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Center for Computational Systems Medicine
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Protein Summary

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AS Summary

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Protein Functional Features

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Gene Isoform Structures and Expression Levels

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Protein Structures

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pLDDT Score Distribution

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Ramachandran Plot of Protein Structures

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Potential Active Site Information

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Protein Structure and Feature Comparision

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Protein-Protein Interaction

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Related Drugs

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Related Diseases

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Clinically Important Variants

Protein:ERN1

Protein Summary

check button Gene summary
Gene name: ERN1
ASpdb.0 ID: 2081
Gene
Gene symbol

ERN1

Gene ID

2081

Gene nameendoplasmic reticulum to nucleus signaling 1
SynonymsIRE1|IRE1P|IRE1a|hIRE1p
Cytomap

17q23.3

Type of geneprotein-coding
Descriptionserine/threonine-protein kinase/endoribonuclease IRE1ER to nucleus signalling 1inositol-requiring 1inositol-requiring enzyme 1inositol-requiring protein 1ire1-alphaprotein kinase/endoribonuclease
Modification date20240416
UniProtAcc

O75460


check button Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
GeneERN1

GO:0000287

magnesium ion binding

9637683

GeneERN1

GO:0001935

endothelial cell proliferation

23529610

GeneERN1

GO:0004521

RNA endonuclease activity

9637683|11779465|19328063|21317875

GeneERN1

GO:0004674

protein serine/threonine kinase activity

9637683|21317875

GeneERN1

GO:0005524

ATP binding

9637683

GeneERN1

GO:0005737

cytoplasm

19622636

GeneERN1

GO:0005783

endoplasmic reticulum

23529610

GeneERN1

GO:0005789

endoplasmic reticulum membrane

9637683

GeneERN1

GO:0006468

protein phosphorylation

9637683

GeneERN1

GO:0033120

positive regulation of RNA splicing

11779464|19622636

GeneERN1

GO:0034620

cellular response to unfolded protein

19328063

GeneERN1

GO:0034976

response to endoplasmic reticulum stress

10650002

GeneERN1

GO:0035924

cellular response to vascular endothelial growth factor stimulus

23529610

GeneERN1

GO:0036289

peptidyl-serine autophosphorylation

20103773

GeneERN1

GO:0036498

IRE1-mediated unfolded protein response

9637683|11779465|19328063|29198525

GeneERN1

GO:0042803

protein homodimerization activity

29198525

GeneERN1

GO:0043507

positive regulation of JUN kinase activity

10650002

GeneERN1

GO:0043531

ADP binding

21317875

GeneERN1

GO:0046777

protein autophosphorylation

9637683|19328063

GeneERN1

GO:0051879

Hsp90 protein binding

12446770

GeneERN1

GO:0070054

mRNA splicing, via endonucleolytic cleavage and ligation

11779464|19328063|19622636|21317875

GeneERN1

GO:0071333

cellular response to glucose stimulus

20103773

GeneERN1

GO:1901142

insulin metabolic process

20103773

GeneERN1

GO:1990604

IRE1-TRAF2-ASK1 complex

23000344

GeneERN1

GO:1990630

IRE1-RACK1-PP2A complex

20103773



AS Summary

check button Information of the canonical protein with experimentally identified structure from PDB (2023).
UniProt AccFile namePDB IDMethodResolutionChainStartEnd
O75460-1O75460-1_6w3c_A.pdb6W3CX-ray2.3A560964

check button ASpdb's canonical and alternatively spliced isoform information.
accession_idgene_namecanonical_idalternative_idcanonical_lengthalternative_lengthcanonical_startcanonical_endtypeoriginalSEQvariationSEQalternative_startalternative_end
O75460ERN1O75460-1O75460-2977701970SubstitutionIFGSTSTVTLPETLLFVSTLDGSLHAVSKRTGSIKWTLKEDPVLQVPTHVEEVSDRGAWGGGQLATAGSGPGQRRGAGAGVRAGSATAAARCPVSPAVGGSGRA1970
O75460ERN1O75460-1O75460-29777071977Deletionnonenone7070

check buttonMultiple sequence alignment of our canonical and alternatively spliced ERN1

check button Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of ERN1
UniProt-idENSGENSTENSP
O75460-1ENSG00000178607.17ENST00000433197.4ENSP00000401445.2
O75460-2ENSG00000178607.17ENST00000606895.2ENSP00000475519.1

UniProt-idNM IDNP ID
O75460-1NM_001433.3NP_001424.3

check buttonAmino acid sequences of our canonical and alternatively spliced ERN1
accession_idProtein sequence
O75460-1MPARRLLLLLTLLLPGLGIFGSTSTVTLPETLLFVSTLDGSLHAVSKRTGSIKWTLKEDPVLQVPTHVEEPAFLPDPNDGSLYTLGSKNN
EGLTKLPFTIPELVQASPCRSSDGILYMGKKQDIWYVIDLLTGEKQQTLSSAFADSLCPSTSLLYLGRTEYTITMYDTKTRELRWNATYF
DYAASLPEDDVDYKMSHFVSNGDGLVVTVDSESGDVLWIQNYASPVVAFYVWQREGLRKVMHINVAVETLRYLTFMSGEVGRITKWKYPF
PKETEAKSKLTPTLYVGKYSTSLYASPSMVHEGVAVVPRGSTLPLLEGPQTDGVTIGDKGECVITPSTDVKFDPGLKSKNKLNYLRNYWL
LIGHHETPLSASTKMLERFPNNLPKHRENVIPADSEKKSFEEVINLVDQTSENAPTTVSRDVEEKPAHAPARPEAPVDSMLKDMATIILS
TFLLIGWVAFIITYPLSMHQQQQLQHQQFQKELEKIQLLQQQQQQLPFHPPGDTAQDGELLDTSGPYSESSGTSSPSTSPRASNHSLCSG
SSASKAGSSPSLEQDDGDEETSVVIVGKISFCPKDVLGHGAEGTIVYRGMFDNRDVAVKRILPECFSFADREVQLLRESDEHPNVIRYFC
TEKDRQFQYIAIELCAATLQEYVEQKDFAHLGLEPITLLQQTTSGLAHLHSLNIVHRDLKPHNILISMPNAHGKIKAMISDFGLCKKLAV
GRHSFSRRSGVPGTEGWIAPEMLSEDCKENPTYTVDIFSAGCVFYYVISEGSHPFGKSLQRQANILLGACSLDCLHPEKHEDVIARELIE
KMIAMDPQKRPSAKHVLKHPFFWSLEKQLQFFQDVSDRIEKESLDGPIVKQLERGGRAVVKMDWRENITVPLQTDLRKFRTYKGGSVRDL
O75460-2

Protein Functional Features

check buttonMain function of this protein. (from UniProt)
ERN1 (go to UniProt):O75460

check buttonRetention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at

download page

* Minus value of BPloci means that the break pointn is located before the CDS.
- Retained protein feature among the 13 regional features.
Accession_idSubsectionStartEndFuncitonal featureSplicing information
O75460Topological domain19443Note=Lumenal;Ontology_term=ECO:0000255;evidence=ECO:0000255Type=Substitution;Start=19;End=70
O75460Topological domain19443Note=Lumenal;Ontology_term=ECO:0000255;evidence=ECO:0000255Type=Deletion;Start=71;End=977
O75460Transmembrane444464Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255Type=Deletion;Start=71;End=977
O75460Topological domain465977Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255Type=Deletion;Start=71;End=977
O75460Domain571832Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159Type=Deletion;Start=71;End=977
O75460Domain835963Note=KEN;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00725Type=Deletion;Start=71;End=977
O75460Region410434Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-liteType=Deletion;Start=71;End=977
O75460Region491559Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-liteType=Deletion;Start=71;End=977
O75460Region906907Note=Interacts with hydroxy-aryl-aldehyde inhibitors;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:Q9EQY0Type=Deletion;Start=71;End=977
O75460Compositional bias511551Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-liteType=Deletion;Start=71;End=977


Gene Isoform Structures and Expression Levels for ERN1

check buttonGene structures of our canonical and alternative spliced genes of ERN1
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
gene isoform structure of ERN1

check button Expression levels of gene isoforms across GTEx.
gtex expression

check button Expression levels of gene isoforms across TCGA.
tcga expression


Protein Structures

check button PDB and CIF files of the predicted protein structures
* Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format.
3D view using mol* of O75460-1
3D view using mol* of O75460-2


pLDDT Score Distribution

check button pLDDT score distribution of the predicted protein structures from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.
pLDDT distribution across the protein length of O75460-1
all structure


Ramachandran Plot of Protein Structures


check button Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide.
Ramachandran plot of O75460-1
all structure
Ramachandran plot of O75460-2
all structure

Potential Active Site Information


check button The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite.
UniProt-idSite scoreSizeD scoreVolumeExposureEnclosureContactPhobicPhilicBalanceDon/AccResidues
O75460-11.0644261.111550.0170.5580.7310.90.7380.8220.8981.04376,77,78,79,81,83,95,99,101,102,105,159,161,179,18
1,182,183,184,186,187,188,191,193,195,196,197,198,
227,228,230,231,233,238,239,240,241,242,243,244,25
3,266,268,269,270,271,272,276,278,279,280,282,297,
298,299,309,367,383,384,385,386,387,388,389,390,39
1,392,393,394,395,396,397,399,400,401,403,404

Protein Structure and Feature Comparision


check button Protein Structure Comparision Using Template Modeling Scores (TM-score).
all structure

check button Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green)
3D view using mol* of O75460-1_O75460-1_6w3c_A.pdb

check button Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green)
3D view using mol* of O75460-1_6w3c_A_O75460-2.pdb

check button Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green)
3D view using mol* of O75460-1_O75460-2.pdb

check button Protein Feature Comparison of the protein sequendary structures among the protiens.
./stats/secondary_structure/figure/O75460-1_vs_O75460-2.png
all structure<

check button Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens.
./stats/relative_asa/O75460-1_vs_O75460-2.png
all structure<


Protein-Protein Interaction


check button Interactors from UniProt.
Accession_idSubsectionStartEndFuncitonal featureSplicing information


check button Interactors from STRING.
Gene nameInteractors


Related Drugs to ERN1


check button Drugs targeting this gene/protein.
(DrugBank)
UniProt accessionGene nameDrugBank IDDrug nameDrug groupActions
O75460ERN1DB12010Fostamatinibapproved, investigationalinhibitor
O75460ERN1DB07382N~2~-1H-benzimidazol-5-yl-N~4~-(3-cyclopropyl-1H-pyrazol-5-yl)pyrimidine-2,4-diamineexperimental

Related Diseases to ERN1


check button Previous studies relating to the alternative splicing of ERN1 and disease information from the MeSH term (PubMed)
GenePMIDTitleAbstractMeSH IDMeSH term


Clinically important variants in ERN1


check button (ClinVar, 04/20/2024)
accession_iduniprot_idgene_nameTypeVariantClinical_significance