Pathway Human Homo sapiens

PKR-mediated signaling

R-HSA-9833482 in Reactome release 97: under Antimicrobial mechanism of IFN-stimulated genes, with 81 genes placed in it by the mapping files and 0 child pathways in the hierarchy.

The same number in the other species

Reactome writes the mouse and rat events it infers from a human pathway under the human number with the species token. A door opens only where that species' own list in this release holds the id: R-MMU-9833482 (mouse), R-RNO-9833482 (rat). Whether the event was inferred from this one is what the record says.

The record
The genes
Parents and children

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This page reads the pathway's record from its source while you read the rest; with scripts off the card stays at its loading line. Reload with scripts on to see it, or open the source's own page from the link in the card.

01The record

Reactome's own record of this pathway

What this tells you

The pathway list, the hierarchy and the genes on this page are read from the files Reactome publishes for Reactome release 97, built into this site on 2026-09-09: the pathway list, the hierarchy relationship file and the two gene mapping files. The record card is the one live read, Reactome's own record of this pathway.

Reactome's download page describes the mapping files: Mapping files link the source database identifier to the lowest level pathway diagram or subset of the pathway, all levels of the pathway hierarchy or database identifier to all reactions. [R13] The gene list here is the all-levels mapping of NCBI Gene ids, filled from the all-levels mapping of Ensembl ids where the NCBI file has no row for a gene; each row names which file it came from by the shape of its source id. Each row carries the evidence codes the file writes for it, as written and unranked, and both where the file writes both; no page of Reactome's documentation the survey read defines the codes, so this page does not expand them. A gene id the identity files do not name is kept as the source's own id with no door rather than turned into a symbol.

On citing what a search finds, Reactome says: It should be remembered that while we strive to contain the most current and accurate data, Reactome should not be used in citations where other primary sources of information are available. [R12] The record card prints the literature Reactome attaches to a curated pathway for that reason. The data are public domain: All data in the Reactome database and files derived from that data are licensed under the Creative Commons Public Domain Dedication (CC0). User may copy, modify, and distribute these data, even for commercial purposes, without asking for permission. Attribution is encouraged but not required. [R10] The pathway illustrations are licensed apart, under CC BY 4.0, and none is shown here.

A gene on this list is one Reactome places in this pathway in this release, and that is all the row says: it does not say the gene is expressed in a tissue or associated with a disease, which are the other two explorers' questions, read from other sources. Reactome's papers of record are [R01] [R02].

[R01] Ragueneau E, Gong C, Sinquin P, Sevilla C, Beavers D, Grentner A, et al. (2026). The Reactome Knowledgebase 2026. Nucleic Acids Research 54:D673-D681. PMID 41251150, doi 10.1093/nar/gkaf1223.
[R02] Milacic M, Beavers D, Conley P, Gong C, Gillespie M, Griss J, et al. (2024). The Reactome Pathway Knowledgebase 2024. Nucleic Acids Research 52:D672-D678. PMID 37941124, doi 10.1093/nar/gkad1025.
[R10] Reactome, reactome.org. License Agreement. https://reactome.org/license, read 2026-09-09.
[R12] Reactome, reactome.org. Citing us. https://reactome.org/cite, read 2026-09-09.
[R13] Reactome, reactome.org. Download. https://reactome.org/download-data, read 2026-09-09.

Stable id: R-HSA-9833482.3
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2023-09-13
Events inside: 40, counted from the record

Interferon-induced, double-stranded RNA-activated protein kinase PKR (EIF2AK2) mainly halts cellular protein translation by phosphorylating eIF2α, which blocks the recycling of GDP-eIF2 to GTP-eIF2 required for cap-dependent translation initiation. PKR is constitutively expressed at low level, and its expression is up-regulated by interferon alpha/beta signaling. PKR is mainly localized in the cytoplasm with a small fraction in the nucleus (Tian & Mathews 2001).

PKR was identified in the 1970s (Friedman et al, 1972; Kerr et al., 1977). Its activation is characterized by the shifting of its monomer/dimer equilibrium towards the dimer, with subsequent autophosphorylation (reviewed by Sadler & Williams, 2007; Bou-Nader et al, 2019). Possible activating factors include binding of viral dsRNA to the PKR dsRNA binding domain (reviewed by Nallagatla et al, 2011), as well as cellular proteins (ISG15, PACT, DCP1A) and heparin (Patel & Sen, 1998; Dougherty et al., 2014; George et al., 1996; Fasciano et al., 2005; reviewed by Zhang et al, 2021). General translation shutdown by PKR can therefore be promoted by both viral infection and the integrated response of the cell to stress stimuli (reviewed by Pizzinga et al, 2019; Costa-Mattioli & Walter, 2020). Several cellular inhibitors of PKR activation and eIF2α phosphorylation by PKR have been identified and binding of PKR to viral proteins from RNA viruses (e.g. HIV, influenza A, RSV) has also been shown to contribute to inhibition (reviewed by Cesaro & Michiels, 2021). In addition to its role in translation shutdown via eIF2α, PKR affects translation through NFAR protein phosphorylation; it can also phosphorylate RNA helicase A, CDC2, and MKK6, thus modulating RNA metabolism, G2 arrest, and p38 MAPK activation. Finally, PKR can bind to TRAF proteins, the IkappaB kinase complex, GSK-3beta, and several inflammasome components leading to NF-kappa B activation, tau phosphorylation, apoptosis, and inflammasome activation (reviewed by Gil & Esteban, 2000; Garcia et al, 2007; Pindel & Sadler, 2011; Marchal et al, 2014; Yim & Williams, 2014; McKey et al, 2021).

Literature Reactome attaches

ISGylation in Innate Antiviral Immunity and Pathogen Defense Responses: A ReviewFront Cell Dev Biol, 2021, vol. 9, p. 788410PubMed 34901029
The search for a PKR code-differential regulation of protein kinase R activity by diverse RNA and protein regulatorsRNA, 2019, vol. 25, p. 539-556PubMed 30770398
Mechanism of interferon action: inhibition of viral messenger ribonucleic acid translation in L-cell extractsJ Virol, 1972, vol. 10, p. 1184-98PubMed 4345494
Nature of inhibitor of cell-free protein synthesis formed in response to interferon and double-stranded RNANature, 1977, vol. 268, p. 540-2PubMed 196217
The cell stress response: extreme times call for post-transcriptional measuresWiley Interdiscip Rev RNA, 2020, vol. 11, p. e1578PubMed 31755249
Inhibition of PKR by VirusesFront Microbiol, 2021, vol. 12, p. 757238PubMed 34759908
The impact of PKR activation: from neurodegeneration to cancerFASEB J, 2014, vol. 28, p. 1965-74PubMed 24522206
Protein kinase R and the inflammasomeJ Interferon Cytokine Res, 2014, vol. 34, p. 447-54PubMed 24905201
The integrated stress response: From mechanism to diseaseScience, 2020, vol. 368PubMed 32327570
Regulation of innate immunity through RNA structure and the protein kinase PKRCurr Opin Struct Biol, 2011, vol. 21, p. 119-27PubMed 21145228
The role of protein kinase R in the interferon responseJ Interferon Cytokine Res, 2011, vol. 31, p. 59-70PubMed 21166592
Functional characterization of and cooperation between the double-stranded RNA-binding motifs of the protein kinase PKRJ Biol Chem, 2001, vol. 276, p. 9936-44PubMed 11134010
The dsRNA protein kinase PKR: virus and cell controlBiochimie, 2007, vol. 89, p. 799-811PubMed 17451862
PHOrming the inflammasome: phosphorylation is a critical switch in inflammasome signallingBiochem Soc Trans, 2021, vol. 49, p. 2495-2507PubMed 34854899
Induction of apoptosis by the dsRNA-dependent protein kinase (PKR): mechanism of actionApoptosis, 2000, vol. 5, p. 107-14PubMed 11232238
Structure and function of the protein kinase RCurr Top Microbiol Immunol, 2007, vol. 316, p. 253-92PubMed 17969452
PACT, a protein activator of the interferon-induced protein kinase, PKREMBO J, 1998, vol. 17, p. 4379-90PubMed 9687506
mRNA decapping enzyme 1a (Dcp1a)-induced translational arrest through protein kinase R (PKR) activation requires the N-terminal enabled vasodilator-stimulated protein homology 1 (EVH1) domainJ Biol Chem, 2014, vol. 289, p. 3936-49PubMed 24382890
Characterization of the heparin-mediated activation of PKR, the interferon-inducible RNA-dependent protein kinaseVirology, 1996, vol. 221, p. 180-8PubMed 8661426
Identification of the heparin-binding domains of the interferon-induced protein kinase, PKRFEBS J, 2005, vol. 272, p. 1425-39PubMed 15752359

Reactome's record lists 14 orthologous events, R-MMU-9833482 (Mus musculus), R-RNO-9833482 (Rattus norvegicus) among the species this site serves, and 12 in species this site opens no page for.

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-10-01 ET · Reactome pathway browser"PKR-mediated signaling". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-9833482 with StableID: R-HSA-9833482.3 (accessed 2026-10-01 ET). Reactome version 97 (CC0).

Reading this pathway's record from Reactome (the pathway record).Still reading. A first read of a pathway can take a while; this page waits up to 35 seconds for it, and its scripts then bring in the panel, or a line saying what did not arrive.

02The genes

Genes Reactome places in this human pathway

The mapping files place 81 genes in this human pathway; showing 1 to 81, in pages of 100, sorted by symbol for reading. The order carries no ranking. 4 of the rows shown carry an id the identity file does not name, kept as the source wrote it.

Genes Reactome places in this human pathway, page 1 of 1
Gene	Authority id	Mapping file id	Evidence codes
GeneADAR	AuthorityHGNC:225	Mapping file id103 NCBI file	EvidenceTAS
GeneARIH1	AuthorityHGNC:689	Mapping file id25820 NCBI file	EvidenceTAS
GeneCDK1	AuthorityHGNC:1722	Mapping file id983 NCBI file	EvidenceTAS
GeneCENPS	AuthorityHGNC:23163	Mapping file id378708 NCBI file	EvidenceTAS
GeneCENPS-CORT	AuthorityHGNC:38843	Mapping file id100526739 NCBI file	EvidenceTAS
GeneCENPX	AuthorityHGNC:11422	Mapping file id201254 NCBI file	EvidenceTAS
GeneCHUK	AuthorityHGNC:1974	Mapping file id1147 NCBI file	EvidenceTAS
GeneDHX9	AuthorityHGNC:2750	Mapping file id1660 NCBI file	EvidenceTAS
GeneDNAJC3	AuthorityHGNC:9439	Mapping file id5611 NCBI file	EvidenceTAS
GeneDUS2	AuthorityHGNC:26014	Mapping file id54920 NCBI file	EvidenceTAS
GeneEIF2AK2	AuthorityHGNC:9437	Mapping file id5610 NCBI file	EvidenceTAS
GeneEIF2S1	AuthorityHGNC:3265	Mapping file id1965 NCBI file	EvidenceTAS
GeneEIF2S2	AuthorityHGNC:3266	Mapping file id8894 NCBI file	EvidenceTAS
GeneEIF2S3	AuthorityHGNC:3267	Mapping file id1968 NCBI file	EvidenceTAS
GeneFAAP100	AuthorityHGNC:26171	Mapping file id80233 NCBI file	EvidenceTAS
GeneFAAP20	AuthorityHGNC:26428	Mapping file id199990 NCBI file	EvidenceTAS
GeneFAAP24	AuthorityHGNC:28467	Mapping file id91442 NCBI file	EvidenceTAS
GeneFANCA	AuthorityHGNC:3582	Mapping file id2175 NCBI file	EvidenceTAS
GeneFANCB	AuthorityHGNC:3583	Mapping file id2187 NCBI file	EvidenceTAS
GeneFANCC	AuthorityHGNC:3584	Mapping file id2176 NCBI file	EvidenceTAS
GeneFANCE	AuthorityHGNC:3586	Mapping file id2178 NCBI file	EvidenceTAS
GeneFANCF	AuthorityHGNC:3587	Mapping file id2188 NCBI file	EvidenceTAS
GeneFANCG	AuthorityHGNC:3588	Mapping file id2189 NCBI file	EvidenceTAS
GeneFANCL	AuthorityHGNC:20748	Mapping file id55120 NCBI file	EvidenceTAS
GeneFANCM	AuthorityHGNC:23168	Mapping file id57697 NCBI file	EvidenceTAS
GeneHERC5	AuthorityHGNC:24368	Mapping file id51191 NCBI file	EvidenceTAS
GeneHSPA1A	AuthorityHGNC:5232	Mapping file id3303 NCBI file	EvidenceTAS
GeneHSPA1B	AuthorityHGNC:5233	Mapping file id3304 NCBI file	EvidenceTAS
GeneHSPA1L	AuthorityHGNC:5234	Mapping file id3305 NCBI file	EvidenceTAS
GeneHSPA2	AuthorityHGNC:5235	Mapping file id3306 NCBI file	EvidenceTAS
GeneHSPA8	AuthorityHGNC:5241	Mapping file id3312 NCBI file	EvidenceTAS
GeneIKBKB	AuthorityHGNC:5960	Mapping file id3551 NCBI file	EvidenceTAS
GeneIKBKG	AuthorityHGNC:5961	Mapping file id8517 NCBI file	EvidenceTAS
GeneILF2	AuthorityHGNC:6037	Mapping file id3608 NCBI file	EvidenceTAS
GeneILF3	AuthorityHGNC:6038	Mapping file id3609 NCBI file	EvidenceTAS
GeneISG15	AuthorityHGNC:4053	Mapping file id9636 NCBI file	EvidenceTAS
GeneMAP2K6	AuthorityHGNC:6846	Mapping file id5608 NCBI file	EvidenceTAS
GeneMAPT	AuthorityHGNC:6893	Mapping file id4137 NCBI file	EvidenceTAS
GeneMAVS	AuthorityHGNC:29233	Mapping file id57506 NCBI file	EvidenceTAS
GeneNCK1	AuthorityHGNC:7664	Mapping file id4690 NCBI file	EvidenceTAS
GeneNPM1	AuthorityHGNC:7910	Mapping file id4869 NCBI file	EvidenceTAS
GenePPP2CA	AuthorityHGNC:9299	Mapping file id5515 NCBI file	EvidenceTAS
GenePPP2CB	AuthorityHGNC:9300	Mapping file id5516 NCBI file	EvidenceTAS
GenePPP2R1A	AuthorityHGNC:9302	Mapping file id5518 NCBI file	EvidenceTAS
GenePPP2R1B	AuthorityHGNC:9303	Mapping file id5519 NCBI file	EvidenceTAS
GenePPP2R5A	AuthorityHGNC:9309	Mapping file id5525 NCBI file	EvidenceTAS
GenePRKRA	AuthorityHGNC:9438	Mapping file id8575 NCBI file	EvidenceTAS
GenePTPN2	AuthorityHGNC:9650	Mapping file id5771 NCBI file	EvidenceTAS
GeneSNCA	AuthorityHGNC:11138	Mapping file id6622 NCBI file	EvidenceTAS
GeneSPHK1	AuthorityHGNC:11240	Mapping file id8877 NCBI file	EvidenceTAS
GeneSTAT1	AuthorityHGNC:11362	Mapping file id6772 NCBI file	EvidenceTAS
GeneSTAT3	AuthorityHGNC:11364	Mapping file id6774 NCBI file	EvidenceTAS
GeneSUMO1	AuthorityHGNC:12502	Mapping file id7341 NCBI file	EvidenceTAS
GeneTARBP2	AuthorityHGNC:11569	Mapping file id6895 NCBI file	EvidenceTAS
GeneTP53	AuthorityHGNC:11998	Mapping file id7157 NCBI file	EvidenceTAS
GeneTRIM25	AuthorityHGNC:12932	Mapping file id7706 NCBI file	EvidenceTAS
GeneTUBA1A	AuthorityHGNC:20766	Mapping file id7846 NCBI file	EvidenceTAS
GeneTUBA1B	AuthorityHGNC:18809	Mapping file id10376 NCBI file	EvidenceTAS
GeneTUBA1C	AuthorityHGNC:20768	Mapping file id84790 NCBI file	EvidenceTAS
GeneTUBA3C	AuthorityHGNC:12408	Mapping file id7278 NCBI file	EvidenceTAS
GeneTUBA3D	AuthorityHGNC:24071	Mapping file id113457 NCBI file	EvidenceTAS
GeneTUBA3E	AuthorityHGNC:20765	Mapping file id112714 NCBI file	EvidenceTAS
GeneTUBA4A	AuthorityHGNC:12407	Mapping file id7277 NCBI file	EvidenceTAS
GeneTUBA4B	AuthorityHGNC:18637	Mapping file id80086 NCBI file	EvidenceTAS
GeneTUBA8	AuthorityHGNC:12410	Mapping file id51807 NCBI file	EvidenceTAS
GeneTUBAL3	AuthorityHGNC:23534	Mapping file id79861 NCBI file	EvidenceTAS
GeneTUBB1	AuthorityHGNC:16257	Mapping file id81027 NCBI file	EvidenceTAS
GeneTUBB2A	AuthorityHGNC:12412	Mapping file id7280 NCBI file	EvidenceTAS
GeneTUBB2B	AuthorityHGNC:30829	Mapping file id347733 NCBI file	EvidenceTAS
GeneTUBB3	AuthorityHGNC:20772	Mapping file id10381 NCBI file	EvidenceTAS
GeneTUBB4A	AuthorityHGNC:20774	Mapping file id10382 NCBI file	EvidenceTAS
GeneTUBB4B	AuthorityHGNC:20771	Mapping file id10383 NCBI file	EvidenceTAS
GeneTUBB6	AuthorityHGNC:20776	Mapping file id84617 NCBI file	EvidenceTAS
GeneTUBB8	AuthorityHGNC:20773	Mapping file id347688 NCBI file	EvidenceTAS
GeneTUBB8B	AuthorityHGNC:24983	Mapping file id260334 NCBI file	EvidenceTAS
GeneUBE2I	AuthorityHGNC:12485	Mapping file id7329 NCBI file	EvidenceTAS
GeneUBE2L6	AuthorityHGNC:12490	Mapping file id9246 NCBI file	EvidenceTAS
Geneno symbol in the identity file	Authoritynone	Mapping file id155871 NCBI file	EvidenceTAS
Geneno symbol in the identity file	Authoritynone	Mapping file id3077523 NCBI file	EvidenceTAS
Geneno symbol in the identity file	Authoritynone	Mapping file id956533 NCBI file	EvidenceTAS
Geneno symbol in the identity file	Authoritynone	Mapping file idNR_030583 as written	EvidenceTAS

Evidence codes on this page: TAS, as the mapping file writes them; a row carrying two was written twice by the file, once under each. The mapping file id says which file placed the gene: an NCBI Gene id from NCBI2Reactome_All_Levels.txt, an Ensembl gene id from Ensembl2Reactome_All_Levels.txt. The two files can disagree about a code, so a row's codes are the one file's view. Measured by this site's build over this release on 2026-09-09: of the 138,908 human pathway-gene pairs both files place, 207 (0.149 per cent, over 47 genes) carry TAS in the Ensembl file where the NCBI rows carry IEA alone.

Reactome mapping files, the human rows for this pathway · Reactome release 97 · read 2026-09-09 · Reactome downloads"NCBI2Reactome_All_Levels.txt" and "Ensembl2Reactome_All_Levels.txt", Reactome, release 97, https://reactome.org/download-data/ (date of access 2026-09-09). Data CC0; attribution encouraged.

03The hierarchy

Parents and children in this release's hierarchy

Parents

Antimicrobial mechanism of IFN-stimulated genesR-HSA-1169410234 genes

Children

None: no pathway of this release's list names this one as a parent.

Reactome's hierarchy is a graph rather than a tree: a pathway can sit under more than one parent, and the gene counts are each pathway's own placements at every level under it, so a parent's count is not the sum of its children's.

Reactome, the human pathway list and hierarchy relationship file · Reactome release 97 · read 2026-09-09 · Reactome downloads"ReactomePathways.txt" and "ReactomePathwaysRelation.txt", Reactome, release 97, https://reactome.org/download-data/ (date of access 2026-09-09). Data CC0; attribution encouraged.