Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Entry version 165 (17 Jun 2020)
Sequence version 2 (05 Apr 2011)
Previous versions | rss
Help videoAdd a publicationFeedback
Protein

Eukaryotic translation initiation factor 2-alpha kinase 1

Gene

Eif2ak1

Organism
Mus musculus (Mouse)
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:11726526, PubMed:12767237, PubMed:16893190). 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:11726526, PubMed:16893190). 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:11726526, PubMed:16893190). 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 (PubMed:16893190). 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 (PubMed:16893190). Thanks to this unique heme-sensing capacity, plays a crucial role to shut off protein synthesis during acute heme-deficient conditions (PubMed:16893190). In red blood cells (RBCs), controls hemoglobin synthesis ensuring a coordinated regulation of the synthesis of its heme and globin moieties (PubMed:11726526, PubMed:11050009, PubMed:15931390). It thereby plays an essential protective role for RBC survival in anemias of iron deficiency (PubMed:11726526). Similarly, in hepatocytes, involved in heme-mediated translational control of CYP2B and CYP3A and possibly other hepatic P450 cytochromes (PubMed:20071449). May also regulate endoplasmic reticulum (ER) stress during acute heme-deficient conditions (PubMed:20071449). 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 (By similarity).By similarity6 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 (PubMed:12767237, PubMed:14752110, PubMed:20071449). 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 (PubMed:12767237, PubMed:14752110, PubMed:20071449). Inhibited by the heme metabolites biliverdin and bilirubin (PubMed:16893190). Induced by oxidative stress generated by arsenite treatment (PubMed:12767237). 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 (PubMed:14752110). 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) (By similarity).By similarity4 Publications

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 sitei440Proton 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

<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 1 (EC:2.7.11.12 Publications1 Publication)
Alternative name(s):
Heme-controlled repressor
Short name:
HCR
Heme-regulated eukaryotic initiation factor eIF-2-alpha kinase1 Publication
Heme-regulated inhibitor1 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
<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>OrganismiMus musculus (Mouse)
<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 identifieri10090 [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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
<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
  • UP000000589 <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 5

Organism-specific databases

Mouse genome database (MGD) from Mouse Genome Informatics (MGI)

More...
MGIi
MGI:1353448 Eif2ak1

<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

Keywords - Cellular componenti

Cytoplasm

<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

<p>This subsection of the 'Pathology and Biotech' section describes the in vivo effects caused by ablation of the gene (or one or more transcripts) coding for the protein described in the entry. This includes gene knockout and knockdown, provided experiments have been performed in the context of a whole organism or a specific tissue, and not at the single-cell level.<p><a href='/help/disruption_phenotype' target='_top'>More...</a></p>Disruption phenotypei

Mice are viable and fertile without gross morphological abnormalities but display hyperchromic anemia in animals suffering from iron deficiency (PubMed:11726526). Dramatically altered response to diet-induced iron deficiency shifting from an adaptive decrease in red blood cells (RBCs) volume and intracellular hemoglobin content to an increased production of abnormally dense red blood cells (RBCs) with decreasing red cell counts (PubMed:11726526). The decrease in RBC number is the result of increased apoptosis of erythroid precursors (PubMed:11726526). Diminished levels of phosphorylated EIF2S1 in bone marrow-derived macrophages (BMDMs) (PubMed:17932563). Impaired maturation of BMDMs and blunted inflammatory response to LPS with a reduced cytokine production. Impaired phagocytosis of senescent RBCs by macrophages, resulting in a lower phagocytosis index and lower percentage of macrophages with ingested RBC (PubMed:17932563). In hepatocytes, cytochromes P450 CYP2B6 and CYP3A induction by phenobarbital is not impaired in response to acute heme depletion and CYP2B6 and CYP3A proteins continue to accumulate to supranormal levels, irrespective of the hepatic heme pool status (PubMed:20071449). These cells also exhibit a weak, albeit significant, elevation of the basal ER-stress as reflected by elevated levels of autophosphorylated EIF2AK3/PERK and EIF2AK4/GCN2, the ER-stress related chaperones HSPA5 and HSP90B1, and total hepatic protein ubiquitination (PubMed:20071449).3 Publications

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>Mutagenesisi196K → R: Abolishes kinase activity. Impaired hemoglobin synthesis and proliferation of differentiating erythroid cells in knockin mice. 3 Publications1
Mutagenesisi483T → A: No effect on kinase activity. 1 Publication1
Mutagenesisi483T → D: No effect on kinase activity. 1 Publication1
Mutagenesisi485T → A: Abolishes kinase activity. 1 Publication1
Mutagenesisi485T → D: Constitutively active kinase; loss of regulation by heme and arsenite. 1 Publication1
Mutagenesisi490T → A: Almost complete loss of kinase activity; even upon arsenite treatment. 1 Publication1
Mutagenesisi490T → D: Almost complete loss of kinase activity; even upon arsenite treatment. 1 Publication1

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...
ChEMBLi
CHEMBL1938213

<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_00000859421 – 619Eukaryotic translation initiation factor 2-alpha kinase 1Add BLAST619

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 residuei283PhosphothreonineBy similarity1
Modified residuei483Phosphothreonine; by autocatalysis1 Publication1
Modified residuei485Phosphothreonine; by autocatalysis1 Publication1
Modified residuei490Phosphothreonine; by autocatalysis1 Publication1

<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 (PubMed:9822714, PubMed:11560503). Autophosphorylation at Thr-485 is required for kinase activation (PubMed:12767237). The active autophosphorylated form apparently is largely refractory to cellular heme fluctuations (PubMed:12767237).3 Publications

Keywords - PTMi

Disulfide bond, Phosphoprotein

Proteomic databases

Encyclopedia of Proteome Dynamics

More...
EPDi
Q9Z2R9

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

More...
PaxDbi
Q9Z2R9

PRoteomics IDEntifications database

More...
PRIDEi
Q9Z2R9

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...
iPTMneti
Q9Z2R9

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

More...
PhosphoSitePlusi
Q9Z2R9

<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, mature reticulocytes, as well as fetal liver nucleated erythroid cells (PubMed:11689689). At much lower levels, expressed in hepatocytes and bone marrow-derived macrophages (at protein level) (PubMed:17932563, PubMed:20071449).3 Publications

<p>This subsection of the 'Expression' section provides information on the expression of the gene product at various stages of a cell, tissue or organism development. By default, the information is derived from experiments at the mRNA level, unless specified 'at the protein level'.<p><a href='/help/developmental_stage' target='_top'>More...</a></p>Developmental stagei

Highly expressed in fetal liver erythroid precursor cells at 14.5 dpc (at protein level).1 Publication

<p>This subsection of the 'Expression' section reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>Inductioni

By phenobarbital.1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...
Bgeei
ENSMUSG00000029613 Expressed in blood and 270 other tissues

Genevisible search portal to normalized and curated expression data from Genevestigator

More...
Genevisiblei
Q9Z2R9 MM

<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 (By similarity). Has to be associated with a multiprotein complex containing Hsp90, CDC37 and PPP5C for maturation and activation by autophosphorylation. The phosphatase PPP5C modulates this activation (By similarity). 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) (By similarity).

By similarity

<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

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...
BioGRIDi
200421, 1 interactor

Protein interaction database and analysis system

More...
IntActi
Q9Z2R9, 2 interactors

Molecular INTeraction database

More...
MINTi
Q9Z2R9

STRING: functional protein association networks

More...
STRINGi
10090.ENSMUSP00000098056

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...
RNActi
Q9Z2R9 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 – 580Protein kinasePROSITE-ProRule annotationAdd BLAST414
<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>Repeati408 – 413HRM 16
Repeati549 – 554HRM 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
ENOG410ISBT Eukaryota
ENOG410YD23 LUCA

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
Q9Z2R9

KEGG Orthology (KO)

More...
KOi
K16194

Identification of Orthologs from Complete Genome Data

More...
OMAi
KATRRDC

Database of Orthologous Groups

More...
OrthoDBi
64059at2759

Database for complete collections of gene phylogenies

More...
PhylomeDBi
Q9Z2R9

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>Sequencei

<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.

Q9Z2R9-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MLGGSSVDGE RDTDDDAAGA VAAPPAIDFP AEVSDPKYDE SDVPAELQVL
60 70 80 90 100
KEPLQQPTFP FLVANQLLLV SLLEHLSHVH EPNPLHSKQV FKLLCQTFIK
110 120 130 140 150
MGLLSSFTCS DEFSSLRLHH NRAITHLMRS AKERVRQDPC QDNSYMQKIR
160 170 180 190 200
SREIAFEAQT SRYLNEFEEL AILGKGGYGR VYKVRNKLDG QHYAIKKILI
210 220 230 240 250
KSATKTDCMK VLREVKVLAG LQHPNIVGYH TAWIEHVHVV QPQDRVPIQL
260 270 280 290 300
PSLEVLSEQE GDRDQGGVKD NESSSSIVFA ELTPEKEKPF GESEVKNENN
310 320 330 340 350
NLVSYTANLV VRNSSESESS IELQEDGLTD LSVRPVVRHQ LPLGHSSELE
360 370 380 390 400
GNFTSTDESS EGNLNLLGQT EVRYHLMLHI QMQLCELSLW DWITERNKRS
410 420 430 440 450
REYVDEAACP YVMASVATKI FQELVEGVFY IHNMGIVHRD LKPRNIFLHG
460 470 480 490 500
PDQQVKIGDF GLACADIIQN ADWTNRNGKG TRTHTSRVGT CLYASPEQLE
510 520 530 540 550
GSQYDAKSDM YSLGVILLEL FQPFGTEMER ATVLTGVRTG RIPESLSKRC
560 570 580 590 600
PVQAKYIQLL TGRNVSQRPS ALQLLQSELF QTTGNVNLTL QMKIIEQEKE
610
IEELKKQLSL LSQDRGLKR
Length:619
Mass (Da):69,702
Last modified:April 5, 2011 - 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:i39DC5FF950C92F2A
GO

<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 BAD32438 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 conflicti20A → S in BAB32242 (PubMed:16141072).Curated1
Sequence conflicti71S → C in BAB32242 (PubMed:16141072).Curated1
Sequence conflicti138 – 150DPCQD…MQKIR → VSPTGCTLYDKYI in BAB32242 (PubMed:16141072).CuratedAdd BLAST13
Sequence conflicti196 – 197KK → IE in BAB29545 (PubMed:16141072).Curated2
Sequence conflicti371E → D in AAC79201 (PubMed:9822714).Curated1
Sequence conflicti371E → D in AAK55766 (PubMed:11726526).Curated1
Sequence conflicti565V → A in AAH28923 (PubMed:15489334).Curated1

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
AF028808 mRNA Translation: AAC79201.1
AY033898 mRNA Translation: AAK55766.1
AK173160 mRNA Translation: BAD32438.1 Different initiation.
BC028923 mRNA Translation: AAH28923.1
BC111035 mRNA Translation: AAI11036.1
AK014775 mRNA Translation: BAB29545.1
AK020887 mRNA Translation: BAB32242.1
AK032508 mRNA Translation: BAC27901.1

The Consensus CDS (CCDS) project

More...
CCDSi
CCDS84994.1

NCBI Reference Sequences

More...
RefSeqi
NP_038585.2, NM_013557.2

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENSMUST00000100487; ENSMUSP00000098056; ENSMUSG00000029613

Database of genes from NCBI RefSeq genomes

More...
GeneIDi
15467

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
mmu:15467

UCSC genome browser

More...
UCSCi
uc029vqe.1 mouse

<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
AF028808 mRNA Translation: AAC79201.1
AY033898 mRNA Translation: AAK55766.1
AK173160 mRNA Translation: BAD32438.1 Different initiation.
BC028923 mRNA Translation: AAH28923.1
BC111035 mRNA Translation: AAI11036.1
AK014775 mRNA Translation: BAB29545.1
AK020887 mRNA Translation: BAB32242.1
AK032508 mRNA Translation: BAC27901.1
CCDSiCCDS84994.1
RefSeqiNP_038585.2, NM_013557.2

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

BioGRIDi200421, 1 interactor
IntActiQ9Z2R9, 2 interactors
MINTiQ9Z2R9
STRINGi10090.ENSMUSP00000098056

Chemistry databases

ChEMBLiCHEMBL1938213

PTM databases

iPTMnetiQ9Z2R9
PhosphoSitePlusiQ9Z2R9

Proteomic databases

EPDiQ9Z2R9
PaxDbiQ9Z2R9
PRIDEiQ9Z2R9

Protocols and materials databases

Antibodypedia a portal for validated antibodies

More...
Antibodypediai
11579 295 antibodies

Genome annotation databases

EnsembliENSMUST00000100487; ENSMUSP00000098056; ENSMUSG00000029613
GeneIDi15467
KEGGimmu:15467
UCSCiuc029vqe.1 mouse

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
27102
MGIiMGI:1353448 Eif2ak1

Phylogenomic databases

eggNOGiENOG410ISBT Eukaryota
ENOG410YD23 LUCA
GeneTreeiENSGT00940000157605
HOGENOMiCLU_000288_134_1_1
InParanoidiQ9Z2R9
KOiK16194
OMAiKATRRDC
OrthoDBi64059at2759
PhylomeDBiQ9Z2R9
TreeFamiTF329383

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...
BioGRID-ORCSi
15467 0 hits in 6 CRISPR screens

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

More...
ChiTaRSi
Eif2ak1 mouse

Protein Ontology

More...
PROi
PR:Q9Z2R9
RNActiQ9Z2R9 protein

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSMUSG00000029613 Expressed in blood and 270 other tissues
GenevisibleiQ9Z2R9 MM

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_MOUSE
<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: Q9Z2R9
Secondary accession number(s): Q2TA96
, Q69ZK8, Q8C024, Q8K123, Q9CTP5, Q9D601
<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: May 30, 2000
Last sequence update: April 5, 2011
Last modified: June 17, 2020
This is version 165 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

<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. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again