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ERN1 Gene

protein-coding GIFtS: 66
GCID: GC17M062122

Endoplasmic Reticulum To Nucleus Signaling 1

(Previous name: ER to nucleus signalling 1)

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(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, ¹⁰fRNAdb, ¹²H-InvDB, ¹³NCBI, ¹⁴NONCODE, and/or ¹⁵RNAdb)
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Aliases
Endoplasmic Reticulum To Nucleus Signaling 1¹ ²		IRE1P²
IRE1² ³ ⁵		Inositol-Requiring 1²
ER To Nucleus Signalling 1¹ ²		ire1-alpha²
Inositol-Requiring Enzyme 1¹ ²		Protein Kinase/Endoribonuclease²
Endoplasmic Reticulum-To-Nucleus Signaling 1² ³		Serine/Threonine-Protein Kinase/Endoribonuclease IRE1²
Inositol-Requiring Protein 1² ³		Ire1-alpha³
IRE1a² ³		IRE1A⁵
hIRE1p² ³		EC 2.7.11⁸

External Ids:	HGNC: 3449¹	Entrez Gene: 2081²	Ensembl: ENSG00000178607⁷	OMIM: 604033⁵	UniProtKB: O75460³

Export aliases for ERN1 gene to outside databases

Previous GC identifers: GC17M061758 GC17M064547 GC17M062461 GC17M062594 GC17M062582 GC17M059474 GC17M062120 GC17M057488

(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for ERN1 Gene:

The protein encoded by this gene is the ER to nucleus signalling 1 protein, a human homologue of the yeast Ire1

gene product. This protein possesses intrinsic kinase activity and an endoribonuclease activity and it is

important in altering gene expression as a response to endoplasmic reticulum-based stress signals. (provided by

RefSeq, Jul 2008)

GeneCards Summary for ERN1 Gene:

ERN1 (endoplasmic reticulum to nucleus signaling 1) is a protein-coding gene. GO annotations related to this gene include magnesium ion binding and identical protein binding. An important paralog of this gene is ERN2.

UniProtKB/Swiss-Prot: ERN1_HUMAN, O75460

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

summary for ERN1 Gene:

IRE1 (also known as endoplasmic reticulum to nucleus signaling (ERN) 1) is a transmembrane resident ER

protein that possesses both kinase and endonuclease domains. Both yeast (IRE1) and mammalian (IRE1alpha)

homologs are involved in the degradation of misfolded proteins, as part of the unfolded protein response

(UPR) pathway. IRE1 (yeast) is involved in the endonucleolytic cleavage of HAC1 mRNA, whereas IRE1alpha

(human) catalyzes the splicing of X-box binding protein (XBP) 1 mRNA. XBP1 mRNA splicing triggers

upregulation of genes involved in the ERAD pathway, induction of XBP1 expression and the synthesis of ER

chaperones.

Gene Wiki entry for ERN1 Gene

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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Regulatory elements:

Regulatory transcription factor binding sites in the ERN1 gene promoter:
Nkx2-2 HSF1short Pax-2 HSF1 (long) POU6F1 (c2) Pax-2a ATF6
Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): ERN1 promoter sequence

Search Chromatin IP Primers for ERN1

Epigenetics:

DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat ERN1

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 17q24.2 Ensembl cytogenetic band: 17q23.3 HGNC cytogenetic band: 17q23

ERN1 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
ERN1 gene location

GeneLoc information about chromosome 17 GeneLoc Exon Structure

GeneLoc location for GC17M062122: view genomic region (about GC identifiers)

Start:	62,116,502 bp from pter	End:	62,208,179 bp from pter
Size:	91,678 bases	Orientation:	minus strand

(According to ¹UniProtKB, HORDE, ²neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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UniProtKB/Swiss-Prot: ERN1_HUMAN, O75460 (See protein sequence)

Recommended Name: Serine/threonine-protein kinase/endoribonuclease IRE1 precursor

Size: 977 amino acids; 109735 Da

Cofactor: Magnesium

Subunit: 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

2 PDB 3D structures from and Proteopedia for ERN1:

2HZ6 (3D)

3P23 (3D)

Secondary accessions: A1L457 A8K8N8 A8MXS7 Q59EE2

Alternative splicing: 2 isoforms: O75460-1 O75460-2

Explore the universe of human proteins at neXtProt for ERN1: NX_O75460

Explore proteomics data for ERN1 at MOPED

Post-translational modifications:

Autophosphorylated¹

ADP-ribosylated by PARP16 upon ER stress, which increases both kinase and endonuclease activities¹

Glycosylation² at Asn176

Modification sites at PhosphoSitePlus

2 DME Specific Peptides for ERN1 (O75460)

VHRDLKP

IVHRDLK

See ERN1 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

REFSEQ proteins: NP_001424.3

ENSEMBL proteins:

ENSP00000401445 ENSP00000475519

Reactome Protein details: O75460

ERN1 Human Recombinant Protein Products:

	EMD Millipore Purified and/or Recombinant ERN1 Protein
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	Search eBioscience for Proteins for ERN1
	antibodies-online proteins for ERN1 (4 products)
	antibodies-online peptides for ERN1

ERN1 Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of ERN1
	Browse R&D Systems for Antibodies
	Cell Signaling Technology (CST) Antibodies for ERN1 (IRE1)
	OriGene Antibodies for ERN1 OriGene Custom Antibody Services for ERN1
	Novus Biologicals ERN1 Antibodies
	Abcam antibodies for ERN1 (Q76MJ5, O75460)
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	ThermoFisher Antibody for ERN1
	antibodies-online antibodies for ERN1 (113 products)

ERN1 Assay Products:

	Browse Kits and Assays available from EMD Millipore
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	GenScript Custom Assay Services for ERN1
	Browse Enzo Life Sciences for kits & assays
	Cloud-Clone Corp. ELISAs for ERN1 Cloud-Clone Corp. CLIAs for ERN1
	Search eBioscience for ELISAs for ERN1
	antibodies-online kits for ERN1 (25 products)

(According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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IUPHAR Guide to PHARMACOLOGY protein family classification: endoplasmic reticulum to nucleus signaling 1

IRE family

Selected InterPro protein domains (see all 8):

IPR011009 Kinase-like_dom

IPR008271 Ser/Thr_kinase_AS

IPR000719 Prot_kinase_dom

IPR006567 PUG-dom

IPR011047 Quinonprotein_ADH-like_supfam

Graphical View of Domain Structure for InterPro Entry O75460

ProtoNet protein and cluster: O75460

3 Blocks protein domains:

IPB002372 Bacterial quinoprotein

IPB006567 PUG

IPB010513 Ribonuclease 2-5A

UniProtKB/Swiss-Prot: ERN1_HUMAN, O75460

Similarity: Belongs to the protein kinase superfamily. Ser/Thr protein kinase family

Similarity: Contains 1 KEN domain

Similarity: Contains 1 protein kinase domain

Find genes that share domains with ERN1 About GenesLikeMe

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, genOway,
transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Molecular Function:

UniProtKB/Swiss-Prot Summary: ERN1_HUMAN, O75460

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

Catalytic activity: ATP + a protein = ADP + a phosphoprotein

Enzyme regulation: The kinase domain is activated by trans-autophosphorylation. Kinase activity is required for

activation of the endoribonuclease domain

Enzyme Number (IUBMB): EC 2.7.11²

Gene Ontology (GO): Selected molecular function terms (see all 12): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000287	magnesium ion binding	IDA	9637683
GO:0004519	endonuclease activity	--	--
GO:0004521	endoribonuclease activity	TAS	--
GO:0004540	ribonuclease activity	--	--
GO:0004672	protein kinase activity	--	--

Find genes that share ontologies with ERN1 About GenesLikeMe

Phenotypes:
5 GenomeRNAi human phenotypes for ERN1:

Decreased Salmonella enterica	Decreased focal adhesion (FA)	Decreased substrate adherent c	Increased G1 DNA content
Increased cell death HMECs cel

11 MGI mutant phenotypes (inferred from 6 alleles) (MGI details for Ern1):

cardiovascular system	cellular	embryogenesis	growth/size/body	hematopoietic system
homeostasis/metabolism	immune system	integument	liver/biliary system	mortality/aging
normal

Find genes that share phenotypes with ERN1 About GenesLikeMe

Animal Models:
MGI mouse knock-outs for ERN1: Ern1^tm1Rjk Ern1^tm1Tiw Ern1^tm1Dron Ern1^tm2.2Tiw

genOway: Develop your customized and physiologically relevant rodent model for ERN1

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		6 qRT-PCR Assays for microRNAs that regulate ERN1:
		hsa-miR-146a* hsa-miR-124 hsa-miR-3166 hsa-miR-532-3p hsa-miR-506 hsa-miR-488
		SwitchGear 3'UTR luciferase reporter plasmid: ERN1 3' UTR sequence

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		Predesigned siRNA for gene silencing in human, mouse, rat ERN1

Gene Editing
Products:

DNA2.0 Custom Protein Engineering Service for ERN1

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		GenScript: all cDNA clones in your preferred vector: ERN1 (NM_001433)
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		Addgene plasmids for ERN1

Cell Line Products:		GenScript Custom overexpressing Cell Line Services for ERN1
		Browse ESI BIO Cell Lines and PureStem Progenitors for ERN1

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for ERN1

(According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Subcellular locations from UniProtKB/Swiss-Prot

ERN1_HUMAN, O75460: Endoplasmic reticulum membrane; Single-pass type I membrane protein

Subcellular locations from COMPARTMENTS:

Compartment	Confidence
endoplasmic reticulum	5
nucleus	2
plasma membrane	2
cytosol	1
extracellular	1
golgi apparatus	1
mitochondrion	1
peroxisome	1

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Gene Ontology (GO): 4 cellular component terms: About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005637	nuclear inner membrane	IEA	--
GO:0005739	mitochondrion	IEA	--
GO:0005789	endoplasmic reticulum membrane	TAS	--
GO:0030176	integral component of endoplasmic reticulum membrane	IDA	9637683

Find genes that share ontologies with ERN1 About GenesLikeMe

(SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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SuperPaths for ERN1 About (see all 7)

See pathways by source

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SuperPath

Contained pathways About

Alzheimer's disease

Alzheimers Disease

0.44

Alzheimer's disease

0.44

Unfolded Protein Response

Unfolded Protein Response

0.61

Activation of Chaperones by IRE1alpha

0.61

Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.

Non-alcoholic fatty liver disease (NAFLD)

0.41

Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein

Metabolism of proteins

0.30

Translational Control

Translational Control

Find genes that share SuperPaths with ERN1 About GenesLikeMe

Pathways by source See SuperPaths
Show all pathways

1 Cell Signaling Technology (CST) Pathway for ERN1

Translational Control

2 BioSystems Pathways for ERN1

	Corticotropin-releasing hormone
	Alzheimers Disease

1 Reactome Pathway for ERN1

IRE1alpha activates chaperones

3 Kegg Pathways (Kegg details for ERN1):

	Protein processing in endoplasmic reticulum
	Non-alcoholic fatty liver disease (NAFLD)
	Alzheimer's disease

Pathway & Disease-focused RT² Profiler PCR Arrays including ERN1:

Alzheimer's Disease in human mouse rat

Apoptosis 384HT in human mouse rat

Unfolded Protein Response in human mouse rat

Interactions:

GeneGlobe Interaction Network for ERN1

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

Selected Interacting proteins for ERN1 (O75460^{1, 2, 3} ENSP00000401445⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 199)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
TAOK3	Q9H2K8¹^,³, ENSP00000376317⁴	EBI-371750,EBI-1384100 I2D: score=2 STRING: ENSP00000376317
BAX	Q07812¹^,³, ENSP00000293288⁴	EBI-371750,EBI-516580 I2D: score=1 STRING: ENSP00000293288
SYVN1	Q86TM6¹^,²^,³, ENSP00000366395⁴	EBI-371750,EBI-947849 MINT-6543145 MINT-6543119 I2D: score=3 STRING: ENSP00000366395
TRAF2	Q12933¹^,³, ENSP00000247668⁴	EBI-371750,EBI-355744 I2D: score=3 STRING: ENSP00000247668
UBC	P0CG48²^,³, ENSP00000344818⁴	MINT-6543131 I2D: score=2 STRING: ENSP00000344818

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Gene Ontology (GO): Selected biological process terms (see all 14): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0006351	transcription, DNA-templated	IEA	--
GO:0006355	regulation of transcription, DNA-templated	IEA	--
GO:0006397	mRNA processing	--	--
GO:0006468	protein phosphorylation	IDA	9637683
GO:0006915	apoptotic process	--	--

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(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse compounds at ApexBio

Compounds for ERN1 available from Tocris Bioscience About this table

Compound	Action	CAS #
STF 083010	Inhibits IRE1alpha endonuclease activity	[307543-71-1]
4mu8C	Inhibits IRE1alpha endoribonuclease activity	[14003-96-4]

3 HMDB Compounds for ERN1 About this table

Compound	Synonyms	CAS #	PubMed Ids
ADP	adenosindiphosphorsaeure (see all 8)	58-64-0	--
Adenosine triphosphate	5'-(tetrahydrogen triphosphate) Adenosine (see all 24)	56-65-5	--
Magnesium	Magnesium (see all 2)	7439-95-4	--

1 DrugBank Compound for ERN1 About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed Ids
N~2~-1H-benzimidazol-5-yl-N~4~-(3-cyclopropyl-1H-pyrazol-5-yl)pyrimidine-2,4-diamine	--	--	target	--	10592235

Selected Novoseek inferred chemical compound relationships for ERN1 gene (see all 11) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
tunicamycin	77.5	1	17525289 (1)
thapsigargin	71.9	5	19428936 (1), 17525289 (1), 19139269 (1)
inositol	40.5	5	17349291 (1), 20146926 (1), 15799970 (1), 18052927 (1) (see all 5)
palmitate	28	3	18559892 (1)
oleic acid	24.6	3	18559892 (1)
glucose	15	11	16950141 (4), 18286202 (3), 17608719 (1), 17526500 (1)
calcium	9.99	1	19700217 (1)
glutamine	8.99	1	20232225 (1)
oxygen	0	1	19925454 (1)
threonine	0	2	11333017 (1), 10835430 (1)

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(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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REFSEQ mRNAs for ERN1 gene (2 alternative transcripts):

NM_001433.3 NM_152461.2

8 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000433197(uc002jdz.2) ENST00000583077 ENST00000583896 ENST00000579249

ENST00000577567 ENST00000584041 ENST00000583028 ENST00000606895

miRNA Products:		Block miRNA regulation of human, mouse, rat ERN1 using miScript Target Protectors
		6 qRT-PCR Assays for microRNAs that regulate ERN1:
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		SwitchGear 3'UTR luciferase reporter plasmid: ERN1 3' UTR sequence

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		GenScript: all cDNA clones in your preferred vector: ERN1 (NM_001433)
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		Addgene plasmids for ERN1

Primer Products:		OriGene qSTAR qPCR primer pairs in human, mouse for ERN1
		Pre-validated RT² qPCR Primer Assay in human, mouse, rat ERN1
		QuantiTect SYBR Green Assays in human, mouse, rat ERN1
		QuantiFast Probe-based Assays in human, mouse, rat ERN1

Selected AceView cDNA sequences (see all 97):

AI734961 NM_152461 AI734969 CK904766 CB990834 AA973421 D82734 AW451601

BQ446956 AI799794 AI222941 BX099892 BE893085 AI792619 CA311378 AA345460

AI733809 AI972997 BX117163 AA687888 Z38435 AI081269 BM559806 BV191080

GeneLoc Exon Structure

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE ¹MOPED, ²PaxDb, and ³MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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ERN1 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS <intensity>^2/3
CGAP TAG: CTGGCAGGTG

About this image

ERN1 expression in embryonic tissues and stem cells About this table

Data from LifeMap, the Embryonic Development and Stem Cells Database
selected tissues (see all 5) fully expand


Brain (Nervous System) fully expand to see all 3 entries
Cerebral Cortex

Ovary (Reproductive System) fully expand to see all 2 entries
Ovarian Mesenchymal Stroma Cells Ovary Interstitium
Oviduct

Trophoblast (Extraembryonic Tissues)
Trophoblast Cells Trophoblast

Testis (Reproductive System)
Leydig Cells Testis Interstitium

Bone (Muscoskeletal System)
Bone Marrow

ERN1 Protein expression data from MOPED¹, PaxDb² and MaxQB³:

About this image

ERN1 Protein Expression

UniProtKB/Swiss-Prot: ERN1_HUMAN, O75460

Tissue specificity: Ubiquitously expressed. High levels observed in pancreatic tissue

Pathway & Disease-focused RT² Profiler PCR Arrays including ERN1:

Alzheimer's Disease in human mouse rat

Apoptosis 384HT in human mouse rat

Unfolded Protein Response in human mouse rat

Primer Products:		OriGene qSTAR qPCR primer pairs in human, mouse for ERN1
		Pre-validated RT² qPCR Primer Assay in human, mouse, rat ERN1
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		QuantiFast Probe-based Assays in human, mouse, rat ERN1

In Situ
Assay Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for ERN1

(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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This gene was present in the common ancestor of animals and fungi.

Orthologs for ERN1 gene from Selected species (see all 17) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
mouse (Mus musculus)	Mammalia	Ern1^{1 , 5}	endoplasmic reticulum (ER) to nucleus signalling 1^{1, 5}	89.08(n)¹ 93.53(a)¹		11 (69.14 cM)⁵ 78943¹ NM_023913.2¹ NP_076402.1¹ 106394650⁵
chicken (Gallus gallus)	Aves	LOC417414¹	serine/threonine-protein kinase/endoribonuclease IRE1	76.63(n) 83.49(a)		417414 XM_004946183.1 XP_004946240.1
lizard (Anolis carolinensis)	Reptilia	ERN1⁶	endoplasmic reticulum to nucleus signaling 1	78(a)	1 ↔ 1	GL343326.1(424086-513103)
African clawed frog (Xenopus laevis)	Amphibia	BJ065023.1²	--	74.39(n)		BJ065023.1
zebrafish (Danio rerio)	Actinopterygii	ern2¹	endoplasmic reticulum to nucleus signaling 2	61.25(n) 61.85(a)		567021 XM_001919315.3 XP_001919350.3
fruit fly (Drosophila melanogaster)	Insecta	ire-1³ Ire1¹	protein amino acid phosphorylation protein kinase³ Inositol-requiring enzyme-1¹	53(a)³ 56.21(n)¹ 52.25(a)¹		92B3³ 42358¹ NM_001104369.2¹ NP_001097839.1¹
worm (Caenorhabditis elegans)	Secernentea	ire-1¹	ire-1	51.29(n) 48.84(a)		174305 NM_001267206.1 NP_001254135.1
baker's yeast (Saccharomyces cerevisiae)	Saccharomycetes	IRE1⁶	Serine-threonine kinase and endoribonuclease; tran...	22(a)	1 → many	VIII(258244-261591) YHR079C

ENSEMBL Gene Tree for ERN1 (if available)
TreeFam Gene Tree for ERN1 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
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Paralogs for ERN1 gene

ERN2²

2 SIMAP similar genes for ERN1 using alignment to 1 protein entry: ERN1_HUMAN:

ERN2 CDK4

Find genes that share paralogs with ERN1 About GenesLikeMe

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, ⁴UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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SNP ID	Valid	Clinical significance	Chr 17 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs186305118^1,2,,4	C	A lung adenocarcinoma sample⁴ --	62133286(+)	`GCTGGA/CGCTGC`	2	R L	mis¹		0	--	--	--	--
VAR_040488⁴		A renal clear cell carcinoma sample⁴	--	see VAR_040488	2	N S	mis⁴		0	--	--	--	--
VAR_040494⁴		An ovarian serous carcinoma sample⁴	--	see VAR_040494	2	P L	mis⁴		0	--	--	--	--
VAR_040493⁴		A glioblastoma multiforme sample⁴	--	see VAR_040493	2	S F	mis⁴		0	--	--	--	--
VAR_040491⁴		A gastric adenocarcinoma sample⁴	--	see VAR_040491	2	R W	mis⁴		0	--	--	--	--
rs183792471^1,2		--	62119905(+)	`GATCCC/TCCAAC`	1	--	ds500¹		0	--	--	--	--
rs196907^1,2	C,F,O,A,H	--	62120045(+)	`GAAAAG/AAAAAT`	1	--	ds500¹		19		NA NS EA WA CSA	816
rs9909893^1,2	C,F	--	62120050(+)	`AAAAAT/AATGGT`	1	--	ds500¹		4		WA NA	242
rs199970630^1,2	C	--	62120050(+)	`AAAAA-/TATGGT`	1	--	ds500¹		0	--	--	--	--
rs148856077^1,2		--	62120064(+)	`AACAAA/TTTAGA`	1	--	ds500¹		0	--	--	--	--

HapMap Linkage Disequilibrium report for ERN1 (62116502 - 62208179 bp)

Structural Variations
Database of Genomic Variants (DGV) 2 variations for ERN1: About this table

Variant ID	Type	Subtype	PubMed ID
nsv483108	CNV	Loss	15286789
nsv833511	CNV	Loss	17160897

Site Specific Mutation Identification with PCR Assays

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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OMIM gene information: 604033 OMIM disorders: --

Find genes that share disorders with ERN1 About GenesLikeMe

3 Novoseek inferred disease relationships for ERN1 gene About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
necrosis	16.9	3	12843613 (1), 16581782 (1), 11278723 (1)
tumors	5.06	6	19252749 (1), 12843613 (1), 16581782 (1), 11278723 (1) (see all 5)
cancer	4.59	3	1962622 (2)

Genetic Association Database (GAD): ERN1
Human Genome Epidemiology (HuGE) Navigator: ERN1 (6 documents)

Export disorders for ERN1 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
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PubMed articles for ERN1 gene, integrated from 10 sources (see all 174):
(articles sorted by number of sources associating them with ERN1)

Utopia: connect your pdf to the dynamic
world of online information

A stress response pathway from the endoplasmic reticulum to the nucleus requires a novel bifunctional protein kinase/endoribonuclease (Ire1p) in mammalian cells. (PubMed id 9637683)^{1, 2, 3, 9} Tirasophon W.... Kaufman R.J. (Genes Dev. 1998)
Structure and intermolecular interactions of the luminal dimerization domain of human IRE1alpha. (PubMed id 12637535)^{1, 2, 9} Liu C.Y.... Kaufman R.J. (J. Biol. Chem. 2003)
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. (PubMed id 11278723)^{1, 2, 9} Yoneda T....Tohyama M. (J. Biol. Chem. 2001)
PARP16 is a tail-anchored endoplasmic reticulum protein required for the PERK-and IRE1alpha-mediated unfolded protein response. (PubMed id 23103912)^{1, 2} Jwa M. and Chang P. (Nat. Cell Biol. 2012)
MicroRNA-related genetic variations as predictors for risk of second primary tumor and/or recurrence in patients with early-stage head and neck cancer. (PubMed id 20819778)^{1, 4} Zhang X....Wu X. (Carcinogenesis 2010)
Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PubMed id 20379614)^{1, 4} Rose J.E....Uhl G.R. (Mol. Med. 2010)
Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. (PubMed id 20628086)^{1, 4} Bailey S.D....Anand S. (Diabetes Care 2010)
Complete sequencing and characterization of 21,243 full-length human cDNAs. (PubMed id 14702039)^{1, 2} Ota T.... Sugano S. (Nat. Genet. 2004)
Translational control by the ER transmembrane kinase/ribonuclease IRE1 under ER stress. (PubMed id 11175748)^{1, 2} Iwawaki T.... Kohno K. (Nat. Cell Biol. 2001)
USP14 inhibits ER-associated degradation via interaction with IRE1alpha. (PubMed id 19135427)^{1, 9} Nagai A.... Ichijo H. (Biochem. Biophys. Res. Commun. 2009)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 2081	HGNC: 3449	AceView: ERN1	Ensembl:ENSG00000178607	euGenes: HUgn2081
ECgene: ERN1	Kegg: 2081	H-InvDB: ERN1

(According to HUGE)
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(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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Name	Description
PharmGKB entry for ERN1	Pharmacogenomics, SNPs, Pathways

Intellectual Property for ERN1 gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

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Patent Information for ERN1 gene:
Search GeneIP for patents involving ERN1

GeneCards and IP:
Japan Patent Office Licenses GeneCards European Patent Office Licenses GeneCards Improving the IP Search

(Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, eBioscience, antibodies-online, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
Advanced Cell Diagnostics, Animal models from genOway)
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ERN1 Gene

Endoplasmic Reticulum To Nucleus Signaling 1

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ERN1 Gene

Endoplasmic Reticulum To Nucleus Signaling 1

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