Pathway Human Homo sapiens

Interleukin-1 signaling

R-HSA-9020702 in Reactome release 97: under Interleukin-1 family signaling, with 102 genes placed in it by the mapping files and 2 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-9020702 (mouse), R-RNO-9020702 (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-9020702.4
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2017-12-13
Last updated: 2022-06-09
Events inside: 37, counted from the record

Interleukin 1 (IL1) signals via Interleukin 1 receptor 1 (IL1R1), the only signaling-capable IL1 receptor. This is a single chain type 1 transmembrane protein comprising an extracellular ligand binding domain and an intracellular region called the Toll/Interleukin-1 receptor (TIR) domain that is structurally conserved and shared by other members of the two families of receptors (Xu et al. 2000). This domain is also shared by the downstream adapter molecule MyD88. IL1 binding to IL1R1 leads to the recruitment of a second receptor chain termed the IL1 receptor accessory protein (IL1RAP or IL1RAcP) enabling the formation of a high-affinity ligand-receptor complex that is capable of signal transduction. Intracellular signaling is initiated by the recruitment of MyD88 to the IL-1R1/IL1RAP complex. IL1RAP is only recruited to IL1R1 when IL1 is present; it is believed that a TIR domain signaling complex is formed between the receptor and the adapter TIR domains. The recruitment of MyD88 leads to the recruitment of Interleukin-1 receptor-associated kinase (IRAK)-1 and -4, probably via their death domains. IRAK4 then activates IRAK1, allowing IRAK1 to autophosphorylate. Both IRAK1 and IRAK4 then dissociate from MyD88 (Brikos et al. 2007) which remains stably complexed with IL-1R1 and IL1RAP. They in turn interact with Tumor Necrosis Factor Receptor (TNFR)-Associated Factor 6 (TRAF6), which is an E3 ubiquitin ligase (Deng et al. 2000). TRAF6 is then thought to auto-ubiquinate, attaching K63-polyubiquitin to itself with the assistance of the E2 conjugating complex Ubc13/Uev1a. K63-pUb-TRAF6 recruits Transforming Growth Factor (TGF) beta-activated protein kinase 1 (TAK1) in a complex with TAK1-binding protein 2 (TAB2) and TAB3, which both contain nuclear zinc finger motifs that interact with K63-polyubiquitin chains (Ninomiya-Tsuji et al. 1999). This activates TAK1, which then activates inhibitor of NF-kappaB (IkappaB) kinase 2 (IKK2 or IKKB) within the IKK complex, the kinase responsible for phosphorylation of IkappaB. The IKK complex also contains the scaffold protein NF-kappa B essential modulator (NEMO). TAK1 also couples to the upstream kinases for p38 and c-jun N-terminal kinase (JNK). IRAK1 undergoes K63-linked polyubiquination; Pellino E3 ligases are important in this process. (Butler et al. 2007; Ordureau et al. 2008). The activity of these proteins is greatly enhanced by IRAK phosphorylation (Schauvliege et al. 2006), leading to K63-linked polyubiquitination of IRAK1. This recruits NEMO to IRAK1, with NEMO binding to polyubiquitin (Conze et al. 2008).

TAK1 activates IKKB (and IKK), resulting in phosphorylation of the inhibitory IkB proteins and enabling translocation of NFkB to the nucleus; IKKB also phosphorylates NFkB p105, leading to its degradation and the subsequent release of active TPL2 that triggers the extracellular-signal regulated kinase (ERK)1/2 MAPK cascade. TAK1 can also trigger the p38 and JNK MAPK pathways via activating the upstream MKKs3, 4 and 6. The MAPK pathways activate a number of downstream kinases and transcription factors that co-operate with NFkB to induce the expression of a range of TLR/IL-1R-responsive genes. There are reports suggesting that IL1 stimulation increases nuclear localization of IRAK1 (Bol et al. 2000) and that nuclear IRAK1 binds to the promoter of NFkB-regulated gene and IkBa, enhancing binding of the NFkB p65 subunit to NFkB responsive elements within the IkBa promoter. IRAK1 is required for IL1-induced Ser-10 phosphorylation of histone H3 in vivo (Liu et al. 2008). However, details of this aspect of IRAK1 signaling mechanisms remain unclear. Interleukin-18 is another Interleukin-1 related cytokine which signals through IL18R and IL18RAP subunit receptors (which share homology with IL1R and IL1RAP in the cytokine signaling cascade). Later it follows a MYD88/IRAK1/TRAF6 cascade signaling until reach the NFKB activation (Moller et al. 2002). Interleukin 33, 36, 37 and 38 are relatively recently discovered Interleukin-1 related citokines which are also able to signal through IL1 receptor subunits or other as IL18R, IL37R (Schmitz et al. 2005, Yi et al. 2016, Lunding et al. 2015, van de Veendorck et al. 2012, Lin et al. 2001).

Literature Reactome attaches

Interleukin signalingCurr Biol, 2002, vol. 12, p. R760-3PubMed 12445398
Interleukin-1 (IL-1) pathwaySci Signal, 2010, vol. 3, p. cm1PubMed 20086235

Reactome's record lists 11 orthologous events, R-MMU-9020702 (Mus musculus), R-RNO-9020702 (Rattus norvegicus) among the species this site serves, and 9 in species this site opens no page for.

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-10-01 ET · Reactome pathway browser"Interleukin-1 signaling". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-9020702 with StableID: R-HSA-9020702.4 (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 102 genes in this human pathway; showing 1 to 100, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 1 of 2
Gene	Authority id	Mapping file id	Evidence codes
GeneADRM1	AuthorityHGNC:15759	Mapping file id11047 NCBI file	EvidenceTAS
GeneAGER	AuthorityHGNC:320	Mapping file id177 NCBI file	EvidenceTAS
GeneALPK1	AuthorityHGNC:20917	Mapping file id80216 NCBI file	EvidenceTAS
GeneAPP	AuthorityHGNC:620	Mapping file id351 NCBI file	EvidenceTAS
GeneBTRC	AuthorityHGNC:1144	Mapping file id8945 NCBI file	EvidenceTAS
GeneCASP8	AuthorityHGNC:1509	Mapping file id841 NCBI file	EvidenceTAS
GeneCHUK	AuthorityHGNC:1974	Mapping file id1147 NCBI file	EvidenceTAS
GeneCUL1	AuthorityHGNC:2551	Mapping file id8454 NCBI file	EvidenceTAS
GeneFBXW11	AuthorityHGNC:13607	Mapping file id23291 NCBI file	EvidenceTAS
GeneHMGB1	AuthorityHGNC:4983	Mapping file id3146 NCBI file	EvidenceTAS
GeneIKBIP	AuthorityHGNC:26430	Mapping file id121457 NCBI file	EvidenceTAS
GeneIKBKB	AuthorityHGNC:5960	Mapping file id3551 NCBI file	EvidenceTAS
GeneIKBKG	AuthorityHGNC:5961	Mapping file id8517 NCBI file	EvidenceTAS
GeneIL1A	AuthorityHGNC:5991	Mapping file id3552 NCBI file	EvidenceTAS
GeneIL1B	AuthorityHGNC:5992	Mapping file id3553 NCBI file	EvidenceTAS
GeneIL1R1	AuthorityHGNC:5993	Mapping file id3554 NCBI file	EvidenceTAS
GeneIL1R2	AuthorityHGNC:5994	Mapping file id7850 NCBI file	EvidenceTAS
GeneIL1RAP	AuthorityHGNC:5995	Mapping file id3556 NCBI file	EvidenceTAS
GeneIL1RN	AuthorityHGNC:6000	Mapping file id3557 NCBI file	EvidenceTAS
GeneIRAK1	AuthorityHGNC:6112	Mapping file id3654 NCBI file	EvidenceTAS
GeneIRAK2	AuthorityHGNC:6113	Mapping file id3656 NCBI file	EvidenceTAS
GeneIRAK3	AuthorityHGNC:17020	Mapping file id11213 NCBI file	EvidenceTAS
GeneIRAK4	AuthorityHGNC:17967	Mapping file id51135 NCBI file	EvidenceTAS
GeneLRRC14	AuthorityHGNC:20419	Mapping file id9684 NCBI file	EvidenceTAS
GeneMAP2K1	AuthorityHGNC:6840	Mapping file id5604 NCBI file	EvidenceIEA
GeneMAP2K4	AuthorityHGNC:6844	Mapping file id6416 NCBI file	EvidenceIEA
GeneMAP2K6	AuthorityHGNC:6846	Mapping file id5608 NCBI file	EvidenceTAS
GeneMAP3K3	AuthorityHGNC:6855	Mapping file id4215 NCBI file	EvidenceTAS
GeneMAP3K7	AuthorityHGNC:6859	Mapping file id6885 NCBI file	EvidenceTAS
GeneMAP3K8	AuthorityHGNC:6860	Mapping file id1326 NCBI file	EvidenceIEA, TAS
GeneMYD88	AuthorityHGNC:7562	Mapping file id4615 NCBI file	EvidenceTAS
GeneN4BP1	AuthorityHGNC:29850	Mapping file id9683 NCBI file	EvidenceTAS
GeneNFKB1	AuthorityHGNC:7794	Mapping file id4790 NCBI file	EvidenceTAS
GeneNFKB2	AuthorityHGNC:7795	Mapping file id4791 NCBI file	EvidenceTAS
GeneNFKBIA	AuthorityHGNC:7797	Mapping file id4792 NCBI file	EvidenceTAS
GeneNFKBIB	AuthorityHGNC:7798	Mapping file id4793 NCBI file	EvidenceTAS
GeneNKIRAS1	AuthorityHGNC:17899	Mapping file id28512 NCBI file	EvidenceTAS
GeneNKIRAS2	AuthorityHGNC:17898	Mapping file id28511 NCBI file	EvidenceTAS
GeneNLRC5	AuthorityHGNC:29933	Mapping file id84166 NCBI file	EvidenceTAS
GeneNLRX1	AuthorityHGNC:29890	Mapping file id79671 NCBI file	EvidenceTAS
GeneNOD1	AuthorityHGNC:16390	Mapping file id10392 NCBI file	EvidenceTAS
GeneNOD2	AuthorityHGNC:5331	Mapping file id64127 NCBI file	EvidenceTAS
GenePELI1	AuthorityHGNC:8827	Mapping file id57162 NCBI file	EvidenceTAS
GenePELI2	AuthorityHGNC:8828	Mapping file id57161 NCBI file	EvidenceTAS
GenePELI3	AuthorityHGNC:30010	Mapping file id246330 NCBI file	EvidenceTAS
GenePSMA1	AuthorityHGNC:9530	Mapping file id5682 NCBI file	EvidenceTAS
GenePSMA2	AuthorityHGNC:9531	Mapping file id5683 NCBI file	EvidenceTAS
GenePSMA3	AuthorityHGNC:9532	Mapping file id5684 NCBI file	EvidenceTAS
GenePSMA4	AuthorityHGNC:9533	Mapping file id5685 NCBI file	EvidenceTAS
GenePSMA5	AuthorityHGNC:9534	Mapping file id5686 NCBI file	EvidenceTAS
GenePSMA6	AuthorityHGNC:9535	Mapping file id5687 NCBI file	EvidenceTAS
GenePSMA7	AuthorityHGNC:9536	Mapping file id5688 NCBI file	EvidenceTAS
GenePSMB1	AuthorityHGNC:9537	Mapping file id5689 NCBI file	EvidenceTAS
GenePSMB2	AuthorityHGNC:9539	Mapping file id5690 NCBI file	EvidenceTAS
GenePSMB3	AuthorityHGNC:9540	Mapping file id5691 NCBI file	EvidenceTAS
GenePSMB4	AuthorityHGNC:9541	Mapping file id5692 NCBI file	EvidenceTAS
GenePSMB5	AuthorityHGNC:9542	Mapping file id5693 NCBI file	EvidenceTAS
GenePSMB6	AuthorityHGNC:9543	Mapping file id5694 NCBI file	EvidenceTAS
GenePSMB7	AuthorityHGNC:9544	Mapping file id5695 NCBI file	EvidenceTAS
GenePSMC1	AuthorityHGNC:9547	Mapping file id5700 NCBI file	EvidenceTAS
GenePSMC2	AuthorityHGNC:9548	Mapping file id5701 NCBI file	EvidenceTAS
GenePSMC3	AuthorityHGNC:9549	Mapping file id5702 NCBI file	EvidenceTAS
GenePSMC4	AuthorityHGNC:9551	Mapping file id5704 NCBI file	EvidenceTAS
GenePSMC5	AuthorityHGNC:9552	Mapping file id5705 NCBI file	EvidenceTAS
GenePSMC6	AuthorityHGNC:9553	Mapping file id5706 NCBI file	EvidenceTAS
GenePSMD1	AuthorityHGNC:9554	Mapping file id5707 NCBI file	EvidenceTAS
GenePSMD11	AuthorityHGNC:9556	Mapping file id5717 NCBI file	EvidenceTAS
GenePSMD12	AuthorityHGNC:9557	Mapping file id5718 NCBI file	EvidenceTAS
GenePSMD13	AuthorityHGNC:9558	Mapping file id5719 NCBI file	EvidenceTAS
GenePSMD14	AuthorityHGNC:16889	Mapping file id10213 NCBI file	EvidenceTAS
GenePSMD2	AuthorityHGNC:9559	Mapping file id5708 NCBI file	EvidenceTAS
GenePSMD3	AuthorityHGNC:9560	Mapping file id5709 NCBI file	EvidenceTAS
GenePSMD6	AuthorityHGNC:9564	Mapping file id9861 NCBI file	EvidenceTAS
GenePSMD7	AuthorityHGNC:9565	Mapping file id5713 NCBI file	EvidenceTAS
GenePSMD8	AuthorityHGNC:9566	Mapping file id5714 NCBI file	EvidenceTAS
GeneRBX1	AuthorityHGNC:9928	Mapping file id9978 NCBI file	EvidenceTAS
GeneRELA	AuthorityHGNC:9955	Mapping file id5970 NCBI file	EvidenceTAS
GeneRIPK2	AuthorityHGNC:10020	Mapping file id8767 NCBI file	EvidenceTAS
GeneRPS27A	AuthorityHGNC:10417	Mapping file id6233 NCBI file	EvidenceTAS
GeneS100A12	AuthorityHGNC:10489	Mapping file id6283 NCBI file	EvidenceTAS
GeneS100B	AuthorityHGNC:10500	Mapping file id6285 NCBI file	EvidenceTAS
GeneSAA1	AuthorityHGNC:10513	Mapping file id6288 NCBI file	EvidenceTAS
GeneSEM1	AuthorityHGNC:10845	Mapping file id7979 NCBI file	EvidenceTAS
GeneSKP1	AuthorityHGNC:10899	Mapping file id6500 NCBI file	EvidenceTAS
GeneSQSTM1	AuthorityHGNC:11280	Mapping file id8878 NCBI file	EvidenceTAS
GeneTAB1	AuthorityHGNC:18157	Mapping file id10454 NCBI file	EvidenceTAS
GeneTAB2	AuthorityHGNC:17075	Mapping file id23118 NCBI file	EvidenceTAS
GeneTAB3	AuthorityHGNC:30681	Mapping file id257397 NCBI file	EvidenceTAS
GeneTIFA	AuthorityHGNC:19075	Mapping file id92610 NCBI file	EvidenceTAS
GeneTNIP2	AuthorityHGNC:19118	Mapping file id79155 NCBI file	EvidenceTAS
GeneTOLLIP	AuthorityHGNC:16476	Mapping file id54472 NCBI file	EvidenceTAS
GeneTP53	AuthorityHGNC:11998	Mapping file id7157 NCBI file	EvidenceTAS
GeneTRAF2	AuthorityHGNC:12032	Mapping file id7186 NCBI file	EvidenceTAS
GeneTRAF6	AuthorityHGNC:12036	Mapping file id7189 NCBI file	EvidenceTAS
GeneUBA52	AuthorityHGNC:12458	Mapping file id7311 NCBI file	EvidenceTAS
GeneUBB	AuthorityHGNC:12463	Mapping file id7314 NCBI file	EvidenceTAS
GeneUBC	AuthorityHGNC:12468	Mapping file id7316 NCBI file	EvidenceTAS
GeneUBE2N	AuthorityHGNC:12492	Mapping file id7334 NCBI file	EvidenceTAS
GeneUBE2V1	AuthorityHGNC:12494	Mapping file id7335 NCBI file	EvidenceTAS
GeneUSP14	AuthorityHGNC:12612	Mapping file id9097 NCBI file	EvidenceTAS

Evidence codes on this page: IEA, 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

Interleukin-1 family signalingR-HSA-446652140 genes

Children

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.