EIF2AK2
Interferon-induced, double-stranded RNA-activated protein kinase
Also known as: E2AK2_HUMAN, PKR, PPP1R83, PRKR
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P19525
- Gene
- EIF2AK2
- Ensembl
- ENSG00000055332
- Chromosome
- 2
- Canonical length
- 551 aa
- Protein class
- Disease related genes, Enzymes, Human disease related genes, Potential drug targets, Predicted intracellular proteins
- Subcellular location
- Cytosol
- Quaternary structure
- Homodimer
OverviewNCBI Gene
The protein encoded by this gene is a serine/threonine protein kinase that is activated by autophosphorylation after binding to dsRNA. The activated form of the encoded protein can phosphorylate translation initiation factor EIF2S1, which in turn inhibits protein synthesis. This protein is also activated by manganese ions and heparin. The encoded protein plays an important role in the innate immune response against multiple DNA and RNA viruses. [provided by RefSeq, Jul 2021]
Canonical amino-acid sequenceUniProt
551 residues, UniProt reviewed canonical sequence.
>P19525|EIF2AK2
1 MAGDLSAGFF MEELNTYRQK QGVVLKYQEL PNSGPPHDRR FTFQVIIDGR EFPEGEGRSK
61 KEAKNAAAKL AVEILNKEKK AVSPLLLTTT NSSEGLSMGN YIGLINRIAQ KKRLTVNYEQ
121 CASGVHGPEG FHYKCKMGQK EYSIGTGSTK QEAKQLAAKL AYLQILSEET SVKSDYLSSG
181 SFATTCESQS NSLVTSTLAS ESSSEGDFSA DTSEINSNSD SLNSSSLLMN GLRNNQRKAK
241 RSLAPRFDLP DMKETKYTVD KRFGMDFKEI ELIGSGGFGQ VFKAKHRIDG KTYVIKRVKY
301 NNEKAEREVK ALAKLDHVNI VHYNGCWDGF DYDPETSDDS LESSDYDPEN SKNSSRSKTK
361 CLFIQMEFCD KGTLEQWIEK RRGEKLDKVL ALELFEQITK GVDYIHSKKL IHRDLKPSNI
421 FLVDTKQVKI GDFGLVTSLK NDGKRTRSKG TLRYMSPEQI SSQDYGKEVD LYALGLILAE
481 LLHVCDTAFE TSKFFTDLRD GIISDIFDKK EKTLLQKLLS KKPEDRPNTS EILRTLTVWK
541 KSPEKNERHT CLocalizationUniProt · AlphaFold · HPA
Whether an antibody against EIF2AK2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.36
- Highest tissue expression
- 29 nTPM
Expression across tissuesHPA
Tissue
- bone marrow: 29 nTPM
- salivary gland: 17 nTPM
- spleen: 11 nTPM
- thymus: 11 nTPM
- cerebral cortex: 11 nTPM
- ovary: 11 nTPM
Single-cell type
- neutrophils: 245 nCPM
- neutrophil progenitors: 242 nCPM
- extravillous trophoblasts: 173 nCPM
- peritubular myoid cells: 136 nCPM
- schwann cells: 128 nCPM
- leydig cells: 125 nCPM
Immune cell
- neutrophil: 16 nTPM
- basophil: 11 nTPM
- non-classical monocyte: 8 nTPM
- intermediate monocyte: 7.9 nTPM
- NK-cell: 6.5 nTPM
- T-reg: 6.5 nTPM
Brain region
- spinal cord: 49 nTPM
- hypothalamus: 43 nTPM
- medulla oblongata: 40 nTPM
- pons: 39 nTPM
- cerebral cortex: 35 nTPM
- choroid plexus: 34 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about EIF2AK2.
Disease | AllUniProt
Conditions EIF2AK2 is implicated in, by any mechanism.
- Leukoencephalopathy, developmental delay, and episodic neurologic regression syndrome (LEUDEN) MIM:618877
- Dystonia 33 (DYT33) MIM:619687
Disease | GeneticClinVar
5 pathogenic / likely-pathogenic of 272 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Leukoencephalopathy, developmental delay, and episodic neurologic regression syndrome
- Dystonia 33
- See cases
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.52
- gnomAD pLI
- 0.02
- gnomAD missense Z
- 1.28
- DepMap mean gene effect
- 0.15
- DepMap dependency class
- none
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- antiviral innate immune response
- cellular response to amino acid starvation
- defense response to virus
- endoplasmic reticulum unfolded protein response
- negative regulation of apoptotic process
- negative regulation of cell population proliferation
- negative regulation of osteoblast proliferation
- negative regulation of translation
- negative regulation of viral genome replication
- positive regulation of chemokine production
- positive regulation of cytokine production
- positive regulation of MAPK cascade
- positive regulation of NF-kappaB transcription factor activity
- positive regulation of non-canonical NF-kappaB signal transduction
- positive regulation of stress-activated MAPK cascade
- protein autophosphorylation
- protein phosphorylation
- regulation of hematopoietic progenitor cell differentiation
- regulation of hematopoietic stem cell differentiation
- regulation of hematopoietic stem cell proliferation
- regulation of NLRP3 inflammasome complex assembly
- regulation of translational initiation
- response to interferon-alpha
- response to virus
- translation
Molecular functions
- ATP binding
- double-stranded RNA binding
- eukaryotic translation initiation factor 2alpha kinase activity
- identical protein binding
- kinase activity
- non-membrane spanning protein tyrosine kinase activity
- protein kinase activity
- protein phosphatase regulator activity
- protein serine kinase activity
- protein serine/threonine kinase activity
- RNA binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Protein kinase domain
- Serine/threonine-protein kinase, active site
- Protein kinase-like domain superfamily
- Double-stranded RNA-binding domain
- Protein kinase, ATP binding site
- Cell Cycle and Stress Response Kinase
- Double-stranded RNA binding motif
- Protein kinase domain
- EIF2AK2, first double-stranded RNA binding domain
- EIF2AK2, second double-stranded RNA binding domain
KeywordsUniProt
- Acetylation
- Antiviral defense
- ATP-binding
- Cytoplasm
- Dystonia
- Host-virus interaction
- Immunity
- Innate immunity
- Isopeptide bond
- Kinase
- Magnesium
- Nucleotide-binding
- Nucleus
- Phosphoprotein
- Repeat
- RNA-binding
- Serine/threonine-protein kinase
- Transcription
- Transcription regulation
- Transferase
- Tyrosine-protein kinase
- Ubl conjugation
InteractionsUniProt · HPA
Protein binding partners of EIF2AK2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads EIF2AK2 as an antibody target. Whether an autoantibody or antibody against EIF2AK2 could matter depends on whether native EIF2AK2 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
EIF2AK2 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label EIF2AK2 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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