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

Scripts are off

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 2026-10-05 ET · Reactome pathway browser"Signal Transduction". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-162582 with StableID: R-HSA-162582.13 (accessed 2026-10-05 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 701 to 800, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 8 of 27
Gene	Authority id	Mapping file id	Evidence codes
GeneEDN3	AuthorityHGNC:3178	Mapping file id1908 NCBI file	EvidenceTAS
GeneEDNRA	AuthorityHGNC:3179	Mapping file id1909 NCBI file	EvidenceTAS
GeneEDNRB	AuthorityHGNC:3180	Mapping file id1910 NCBI file	EvidenceTAS
GeneEED	AuthorityHGNC:3188	Mapping file id8726 NCBI file	EvidenceIEA, TAS
GeneEEF1AKMT4-ECE2	AuthorityHGNC:53615	Mapping file id110599583 NCBI file	EvidenceTAS
GeneEEF2K	AuthorityHGNC:24615	Mapping file id29904 NCBI file	EvidenceTAS
GeneEEPD1	AuthorityHGNC:22223	Mapping file id80820 NCBI file	EvidenceTAS
GeneEFCAB7	AuthorityHGNC:29379	Mapping file id84455 NCBI file	EvidenceTAS
GeneEFHD2	AuthorityHGNC:28670	Mapping file id79180 NCBI file	EvidenceTAS
GeneEGF	AuthorityHGNC:3229	Mapping file id1950 NCBI file	EvidenceIEA, TAS
GeneEGFR	AuthorityHGNC:3236	Mapping file id1956 NCBI file	EvidenceIEA, TAS
GeneEGR1	AuthorityHGNC:3238	Mapping file id1958 NCBI file	EvidenceIEA, TAS
GeneEGR2	AuthorityHGNC:3239	Mapping file id1959 NCBI file	EvidenceIEA, TAS
GeneEGR3	AuthorityHGNC:3240	Mapping file id1960 NCBI file	EvidenceIEA, TAS
GeneEGR4	AuthorityHGNC:3241	Mapping file id1961 NCBI file	EvidenceTAS
GeneEIF4B	AuthorityHGNC:3285	Mapping file id1975 NCBI file	EvidenceTAS
GeneEIF4E	AuthorityHGNC:3287	Mapping file id1977 NCBI file	EvidenceTAS
GeneEIF4EBP1	AuthorityHGNC:3288	Mapping file id1978 NCBI file	EvidenceTAS
GeneEIF4G1	AuthorityHGNC:3296	Mapping file id1981 NCBI file	EvidenceTAS
GeneELANE	AuthorityHGNC:3309	Mapping file id1991 NCBI file	EvidenceTAS
GeneELF3	AuthorityHGNC:3318	Mapping file id1999 NCBI file	EvidenceTAS
GeneELK1	AuthorityHGNC:3321	Mapping file id2002 NCBI file	EvidenceIEA, TAS
GeneELMO1	AuthorityHGNC:16286	Mapping file id9844 NCBI file	EvidenceTAS
GeneELMO2	AuthorityHGNC:17233	Mapping file id63916 NCBI file	EvidenceTAS
GeneEMC3	AuthorityHGNC:23999	Mapping file id55831 NCBI file	EvidenceTAS
GeneEMD	AuthorityHGNC:3331	Mapping file id2010 NCBI file	EvidenceTAS
GeneEP300	AuthorityHGNC:3373	Mapping file id2033 NCBI file	EvidenceIEA, TAS
GeneEPAS1	AuthorityHGNC:3374	Mapping file id2034 NCBI file	EvidenceTAS
GeneEPGN	AuthorityHGNC:17470	Mapping file id255324 NCBI file	EvidenceTAS
GeneEPHA2	AuthorityHGNC:3386	Mapping file id1969 NCBI file	EvidenceTAS
GeneEPN1	AuthorityHGNC:21604	Mapping file id29924 NCBI file	EvidenceTAS
GeneEPO	AuthorityHGNC:3415	Mapping file id2056 NCBI file	EvidenceIEA, TAS
GeneEPOR	AuthorityHGNC:3416	Mapping file id2057 NCBI file	EvidenceIEA, TAS
GeneEPS15	AuthorityHGNC:3419	Mapping file id2060 NCBI file	EvidenceTAS
GeneEPS15L1	AuthorityHGNC:24634	Mapping file id58513 NCBI file	EvidenceTAS
GeneEPSTI1	AuthorityHGNC:16465	Mapping file id94240 NCBI file	EvidenceTAS
GeneERBB2	AuthorityHGNC:3430	Mapping file id2064 NCBI file	EvidenceIEA, TAS
GeneERBB3	AuthorityHGNC:3431	Mapping file id2065 NCBI file	EvidenceIEA, TAS
GeneERBB4	AuthorityHGNC:3432	Mapping file id2066 NCBI file	EvidenceIEA, TAS
GeneERBIN	AuthorityHGNC:15842	Mapping file id55914 NCBI file	EvidenceTAS
GeneERCC6L	AuthorityHGNC:20794	Mapping file id54821 NCBI file	EvidenceTAS
GeneEREG	AuthorityHGNC:3443	Mapping file id2069 NCBI file	EvidenceIEA, TAS
GeneERLEC1	AuthorityHGNC:25222	Mapping file id27248 NCBI file	EvidenceTAS
GeneESR1	AuthorityHGNC:3467	Mapping file id2099 NCBI file	EvidenceTAS
GeneESR2	AuthorityHGNC:3468	Mapping file id2100 NCBI file	EvidenceTAS
GeneESRP1	AuthorityHGNC:25966	Mapping file id54845 NCBI file	EvidenceTAS
GeneESRP2	AuthorityHGNC:26152	Mapping file id80004 NCBI file	EvidenceTAS
GeneESYT1	AuthorityHGNC:29534	Mapping file id23344 NCBI file	EvidenceTAS
GeneETV4	AuthorityHGNC:3493	Mapping file id2118 NCBI file	EvidenceTAS
GeneEVC	AuthorityHGNC:3497	Mapping file id2121 NCBI file	EvidenceIEA, TAS
GeneEVC2	AuthorityHGNC:19747	Mapping file id132884 NCBI file	EvidenceIEA, TAS
GeneEVL	AuthorityHGNC:20234	Mapping file id51466 NCBI file	EvidenceTAS
GeneEZH2	AuthorityHGNC:3527	Mapping file id2146 NCBI file	EvidenceIEA, TAS
GeneF11R	AuthorityHGNC:14685	Mapping file id50848 NCBI file	EvidenceIEA, TAS
GeneF2	AuthorityHGNC:3535	Mapping file id2147 NCBI file	EvidenceTAS
GeneF2R	AuthorityHGNC:3537	Mapping file id2149 NCBI file	EvidenceTAS
GeneF2RL1	AuthorityHGNC:3538	Mapping file id2150 NCBI file	EvidenceTAS
GeneF2RL2	AuthorityHGNC:3539	Mapping file id2151 NCBI file	EvidenceTAS
GeneF2RL3	AuthorityHGNC:3540	Mapping file id9002 NCBI file	EvidenceTAS
GeneF3	AuthorityHGNC:3541	Mapping file id2152 NCBI file	EvidenceTAS
GeneFABP5	AuthorityHGNC:3560	Mapping file id2171 NCBI file	EvidenceTAS
GeneFABP6	AuthorityHGNC:3561	Mapping file id2172 NCBI file	EvidenceTAS
GeneFABP7	AuthorityHGNC:3562	Mapping file id2173 NCBI file	EvidenceIEA
GeneFADD	AuthorityHGNC:3573	Mapping file id8772 NCBI file	EvidenceTAS
GeneFAF2	AuthorityHGNC:24666	Mapping file id23197 NCBI file	EvidenceTAS
GeneFAM135A	AuthorityHGNC:21084	Mapping file id57579 NCBI file	EvidenceTAS
GeneFAM13A	AuthorityHGNC:19367	Mapping file id10144 NCBI file	EvidenceTAS
GeneFAM13B	AuthorityHGNC:1335	Mapping file id51306 NCBI file	EvidenceTAS
GeneFAM169A	AuthorityHGNC:29138	Mapping file id26049 NCBI file	EvidenceTAS
GeneFAM91A1	AuthorityHGNC:26306	Mapping file id157769 NCBI file	EvidenceTAS
GeneFARP1	AuthorityHGNC:3591	Mapping file id10160 NCBI file	EvidenceTAS
GeneFARP2	AuthorityHGNC:16460	Mapping file id9855 NCBI file	EvidenceTAS
GeneFAS	AuthorityHGNC:11920	Mapping file id355 NCBI file	EvidenceTAS
GeneFASLG	AuthorityHGNC:11936	Mapping file id356 NCBI file	EvidenceTAS
GeneFASN	AuthorityHGNC:3594	Mapping file id2194 NCBI file	EvidenceTAS
GeneFBN1	AuthorityHGNC:3603	Mapping file id2200 NCBI file	EvidenceTAS
GeneFBXW7	AuthorityHGNC:16712	Mapping file id55294 NCBI file	EvidenceIEA
GeneFCER2	AuthorityHGNC:3612	Mapping file id2208 NCBI file	EvidenceTAS
GeneFER	AuthorityHGNC:3655	Mapping file id2241 NCBI file	EvidenceTAS
GeneFERMT2	AuthorityHGNC:15767	Mapping file id10979 NCBI file	EvidenceTAS
GeneFES	AuthorityHGNC:3657	Mapping file id2242 NCBI file	EvidenceTAS
GeneFFAR1	AuthorityHGNC:4498	Mapping file id2864 NCBI file	EvidenceTAS
GeneFFAR2	AuthorityHGNC:4501	Mapping file id2867 NCBI file	EvidenceTAS
GeneFFAR3	AuthorityHGNC:4499	Mapping file id2865 NCBI file	EvidenceTAS
GeneFFAR4	AuthorityHGNC:19061	Mapping file id338557 NCBI file	EvidenceIEA, TAS
GeneFGA	AuthorityHGNC:3661	Mapping file id2243 NCBI file	EvidenceTAS
GeneFGB	AuthorityHGNC:3662	Mapping file id2244 NCBI file	EvidenceTAS
GeneFGD1	AuthorityHGNC:3663	Mapping file id2245 NCBI file	EvidenceTAS
GeneFGD2	AuthorityHGNC:3664	Mapping file id221472 NCBI file	EvidenceTAS
GeneFGD3	AuthorityHGNC:16027	Mapping file id89846 NCBI file	EvidenceTAS
GeneFGD4	AuthorityHGNC:19125	Mapping file id121512 NCBI file	EvidenceTAS
GeneFGD5	AuthorityHGNC:19117	Mapping file id152273 NCBI file	EvidenceTAS
GeneFGF1	AuthorityHGNC:3665	Mapping file id2246 NCBI file	EvidenceTAS
GeneFGF10	AuthorityHGNC:3666	Mapping file id2255 NCBI file	EvidenceTAS
GeneFGF16	AuthorityHGNC:3672	Mapping file id8823 NCBI file	EvidenceTAS
GeneFGF17	AuthorityHGNC:3673	Mapping file id8822 NCBI file	EvidenceTAS
GeneFGF18	AuthorityHGNC:3674	Mapping file id8817 NCBI file	EvidenceTAS
GeneFGF19	AuthorityHGNC:3675	Mapping file id9965 NCBI file	EvidenceTAS
GeneFGF2	AuthorityHGNC:3676	Mapping file id2247 NCBI file	EvidenceTAS
GeneFGF20	AuthorityHGNC:3677	Mapping file id26281 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.