined sources
Beta strandi563 – 5664Combined sources
Beta strandi569 – 57810Combined sources
Helixi581 – 5833Combined sources
Beta strandi585 – 5917Combined sources
Beta strandi594 – 6018Combined sources
Helixi603 – 6053Combined sources
Helixi606 – 6149Combined sources
Turni615 – 6184Combined sources
Beta strandi628 – 6336Combined sources
Beta strandi638 – 6436Combined sources
Beta strandi645 – 6484Combined sources
Helixi649 – 6557Combined sources
Helixi658 – 6603Combined sources
Helixi664 – 68118Combined sources
Turni691 – 6933Combined sources
Beta strandi694 – 6974Combined sources
Beta strandi707 – 7093Combined sources
Beta strandi714 – 7163Combined sources
Helixi740 – 7423Combined sources
Helixi754 – 76815Combined sources
Turni778 – 7803Combined sources
Helixi781 – 7877Combined sources
Helixi800 – 81213Combined sources
Helixi817 – 8193Combined sources
Helixi823 – 8286Combined sources
Helixi830 – 8323Combined sources
Helixi835 – 84915Combined sources
Helixi857 – 8637Combined sources
Helixi866 – 8705Combined sources
Helixi875 – 8773Combined sources
Helixi880 – 8878Combined sources
Helixi897 – 90913Combined sources
Turni910 – 9134Combined sources
Helixi916 – 9227Combined sources
Helixi927 – 93610Combined sources
Helixi940 – 9478Combined sources
Helixi948 – 9514Combined sources
Beta strandi952 – 9543Combined sources
Helixi955 – 9573Combined sources
Turni958 – 9603Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2HZ6X-ray3.10A24-390[»]
3P23X-ray2.70A/B/C/D547-977[»]
4U6RX-ray2.50A547-977[»]
4Z7GX-ray2.60A/B562-977[»]
4Z7HX-ray2.90A/B562-977[»]
ProteinModelPortaliO75460.
SMRiO75460. Positions 29-368, 561-963.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO75460.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini571 – 832262Protein kinasePROSITE-ProRule annotationAdd
BLAST
Domaini835 – 963129KENPROSITE-ProRule annotationAdd
BLAST

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

eggNOGiCOG0515.
GeneTreeiENSGT00390000015684.
HOGENOMiHOG000012929.
HOVERGENiHBG051506.
InParanoidiO75460.
KOiK08852.
OMAiYVWQREG.
OrthoDBiEOG7C2R0H.
PhylomeDBiO75460.
TreeFamiTF313986.

Family and domain databases

Gene3Di2.140.10.10. 1 hit.
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. AlignAdd to basket

Isoform 1 (identifier: O75460-1) [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
MPARRLLLLL TLLLPGLGIF GSTSTVTLPE TLLFVSTLDG SLHAVSKRTG
60 70 80 90 100
SIKWTLKEDP VLQVPTHVEE PAFLPDPNDG SLYTLGSKNN EGLTKLPFTI
110 120 130 140 150
PELVQASPCR SSDGILYMGK KQDIWYVIDL LTGEKQQTLS SAFADSLCPS
160 170 180 190 200
TSLLYLGRTE YTITMYDTKT RELRWNATYF DYAASLPEDD VDYKMSHFVS
210 220 230 240 250
NGDGLVVTVD SESGDVLWIQ NYASPVVAFY VWQREGLRKV MHINVAVETL
260 270 280 290 300
RYLTFMSGEV GRITKWKYPF PKETEAKSKL TPTLYVGKYS TSLYASPSMV
310 320 330 340 350
HEGVAVVPRG STLPLLEGPQ TDGVTIGDKG ECVITPSTDV KFDPGLKSKN
360 370 380 390 400
KLNYLRNYWL LIGHHETPLS ASTKMLERFP NNLPKHRENV IPADSEKKSF
410 420 430 440 450
EEVINLVDQT SENAPTTVSR DVEEKPAHAP ARPEAPVDSM LKDMATIILS
460 470 480 490 500
TFLLIGWVAF IITYPLSMHQ QQQLQHQQFQ KELEKIQLLQ QQQQQLPFHP
510 520 530 540 550
PGDTAQDGEL LDTSGPYSES SGTSSPSTSP RASNHSLCSG SSASKAGSSP
560 570 580 590 600
SLEQDDGDEE TSVVIVGKIS FCPKDVLGHG AEGTIVYRGM FDNRDVAVKR
610 620 630 640 650
ILPECFSFAD REVQLLRESD EHPNVIRYFC TEKDRQFQYI AIELCAATLQ
660 670 680 690 700
EYVEQKDFAH LGLEPITLLQ QTTSGLAHLH SLNIVHRDLK PHNILISMPN
710 720 730 740 750
AHGKIKAMIS DFGLCKKLAV GRHSFSRRSG VPGTEGWIAP EMLSEDCKEN
760 770 780 790 800
PTYTVDIFSA GCVFYYVISE GSHPFGKSLQ RQANILLGAC SLDCLHPEKH
810 820 830 840 850
EDVIARELIE KMIAMDPQKR PSAKHVLKHP FFWSLEKQLQ FFQDVSDRIE
860 870 880 890 900
KESLDGPIVK QLERGGRAVV KMDWRENITV PLQTDLRKFR TYKGGSVRDL
910 920 930 940 950
LRAMRNKKHH YRELPAEVRE TLGSLPDDFV CYFTSRFPHL LAHTYRAMEL
960 970
CSHERLFQPY YFHEPPEPQP PVTPDAL
Length:977
Mass (Da):109,735
Last modified:July 1, 2008 - v2
Checksum:iA2DF808CCE015536
GO
Isoform 2 (identifier: O75460-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     19-70: IFGSTSTVTL...VLQVPTHVEE → VSDRGAWGGG...SPAVGGSGRA
     71-977: Missing.

Show »
Length:70
Mass (Da):6,649
Checksum:iC93BA0CB092E6204
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti190 – 1912DV → EG in AAC25991 (PubMed:9637683).Curated
Sequence conflicti768 – 7681I → V in AAC25991 (PubMed:9637683).Curated
Sequence conflicti816 – 8161D → G in BAF85092 (PubMed:14702039).Curated
Sequence conflicti824 – 8252KH → ND in AAC25991 (PubMed:9637683).Curated
Sequence conflicti880 – 8801V → D in AAC25991 (PubMed:9637683).Curated
Sequence conflicti904 – 9041M → T in BAF85092 (PubMed:14702039).Curated
Sequence conflicti924 – 9241S → T in AAC25991 (PubMed:9637683).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti244 – 2441N → S in a renal clear cell carcinoma sample; somatic mutation. 1 Publication
VAR_040488
Natural varianti418 – 4181V → M.1 Publication
Corresponds to variant rs55869215 [ dbSNP | Ensembl ].
VAR_040489
Natural varianti474 – 4741L → R in a lung adenocarcinoma sample; somatic mutation. 1 Publication
Corresponds to variant rs186305118 [ dbSNP | Ensembl ].
VAR_040490
Natural varianti635 – 6351R → W in a gastric adenocarcinoma sample; somatic mutation. 1 Publication
VAR_040491
Natural varianti700 – 7001N → S.1 Publication
VAR_040492
Natural varianti769 – 7691S → F in a glioblastoma multiforme sample; somatic mutation. 1 Publication
VAR_040493
Natural varianti830 – 8301P → L in an ovarian serous carcinoma sample; somatic mutation. 1 Publication
VAR_040494

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei19 – 7052IFGST…THVEE → VSDRGAWGGGQLATAGSGPG QRRGAGAGVRAGSATAAARC PVSPAVGGSGRA in isoform 2. 2 PublicationsVSP_034582Add
BLAST
Alternative sequencei71 – 977907Missing in isoform 2. 2 PublicationsVSP_034583Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF059198 mRNA. Translation: AAC25991.1.
AK292403 mRNA. Translation: BAF85092.1.
DA254477 mRNA. No translation available.
AB209869 mRNA. Translation: BAD93106.1.
AC005803 Genomic DNA. No translation available.
AC025362 Genomic DNA. No translation available.
CH471109 Genomic DNA. Translation: EAW94214.1.
BC130405 mRNA. Translation: AAI30406.1.
BC130407 mRNA. Translation: AAI30408.1.
BI912495 mRNA. No translation available.
CCDSiCCDS45762.1. [O75460-1]
RefSeqiNP_001424.3. NM_001433.3. [O75460-1]
UniGeneiHs.133982.
Hs.700027.
Hs.744953.

Genome annotation databases

EnsembliENST00000433197; ENSP00000401445; ENSG00000178607.
ENST00000606895; ENSP00000475519; ENSG00000178607. [O75460-2]
GeneIDi2081.
KEGGihsa:2081.
UCSCiuc002jdz.2. human. [O75460-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF059198 mRNA. Translation: AAC25991.1.
AK292403 mRNA. Translation: BAF85092.1.
DA254477 mRNA. No translation available.
AB209869 mRNA. Translation: BAD93106.1.
AC005803 Genomic DNA. No translation available.
AC025362 Genomic DNA. No translation available.
CH471109 Genomic DNA. Translation: EAW94214.1.
BC130405 mRNA. Translation: AAI30406.1.
BC130407 mRNA. Translation: AAI30408.1.
BI912495 mRNA. No translation available.
CCDSiCCDS45762.1. [O75460-1]
RefSeqiNP_001424.3. NM_001433.3. [O75460-1]
UniGeneiHs.133982.
Hs.700027.
Hs.744953.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2HZ6X-ray3.10A24-390[»]
3P23X-ray2.70A/B/C/D547-977[»]
4U6RX-ray2.50A547-977[»]
4Z7GX-ray2.60A/B562-977[»]
4Z7HX-ray2.90A/B562-977[»]
ProteinModelPortaliO75460.
SMRiO75460. Positions 29-368, 561-963.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108391. 21 interactions.
DIPiDIP-31711N.
IntActiO75460. 11 interactions.
MINTiMINT-3001268.
STRINGi9606.ENSP00000401445.

Chemistry

BindingDBiO75460.
ChEMBLiCHEMBL1163101.
GuidetoPHARMACOLOGYi2020.

PTM databases

PhosphoSiteiO75460.

Polymorphism and mutation databases

BioMutaiERN1.

Proteomic databases

MaxQBiO75460.
PaxDbiO75460.
PRIDEiO75460.

Protocols and materials databases

DNASUi2081.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000433197; ENSP00000401445; ENSG00000178607.
ENST00000606895; ENSP00000475519; ENSG00000178607. [O75460-2]
GeneIDi2081.
KEGGihsa:2081.
UCSCiuc002jdz.2. human. [O75460-1]

Organism-specific databases

CTDi2081.
GeneCardsiGC17M062122.
H-InvDBHIX0014084.
HGNCiHGNC:3449. ERN1.
HPAiCAB009495.
HPA027730.
MIMi604033. gene.
neXtProtiNX_O75460.
PharmGKBiPA27861.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00390000015684.
HOGENOMiHOG000012929.
HOVERGENiHBG051506.
InParanoidiO75460.
KOiK08852.
OMAiYVWQREG.
OrthoDBiEOG7C2R0H.
PhylomeDBiO75460.
TreeFamiTF313986.

Enzyme and pathway databases

ReactomeiREACT_18368. IRE1alpha activates chaperones.
SignaLinkiO75460.

Miscellaneous databases

ChiTaRSiERN1. human.
EvolutionaryTraceiO75460.
GeneWikiiERN1.
GenomeRNAii2081.
NextBioi8459.
PROiO75460.
SOURCEiSearch...

Gene expression databases

BgeeiO75460.
CleanExiHS_ERN1.
GenevisibleiO75460. HS.

Family and domain databases

Gene3Di2.140.10.10. 1 hit.
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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "A stress response pathway from the endoplasmic reticulum to the nucleus requires a novel bifunctional protein kinase/endoribonuclease (Ire1p) in mammalian cells."
    Tirasophon W., Welihinda A.A., Kaufman R.J.
    Genes Dev. 12:1812-1824(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, ENZYME REGULATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AUTOPHOSPHORYLATION, GLYCOSYLATION, MUTAGENESIS OF LYS-599.
    Tissue: LiverImported.
  2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
    Tissue: Testis.
  3. Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F.
    Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Endothelial cell.
  4. "DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
    Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L.
    , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
    Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2-977 (ISOFORM 2).
    Tissue: Brain and Leukocyte.
  7. "Activation of caspase-12, an endoplastic reticulum (ER) resident caspase, through tumor necrosis factor receptor-associated factor 2-dependent mechanism in response to the ER stress."
    Yoneda T., Imaizumi K., Oono K., Yui D., Gomi F., Katayama T., Tohyama M.
    J. Biol. Chem. 276:13935-13940(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TAOK3 AND TRAF2.
  8. "Translational control by the ER transmembrane kinase/ribonuclease IRE1 under ER stress."
    Iwawaki T., Hosoda A., Okuda T., Kamigori Y., Nomura-Furuwatari C., Kimata Y., Tsuru A., Kohno K.
    Nat. Cell Biol. 3:158-164(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, MUTAGENESIS OF LYS-599.
  9. "Structure and intermolecular interactions of the luminal dimerization domain of human IRE1alpha."
    Liu C.Y., Xu Z., Kaufman R.J.
    J. Biol. Chem. 278:17680-17687(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, HOMODIMERIZATION, ENZYME REGULATION, INTERACTION WITH HSPA5, MUTAGENESIS OF CYS-109; CYS-148 AND CYS-332.
  10. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-973, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  11. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  12. "PARP16 is a tail-anchored endoplasmic reticulum protein required for the PERK-and IRE1alpha-mediated unfolded protein response."
    Jwa M., Chang P.
    Nat. Cell Biol. 14:1223-1230(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: ADP-RIBOSYLATION BY PARP16.
  13. "The crystal structure of human IRE1 luminal domain reveals a conserved dimerization interface required for activation of the unfolded protein response."
    Zhou J., Liu C.Y., Back S.H., Clark R.L., Peisach D., Xu Z., Kaufman R.J.
    Proc. Natl. Acad. Sci. U.S.A. 103:14343-14348(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 24-390.
  14. "Patterns of somatic mutation in human cancer genomes."
    Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.
    , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
    Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS [LARGE SCALE ANALYSIS] SER-244; MET-418; ARG-474; TRP-635; SER-700; PHE-769 AND LEU-830.

Entry informationi

Entry nameiERN1_HUMAN
AccessioniPrimary (citable) accession number: O75460
Secondary accession number(s): A1L457
, A8K8N8, A8MXS7, Q59EE2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 16, 2004
Last sequence update: July 1, 2008
Last modified: July 22, 2015
This is version 151 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

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

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.