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Protein

eIF-2-alpha kinase GCN2

Gene

EIF2AK4

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 (eIF-2-alpha/EIF2S1) on 'Ser-52' in response to low amino acid availability (PubMed:25329545). Plays a role as an activator of the integrated stress response (ISR) required for adapatation to amino acid starvation. Converts phosphorylated eIF-2-alpha/EIF2S1 either to a competitive inhibitor of the translation initiation factor eIF-2B, leading to a global protein synthesis repression, and thus to a reduced overall utilization of amino acids, or to a translational initiation activation of specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion. Binds uncharged tRNAs (By similarity). Involved in cell cycle arrest by promoting cyclin D1 mRNA translation repression after the unfolded protein response pathway (UPR) activation or cell cycle inhibitor CDKN1A/p21 mRNA translation activation in response to amino acid deprivation (PubMed:26102367). Plays a role in the consolidation of synaptic plasticity, learning as well as formation of long-term memory. Plays a role in neurite outgrowth inhibition. Plays a proapoptotic role in response to glucose deprivation. Promotes global cellular protein synthesis repression in response to UV irradiation independently of the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p38 MAPK signaling pathways (By similarity). Plays a role in the antiviral response against alphavirus infection; impairs early viral mRNA translation of the incoming genomic virus RNA, thus preventing alphavirus replication (By similarity).By similarity2 Publications
(Microbial infection) Plays a role in modulating the adaptive immune response to yellow fever virus infection; promotes dendritic cells to initiate autophagy and antigene presentation to both CD4+ and CD8+ T-cells under amino acid starvation (PubMed:24310610).1 Publication

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Function’ 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 sitei619ATPPROSITE-ProRule annotation1
<p>This subsection of the ‘Function’ 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 sitei848Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Function’ 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 bindingi596 – 604ATPPROSITE-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

  • ATP binding Source: UniProtKB-KW
  • eukaryotic translation initiation factor 2alpha kinase activity Source: UniProtKB
  • protein kinase activity Source: GO_Central
  • protein serine/threonine kinase activity Source: UniProtKB
  • tRNA binding Source: UniProtKB

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 functionActivator, Kinase, RNA-binding, Serine/threonine-protein kinase, Transferase, tRNA-binding
Biological processActivation of host autophagy by virus, Adaptive immunity, Antiviral defense, Cell cycle, Growth arrest, Host-virus interaction, Immunity, Neurogenesis, Stress response, Translation regulation
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

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

More...
SignaLinki
Q9P2K8

SIGNOR Signaling Network Open Resource

More...
SIGNORi
Q9P2K8

<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_and_taxonomy_section">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:
eIF-2-alpha kinase GCN2By similarity (EC:2.7.11.1By similarity)
Alternative name(s):
Eukaryotic translation initiation factor 2-alpha kinase 4Imported
GCN2-like protein
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">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:EIF2AK4Imported
Synonyms:GCN2, KIAA1338
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">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_and_taxonomy_section">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_and_taxonomy_section">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_and_taxonomy_section">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_manual">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 15

Organism-specific databases

Eukaryotic Pathogen Database Resources

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EuPathDBi
HostDB:ENSG00000128829.11

Human Gene Nomenclature Database

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HGNCi
HGNC:19687 EIF2AK4

Online Mendelian Inheritance in Man (OMIM)

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MIMi
609280 gene

neXtProt; the human protein knowledge platform

More...
neXtProti
NX_Q9P2K8

<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; Source: COMPARTMENTS

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 provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Pulmonary venoocclusive disease 2, autosomal recessive (PVOD2)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disease characterized by widespread fibrous obstruction and intimal thickening of septal veins and preseptal venules, a low diffusing capacity for carbon monoxide, occult alveolar hemorrhage, and nodular ground-glass opacities, septal lines and lymph node enlargement showed by high-resolution computed tomography of the chest. It is frequently associated with pulmonary capillary dilatation and proliferation, and is a rare and devastating cause of pulmonary hypertension.
See also OMIM:234810
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_070990585R → Q in PVOD2. 1 PublicationCorresponds to variant dbSNP:rs587777106EnsemblClinVar.1
Natural variantiVAR_070991643L → R in PVOD2. 1 PublicationCorresponds to variant dbSNP:rs757852728EnsemblClinVar.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNET

More...
DisGeNETi
440275

MalaCards human disease database

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MalaCardsi
EIF2AK4
MIMi234810 phenotype

Open Targets

More...
OpenTargetsi
ENSG00000128829

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...
Orphaneti
275777 Heritable pulmonary arterial hypertension
199241 Pulmonary capillary hemangiomatosis
31837 Pulmonary venoocclusive disease

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA134947616

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

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ChEMBLi
CHEMBL5358

IUPHAR/BPS Guide to PHARMACOLOGY

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GuidetoPHARMACOLOGYi
2018

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

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BioMutai
EIF2AK4

Domain mapping of disease mutations (DMDM)

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DMDMi
296439368

<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.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000859471 – 1649eIF-2-alpha kinase GCN2Add BLAST1649

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 residuei230PhosphoserineCombined sources1
Modified residuei667PhosphothreonineCombined sources1
Modified residuei871PhosphothreonineCombined sources1
Modified residuei899Phosphothreonine; by autocatalysisBy similarity1
Modified residuei904Phosphothreonine; by autocatalysisBy similarity1
Modified residuei1259N6-acetyllysineCombined sources1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">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; autophosphorylation on Thr-899 is increased upon amino acid starvation and in UV irradiation cells and inhibited in presence of IMPACT.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

Encyclopedia of Proteome Dynamics

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EPDi
Q9P2K8

jPOST - Japan Proteome Standard Repository/Database

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jPOSTi
Q9P2K8

MaxQB - The MaxQuant DataBase

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MaxQBi
Q9P2K8

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

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PaxDbi
Q9P2K8

PeptideAtlas

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PeptideAtlasi
Q9P2K8

PRoteomics IDEntifications database

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PRIDEi
Q9P2K8

ProteomicsDB human proteome resource

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ProteomicsDBi
83838
83839 [Q9P2K8-2]
83840 [Q9P2K8-3]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
Q9P2K8

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

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PhosphoSitePlusi
Q9P2K8

<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

Widely expressed (PubMed:10504407). Expressed in lung, smooth muscle cells and macrophages (PubMed:24292273).2 Publications

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSG00000128829 Expressed in 202 organ(s), highest expression level in adenohypophysis

CleanEx database of gene expression profiles

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CleanExi
HS_EIF2AK4

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
Q9P2K8 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
Q9P2K8 HS

Organism-specific databases

Human Protein Atlas

More...
HPAi
HPA011811

<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_section">'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_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Homodimer; homodimerization is important for kinase activation by uncharged tRNAs. Interacts with GCN1; this interaction stimulates EIF2AK4/GCN2 kinase activity and is impaired by IMPACT upon a variety of stress conditions, such as amino acid depletion, UV-C irradiation, proteasome inhibitor treatment and glucose deprivation. Interacts with DNAJC3; this interaction inhibits EIF2AK4/GCN2 kinase activity during endoplasmic reticulum (ER), hypothermic and amino acid-starving stress conditions.By similarity

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
136426, 27 interactors

Protein interaction database and analysis system

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IntActi
Q9P2K8, 20 interactors

STRING: functional protein association networks

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STRINGi
9606.ENSP00000263791

Chemistry databases

BindingDB database of measured binding affinities

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BindingDBi
Q9P2K8

<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

3D structure databases

Protein Model Portal of the PSI-Nature Structural Biology Knowledgebase

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ProteinModelPortali
Q9P2K8

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

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SMRi
Q9P2K8

Database of comparative protein structure models

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ModBasei
Search...

MobiDB: a database of protein disorder and mobility annotations

More...
MobiDBi
Search...

<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_and_domains_section">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>Domaini25 – 137RWDPROSITE-ProRule annotationAdd BLAST113
Domaini296 – 539Protein kinase 1PROSITE-ProRule annotationAdd BLAST244
Domaini590 – 1001Protein kinase 2PROSITE-ProRule annotationAdd BLAST412

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>Regioni1022 – 1493Histidyl-tRNA synthetase-likeAdd BLAST472

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and domains’ section denotes the positions of regions of coiled coil within the protein.<p><a href='/help/coiled' target='_top'>More...</a></p>Coiled coili146 – 205Sequence analysisAdd BLAST60

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes the position of regions of compositional bias within the protein and the particular amino acids that are over-represented within those regions.<p><a href='/help/compbias' target='_top'>More...</a></p>Compositional biasi484 – 491Poly-Leu8

<p>This subsection of the ‘Family and domains’ section provides general information on the biological role of a domain. The term ‘domain’ is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

The histidyl-tRNA synthetase-like region and protein kinase domains are necessary for eIF-2-alpha kinase activity and eIF-2-alpha-mediated translational control. The histidyl-tRNA synthetase-like domain is necessary for binding to uncharged tRNAs. Kinase domain 1 is a degenerate kinase domain.By similarity

<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

Coiled coil, Repeat

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

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eggNOGi
KOG1035 Eukaryota
COG0124 LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00940000156798

The HOVERGEN Database of Homologous Vertebrate Genes

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HOVERGENi
HBG051432

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
Q9P2K8

KEGG Orthology (KO)

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KOi
K16196

Identification of Orthologs from Complete Genome Data

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OMAi
TDVWDLG

Database of Orthologous Groups

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OrthoDBi
1189098at2759

Database for complete collections of gene phylogenies

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PhylomeDBi
Q9P2K8

TreeFam database of animal gene trees

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TreeFami
TF101512

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

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Gene3Di
3.10.110.10, 1 hit
3.40.50.800, 1 hit

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR036621 Anticodon-bd_dom_sf
IPR016255 Gcn2
IPR024435 HisRS-related_dom
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR006575 RWD-domain
IPR008271 Ser/Thr_kinase_AS
IPR016135 UBQ-conjugating_enzyme/RWD

Pfam protein domain database

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Pfami
View protein in Pfam
PF12745 HGTP_anticodon2, 1 hit
PF00069 Pkinase, 3 hits
PF05773 RWD, 1 hit

PIRSF; a whole-protein classification database

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PIRSFi
PIRSF000660 Ser/Thr_PK_GCN2, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

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SMARTi
View protein in SMART
SM00591 RWD, 1 hit
SM00220 S_TKc, 2 hits

Superfamily database of structural and functional annotation

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SUPFAMi
SSF54495 SSF54495, 1 hit
SSF56112 SSF56112, 2 hits

PROSITE; a protein domain and family database

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PROSITEi
View protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 2 hits
PS00108 PROTEIN_KINASE_ST, 1 hit
PS50908 RWD, 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_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (3+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">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 3 <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.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

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

Isoform 1 (identifier: Q9P2K8-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' 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
MAGGRGAPGR GRDEPPESYP QRQDHELQAL EAIYGADFQD LRPDACGPVK
60 70 80 90 100
EPPEINLVLY PQGLTGEEVY VKVDLRVKCP PTYPDVVPEI ELKNAKGLSN
110 120 130 140 150
ESVNLLKSRL EELAKKHCGE VMIFELAYHV QSFLSEHNKP PPKSFHEEML
160 170 180 190 200
ERRAQEEQQR LLEAKRKEEQ EQREILHEIQ RRKEEIKEEK KRKEMAKQER
210 220 230 240 250
LEIASLSNQD HTSKKDPGGH RTAAILHGGS PDFVGNGKHR ANSSGRSRRE
260 270 280 290 300
RQYSVCNSED SPGSCEILYF NMGSPDQLMV HKGKCIGSDE QLGKLVYNAL
310 320 330 340 350
ETATGGFVLL YEWVLQWQKK MGPFLTSQEK EKIDKCKKQI QGTETEFNSL
360 370 380 390 400
VKLSHPNVVR YLAMNLKEQD DSIVVDILVE HISGVSLAAH LSHSGPIPVH
410 420 430 440 450
QLRRYTAQLL SGLDYLHSNS VVHKVLSASN VLVDAEGTVK ITDYSISKRL
460 470 480 490 500
ADICKEDVFE QTRVRFSDNA LPYKTGKKGD VWRLGLLLLS LSQGQECGEY
510 520 530 540 550
PVTIPSDLPA DFQDFLKKCV CLDDKERWSP QQLLKHSFIN PQPKMPLVEQ
560 570 580 590 600
SPEDSEGQDY VETVIPSNRL PSAAFFSETQ RQFSRYFIEF EELQLLGKGA
610 620 630 640 650
FGAVIKVQNK LDGCCYAVKR IPINPASRQF RRIKGEVTLL SRLHHENIVR
660 670 680 690 700
YYNAWIERHE RPAGPGTPPP DSGPLAKDDR AARGQPASDT DGLDSVEAAA
710 720 730 740 750
PPPILSSSVE WSTSGERSAS ARFPATGPGS SDDEDDDEDE HGGVFSQSFL
760 770 780 790 800
PASDSESDII FDNEDENSKS QNQDEDCNEK NGCHESEPSV TTEAVHYLYI
810 820 830 840 850
QMEYCEKSTL RDTIDQGLYR DTVRLWRLFR EILDGLAYIH EKGMIHRDLK
860 870 880 890 900
PVNIFLDSDD HVKIGDFGLA TDHLAFSADS KQDDQTGDLI KSDPSGHLTG
910 920 930 940 950
MVGTALYVSP EVQGSTKSAY NQKVDLFSLG IIFFEMSYHP MVTASERIFV
960 970 980 990 1000
LNQLRDPTSP KFPEDFDDGE HAKQKSVISW LLNHDPAKRP TATELLKSEL
1010 1020 1030 1040 1050
LPPPQMEESE LHEVLHHTLT NVDGKAYRTM MAQIFSQRIS PAIDYTYDSD
1060 1070 1080 1090 1100
ILKGNFSIRT AKMQQHVCET IIRIFKRHGA VQLCTPLLLP RNRQIYEHNE
1110 1120 1130 1140 1150
AALFMDHSGM LVMLPFDLRI PFARYVARNN ILNLKRYCIE RVFRPRKLDR
1160 1170 1180 1190 1200
FHPKELLECA FDIVTSTTNS FLPTAEIIYT IYEIIQEFPA LQERNYSIYL
1210 1220 1230 1240 1250
NHTMLLKAIL LHCGIPEDKL SQVYIILYDA VTEKLTRREV EAKFCNLSLS
1260 1270 1280 1290 1300
SNSLCRLYKF IEQKGDLQDL MPTINSLIKQ KTGIAQLVKY GLKDLEEVVG
1310 1320 1330 1340 1350
LLKKLGIKLQ VLINLGLVYK VQQHNGIIFQ FVAFIKRRQR AVPEILAAGG
1360 1370 1380 1390 1400
RYDLLIPQFR GPQALGPVPT AIGVSIAIDK ISAAVLNMEE SVTISSCDLL
1410 1420 1430 1440 1450
VVSVGQMSMS RAINLTQKLW TAGITAEIMY DWSQSQEELQ EYCRHHEITY
1460 1470 1480 1490 1500
VALVSDKEGS HVKVKSFEKE RQTEKRVLET ELVDHVLQKL RTKVTDERNG
1510 1520 1530 1540 1550
REASDNLAVQ NLKGSFSNAS GLFEIHGATV VPIVSVLAPE KLSASTRRRY
1560 1570 1580 1590 1600
ETQVQTRLQT SLANLHQKSS EIEILAVDLP KETILQFLSL EWDADEQAFN
1610 1620 1630 1640
TTVKQLLSRL PKQRYLKLVC DEIYNIKVEK KVSVLFLYSY RDDYYRILF
Length:1,649
Mass (Da):186,911
Last modified:May 18, 2010 - v3
<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:iECF3CFFA51AEE67C
GO
Isoform 2 (identifier: Q9P2K8-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     774-801: Missing.

Note: No experimental confirmation available.
Show »
Length:1,621
Mass (Da):183,717
Checksum:i40B21FA4D721C758
GO
Isoform 3 (identifier: Q9P2K8-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     608-616: QNKLDGCCY → WYRVIPSPL
     617-1649: Missing.

Note: No experimental confirmation available.
Show »
Length:616
Mass (Da):69,797
Checksum:iCBFF2B4F683C5DB3
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
H0YME5H0YME5_HUMAN
eIF-2-alpha kinase GCN2
EIF2AK4
1,427Annotation score:

Annotation score:2 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>
H0YND8H0YND8_HUMAN
eIF-2-alpha kinase GCN2
EIF2AK4
136Annotation 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>
H0YNY9H0YNY9_HUMAN
eIF-2-alpha kinase GCN2
EIF2AK4
80Annotation 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 BAA92576 differs from that shown. Contaminating sequence. Sequence of unknown origin in the N-terminal part.Curated
The sequence BAB15625 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.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 conflicti556E → G in BAA92576 (PubMed:10718198).Curated1
Sequence conflicti556E → G in CAH10626 (PubMed:17974005).Curated1
Sequence conflicti629Q → K in CAH10626 (PubMed:17974005).Curated1
Sequence conflicti858S → F in BAB15625 (PubMed:14702039).Curated1
Sequence conflicti1133N → I in CAB58360 (PubMed:10504407).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_040479137H → R1 PublicationCorresponds to variant dbSNP:rs35509999Ensembl.1
Natural variantiVAR_040480166R → W1 PublicationCorresponds to variant dbSNP:rs34439704Ensembl.1
Natural variantiVAR_040481441I → L2 PublicationsCorresponds to variant dbSNP:rs2291627EnsemblClinVar.1
Natural variantiVAR_070990585R → Q in PVOD2. 1 PublicationCorresponds to variant dbSNP:rs587777106EnsemblClinVar.1
Natural variantiVAR_070991643L → R in PVOD2. 1 PublicationCorresponds to variant dbSNP:rs757852728EnsemblClinVar.1
Natural variantiVAR_040482872D → V1 PublicationCorresponds to variant dbSNP:rs34665481Ensembl.1
Natural variantiVAR_040483939H → Y in a lung neuroendocrine carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_0404841060T → R1 PublicationCorresponds to variant dbSNP:rs55781333Ensembl.1
Natural variantiVAR_0404851306G → C2 PublicationsCorresponds to variant dbSNP:rs35602605EnsemblClinVar.1
Natural variantiVAR_0404861336K → R1 PublicationCorresponds to variant dbSNP:rs35480871Ensembl.1
Natural variantiVAR_0404871406Q → H1 PublicationCorresponds to variant dbSNP:rs55721315EnsemblClinVar.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. The information stored in this subsection is used to automatically construct alternative protein sequence(s) for display.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_039185608 – 616QNKLDGCCY → WYRVIPSPL in isoform 3. 1 Publication9
Alternative sequenceiVSP_039186617 – 1649Missing in isoform 3. 1 PublicationAdd BLAST1033
Alternative sequenceiVSP_013038774 – 801Missing in isoform 2. CuratedAdd BLAST28

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
AC012377 Genomic DNA No translation available.
AC025168 Genomic DNA No translation available.
BC009350 mRNA Translation: AAH09350.2
BC078179 mRNA Translation: AAH78179.1
AB037759 mRNA Translation: BAA92576.1 Sequence problems.
AL137627 mRNA Translation: CAB70849.1
AL157497 mRNA Translation: CAB75678.1
AL832907 mRNA Translation: CAH10626.1
AK027011 mRNA Translation: BAB15625.1 Different initiation.
AJ243428 mRNA Translation: CAB58360.1

The Consensus CDS (CCDS) project

More...
CCDSi
CCDS42016.1 [Q9P2K8-1]

Protein sequence database of the Protein Information Resource

More...
PIRi
T46924

NCBI Reference Sequences

More...
RefSeqi
NP_001013725.2, NM_001013703.3 [Q9P2K8-1]

UniGene gene-oriented nucleotide sequence clusters

More...
UniGenei
Hs.656673

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENST00000263791; ENSP00000263791; ENSG00000128829 [Q9P2K8-1]
ENST00000559624; ENSP00000453148; ENSG00000128829 [Q9P2K8-3]

Database of genes from NCBI RefSeq genomes

More...
GeneIDi
440275

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
hsa:440275

UCSC genome browser

More...
UCSCi
uc001zkl.4 human [Q9P2K8-1]

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
AC012377 Genomic DNA No translation available.
AC025168 Genomic DNA No translation available.
BC009350 mRNA Translation: AAH09350.2
BC078179 mRNA Translation: AAH78179.1
AB037759 mRNA Translation: BAA92576.1 Sequence problems.
AL137627 mRNA Translation: CAB70849.1
AL157497 mRNA Translation: CAB75678.1
AL832907 mRNA Translation: CAH10626.1
AK027011 mRNA Translation: BAB15625.1 Different initiation.
AJ243428 mRNA Translation: CAB58360.1
CCDSiCCDS42016.1 [Q9P2K8-1]
PIRiT46924
RefSeqiNP_001013725.2, NM_001013703.3 [Q9P2K8-1]
UniGeneiHs.656673

3D structure databases

ProteinModelPortaliQ9P2K8
SMRiQ9P2K8
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi136426, 27 interactors
IntActiQ9P2K8, 20 interactors
STRINGi9606.ENSP00000263791

Chemistry databases

BindingDBiQ9P2K8
ChEMBLiCHEMBL5358
GuidetoPHARMACOLOGYi2018

PTM databases

iPTMnetiQ9P2K8
PhosphoSitePlusiQ9P2K8

Polymorphism and mutation databases

BioMutaiEIF2AK4
DMDMi296439368

Proteomic databases

EPDiQ9P2K8
jPOSTiQ9P2K8
MaxQBiQ9P2K8
PaxDbiQ9P2K8
PeptideAtlasiQ9P2K8
PRIDEiQ9P2K8
ProteomicsDBi83838
83839 [Q9P2K8-2]
83840 [Q9P2K8-3]

Protocols and materials databases

The DNASU plasmid repository

More...
DNASUi
440275
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000263791; ENSP00000263791; ENSG00000128829 [Q9P2K8-1]
ENST00000559624; ENSP00000453148; ENSG00000128829 [Q9P2K8-3]
GeneIDi440275
KEGGihsa:440275
UCSCiuc001zkl.4 human [Q9P2K8-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
440275
DisGeNETi440275
EuPathDBiHostDB:ENSG00000128829.11

GeneCards: human genes, protein and diseases

More...
GeneCardsi
EIF2AK4

H-Invitational Database, human transcriptome db

More...
H-InvDBi
HIX0012119
HGNCiHGNC:19687 EIF2AK4
HPAiHPA011811
MalaCardsiEIF2AK4
MIMi234810 phenotype
609280 gene
neXtProtiNX_Q9P2K8
OpenTargetsiENSG00000128829
Orphaneti275777 Heritable pulmonary arterial hypertension
199241 Pulmonary capillary hemangiomatosis
31837 Pulmonary venoocclusive disease
PharmGKBiPA134947616

Human Unidentified Gene-Encoded large proteins database

More...
HUGEi
Search...

GenAtlas: human gene database

More...
GenAtlasi
Search...

Phylogenomic databases

eggNOGiKOG1035 Eukaryota
COG0124 LUCA
GeneTreeiENSGT00940000156798
HOVERGENiHBG051432
InParanoidiQ9P2K8
KOiK16196
OMAiTDVWDLG
OrthoDBi1189098at2759
PhylomeDBiQ9P2K8
TreeFamiTF101512

Enzyme and pathway databases

SignaLinkiQ9P2K8
SIGNORiQ9P2K8

Miscellaneous databases

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

More...
ChiTaRSi
EIF2AK4 human

The Gene Wiki collection of pages on human genes and proteins

More...
GeneWikii
EIF2AK4

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

More...
GenomeRNAii
440275

Protein Ontology

More...
PROi
PR:Q9P2K8

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSG00000128829 Expressed in 202 organ(s), highest expression level in adenohypophysis
CleanExiHS_EIF2AK4
ExpressionAtlasiQ9P2K8 baseline and differential
GenevisibleiQ9P2K8 HS

Family and domain databases

Gene3Di3.10.110.10, 1 hit
3.40.50.800, 1 hit
InterProiView protein in InterPro
IPR036621 Anticodon-bd_dom_sf
IPR016255 Gcn2
IPR024435 HisRS-related_dom
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR006575 RWD-domain
IPR008271 Ser/Thr_kinase_AS
IPR016135 UBQ-conjugating_enzyme/RWD
PfamiView protein in Pfam
PF12745 HGTP_anticodon2, 1 hit
PF00069 Pkinase, 3 hits
PF05773 RWD, 1 hit
PIRSFiPIRSF000660 Ser/Thr_PK_GCN2, 1 hit
SMARTiView protein in SMART
SM00591 RWD, 1 hit
SM00220 S_TKc, 2 hits
SUPFAMiSSF54495 SSF54495, 1 hit
SSF56112 SSF56112, 2 hits
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 2 hits
PS00108 PROTEIN_KINASE_ST, 1 hit
PS50908 RWD, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
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 nameiE2AK4_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: Q9P2K8
Secondary accession number(s): C9JEC4
, Q69YL7, Q6DC97, Q96GN6, Q9H5K1, Q9NSQ3, Q9NSZ5, Q9UJ56
<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_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 15, 2005
Last sequence update: May 18, 2010
Last modified: January 16, 2019
This is version 166 of the entry and version 3 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

Complete proteome, Reference proteome

Documents

  1. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  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 entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
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