Pathway Human Homo sapiens

Signal Transduction

R-HSA-162582 in Reactome release 97: a top-level pathway, with 2,631 genes placed in it by the mapping files and 17 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-162582 (mouse), R-RNO-162582 (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-162582.13
Class: TopLevelPathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2011-09-20
Last updated: 2023-06-07
Events inside: 17, counted from the record
Also named: Signaling Pathways

Signal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such as hormones and growth factors, or reacting to other types of stimuli, such as light. Stimulation of transmembrane receptors leads to their conformational change which propagates the signal to the intracellular environment by activating downstream signaling cascades. Depending on the cellular context, this may impact cellular proliferation, differentiation, and survival. On the organism level, signal transduction regulates overall growth and behavior.

Receptor tyrosine kinases (RTKs) transmit extracellular signals by phosphorylating their protein partners on conserved tyrosine residues. Some of the best studied RTKs are EGFR (reviewed in Avraham and Yarden, 2011), FGFR (reviewed in Eswarakumar et al, 2005), insulin receptor (reviewed in Saltiel and Kahn, 2001), NGF (reviewed in Reichardt, 2006), PDGF (reviewed in Andrae et al, 2008) and VEGF (reviewed in Xie et al, 2004). RTKs frequently activate downstream signaling through RAF/MAP kinases (reviewed in McKay and Morrison, 2007 and Wellbrock et al 2004), AKT (reviewed in Manning and Cantley, 2007) and PLC- gamma (reviewed in Patterson et al, 2005), which ultimately results in changes in gene expression and cellular metabolism.

Receptor serine/threonine kinases of the TGF-beta family, such as TGF-beta receptors (reviewed in Kang et al. 2009) and BMP receptors (reviewed in Miyazono et al. 2009), transmit extracellular signals by phosphorylating regulatory SMAD proteins on conserved serine and threonine residues. This leads to formation of complexes of regulatory SMADs and SMAD4, which translocate to the nucleus where they act as transcription factors.

WNT receptors transmit their signal through beta-catenin. In the absence of ligand, beta-catenin is constitutively degraded in a ubiquitin-dependent manner. WNT receptor stimulation releases beta-catenin from the destruction complex, allowing it to translocate to the nucleus where it acts as a transcriptional regulator (reviewed in MacDonald et al, 2009 and Angers and Moon, 2009). WNT receptors were originally classified as G-protein coupled receptors (GPCRs). Although they are structurally related, GPCRs primarily transmit their signals through G-proteins, which are trimers of alpha, beta and gamma subunits. When a GPCR is activated, it acts as a guanine nucleotide exchange factor, catalyzing GDP to GTP exchange on the G-alpha subunit of the G protein and its dissociation from the gamma-beta heterodimer. The G-alpha subunit regulates the activity of adenylate cyclase, while the gamma-beta heterodimer can activate AKT and PLC signaling (reviewed in Rosenbaum et al. 2009, Oldham and Hamm 2008, Ritter and Hall 2009).

NOTCH receptors are activated by transmembrane ligands expressed on neighboring cells, which results in cleavage of NOTCH receptor and release of its intracellular domain. NOTCH intracellular domain translocates to the nucleus where it acts as a transcription factor (reviewed in Kopan and Ilagan, 2009).

Integrins are activated by extracellular matrix components, such as fibronectin and collagen, leading to conformational change and clustering of integrins on the cell surface. This results in activation of integrin-linked kinase and other cytosolic kinases and, in co-operation with RTK signaling, regulates survival, proliferation and cell shape and adhesion (reviewed in Hehlgans et al, 2007) .

Besides inducing changes in gene expression and cellular metabolism, extracellular signals that trigger the activation of Rho GTP-ases can trigger changes in the organization of cytoskeleton, thereby regulating cell polarity and cell-cell junctions (reviewed in Citi et al, 2011).

Literature Reactome attaches

AKT/PKB signaling: navigating downstreamCell, 2007, vol. 129, p. 1261-74PubMed 17604717
The canonical Notch signaling pathway: unfolding the activation mechanismCell, 2009, vol. 137, p. 216-33PubMed 19379690
New regulatory mechanisms of TGF-beta receptor functionTrends Cell Biol, 2009, vol. 19, p. 385-94PubMed 19648010
Bone morphogenetic protein receptors and signal transductionJ Biochem, 2010, vol. 147, p. 35-51PubMed 19762341
Feedback regulation of EGFR signalling: decision making by early and delayed loopsNat Rev Mol Cell Biol, 2011, vol. 12, p. 104-17PubMed 21252999
Heterotrimeric G protein activation by G-protein-coupled receptorsNat Rev Mol Cell Biol, 2008, vol. 9, p. 60-71PubMed 18043707
Fine-tuning of GPCR activity by receptor-interacting proteinsNat Rev Mol Cell Biol, 2009, vol. 10, p. 819-30PubMed 19935667

Reactome's record lists 14 orthologous events, R-MMU-162582 (Mus musculus), R-RNO-162582 (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 2026-10-06 ET · Reactome pathway browser"Signal Transduction". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-162582 with StableID: R-HSA-162582.13 (accessed 2026-10-06 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 2,631 genes in this human pathway; showing 1,101 to 1,200, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 12 of 27
Gene	Authority id	Mapping file id	Evidence codes
GeneHDAC1	AuthorityHGNC:4852	Mapping file id3065 NCBI file	EvidenceIEA, TAS
GeneHDAC10	AuthorityHGNC:18128	Mapping file id83933 NCBI file	EvidenceIEA
GeneHDAC11	AuthorityHGNC:19086	Mapping file id79885 NCBI file	EvidenceIEA
GeneHDAC2	AuthorityHGNC:4853	Mapping file id3066 NCBI file	EvidenceIEA, TAS
GeneHDAC3	AuthorityHGNC:4854	Mapping file id8841 NCBI file	EvidenceIEA, TAS
GeneHDAC4	AuthorityHGNC:14063	Mapping file id9759 NCBI file	EvidenceIEA
GeneHDAC5	AuthorityHGNC:14068	Mapping file id10014 NCBI file	EvidenceIEA
GeneHDAC6	AuthorityHGNC:14064	Mapping file id10013 NCBI file	EvidenceIEA
GeneHDAC7	AuthorityHGNC:14067	Mapping file id51564 NCBI file	EvidenceIEA
GeneHDAC8	AuthorityHGNC:13315	Mapping file id55869 NCBI file	EvidenceIEA
GeneHDAC9	AuthorityHGNC:14065	Mapping file id9734 NCBI file	EvidenceIEA
GeneHEBP1	AuthorityHGNC:17176	Mapping file id50865 NCBI file	EvidenceTAS
GeneHECW1	AuthorityHGNC:22195	Mapping file id23072 NCBI file	EvidenceTAS
GeneHELLS	AuthorityHGNC:4861	Mapping file id3070 NCBI file	EvidenceTAS
GeneHES1	AuthorityHGNC:5192	Mapping file id3280 NCBI file	EvidenceIEA, TAS
GeneHES5	AuthorityHGNC:19764	Mapping file id388585 NCBI file	EvidenceIEA, TAS
GeneHEY1	AuthorityHGNC:4880	Mapping file id23462 NCBI file	EvidenceIEA, TAS
GeneHEY2	AuthorityHGNC:4881	Mapping file id23493 NCBI file	EvidenceIEA, TAS
GeneHEYL	AuthorityHGNC:4882	Mapping file id26508 NCBI file	EvidenceIEA, TAS
GeneHGF	AuthorityHGNC:4893	Mapping file id3082 NCBI file	EvidenceTAS
GeneHGFAC	AuthorityHGNC:4894	Mapping file id3083 NCBI file	EvidenceTAS
GeneHGS	AuthorityHGNC:4897	Mapping file id9146 NCBI file	EvidenceTAS
GeneHHAT	AuthorityHGNC:18270	Mapping file id55733 NCBI file	EvidenceTAS
GeneHHIP	AuthorityHGNC:14866	Mapping file id64399 NCBI file	EvidenceTAS
GeneHIF1A	AuthorityHGNC:4910	Mapping file id3091 NCBI file	EvidenceIEA, TAS
GeneHINT2	AuthorityHGNC:18344	Mapping file id84681 NCBI file	EvidenceTAS
GeneHMOX2	AuthorityHGNC:5014	Mapping file id3163 NCBI file	EvidenceTAS
GeneHNRNPA1	AuthorityHGNC:5031	Mapping file id3178 NCBI file	EvidenceTAS
GeneHNRNPC	AuthorityHGNC:5035	Mapping file id3183 NCBI file	EvidenceTAS
GeneHNRNPF	AuthorityHGNC:5039	Mapping file id3185 NCBI file	EvidenceTAS
GeneHNRNPH1	AuthorityHGNC:5041	Mapping file id3187 NCBI file	EvidenceTAS
GeneHNRNPM	AuthorityHGNC:5046	Mapping file id4670 NCBI file	EvidenceTAS
GeneHPN	AuthorityHGNC:5155	Mapping file id3249 NCBI file	EvidenceTAS
GeneHRAS	AuthorityHGNC:5173	Mapping file id3265 NCBI file	EvidenceIEA, TAS
GeneHRH1	AuthorityHGNC:5182	Mapping file id3269 NCBI file	EvidenceTAS
GeneHRH2	AuthorityHGNC:5183	Mapping file id3274 NCBI file	EvidenceTAS
GeneHRH3	AuthorityHGNC:5184	Mapping file id11255 NCBI file	EvidenceTAS
GeneHRH4	AuthorityHGNC:17383	Mapping file id59340 NCBI file	EvidenceTAS
GeneHSP90AA1	AuthorityHGNC:5253	Mapping file id3320 NCBI file	EvidenceIEA, TAS
GeneHSP90AB1	AuthorityHGNC:5258	Mapping file id3326 NCBI file	EvidenceTAS
GeneHSPB1	AuthorityHGNC:5246	Mapping file id3315 NCBI file	EvidenceTAS
GeneHSPE1	AuthorityHGNC:5269	Mapping file id3336 NCBI file	EvidenceTAS
GeneHTR1A	AuthorityHGNC:5286	Mapping file id3350 NCBI file	EvidenceTAS
GeneHTR1B	AuthorityHGNC:5287	Mapping file id3351 NCBI file	EvidenceTAS
GeneHTR1D	AuthorityHGNC:5289	Mapping file id3352 NCBI file	EvidenceTAS
GeneHTR1E	AuthorityHGNC:5291	Mapping file id3354 NCBI file	EvidenceTAS
GeneHTR1F	AuthorityHGNC:5292	Mapping file id3355 NCBI file	EvidenceTAS
GeneHTR2A	AuthorityHGNC:5293	Mapping file id3356 NCBI file	EvidenceTAS
GeneHTR2B	AuthorityHGNC:5294	Mapping file id3357 NCBI file	EvidenceTAS
GeneHTR2C	AuthorityHGNC:5295	Mapping file id3358 NCBI file	EvidenceTAS
GeneHTR4	AuthorityHGNC:5299	Mapping file id3360 NCBI file	EvidenceTAS
GeneHTR5A	AuthorityHGNC:5300	Mapping file id3361 NCBI file	EvidenceTAS
GeneHTR6	AuthorityHGNC:5301	Mapping file id3362 NCBI file	EvidenceTAS
GeneHTR7	AuthorityHGNC:5302	Mapping file id3363 NCBI file	EvidenceTAS
GeneIAPP	AuthorityHGNC:5329	Mapping file id3375 NCBI file	EvidenceTAS
GeneICMT	AuthorityHGNC:5350	Mapping file id23463 NCBI file	EvidenceTAS
GeneICOS	AuthorityHGNC:5351	Mapping file id29851 NCBI file	EvidenceTAS
GeneID1	AuthorityHGNC:5360	Mapping file id3397 NCBI file	EvidenceTAS
GeneID2	AuthorityHGNC:5361	Mapping file id3398 NCBI file	EvidenceTAS
GeneID3	AuthorityHGNC:5362	Mapping file id3399 NCBI file	EvidenceTAS
GeneID4	AuthorityHGNC:5363	Mapping file id3400 NCBI file	EvidenceTAS
GeneIDE	AuthorityHGNC:5381	Mapping file id3416 NCBI file	EvidenceTAS
GeneIER3	AuthorityHGNC:5392	Mapping file id8870 NCBI file	EvidenceTAS
GeneIFT122	AuthorityHGNC:13556	Mapping file id55764 NCBI file	EvidenceTAS
GeneIFT140	AuthorityHGNC:29077	Mapping file id9742 NCBI file	EvidenceTAS
GeneIFT172	AuthorityHGNC:30391	Mapping file id26160 NCBI file	EvidenceTAS
GeneIFT52	AuthorityHGNC:15901	Mapping file id51098 NCBI file	EvidenceTAS
GeneIFT57	AuthorityHGNC:17367	Mapping file id55081 NCBI file	EvidenceTAS
GeneIFT88	AuthorityHGNC:20606	Mapping file id8100 NCBI file	EvidenceTAS
GeneIGF1	AuthorityHGNC:5464	Mapping file id3479 NCBI file	EvidenceTAS
GeneIGF1R	AuthorityHGNC:5465	Mapping file id3480 NCBI file	EvidenceTAS
GeneIGF2	AuthorityHGNC:5466	Mapping file id3481 NCBI file	EvidenceTAS
GeneIGF2BP1	AuthorityHGNC:28866	Mapping file id10642 NCBI file	EvidenceTAS
GeneIHH	AuthorityHGNC:5956	Mapping file id3549 NCBI file	EvidenceIEA, TAS
GeneIKBKB	AuthorityHGNC:5960	Mapping file id3551 NCBI file	EvidenceTAS
GeneIKBKE	AuthorityHGNC:14552	Mapping file id9641 NCBI file	EvidenceTAS
GeneIKBKG	AuthorityHGNC:5961	Mapping file id8517 NCBI file	EvidenceTAS
GeneIKZF1	AuthorityHGNC:13176	Mapping file id10320 NCBI file	EvidenceIEA
GeneIL17RD	AuthorityHGNC:17616	Mapping file id54756 NCBI file	EvidenceTAS
GeneIL1RAP	AuthorityHGNC:5995	Mapping file id3556 NCBI file	EvidenceTAS
GeneIL2	AuthorityHGNC:6001	Mapping file id3558 NCBI file	EvidenceTAS
GeneIL2RA	AuthorityHGNC:6008	Mapping file id3559 NCBI file	EvidenceTAS
GeneIL2RB	AuthorityHGNC:6009	Mapping file id3560 NCBI file	EvidenceTAS
GeneIL2RG	AuthorityHGNC:6010	Mapping file id3561 NCBI file	EvidenceTAS
GeneIL3	AuthorityHGNC:6011	Mapping file id3562 NCBI file	EvidenceTAS
GeneIL32	AuthorityHGNC:16830	Mapping file id9235 NCBI file	EvidenceTAS
GeneIL33	AuthorityHGNC:16028	Mapping file id90865 NCBI file	EvidenceTAS
GeneIL33R	AuthorityHGNC:5998	Mapping file id9173 NCBI file	EvidenceTAS
GeneIL3RA	AuthorityHGNC:6012	Mapping file id3563 NCBI file	EvidenceTAS
GeneIL5	AuthorityHGNC:6016	Mapping file id3567 NCBI file	EvidenceTAS
GeneIL5RA	AuthorityHGNC:6017	Mapping file id3568 NCBI file	EvidenceTAS
GeneIL6	AuthorityHGNC:6018	Mapping file id3569 NCBI file	EvidenceTAS
GeneIL6R	AuthorityHGNC:6019	Mapping file id3570 NCBI file	EvidenceTAS
GeneIL6ST	AuthorityHGNC:6021	Mapping file id3572 NCBI file	EvidenceTAS
GeneINCENP	AuthorityHGNC:6058	Mapping file id3619 NCBI file	EvidenceTAS
GeneINHA	AuthorityHGNC:6065	Mapping file id3623 NCBI file	EvidenceIEA, TAS
GeneINHBA	AuthorityHGNC:6066	Mapping file id3624 NCBI file	EvidenceIEA, TAS
GeneINHBB	AuthorityHGNC:6067	Mapping file id3625 NCBI file	EvidenceIEA, TAS
GeneINS	AuthorityHGNC:6081	Mapping file id3630 NCBI file	EvidenceTAS
GeneINSL3	AuthorityHGNC:6086	Mapping file id3640 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

None: this is a top-level pathway of the release.

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.