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UniProtKB - O75460 (ERN1_HUMAN)

Entry version 199 (17 Jun 2020)
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:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<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

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). Acts as an upstream signal for ER stress-induced GORASP2-mediated unconventional (ER/Golgi-independent) trafficking of CFTR to cell membrane by modulating the expression and localization of SEC16A (PubMed:21884936, PubMed:28067262).1 Publication7 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the 'Function' section provides information relevant to cofactors. A cofactor is any non-protein substance required for a protein to be catalytically active. Some cofactors are inorganic, such as the metal atoms zinc, iron, and copper in various oxidation states. Others, such as most vitamins, are organic.<p><a href='/help/cofactor' target='_top'>More...</a></p>Cofactori

Mg2+2 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>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 keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei599ATPPROSITE-ProRule annotationCombined sources2 Publications1
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei688Proton acceptorPROSITE-ProRule annotationBy similarity1
Binding sitei711ATPCombined sources1 Publication1
Binding sitei892Hydroxy-aryl-aldehyde inhibitorBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes a region in the protein which binds nucleotide phosphates. It always involves more than one amino acid and includes all residues involved in nucleotide-binding.<p><a href='/help/np_bind' target='_top'>More...</a></p>Nucleotide bindingi577 – 585ATPPROSITE-ProRule annotationBy similarity9
Nucleotide bindingi643 – 645ATPCombined sources1 Publication3
Nucleotide bindingi690 – 693ATPCombined sources1 Publication4

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionHydrolase, Kinase, Multifunctional enzyme, Serine/threonine-protein kinase, Transferase
Biological processApoptosis, Transcription, Transcription regulation, Unfolded protein response
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

More...Reactomei		R-HSA-381070 IRE1alpha activates chaperones

SignaLink: a signaling pathway resource with multi-layered regulatory networks

More...SignaLinki		O75460

SIGNOR Signaling Network Open Resource

More...SIGNORi		O75460

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>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)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:ERN1Imported
Synonyms:IRE1Imported
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 17

Organism-specific databases

Eukaryotic Pathogen Database Resources

More...EuPathDBi		HostDB:ENSG00000178607.15

Human Gene Nomenclature Database

More...HGNCi		HGNC:3449 ERN1

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		604033 gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_O75460

<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

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.<p><a href='/help/topo_dom' target='_top'>More...</a></p>Topological domaini19 – 443LumenalSequence analysisAdd BLAST425
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>Transmembranei444 – 464HelicalSequence analysisAdd BLAST21
Topological domaini465 – 977CytoplasmicSequence analysisAdd BLAST513

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

<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

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi105Q → E: Impaired ability to homodimerize. 1 Publication1
Mutagenesisi109C → S: No effect on dimerization. 1 Publication1
Mutagenesisi123D → P: Abolishes ability to homodimerize. 1 Publication1
Mutagenesisi125W → A: Abolishes ability to homodimerize. 1 Publication1
Mutagenesisi148C → 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 Publications1
Mutagenesisi332C → S: No effect on dimerization. Weakens dimer; when associated with S-148. 1 Publication1
Mutagenesisi599K → A: Loss of autophosphorylation and of endoribonuclease activity. Inhibition of growth arrest. 2 Publications1

Organism-specific databases

DisGeNET

More...DisGeNETi		2081

Open Targets

More...OpenTargetsi		ENSG00000178607

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA27861

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		O75460 Tchem

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...ChEMBLi		CHEMBL1163101

Drug and drug target database

More...DrugBanki		DB12010 Fostamatinib
DB07382 N~2~-1H-benzimidazol-5-yl-N~4~-(3-cyclopropyl-1H-pyrazol-5-yl)pyrimidine-2,4-diamine

DrugCentral

More...DrugCentrali		O75460

IUPHAR/BPS Guide to PHARMACOLOGY

More...GuidetoPHARMACOLOGYi		2020

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		ERN1

<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

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section denotes the presence of an N-terminal signal peptide.<p><a href='/help/signal' target='_top'>More...</a></p>Signal peptidei1 – 18Sequence analysisAdd BLAST18
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_000002432719 – 977Serine/threonine-protein kinase/endoribonuclease IRE1Add BLAST959

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>Glycosylationi176N-linked (GlcNAc...) asparagineSequence analysis1
<p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei973PhosphothreonineCombined sources1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>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

Encyclopedia of Proteome Dynamics

More...EPDi		O75460

jPOST - Japan Proteome Standard Repository/Database

More...jPOSTi		O75460

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		O75460

MaxQB - The MaxQuant DataBase

More...MaxQBi		O75460

PaxDb, a database of protein abundance averages across all three domains of life

More...PaxDbi		O75460

PeptideAtlas

More...PeptideAtlasi		O75460

PRoteomics IDEntifications database

More...PRIDEi		O75460

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		50021 [O75460-1]
50022 [O75460-2]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		O75460

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...PhosphoSitePlusi		O75460

<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

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

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

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000178607 Expressed in adrenal gland and 179 other tissues

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		O75460 HS

Organism-specific databases

Human Protein Atlas

More...HPAi		ENSG00000178607 Low tissue specificity

<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

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>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).

Interacts with RNF13 (PubMed:23378536).

Interacts with LACC1 (PubMed:31875558).

By similarity7 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Hide details

GO - Molecular functioni

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...BioGRIDi		108391, 38 interactors

Database of interacting proteins

More...DIPi		DIP-31711N

Protein interaction database and analysis system

More...IntActi		O75460, 26 interactors

Molecular INTeraction database

More...MINTi		O75460

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000401445

Chemistry databases

BindingDB database of measured binding affinities

More...BindingDBi		O75460

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		O75460 protein

<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

Secondary structure

1977
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...SMRi		O75460

Database of comparative protein structure models

More...ModBasei		Search...

Protein Data Bank in Europe - Knowledge Base

More...PDBe-KBi		Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

More...EvolutionaryTracei		O75460

<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

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family%5Fand%5Fdomains%5Fsection">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini571 – 832Protein kinasePROSITE-ProRule annotationAdd BLAST262
Domaini835 – 963KENPROSITE-ProRule annotationAdd BLAST129

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni906 – 907Hydroxy-aryl-aldehyde inhibitor bindingBy similarity2

<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

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

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		KOG1027 Eukaryota
COG0515 LUCA

Ensembl GeneTree

More...GeneTreei		ENSGT00940000159761

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...HOGENOMi		CLU_004875_1_1_1

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		O75460

KEGG Orthology (KO)

More...KOi		K08852

Identification of Orthologs from Complete Genome Data

More...OMAi		IADDPPI

Database of Orthologous Groups

More...OrthoDBi		1019877at2759

Database for complete collections of gene phylogenies

More...PhylomeDBi		O75460

TreeFam database of animal gene trees

More...TreeFami		TF313986

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

More...Gene3Di		1.20.1440.180, 1 hit
2.130.10.10, 1 hit

Integrated resource of protein families, domains and functional sites

More...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

Simple Modular Architecture Research Tool; a protein domain database

More...SMARTi		View protein in SMART
SM00564 PQQ, 5 hits
SM00580 PUG, 1 hit
SM00220 S_TKc, 1 hit

Superfamily database of structural and functional annotation

More...SUPFAMi		SSF50998 SSF50998, 1 hit
SSF56112 SSF56112, 1 hit

PROSITE; a protein domain and family database

More...PROSITEi		View protein in PROSITE
PS51392 KEN, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (2)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 <p>This subsection of the 'Sequence' section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform. This section is only present in reviewed entries, i.e. in UniProtKB/Swiss-Prot.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: O75460-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali 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
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> 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)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti190 – 191DV → EG in AAC25991 (PubMed:9637683).Curated2
Sequence conflicti768I → V in AAC25991 (PubMed:9637683).Curated1
Sequence conflicti816D → G in BAF85092 (PubMed:14702039).Curated1
Sequence conflicti824 – 825KH → ND in AAC25991 (PubMed:9637683).Curated2
Sequence conflicti880V → D in AAC25991 (PubMed:9637683).Curated1
Sequence conflicti904M → T in BAF85092 (PubMed:14702039).Curated1
Sequence conflicti924S → T in AAC25991 (PubMed:9637683).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_040488244N → S in a renal clear cell carcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs1397145500Ensembl.1
Natural variantiVAR_040489418V → M1 PublicationCorresponds to variant dbSNP:rs55869215Ensembl.1
Natural variantiVAR_040490474L → R in a lung adenocarcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs186305118Ensembl.1
Natural variantiVAR_040491635R → W in a gastric adenocarcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs146710304Ensembl.1
Natural variantiVAR_040492700N → S1 PublicationCorresponds to variant dbSNP:rs918253870Ensembl.1
Natural variantiVAR_040493769S → F in a glioblastoma multiforme sample; somatic mutation. 1 Publication1
Natural variantiVAR_040494830P → L in an ovarian serous carcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs1279653488Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_03458219 – 70IFGST…THVEE → VSDRGAWGGGQLATAGSGPG QRRGAGAGVRAGSATAAARC PVSPAVGGSGRA in isoform 2. 2 PublicationsAdd BLAST52
Alternative sequenceiVSP_03458371 – 977Missing in isoform 2. 2 PublicationsAdd BLAST907

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...EMBLi

GenBank nucleotide sequence database

More...GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...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]

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		ENST00000433197; ENSP00000401445; ENSG00000178607 [O75460-1]
ENST00000606895; ENSP00000475519; ENSG00000178607 [O75460-2]

Database of genes from NCBI RefSeq genomes

More...GeneIDi		2081

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:2081

UCSC genome browser

More...UCSCi		uc002jdz.3 human [O75460-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>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]

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 entryMethodResolution (Å)ChainPositionsPDBsum
2HZ6X-ray3.10A24-390[»]
3P23X-ray2.70A/B/C/D547-977[»]
4U6RX-ray2.50A547-977[»]
4YZ9X-ray2.46A/B/C562-966[»]
4YZCX-ray2.49A/B562-966[»]
4YZDX-ray3.10A/B/C562-966[»]
4Z7GX-ray2.60A/B562-977[»]
4Z7HX-ray2.90A/B562-977[»]
5HGIX-ray2.58A547-977[»]
6HV0X-ray2.73A562-977[»]
6HX1X-ray2.14A562-964[»]
6SHCX-ray3.55A24-390[»]
6URCX-ray2.20A/B547-977[»]
SMRiO75460
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGRIDi108391, 38 interactors
DIPiDIP-31711N
IntActiO75460, 26 interactors
MINTiO75460
STRINGi9606.ENSP00000401445

Chemistry databases

BindingDBiO75460
ChEMBLiCHEMBL1163101
DrugBankiDB12010 Fostamatinib
DB07382 N~2~-1H-benzimidazol-5-yl-N~4~-(3-cyclopropyl-1H-pyrazol-5-yl)pyrimidine-2,4-diamine
DrugCentraliO75460
GuidetoPHARMACOLOGYi2020

PTM databases

iPTMnetiO75460
PhosphoSitePlusiO75460

Polymorphism and mutation databases

BioMutaiERN1

Proteomic databases

EPDiO75460
jPOSTiO75460
MassIVEiO75460
MaxQBiO75460
PaxDbiO75460
PeptideAtlasiO75460
PRIDEiO75460
ProteomicsDBi50021 [O75460-1]
50022 [O75460-2]

Protocols and materials databases

Antibodypedia a portal for validated antibodies

More...Antibodypediai		4011 667 antibodies

The DNASU plasmid repository

More...DNASUi		2081

Genome annotation databases

EnsembliENST00000433197; ENSP00000401445; ENSG00000178607 [O75460-1]
ENST00000606895; ENSP00000475519; ENSG00000178607 [O75460-2]
GeneIDi2081
KEGGihsa:2081
UCSCiuc002jdz.3 human [O75460-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		2081
DisGeNETi2081
EuPathDBiHostDB:ENSG00000178607.15

GeneCards: human genes, protein and diseases

More...GeneCardsi		ERN1
HGNCiHGNC:3449 ERN1
HPAiENSG00000178607 Low tissue specificity
MIMi604033 gene
neXtProtiNX_O75460
OpenTargetsiENSG00000178607
PharmGKBiPA27861

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

eggNOGiKOG1027 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00940000159761
HOGENOMiCLU_004875_1_1_1
InParanoidiO75460
KOiK08852
OMAiIADDPPI
OrthoDBi1019877at2759
PhylomeDBiO75460
TreeFamiTF313986

Enzyme and pathway databases

ReactomeiR-HSA-381070 IRE1alpha activates chaperones
SignaLinkiO75460
SIGNORiO75460

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...BioGRID-ORCSi		2081 4 hits in 816 CRISPR screens

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...ChiTaRSi		ERN1 human
EvolutionaryTraceiO75460

The Gene Wiki collection of pages on human genes and proteins

More...GeneWikii		ERN1

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...GenomeRNAii		2081
PharosiO75460 Tchem

Protein Ontology

More...PROi		PR:O75460
RNActiO75460 protein

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000178607 Expressed in adrenal gland and 179 other tissues
GenevisibleiO75460 HS

Family and domain databases

Gene3Di1.20.1440.180, 1 hit
2.130.10.10, 1 hit
InterProiView 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
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PF06479 Ribonuc_2-5A, 1 hit
SMARTiView protein in SMART
SM00564 PQQ, 5 hits
SM00580 PUG, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF50998 SSF50998, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS51392 KEN, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...ProtoNeti		Search...

MobiDB: a database of protein disorder and mobility annotations

More...MobiDBi		Search...

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

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiERN1_HUMAN
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: O75460
Secondary accession number(s): A1L457
, A8K8N8, A8MXS7, Q59EE2
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 16, 2004
Last sequence update: July 1, 2008
Last modified: June 17, 2020
This is version 199 of the entry and version 2 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>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.

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Reference proteome

Documents

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