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Entry version 191 (12 Aug 2020)
Sequence version 2 (20 Jun 2003)
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Protein

Eukaryotic translation initiation factor 2-alpha kinase 1

Gene

EIF2AK1

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

Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to various stress conditions (PubMed:32132706, PubMed:32132707). Key activator of the integrated stress response (ISR) required for adaptation to various stress, such as heme deficiency, oxidative stress, osmotic shock, mitochondrial dysfunction and heat shock (PubMed:32132706, PubMed:32132707). EIF2S1/eIF-2-alpha phosphorylation in response to stress converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, leading to a global attenuation of cap-dependent translation, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming (PubMed:32132706, PubMed:32132707). Acts as a key sensor of heme-deficiency: in normal conditions, binds hemin via a cysteine thiolate and histidine nitrogenous coordination, leading to inhibit the protein kinase activity (By similarity). This binding occurs with moderate affinity, allowing it to sense the heme concentration within the cell: heme depletion relieves inhibition and stimulates kinase activity, activating the ISR (By similarity). Thanks to this unique heme-sensing capacity, plays a crucial role to shut off protein synthesis during acute heme-deficient conditions (By similarity). In red blood cells (RBCs), controls hemoglobin synthesis ensuring a coordinated regulation of the synthesis of its heme and globin moieties (By similarity). It thereby plays an essential protective role for RBC survival in anemias of iron deficiency (By similarity). Similarly, in hepatocytes, involved in heme-mediated translational control of CYP2B and CYP3A and possibly other hepatic P450 cytochromes (By similarity). May also regulate endoplasmic reticulum (ER) stress during acute heme-deficient conditions (By similarity). Also activates the ISR in response to mitochondrial dysfunction: HRI/EIF2AK1 protein kinase activity is activated upon binding to the processed form of DELE1 (S-DELE1), thereby promoting the ATF4-mediated reprogramming (PubMed:32132706, PubMed:32132707).By similarity2 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 <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

In normal conditions, the protein kinase activity is inhibited; inhibition is relieved by various stress conditions (By similarity). Inhibited by heme: in presence of heme, forms a disulfide-linked inactive homodimer (By similarity). Heme depletion relieves inhibition and stimulates kinase activity by autophosphorylation. Inhibited by the heme metabolites biliverdin and bilirubin (By similarity). Induced by oxidative stress generated by arsenite treatment. Binding of nitric oxide (NO) to the heme iron in the N-terminal heme-binding domain activates the kinase activity, while binding of carbon monoxide (CO) suppresses kinase activity (By similarity). Protein kinase activity is also activated upon binding to the processed form of DELE1 (S-DELE1): interaction with S-DELE1 takes place in response to mitochondrial stress and triggers the integrated stress response (ISR) (PubMed:32132706, PubMed:32132707).By similarity2 Publications

<p>This subsection of the 'Function' section describes biophysical and chemical properties, such as maximal absorption, kinetic parameters, pH dependence, redox potentials and temperature dependence.<p><a href='/help/biophysicochemical_properties' target='_top'>More...</a></p>Kineticsi

  1. KM=3.88 µM for eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) (in absence of DELE1 and in absence of hemin)1 Publication
  2. KM=1.13 µM for eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) (in presence of DELE1 and in absence of hemin)1 Publication
  3. KM=71.91 µM for eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) (in absence of DELE1 and in presence of hemin)1 Publication
  4. KM=6.56 µM for eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) (in presence of DELE1 and in presence of hemin)1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections ('Function', 'PTM / Processing', 'Pathology and Biotech') according to its content.<p><a href='/help/site' target='_top'>More...</a></p>Sitei80Heme-bindingBy similarity1
    <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 sitei196ATPPROSITE-ProRule annotation1
    <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 sitei442Proton acceptorPROSITE-ProRule annotation1

    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 bindingi173 – 181ATPPROSITE-ProRule annotation9

    <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

    GO - Biological processi

    <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 functionKinase, Protein synthesis inhibitor, Serine/threonine-protein kinase, Transferase
    LigandATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    Pathway Commons web resource for biological pathway data

    More...
    PathwayCommonsi
    Q9BQI3

    Reactome - a knowledgebase of biological pathways and processes

    More...
    Reactomei
    R-HSA-9648895, Response of EIF2AK1 (HRI) to heme deficiency

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

    More...
    SignaLinki
    Q9BQI3

    SIGNOR Signaling Network Open Resource

    More...
    SIGNORi
    Q9BQI3

    <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:
    Eukaryotic translation initiation factor 2-alpha kinase 1Curated (EC:2.7.11.11 Publication)
    Alternative name(s):
    Heme-controlled repressor
    Short name:
    HCR
    Heme-regulated eukaryotic initiation factor eIF-2-alpha kinase1 Publication
    Heme-regulated inhibitor1 Publication
    Short name:
    hHRI1 Publication
    Hemin-sensitive initiation factor 2-alpha kinase1 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:EIF2AK1Imported
    Synonyms:HRI1 Publication, KIAA13691 Publication
    ORF Names:PRO1362
    <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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    <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 7

    Organism-specific databases

    Eukaryotic Pathogen Database Resources

    More...
    EuPathDBi
    HostDB:ENSG00000086232.12

    Human Gene Nomenclature Database

    More...
    HGNCi
    HGNC:24921, EIF2AK1

    neXtProt; the human protein knowledge platform

    More...
    neXtProti
    NX_Q9BQI3

    <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

    <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

    Organism-specific databases

    DisGeNET

    More...
    DisGeNETi
    27102

    Open Targets

    More...
    OpenTargetsi
    ENSG00000086232

    The Pharmacogenetics and Pharmacogenomics Knowledge Base

    More...
    PharmGKBi
    PA134919097

    Miscellaneous databases

    Pharos NIH Druggable Genome Knowledgebase

    More...
    Pharosi
    Q9BQI3, Tchem

    Chemistry databases

    ChEMBL database of bioactive drug-like small molecules

    More...
    ChEMBLi
    CHEMBL6029

    Drug and drug target database

    More...
    DrugBanki
    DB12010, Fostamatinib

    DrugCentral

    More...
    DrugCentrali
    Q9BQI3

    IUPHAR/BPS Guide to PHARMACOLOGY

    More...
    GuidetoPHARMACOLOGYi
    2015

    Polymorphism and mutation databases

    BioMuta curated single-nucleotide variation and disease association database

    More...
    BioMutai
    EIF2AK1

    Domain mapping of disease mutations (DMDM)

    More...
    DMDMi
    32172458

    <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 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_00000859411 – 630Eukaryotic translation initiation factor 2-alpha kinase 1Add BLAST630

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <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 residuei285PhosphothreonineBy similarity1
    Modified residuei486Phosphothreonine; by autocatalysisBy similarity1
    Modified residuei488Phosphothreonine; by autocatalysisBy similarity1
    Modified residuei493PhosphothreonineBy similarity1

    <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

    Activated by autophosphorylation; phosphorylated predominantly on serine and threonine residues, but also on tyrosine residues. Autophosphorylation at Thr-488 is required for kinase activation. The active autophosphorylated form apparently is largely refractory to cellular heme fluctuations.By similarity

    Keywords - PTMi

    Disulfide bond, Phosphoprotein

    Proteomic databases

    Encyclopedia of Proteome Dynamics

    More...
    EPDi
    Q9BQI3

    jPOST - Japan Proteome Standard Repository/Database

    More...
    jPOSTi
    Q9BQI3

    MassIVE - Mass Spectrometry Interactive Virtual Environment

    More...
    MassIVEi
    Q9BQI3

    MaxQB - The MaxQuant DataBase

    More...
    MaxQBi
    Q9BQI3

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

    More...
    PaxDbi
    Q9BQI3

    PeptideAtlas

    More...
    PeptideAtlasi
    Q9BQI3

    PRoteomics IDEntifications database

    More...
    PRIDEi
    Q9BQI3

    ProteomicsDB: a multi-organism proteome resource

    More...
    ProteomicsDBi
    78682 [Q9BQI3-1]
    78683 [Q9BQI3-2]

    PTM databases

    iPTMnet integrated resource for PTMs in systems biology context

    More...
    iPTMneti
    Q9BQI3

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

    More...
    PhosphoSitePlusi
    Q9BQI3

    <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

    Expressed predominantly in erythroid cells (PubMed:20071449). Expressed at much lower levels in hepatocytes (at protein level) (PubMed:20071449).1 Publication

    Gene expression databases

    Bgee dataBase for Gene Expression Evolution

    More...
    Bgeei
    ENSG00000086232, Expressed in trabecular bone tissue and 240 other tissues

    ExpressionAtlas, Differential and Baseline Expression

    More...
    ExpressionAtlasi
    Q9BQI3, baseline and differential

    Genevisible search portal to normalized and curated expression data from Genevestigator

    More...
    Genevisiblei
    Q9BQI3, HS

    Organism-specific databases

    Human Protein Atlas

    More...
    HPAi
    ENSG00000086232, 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

    Synthesized in an inactive form that binds to the N-terminal domain of CDC37 (PubMed:11036079). Has to be associated with a multiprotein complex containing Hsp90, CDC37 and PPP5C for maturation and activation by autophosphorylation (PubMed:11036079). The phosphatase PPP5C modulates this activation (PubMed:11036079). Homodimer; homodimerizes in presence of heme, forming a disulfide-linked inactive homodimer (By similarity).

    Interacts with DELE1; binds to the processed form of DELE1 (S-DELE1) in response to mitochondrial stress, leading to activate its protein kinase activity and trigger the integrated stress response (ISR) (PubMed:32132706, PubMed:32132707).

    By similarity3 Publications

    <p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">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

    GO - Molecular functioni

    Protein-protein interaction databases

    The Biological General Repository for Interaction Datasets (BioGRID)

    More...
    BioGRIDi
    118002, 16 interactors

    Protein interaction database and analysis system

    More...
    IntActi
    Q9BQI3, 11 interactors

    STRING: functional protein association networks

    More...
    STRINGi
    9606.ENSP00000199389

    Chemistry databases

    BindingDB database of measured binding affinities

    More...
    BindingDBi
    Q9BQI3

    Miscellaneous databases

    RNAct, Protein-RNA interaction predictions for model organisms.

    More...
    RNActi
    Q9BQI3, protein

    <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>Domaini167 – 583Protein kinasePROSITE-ProRule annotationAdd BLAST417
    <p>This subsection of the 'Family and Domains' section indicates the positions and types of repeated sequence motifs or repeated domains within the protein.<p><a href='/help/repeat' target='_top'>More...</a></p>Repeati410 – 415HRM 16
    Repeati552 – 557HRM 26

    <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. GCN2 subfamily.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat

    Phylogenomic databases

    evolutionary genealogy of genes: Non-supervised Orthologous Groups

    More...
    eggNOGi
    KOG1035, Eukaryota

    Ensembl GeneTree

    More...
    GeneTreei
    ENSGT00940000157605

    The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

    More...
    HOGENOMi
    CLU_000288_134_1_1

    InParanoid: Eukaryotic Ortholog Groups

    More...
    InParanoidi
    Q9BQI3

    KEGG Orthology (KO)

    More...
    KOi
    K16194

    Identification of Orthologs from Complete Genome Data

    More...
    OMAi
    KATRRDC

    Database of Orthologous Groups

    More...
    OrthoDBi
    124090at2759

    Database for complete collections of gene phylogenies

    More...
    PhylomeDBi
    Q9BQI3

    TreeFam database of animal gene trees

    More...
    TreeFami
    TF329383

    Family and domain databases

    Integrated resource of protein families, domains and functional sites

    More...
    InterProi
    View protein in InterPro
    IPR011009, Kinase-like_dom_sf
    IPR000719, Prot_kinase_dom
    IPR017441, Protein_kinase_ATP_BS
    IPR008271, Ser/Thr_kinase_AS

    Pfam protein domain database

    More...
    Pfami
    View protein in Pfam
    PF00069, Pkinase, 2 hits

    Simple Modular Architecture Research Tool; a protein domain database

    More...
    SMARTi
    View protein in SMART
    SM00220, S_TKc, 1 hit

    Superfamily database of structural and functional annotation

    More...
    SUPFAMi
    SSF56112, SSF56112, 1 hit

    PROSITE; a protein domain and family database

    More...
    PROSITEi
    View protein in PROSITE
    PS00107, PROTEIN_KINASE_ATP, 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.

    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

    This entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

    Isoform 1 (identifier: Q9BQI3-1) [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
    MQGGNSGVRK REEEGDGAGA VAAPPAIDFP AEGPDPEYDE SDVPAEIQVL
    60 70 80 90 100
    KEPLQQPTFP FAVANQLLLV SLLEHLSHVH EPNPLRSRQV FKLLCQTFIK
    110 120 130 140 150
    MGLLSSFTCS DEFSSLRLHH NRAITHLMRS AKERVRQDPC EDISRIQKIR
    160 170 180 190 200
    SREVALEAQT SRYLNEFEEL AILGKGGYGR VYKVRNKLDG QYYAIKKILI
    210 220 230 240 250
    KGATKTVCMK VLREVKVLAG LQHPNIVGYH TAWIEHVHVI QPRADRAAIE
    260 270 280 290 300
    LPSLEVLSDQ EEDREQCGVK NDESSSSSII FAEPTPEKEK RFGESDTENQ
    310 320 330 340 350
    NNKSVKYTTN LVIRESGELE STLELQENGL AGLSASSIVE QQLPLRRNSH
    360 370 380 390 400
    LEESFTSTEE SSEENVNFLG QTEAQYHLML HIQMQLCELS LWDWIVERNK
    410 420 430 440 450
    RGREYVDESA CPYVMANVAT KIFQELVEGV FYIHNMGIVH RDLKPRNIFL
    460 470 480 490 500
    HGPDQQVKIG DFGLACTDIL QKNTDWTNRN GKRTPTHTSR VGTCLYASPE
    510 520 530 540 550
    QLEGSEYDAK SDMYSLGVVL LELFQPFGTE MERAEVLTGL RTGQLPESLR
    560 570 580 590 600
    KRCPVQAKYI QHLTRRNSSQ RPSAIQLLQS ELFQNSGNVN LTLQMKIIEQ
    610 620 630
    EKEIAELKKQ LNLLSQDKGV RDDGKDGGVG
    Length:630
    Mass (Da):71,106
    Last modified:June 20, 2003 - 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:iD63021651806620B
    GO
    Isoform 2 (identifier: Q9BQI3-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         244-244: Missing.

    Show »
    Length:629
    Mass (Da):71,035
    Checksum:iB90159795D580809
    GO

    <p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

    There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    H7C033H7C033_HUMAN
    Eukaryotic translation initiation f...
    EIF2AK1
    72Annotation score:

    Annotation score:1 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>
    C9J7U7C9J7U7_HUMAN
    Eukaryotic translation initiation f...
    EIF2AK1
    164Annotation score:

    Annotation score:1 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>
    F8WCM0F8WCM0_HUMAN
    Eukaryotic translation initiation f...
    EIF2AK1
    81Annotation score:

    Annotation score:1 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>

    <p>This subsection of the 'Sequence' section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

    The sequence AAF70289 differs from that shown. Reason: Frameshift.Curated
    The sequence AAF71057 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated
    The sequence BAA92607 differs from that shown. Reason: Erroneous initiation. Extended N-terminus.Curated

    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 conflicti2Q → L in AAF18391 (Ref. 3) Curated1
    Sequence conflicti4G → D in BAF83016 (PubMed:14702039).Curated1
    Sequence conflicti24 – 32PPAIDFPAE → RRHRLSRR in AAF70289 (PubMed:11101152).Curated9
    Sequence conflicti137Q → R in AAF70289 (PubMed:11101152).Curated1
    Sequence conflicti149I → T in BAF83016 (PubMed:14702039).Curated1
    Sequence conflicti171A → V in AAF18391 (Ref. 3) Curated1
    Sequence conflicti206T → P in AAF66736 (PubMed:12391722).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_040466117R → T1 PublicationCorresponds to variant dbSNP:rs34889754Ensembl.1
    Natural variantiVAR_040467132K → T1 PublicationCorresponds to variant dbSNP:rs34851195Ensembl.1
    Natural variantiVAR_040468134R → K1 PublicationCorresponds to variant dbSNP:rs55744865Ensembl.1
    Natural variantiVAR_040469139P → S1 PublicationCorresponds to variant dbSNP:rs55963745Ensembl.1
    Natural variantiVAR_040470145R → H1 PublicationCorresponds to variant dbSNP:rs55971369Ensembl.1
    Natural variantiVAR_040471202G → S in a lung adenocarcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs1216460058Ensembl.1
    Natural variantiVAR_040472292F → L1 PublicationCorresponds to variant dbSNP:rs55982710Ensembl.1
    Natural variantiVAR_040473319L → H1 PublicationCorresponds to variant dbSNP:rs34909691Ensembl.1
    Natural variantiVAR_015732558K → R3 PublicationsCorresponds to variant dbSNP:rs2640Ensembl.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_007589244Missing in isoform 2. 3 Publications1

    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
    AF255050 mRNA Translation: AAF70289.1 Frameshift.
    AF100784 mRNA Translation: AAP97223.1
    AF181071 mRNA Translation: AAF18391.1
    AB037790 mRNA Translation: BAA92607.1 Different initiation.
    AF183414 mRNA Translation: AAG09683.1
    AL136563 mRNA Translation: CAB66498.1
    AF147094 mRNA Translation: AAF66736.1
    AK075192 mRNA Translation: BAC11461.1
    AK290327 mRNA Translation: BAF83016.1
    AL834494 mRNA Translation: CAD39152.1
    CH236963 Genomic DNA Translation: EAL23714.1
    CH878731 Genomic DNA Translation: EAW55049.1
    BC006524 mRNA Translation: AAH06524.1
    AF116634 mRNA Translation: AAF71057.1 Different initiation.

    The Consensus CDS (CCDS) project

    More...
    CCDSi
    CCDS5345.1 [Q9BQI3-1]

    NCBI Reference Sequences

    More...
    RefSeqi
    NP_001127807.1, NM_001134335.1 [Q9BQI3-2]
    NP_055228.2, NM_014413.3 [Q9BQI3-1]

    Genome annotation databases

    Ensembl eukaryotic genome annotation project

    More...
    Ensembli
    ENST00000199389; ENSP00000199389; ENSG00000086232 [Q9BQI3-1]

    Database of genes from NCBI RefSeq genomes

    More...
    GeneIDi
    27102

    KEGG: Kyoto Encyclopedia of Genes and Genomes

    More...
    KEGGi
    hsa:27102

    UCSC genome browser

    More...
    UCSCi
    uc003spp.4, human [Q9BQI3-1]

    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
    AF255050 mRNA Translation: AAF70289.1 Frameshift.
    AF100784 mRNA Translation: AAP97223.1
    AF181071 mRNA Translation: AAF18391.1
    AB037790 mRNA Translation: BAA92607.1 Different initiation.
    AF183414 mRNA Translation: AAG09683.1
    AL136563 mRNA Translation: CAB66498.1
    AF147094 mRNA Translation: AAF66736.1
    AK075192 mRNA Translation: BAC11461.1
    AK290327 mRNA Translation: BAF83016.1
    AL834494 mRNA Translation: CAD39152.1
    CH236963 Genomic DNA Translation: EAL23714.1
    CH878731 Genomic DNA Translation: EAW55049.1
    BC006524 mRNA Translation: AAH06524.1
    AF116634 mRNA Translation: AAF71057.1 Different initiation.
    CCDSiCCDS5345.1 [Q9BQI3-1]
    RefSeqiNP_001127807.1, NM_001134335.1 [Q9BQI3-2]
    NP_055228.2, NM_014413.3 [Q9BQI3-1]

    3D structure databases

    Database of comparative protein structure models

    More...
    ModBasei
    Search...

    SWISS-MODEL Interactive Workspace

    More...
    SWISS-MODEL-Workspacei
    Submit a new modelling project...

    Protein-protein interaction databases

    BioGRIDi118002, 16 interactors
    IntActiQ9BQI3, 11 interactors
    STRINGi9606.ENSP00000199389

    Chemistry databases

    BindingDBiQ9BQI3
    ChEMBLiCHEMBL6029
    DrugBankiDB12010, Fostamatinib
    DrugCentraliQ9BQI3
    GuidetoPHARMACOLOGYi2015

    PTM databases

    iPTMnetiQ9BQI3
    PhosphoSitePlusiQ9BQI3

    Polymorphism and mutation databases

    BioMutaiEIF2AK1
    DMDMi32172458

    Proteomic databases

    EPDiQ9BQI3
    jPOSTiQ9BQI3
    MassIVEiQ9BQI3
    MaxQBiQ9BQI3
    PaxDbiQ9BQI3
    PeptideAtlasiQ9BQI3
    PRIDEiQ9BQI3
    ProteomicsDBi78682 [Q9BQI3-1]
    78683 [Q9BQI3-2]

    Protocols and materials databases

    Antibodypedia a portal for validated antibodies

    More...
    Antibodypediai
    11579, 294 antibodies

    The DNASU plasmid repository

    More...
    DNASUi
    27102

    Genome annotation databases

    EnsembliENST00000199389; ENSP00000199389; ENSG00000086232 [Q9BQI3-1]
    GeneIDi27102
    KEGGihsa:27102
    UCSCiuc003spp.4, human [Q9BQI3-1]

    Organism-specific databases

    Comparative Toxicogenomics Database

    More...
    CTDi
    27102
    DisGeNETi27102
    EuPathDBiHostDB:ENSG00000086232.12

    GeneCards: human genes, protein and diseases

    More...
    GeneCardsi
    EIF2AK1
    HGNCiHGNC:24921, EIF2AK1
    HPAiENSG00000086232, Low tissue specificity
    neXtProtiNX_Q9BQI3
    OpenTargetsiENSG00000086232
    PharmGKBiPA134919097

    Human Unidentified Gene-Encoded large proteins database

    More...
    HUGEi
    Search...

    GenAtlas: human gene database

    More...
    GenAtlasi
    Search...

    Phylogenomic databases

    eggNOGiKOG1035, Eukaryota
    GeneTreeiENSGT00940000157605
    HOGENOMiCLU_000288_134_1_1
    InParanoidiQ9BQI3
    KOiK16194
    OMAiKATRRDC
    OrthoDBi124090at2759
    PhylomeDBiQ9BQI3
    TreeFamiTF329383

    Enzyme and pathway databases

    PathwayCommonsiQ9BQI3
    ReactomeiR-HSA-9648895, Response of EIF2AK1 (HRI) to heme deficiency
    SignaLinkiQ9BQI3
    SIGNORiQ9BQI3

    Miscellaneous databases

    BioGRID ORCS database of CRISPR phenotype screens

    More...
    BioGRID-ORCSi
    27102, 11 hits in 901 CRISPR screens

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

    More...
    ChiTaRSi
    EIF2AK1, human

    The Gene Wiki collection of pages on human genes and proteins

    More...
    GeneWikii
    EIF2AK1

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

    More...
    GenomeRNAii
    27102
    PharosiQ9BQI3, Tchem

    Protein Ontology

    More...
    PROi
    PR:Q9BQI3
    RNActiQ9BQI3, protein

    Gene expression databases

    BgeeiENSG00000086232, Expressed in trabecular bone tissue and 240 other tissues
    ExpressionAtlasiQ9BQI3, baseline and differential
    GenevisibleiQ9BQI3, HS

    Family and domain databases

    InterProiView protein in InterPro
    IPR011009, Kinase-like_dom_sf
    IPR000719, Prot_kinase_dom
    IPR017441, Protein_kinase_ATP_BS
    IPR008271, Ser/Thr_kinase_AS
    PfamiView protein in Pfam
    PF00069, Pkinase, 2 hits
    SMARTiView protein in SMART
    SM00220, S_TKc, 1 hit
    SUPFAMiSSF56112, SSF56112, 1 hit
    PROSITEiView protein in PROSITE
    PS00107, PROTEIN_KINASE_ATP, 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 nameiE2AK1_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: Q9BQI3
    Secondary accession number(s): A8K2R2
    , Q549K6, Q8NBW3, Q9HC02, Q9NYE0, Q9P0V6, Q9P1J5, Q9P2H8, Q9UHG4
    <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: July 11, 2001
    Last sequence update: June 20, 2003
    Last modified: August 12, 2020
    This is version 191 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

    Reference proteome

    Documents

    1. Human chromosome 7
      Human chromosome 7: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. SIMILARITY comments
      Index of protein domains and families
    5. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
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