UniProtKB - O75460 (ERN1_HUMAN)

BLAST

>sp|O75460|ERN1_HUMAN Serine/threonine-protein kinase/endoribonuclease IRE1 OS=Homo sapiens OX=9606 GN=ERN1 PE=1 SV=2
MPARRLLLLLTLLLPGLGIFGSTSTVTLPETLLFVSTLDGSLHAVSKRTGSIKWTLKEDP
VLQVPTHVEEPAFLPDPNDGSLYTLGSKNNEGLTKLPFTIPELVQASPCRSSDGILYMGK
KQDIWYVIDLLTGEKQQTLSSAFADSLCPSTSLLYLGRTEYTITMYDTKTRELRWNATYF
DYAASLPEDDVDYKMSHFVSNGDGLVVTVDSESGDVLWIQNYASPVVAFYVWQREGLRKV
MHINVAVETLRYLTFMSGEVGRITKWKYPFPKETEAKSKLTPTLYVGKYSTSLYASPSMV
HEGVAVVPRGSTLPLLEGPQTDGVTIGDKGECVITPSTDVKFDPGLKSKNKLNYLRNYWL
LIGHHETPLSASTKMLERFPNNLPKHRENVIPADSEKKSFEEVINLVDQTSENAPTTVSR
DVEEKPAHAPARPEAPVDSMLKDMATIILSTFLLIGWVAFIITYPLSMHQQQQLQHQQFQ
KELEKIQLLQQQQQQLPFHPPGDTAQDGELLDTSGPYSESSGTSSPSTSPRASNHSLCSG
SSASKAGSSPSLEQDDGDEETSVVIVGKISFCPKDVLGHGAEGTIVYRGMFDNRDVAVKR
ILPECFSFADREVQLLRESDEHPNVIRYFCTEKDRQFQYIAIELCAATLQEYVEQKDFAH
LGLEPITLLQQTTSGLAHLHSLNIVHRDLKPHNILISMPNAHGKIKAMISDFGLCKKLAV
GRHSFSRRSGVPGTEGWIAPEMLSEDCKENPTYTVDIFSAGCVFYYVISEGSHPFGKSLQ
RQANILLGACSLDCLHPEKHEDVIARELIEKMIAMDPQKRPSAKHVLKHPFFWSLEKQLQ
FFQDVSDRIEKESLDGPIVKQLERGGRAVVKMDWRENITVPLQTDLRKFRTYKGGSVRDL
LRAMRNKKHHYRELPAEVRETLGSLPDDFVCYFTSRFPHLLAHTYRAMELCSHERLFQPY
YFHEPPEPQPPVTPDAL

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History
Entry version 185 (10 Oct 2018)
Sequence version 2 (01 Jul 2008)
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Protein

Serine/threonine-protein kinase/endoribonuclease IRE1

Gene

ERN1

Organism

Homo sapiens (Human)

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:11779464, PubMed:11175748, PubMed:12637535, PubMed:9637683, PubMed:21317875). In unstressed cells, the endoplasmic reticulum luminal domain is maintained in its inactive monomeric state by binding to the endoplasmic reticulum chaperone HSPA5/BiP (PubMed:21317875). 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:21317875). The endoribonuclease activity is specific for XBP1 mRNA and excises 26 nucleotides from XBP1 mRNA (PubMed:11779464, PubMed:24508390, PubMed:21317875). The resulting spliced transcript of XBP1 encodes a transcriptional activator protein that up-regulates expression of UPR target genes (PubMed:11779464, PubMed:24508390, PubMed:21317875).1 Publication5 Publications

Catalytic activityⁱ

ATP + a protein = ADP + a phosphoprotein.2 Publications

Cofactorⁱ

Mg²⁺2 Publications

Activity regulationⁱ

The kinase domain is activated by trans-autophosphorylation following homodimerization (PubMed:12637535, PubMed:9637683). Kinase activity is required for activation of the endoribonuclease domain (PubMed:12637535, PubMed:9637683). Endoribonuclease activity is specifically inhibited by hydroxy-aryl-aldehydes (HAA) (By similarity).By similarity2 Publications

Sites

Feature key	Position(s)	DescriptionActions	Length
Binding siteⁱ	599	ATPPROSITE-ProRule annotationCombined sources2 Publications	1
Active siteⁱ	688	Proton acceptorPROSITE-ProRule annotationBy similarity	1
Binding siteⁱ	711	ATPCombined sources1 Publication	1
Binding siteⁱ	892	Hydroxy-aryl-aldehyde inhibitorBy similarity	1

Regions

Feature key	Position(s)	DescriptionActions	Length
Nucleotide bindingⁱ	577 – 585	ATPPROSITE-ProRule annotationBy similarity	9
Nucleotide bindingⁱ	643 – 645	ATPCombined sources1 Publication	3
Nucleotide bindingⁱ	690 – 693	ATPCombined sources1 Publication	4

GO - Molecular functionⁱ

ADP binding
Source: ParkinsonsUK-UCL
Inferred from direct assayⁱ
- 21317875
ATP binding
Source: UniProtKB
Inferred from direct assayⁱ
- 9637683
endoribonuclease activity
Source: UniProtKB
Inferred from direct assayⁱ
- 9637683
enzyme binding
Source: UniProtKB
Inferred from physical interactionⁱ
- 23103912
Hsp70 protein binding
Source: ParkinsonsUK-UCL
Inferred from physical interactionⁱ
- 20625543
Hsp90 protein binding
Source: ParkinsonsUK-UCL
Inferred from direct assayⁱ
- 12446770
identical protein binding
Source: IntAct
Inferred from physical interactionⁱ
magnesium ion binding
Source: UniProtKB
Inferred from direct assayⁱ
- 9637683
platelet-derived growth factor receptor binding
Source: BHF-UCL
Inferred from physical interactionⁱ
- 26315405
protein homodimerization activity
Source: UniProtKB
Inferred from direct assayⁱ
- 29198525
protein serine/threonine kinase activity
Source: UniProtKB
Inferred from direct assayⁱ
- 9637683

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

activation of JUN kinase activity
Source: ParkinsonsUK-UCL
Inferred from direct assayⁱ
- 10650002
cell cycle arrest Source: UniProtKB
cellular response to glucose stimulus
Source: ParkinsonsUK-UCL
Inferred from direct assayⁱ
- 20103773
cellular response to unfolded protein
Source: ParkinsonsUK-UCL
Inferred from direct assayⁱ
- 19328063
cellular response to vascular endothelial growth factor stimulus
Source: UniProtKB
Inferred from direct assayⁱ
- 23529610
endothelial cell proliferation
Source: UniProtKB
Inferred from direct assayⁱ
- 23529610
insulin metabolic process
Source: ParkinsonsUK-UCL
Inferred from direct assayⁱ
- 20103773
intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress Source: Ensembl
IRE1-mediated unfolded protein response
Source: UniProtKB
Inferred from direct assayⁱ
- 29198525
- 9637683
mRNA catabolic process
Source: ParkinsonsUK-UCL
Traceable author statementⁱ
- 22013210
mRNA cleavage Source: UniProtKB
mRNA cleavage involved in mRNA processing
Source: ParkinsonsUK-UCL
Inferred from direct assayⁱ
- 21317875
mRNA splicing, via endonucleolytic cleavage and ligation
Source: UniProtKB
Inferred from direct assayⁱ
- 11779464
- 19622636
peptidyl-serine autophosphorylation
Source: ParkinsonsUK-UCL
Inferred from direct assayⁱ
- 20103773
peptidyl-serine trans-autophosphorylation
Source: ParkinsonsUK-UCL
Inferred from mutant phenotypeⁱ
- 21317875
positive regulation of endoplasmic reticulum unfolded protein response
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 16645094
positive regulation of RNA splicing
Source: UniProtKB
Inferred from direct assayⁱ
- 11779464
- 19622636
positive regulation of vascular smooth muscle cell proliferation
Source: BHF-UCL
Inferred from mutant phenotypeⁱ
- 26315405
protein autophosphorylation
Source: ParkinsonsUK-UCL
Inferred from direct assayⁱ
- 19328063
- 9637683
protein phosphorylation
Source: UniProtKB
Inferred from direct assayⁱ
- 9637683
regulation of macroautophagy
Source: ParkinsonsUK-UCL
Traceable author statementⁱ
- 22013210
regulation of transcription, DNA-templated Source: UniProtKB-KW
response to endoplasmic reticulum stress
Source: ParkinsonsUK-UCL
Inferred from direct assayⁱ
- 10650002
transcription, DNA-templated Source: UniProtKB-KW

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Hydrolase, Kinase, Multifunctional enzyme, Serine/threonine-protein kinase, Transferase
Biological process	Apoptosis, Transcription, Transcription regulation, Unfolded protein response
Ligand	ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

Reactomeⁱ	R-HSA-381070 IRE1alpha activates chaperones
SignaLinkⁱ	O75460
SIGNORⁱ	O75460

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 Short name: hIRE1p1 Publication Ire1-alpha1 Publication Short name: IRE1a1 Publication Including the following 2 domains: Serine/threonine-protein kinase (EC:2.7.11.12 Publications) Endoribonuclease (EC:3.1.26.-1 Publication)
Gene namesⁱ	Name:ERN1Imported Synonyms:IRE1Imported
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 17

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000178607.15
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:3449 ERN1
MIMⁱ	604033 gene
neXtProtⁱ	NX_O75460

Topology

Feature key	Position(s)	DescriptionActions	Length
Topological domainⁱ	19 – 443	LumenalSequence analysisAdd BLAST	425
Transmembraneⁱ	444 – 464	HelicalSequence analysisAdd BLAST	21
Topological domainⁱ	465 – 977	CytoplasmicSequence analysisAdd BLAST	513

Keywords - Cellular componentⁱ

Endoplasmic reticulum, Membrane

Pathology & Biotechⁱ

Mutagenesis

Feature key	Position(s)	DescriptionActions	Length
Mutagenesisⁱ	105	Q → E: Impaired ability to homodimerize. 1 Publication	1
Mutagenesisⁱ	109	C → S: No effect on dimerization. 1 Publication	1
Mutagenesisⁱ	123	D → P: Abolishes ability to homodimerize. 1 Publication	1
Mutagenesisⁱ	125	W → A: Abolishes ability to homodimerize. 1 Publication	1
Mutagenesisⁱ	148	C → S: No effect on dimerization. Weakens dimer; when associated with S-332. Abolishes interaction with PDIA6. Prolonged splicing of XBP1, probably due to prolonged activation of PDIA6. Inhibits formation of oxidized multimeric forms of ERN1 in response to ER stress. 2 Publications	1
Mutagenesisⁱ	332	C → S: No effect on dimerization. Weakens dimer; when associated with S-148. 1 Publication	1
Mutagenesisⁱ	599	K → A: Loss of autophosphorylation and of endoribonuclease activity. Inhibition of growth arrest. 2 Publications	1

Organism-specific databases

DisGeNET More...DisGeNETⁱ	2081
Open Targets More...OpenTargetsⁱ	ENSG00000178607
PharmGKBⁱ	PA27861

Chemistry databases

ChEMBLⁱ	CHEMBL1163101
IUPHAR/BPS Guide to PHARMACOLOGY More...GuidetoPHARMACOLOGYⁱ	2020

Polymorphism and mutation databases

BioMutaⁱ	ERN1

BioMutaⁱ

ERN1

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Signal peptideⁱ	1 – 18	Sequence analysisAdd BLAST		18
ChainⁱPRO_0000024327	19 – 977	Serine/threonine-protein kinase/endoribonuclease IRE1Add BLAST		959

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Glycosylationⁱ	176	N-linked (GlcNAc...) asparagineSequence analysis		1
Modified residueⁱ	973	PhosphothreonineCombined sources		1

Post-translational modificationⁱ

Autophosphorylated following homodimerization. Autophosphorylation promotes activation of the endoribonuclease domain.3 Publications

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

Keywords - PTMⁱ

ADP-ribosylation, Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDⁱ	O75460
MaxQB - The MaxQuant DataBase More...MaxQBⁱ	O75460
PaxDbⁱ	O75460
PeptideAtlas More...PeptideAtlasⁱ	O75460
PRIDEⁱ	O75460
ProteomicsDBⁱ	50021 50022 [O75460-2]

PTM databases

iPTMnetⁱ	O75460
PhosphoSitePlusⁱ	O75460

Expressionⁱ

Tissue specificityⁱ

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

Gene expression databases

Bgeeⁱ	ENSG00000178607 Expressed in 180 organ(s), highest expression level in adrenal gland
CleanExⁱ	HS_ERN1
Genevisibleⁱ	O75460 HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	CAB009495 HPA027730

HPAⁱ

CAB009495
HPA027730

Interactionⁱ

Subunit structureⁱ

Monomer (PubMed:29198525, PubMed:16973740). Homodimer; disulfide-linked; homodimerization takes place in response to endoplasmic reticulum stress and promotes activation of the kinase and endoribonuclease activities (PubMed:12637535, PubMed:24508390, PubMed:16973740, PubMed:21317875). Dimer formation is driven by hydrophobic interactions within the N-terminal luminal domains and stabilized by disulfide bridges (PubMed:12637535). Interacts (via the luminal region) with DNAJB9/ERdj4; interaction takes place in unstressed cells and promotes recruitment of HSPA5/BiP (PubMed:29198525). 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 (PubMed:12637535, PubMed:29198525). Interacts with PDIA6, a negative regulator of the UPR; the interaction is direct and disrupts homodimerization (PubMed:24508390). 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 (By similarity). Interacts with TAOK3 and TRAF2 (PubMed:11278723).By similarity5 Publications

Binary interactionsⁱ

With	Entry	#Exp.	IntAct	Notes
itself		2	EBI-371750,EBI-371750
Bak1	O08734	2	EBI-371750,EBI-822441	From Mus musculus.
BAX	Q07812	2	EBI-371750,EBI-516580
Bax	Q07813	2	EBI-371750,EBI-700711	From Mus musculus.
HSPA1A	P0DMV8	5	EBI-15600828,EBI-11820565
HSPA5	P11021	4	EBI-15600828,EBI-354921
Hspa5	P20029	2	EBI-371750,EBI-772325	From Mus musculus.
OS9	Q13438	2	EBI-15600828,EBI-725454
SEL1L	Q9UBV2	2	EBI-15600828,EBI-358766
SYVN1	Q86TM6	3	EBI-15600828,EBI-947849
TAOK3	Q9H2K8	3	EBI-371750,EBI-1384100
TRAF2	Q12933	3	EBI-371750,EBI-355744
YIPF5	Q969M3	3	EBI-371750,EBI-2124787

GO - Molecular functionⁱ

enzyme binding
Source: UniProtKB
Inferred from physical interactionⁱ
- 23103912
Hsp70 protein binding
Source: ParkinsonsUK-UCL
Inferred from physical interactionⁱ
- 20625543
Hsp90 protein binding
Source: ParkinsonsUK-UCL
Inferred from direct assayⁱ
- 12446770
identical protein binding
Source: IntAct
Inferred from physical interactionⁱ
platelet-derived growth factor receptor binding
Source: BHF-UCL
Inferred from physical interactionⁱ
- 26315405
protein homodimerization activity
Source: UniProtKB
Inferred from direct assayⁱ
- 29198525

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridⁱ	108391, 33 interactors
Database of interacting proteins More...DIPⁱ	DIP-31711N
IntActⁱ	O75460, 22 interactors
Molecular INTeraction database More...MINTⁱ	O75460
STRINGⁱ	9606.ENSP00000401445

Chemistry databases

BindingDBⁱ

O75460

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Beta strandⁱ	32 – 37	Combined sources	6
Beta strandⁱ	40 – 46	Combined sources	7
Turnⁱ	47 – 49	Combined sources	3
Beta strandⁱ	52 – 57	Combined sources	6
Beta strandⁱ	73 – 75	Combined sources	3
Turnⁱ	77 – 79	Combined sources	3
Beta strandⁱ	82 – 84	Combined sources	3
Beta strandⁱ	93 – 95	Combined sources	3
Helixⁱ	100 – 104	Combined sources	5
Beta strandⁱ	120 – 128	Combined sources	9
Beta strandⁱ	154 – 164	Combined sources	11
Beta strandⁱ	168 – 172	Combined sources	5
Beta strandⁱ	176 – 182	Combined sources	7
Beta strandⁱ	197 – 201	Combined sources	5
Beta strandⁱ	205 – 209	Combined sources	5
Turnⁱ	211 – 213	Combined sources	3
Beta strandⁱ	216 – 221	Combined sources	6
Beta strandⁱ	226 – 231	Combined sources	6
Beta strandⁱ	238 – 240	Combined sources	3
Beta strandⁱ	243 – 246	Combined sources	4
Helixⁱ	247 – 264	Combined sources	18
Helixⁱ	273 – 279	Combined sources	7
Beta strandⁱ	280 – 284	Combined sources	5
Beta strandⁱ	286 – 288	Combined sources	3
Beta strandⁱ	297 – 300	Combined sources	4
Turnⁱ	359 – 361	Combined sources	3
Beta strandⁱ	564 – 566	Combined sources	3
Beta strandⁱ	567 – 580	Combined sources	14
Turnⁱ	581 – 583	Combined sources	3
Beta strandⁱ	584 – 591	Combined sources	8
Beta strandⁱ	594 – 601	Combined sources	8
Helixⁱ	603 – 605	Combined sources	3
Helixⁱ	606 – 617	Combined sources	12
Beta strandⁱ	628 – 633	Combined sources	6
Beta strandⁱ	638 – 642	Combined sources	5
Beta strandⁱ	645 – 648	Combined sources	4
Helixⁱ	649 – 655	Combined sources	7
Helixⁱ	657 – 661	Combined sources	5
Helixⁱ	665 – 681	Combined sources	17
Turnⁱ	691 – 693	Combined sources	3
Beta strandⁱ	694 – 697	Combined sources	4
Turnⁱ	701 – 703	Combined sources	3
Beta strandⁱ	707 – 709	Combined sources	3
Helixⁱ	712 – 714	Combined sources	3
Helixⁱ	740 – 743	Combined sources	4
Helixⁱ	754 – 768	Combined sources	15
Helixⁱ	778 – 780	Combined sources	3
Helixⁱ	781 – 787	Combined sources	7
Beta strandⁱ	793 – 795	Combined sources	3
Helixⁱ	800 – 812	Combined sources	13
Helixⁱ	817 – 819	Combined sources	3
Helixⁱ	823 – 827	Combined sources	5
Helixⁱ	830 – 832	Combined sources	3
Helixⁱ	835 – 849	Combined sources	15
Beta strandⁱ	854 – 856	Combined sources	3
Helixⁱ	857 – 865	Combined sources	9
Helixⁱ	867 – 870	Combined sources	4
Beta strandⁱ	874 – 878	Combined sources	5
Helixⁱ	880 – 887	Combined sources	8
Beta strandⁱ	888 – 890	Combined sources	3
Helixⁱ	897 – 909	Combined sources	13
Helixⁱ	911 – 913	Combined sources	3
Helixⁱ	916 – 922	Combined sources	7
Helixⁱ	927 – 936	Combined sources	10
Helixⁱ	940 – 947	Combined sources	8
Helixⁱ	948 – 951	Combined sources	4
Beta strandⁱ	952 – 954	Combined sources	3
Helixⁱ	955 – 957	Combined sources	3
Turnⁱ	958 – 960	Combined sources	3

Show more details

3D structure databases

ProteinModelPortalⁱ	O75460
SMRⁱ	O75460
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Miscellaneous databases

EvolutionaryTraceⁱ	O75460

EvolutionaryTraceⁱ

O75460

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Domainⁱ	571 – 832	Protein kinasePROSITE-ProRule annotationAdd BLAST		262
Domainⁱ	835 – 963	KENPROSITE-ProRule annotationAdd BLAST		129

Region

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Regionⁱ	906 – 907	Hydroxy-aryl-aldehyde inhibitor bindingBy similarity		2

Sequence similaritiesⁱ

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

Keywords - Domainⁱ

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGⁱ	KOG1027 Eukaryota COG0515 LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00390000015684
HOGENOMⁱ	HOG000012929
HOVERGENⁱ	HBG051506
InParanoidⁱ	O75460
KEGG Orthology (KO) More...KOⁱ	K08852
OMAⁱ	MDWRENI
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G049V
PhylomeDBⁱ	O75460
TreeFamⁱ	TF313986

Family and domain databases

Gene3Dⁱ	1.20.1440.180, 1 hit 2.130.10.10, 1 hit
InterProⁱ	View 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
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00069 Pkinase, 1 hit PF06479 Ribonuc_2-5A, 1 hit
SMARTⁱ	View protein in SMART SM00564 PQQ, 5 hits SM00580 PUG, 1 hit SM00220 S_TKc, 1 hit
SUPFAMⁱ	SSF50998 SSF50998, 1 hit SSF56112 SSF56112, 1 hit
PROSITEⁱ	View 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. Align Add to basket

Isoform 1 (identifier: O75460-1) [UniParc]FASTA Add 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.

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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

Isoform 2 (identifier: O75460-2) [UniParc]FASTA Add to basket

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

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MPARRLLLLL TLLLPGLGVS DRGAWGGGQL ATAGSGPGQR RGAGAGVRAG 
        60         70
SATAAARCPV SPAVGGSGRA

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Length:70

Mass (Da):6,649

Checksum:ⁱC93BA0CB092E6204

Experimental Info

Feature key	Position(s)	DescriptionActions	Length
Sequence conflictⁱ	190 – 191	DV → EG in AAC25991 (PubMed:9637683).Curated	2
Sequence conflictⁱ	768	I → V in AAC25991 (PubMed:9637683).Curated	1
Sequence conflictⁱ	816	D → G in BAF85092 (PubMed:14702039).Curated	1
Sequence conflictⁱ	824 – 825	KH → ND in AAC25991 (PubMed:9637683).Curated	2
Sequence conflictⁱ	880	V → D in AAC25991 (PubMed:9637683).Curated	1
Sequence conflictⁱ	904	M → T in BAF85092 (PubMed:14702039).Curated	1
Sequence conflictⁱ	924	S → T in AAC25991 (PubMed:9637683).Curated	1

Natural variant

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_040488	244	N → S in a renal clear cell carcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs1397145500Ensembl.	1
Natural variantⁱVAR_040489	418	V → M1 PublicationCorresponds to variant dbSNP:rs55869215Ensembl.	1
Natural variantⁱVAR_040490	474	L → R in a lung adenocarcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs186305118Ensembl.	1
Natural variantⁱVAR_040491	635	R → W in a gastric adenocarcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs146710304Ensembl.	1
Natural variantⁱVAR_040492	700	N → S1 PublicationCorresponds to variant dbSNP:rs918253870Ensembl.	1
Natural variantⁱVAR_040493	769	S → F in a glioblastoma multiforme sample; somatic mutation. 1 Publication	1
Natural variantⁱVAR_040494	830	P → L in an ovarian serous carcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs1279653488Ensembl.	1

Alternative sequence

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Alternative sequenceⁱVSP_034582	19 – 70	IFGST…THVEE → VSDRGAWGGGQLATAGSGPG QRRGAGAGVRAGSATAAARC PVSPAVGGSGRA in isoform 2. 2 PublicationsAdd BLAST		52
Alternative sequenceⁱVSP_034583	71 – 977	Missing in isoform 2. 2 PublicationsAdd BLAST		907

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.
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS45762.1 [O75460-1]
NCBI Reference Sequences More...RefSeqⁱ	NP_001424.3, NM_001433.3 [O75460-1]
UniGeneⁱ	Hs.133982 Hs.700027 Hs.744953

Genome annotation databases

Ensemblⁱ	ENST00000433197; ENSP00000401445; ENSG00000178607 [O75460-1] ENST00000606895; ENSP00000475519; ENSG00000178607 [O75460-2]
GeneIDⁱ	2081
KEGGⁱ	hsa:2081
UCSC genome browser More...UCSCⁱ	uc002jdz.3 human [O75460-1]

Keywords - Coding sequence diversityⁱ

Alternative splicing, Polymorphism

Similar proteinsⁱ

90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
O75460	Serine/threonine-protein kinase/endoribonuclease IRE1	)	MOUSE		977	UniRef90_O75460
Uncharacterized protein		RHIRO		980
Endoplasmic reticulum to nucleus signaling 1		CALJA		980
Uncharacterized protein		RHIBE		980
Uncharacterized protein		COLAP		979
+151
O75460-2	ERN1 isoform 8		PONAB		70	UniRef90_O75460-2
ERN1 isoform 1		PANTR		70

Protein	Similar proteins		Species	Score	Length	Source
O75460	Serine/threonine-protein kinase/endoribonuclease IRE1	)	MOUSE		977	UniRef50_O75460
Uncharacterized protein		RHIBE		980
Uncharacterized protein		RHIRO		980
Endoplasmic reticulum to nucleus signaling 1		CALJA		980
Uncharacterized protein		COLAP		979
+320
O75460-2	ERN1 isoform 1		PANTR		70	UniRef50_O75460-2
ERN1 isoform 8		PONAB		70
Uncharacterized protein		MACMU		61

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.
CCDSⁱ	CCDS45762.1 [O75460-1]
RefSeqⁱ	NP_001424.3, NM_001433.3 [O75460-1]
UniGeneⁱ	Hs.133982 Hs.700027 Hs.744953

3D structure databases

Select the link destinations: Protein Data Bank Europe More...PDBeⁱ Protein Data Bank RCSB More...RCSB PDBⁱ Protein Data Bank Japan More...PDBjⁱ Links Updated	PDB entry	Method	Resolution (Å)	Chain	Positions	PDBsum
	2HZ6	X-ray	3.10	A	24-390	[»]
	3P23	X-ray	2.70	A/B/C/D	547-977	[»]
	4U6R	X-ray	2.50	A	547-977	[»]
	4YZ9	X-ray	2.46	A/B/C	562-966	[»]
	4YZC	X-ray	2.49	A/B	562-966	[»]
	4YZD	X-ray	3.10	A/B/C	562-966	[»]
	4Z7G	X-ray	2.60	A/B	562-977	[»]
	4Z7H	X-ray	2.90	A/B	562-977	[»]
	5HGI	X-ray	2.58	A	547-977	[»]
ProteinModelPortalⁱ	O75460
SMRⁱ	O75460
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	108391, 33 interactors
DIPⁱ	DIP-31711N
IntActⁱ	O75460, 22 interactors
MINTⁱ	O75460
STRINGⁱ	9606.ENSP00000401445

Chemistry databases

BindingDBⁱ	O75460
ChEMBLⁱ	CHEMBL1163101
GuidetoPHARMACOLOGYⁱ	2020

PTM databases

iPTMnetⁱ	O75460
PhosphoSitePlusⁱ	O75460

Polymorphism and mutation databases

BioMutaⁱ	ERN1

BioMutaⁱ

ERN1

Proteomic databases

EPDⁱ	O75460
MaxQBⁱ	O75460
PaxDbⁱ	O75460
PeptideAtlasⁱ	O75460
PRIDEⁱ	O75460
ProteomicsDBⁱ	50021 50022 [O75460-2]

Protocols and materials databases

The DNASU plasmid repository More...DNASUⁱ	2081
Structural Biology Knowledgebase	Search...

Genome annotation databases

Ensemblⁱ	ENST00000433197; ENSP00000401445; ENSG00000178607 [O75460-1] ENST00000606895; ENSP00000475519; ENSG00000178607 [O75460-2]
GeneIDⁱ	2081
KEGGⁱ	hsa:2081
UCSCⁱ	uc002jdz.3 human [O75460-1]

Organism-specific databases

CTDⁱ	2081
DisGeNETⁱ	2081
EuPathDBⁱ	HostDB:ENSG00000178607.15
GeneCardsⁱ	ERN1
H-InvDBⁱ	HIX0014084
HGNCⁱ	HGNC:3449 ERN1
HPAⁱ	CAB009495 HPA027730
MIMⁱ	604033 gene
neXtProtⁱ	NX_O75460
OpenTargetsⁱ	ENSG00000178607
PharmGKBⁱ	PA27861
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	KOG1027 Eukaryota COG0515 LUCA
GeneTreeⁱ	ENSGT00390000015684
HOGENOMⁱ	HOG000012929
HOVERGENⁱ	HBG051506
InParanoidⁱ	O75460
KOⁱ	K08852
OMAⁱ	MDWRENI
OrthoDBⁱ	EOG091G049V
PhylomeDBⁱ	O75460
TreeFamⁱ	TF313986

Enzyme and pathway databases

Reactomeⁱ	R-HSA-381070 IRE1alpha activates chaperones
SignaLinkⁱ	O75460
SIGNORⁱ	O75460

Miscellaneous databases

ChiTaRSⁱ	ERN1 human
EvolutionaryTraceⁱ	O75460
GeneWikiⁱ	ERN1
GenomeRNAiⁱ	2081
Protein Ontology More...PROⁱ	PR:O75460
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000178607 Expressed in 180 organ(s), highest expression level in adrenal gland
CleanExⁱ	HS_ERN1
Genevisibleⁱ	O75460 HS

Family and domain databases

Gene3Dⁱ	1.20.1440.180, 1 hit 2.130.10.10, 1 hit
InterProⁱ	View 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
Pfamⁱ	View protein in Pfam PF00069 Pkinase, 1 hit PF06479 Ribonuc_2-5A, 1 hit
SMARTⁱ	View protein in SMART SM00564 PQQ, 5 hits SM00580 PUG, 1 hit SM00220 S_TKc, 1 hit
SUPFAMⁱ	SSF50998 SSF50998, 1 hit SSF56112 SSF56112, 1 hit
PROSITEⁱ	View protein in PROSITE PS51392 KEN, 1 hit PS50011 PROTEIN_KINASE_DOM, 1 hit PS00108 PROTEIN_KINASE_ST, 1 hit
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	ERN1_HUMAN
Accessionⁱ	O75460Primary (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:	October 10, 2018
	This is version 185 of the entry and version 2 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program
Disclaimer	Any 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, Reference proteome

Documents

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

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UniProtKB - O75460 (ERN1_HUMAN)

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Serine/threonine-protein kinase/endoribonuclease IRE1

ERN1

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<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

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GO - Biological processi

Enzyme and pathway databases

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<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Endoplasmic reticulum

Endoplasmic reticulum

Mitochondrion

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Topology

Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

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<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Keywords - PTMi

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

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<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

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<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

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3D structure databases

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<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

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<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

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Experimental Info

Natural variant

Alternative sequence

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityi

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Sequence databases

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Chemistry databases

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Polymorphism and mutation databases

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Protocols and materials databases

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<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Domainⁱ

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ