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 2026-10-05 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 801 to 900, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 9 of 27
Gene	Authority id	Mapping file id	Evidence codes
GeneFGF22	AuthorityHGNC:3679	Mapping file id27006 NCBI file	EvidenceTAS
GeneFGF23	AuthorityHGNC:3680	Mapping file id8074 NCBI file	EvidenceTAS
GeneFGF3	AuthorityHGNC:3681	Mapping file id2248 NCBI file	EvidenceTAS
GeneFGF4	AuthorityHGNC:3682	Mapping file id2249 NCBI file	EvidenceTAS
GeneFGF5	AuthorityHGNC:3683	Mapping file id2250 NCBI file	EvidenceTAS
GeneFGF6	AuthorityHGNC:3684	Mapping file id2251 NCBI file	EvidenceTAS
GeneFGF7	AuthorityHGNC:3685	Mapping file id2252 NCBI file	EvidenceTAS
GeneFGF8	AuthorityHGNC:3686	Mapping file id2253 NCBI file	EvidenceTAS
GeneFGF9	AuthorityHGNC:3687	Mapping file id2254 NCBI file	EvidenceTAS
GeneFGFBP1	AuthorityHGNC:19695	Mapping file id9982 NCBI file	EvidenceTAS
GeneFGFBP2	AuthorityHGNC:29451	Mapping file id83888 NCBI file	EvidenceTAS
GeneFGFBP3	AuthorityHGNC:23428	Mapping file id143282 NCBI file	EvidenceTAS
GeneFGFR1	AuthorityHGNC:3688	Mapping file id2260 NCBI file	EvidenceTAS
GeneFGFR2	AuthorityHGNC:3689	Mapping file id2263 NCBI file	EvidenceTAS
GeneFGFR3	AuthorityHGNC:3690	Mapping file id2261 NCBI file	EvidenceTAS
GeneFGFR4	AuthorityHGNC:3691	Mapping file id2264 NCBI file	EvidenceTAS
GeneFGFRL1	AuthorityHGNC:3693	Mapping file id53834 NCBI file	EvidenceTAS
GeneFGG	AuthorityHGNC:3694	Mapping file id2266 NCBI file	EvidenceTAS
GeneFILIP1	AuthorityHGNC:21015	Mapping file id27145 NCBI file	EvidenceTAS
GeneFKBP1A	AuthorityHGNC:3711	Mapping file id2280 NCBI file	EvidenceIEA, TAS
GeneFKBP4	AuthorityHGNC:3720	Mapping file id2288 NCBI file	EvidenceTAS
GeneFKBP5	AuthorityHGNC:3721	Mapping file id2289 NCBI file	EvidenceTAS
GeneFLNA	AuthorityHGNC:3754	Mapping file id2316 NCBI file	EvidenceTAS
GeneFLOT1	AuthorityHGNC:3757	Mapping file id10211 NCBI file	EvidenceTAS
GeneFLOT2	AuthorityHGNC:3758	Mapping file id2319 NCBI file	EvidenceTAS
GeneFLRT1	AuthorityHGNC:3760	Mapping file id23769 NCBI file	EvidenceTAS
GeneFLRT2	AuthorityHGNC:3761	Mapping file id23768 NCBI file	EvidenceTAS
GeneFLRT3	AuthorityHGNC:3762	Mapping file id23767 NCBI file	EvidenceTAS
GeneFLT1	AuthorityHGNC:3763	Mapping file id2321 NCBI file	EvidenceTAS
GeneFLT3	AuthorityHGNC:3765	Mapping file id2322 NCBI file	EvidenceTAS
GeneFLT3LG	AuthorityHGNC:3766	Mapping file id2323 NCBI file	EvidenceTAS
GeneFLT4	AuthorityHGNC:3767	Mapping file id2324 NCBI file	EvidenceIEA, TAS
GeneFMNL1	AuthorityHGNC:1212	Mapping file id752 NCBI file	EvidenceIEA, TAS
GeneFMNL2	AuthorityHGNC:18267	Mapping file id114793 NCBI file	EvidenceTAS
GeneFMNL3	AuthorityHGNC:23698	Mapping file id91010 NCBI file	EvidenceTAS
GeneFN1	AuthorityHGNC:3778	Mapping file id2335 NCBI file	EvidenceTAS
GeneFNBP1	AuthorityHGNC:17069	Mapping file id23048 NCBI file	EvidenceTAS
GeneFNBP1L	AuthorityHGNC:20851	Mapping file id54874 NCBI file	EvidenceTAS
GeneFNTA	AuthorityHGNC:3782	Mapping file id2339 NCBI file	EvidenceTAS
GeneFNTB	AuthorityHGNC:3785	Mapping file id2342 NCBI file	EvidenceTAS
GeneFOS	AuthorityHGNC:3796	Mapping file id2353 NCBI file	EvidenceIEA, TAS
GeneFOSB	AuthorityHGNC:3797	Mapping file id2354 NCBI file	EvidenceIEA, TAS
GeneFOSL1	AuthorityHGNC:13718	Mapping file id8061 NCBI file	EvidenceIEA, TAS
GeneFOXA1	AuthorityHGNC:5021	Mapping file id3169 NCBI file	EvidenceTAS
GeneFOXH1	AuthorityHGNC:3814	Mapping file id8928 NCBI file	EvidenceIEA
GeneFOXO1	AuthorityHGNC:3819	Mapping file id2308 NCBI file	EvidenceTAS
GeneFOXO3	AuthorityHGNC:3821	Mapping file id2309 NCBI file	EvidenceTAS
GeneFOXO4	AuthorityHGNC:7139	Mapping file id4303 NCBI file	EvidenceTAS
GeneFOXO6	AuthorityHGNC:24814	Mapping file idENSG00000204060 Ensembl file	EvidenceTAS
GeneFPR1	AuthorityHGNC:3826	Mapping file id2357 NCBI file	EvidenceTAS
GeneFPR2	AuthorityHGNC:3827	Mapping file id2358 NCBI file	EvidenceTAS
GeneFPR3	AuthorityHGNC:3828	Mapping file id2359 NCBI file	EvidenceTAS
GeneFRAT1	AuthorityHGNC:3944	Mapping file id10023 NCBI file	EvidenceTAS
GeneFRAT2	AuthorityHGNC:16048	Mapping file id23401 NCBI file	EvidenceTAS
GeneFRK	AuthorityHGNC:3955	Mapping file id2444 NCBI file	EvidenceTAS
GeneFRS2	AuthorityHGNC:16971	Mapping file id10818 NCBI file	EvidenceIEA, TAS
GeneFRS3	AuthorityHGNC:16970	Mapping file id10817 NCBI file	EvidenceIEA, TAS
GeneFSHB	AuthorityHGNC:3964	Mapping file id2488 NCBI file	EvidenceTAS
GeneFSHR	AuthorityHGNC:3969	Mapping file id2492 NCBI file	EvidenceTAS
GeneFST	AuthorityHGNC:3971	Mapping file id10468 NCBI file	EvidenceTAS
GeneFSTL1	AuthorityHGNC:3972	Mapping file id11167 NCBI file	EvidenceTAS
GeneFSTL3	AuthorityHGNC:3973	Mapping file id10272 NCBI file	EvidenceTAS
GeneFURIN	AuthorityHGNC:8568	Mapping file id5045 NCBI file	EvidenceTAS
GeneFUZ	AuthorityHGNC:26219	Mapping file id80199 NCBI file	EvidenceTAS
GeneFYN	AuthorityHGNC:4037	Mapping file id2534 NCBI file	EvidenceIEA, TAS
GeneFZD1	AuthorityHGNC:4038	Mapping file id8321 NCBI file	EvidenceIEA, TAS
GeneFZD10	AuthorityHGNC:4039	Mapping file id11211 NCBI file	EvidenceIEA
GeneFZD2	AuthorityHGNC:4040	Mapping file id2535 NCBI file	EvidenceIEA, TAS
GeneFZD3	AuthorityHGNC:4041	Mapping file id7976 NCBI file	EvidenceIEA, TAS
GeneFZD4	AuthorityHGNC:4042	Mapping file id8322 NCBI file	EvidenceIEA, TAS
GeneFZD5	AuthorityHGNC:4043	Mapping file id7855 NCBI file	EvidenceIEA, TAS
GeneFZD6	AuthorityHGNC:4044	Mapping file id8323 NCBI file	EvidenceIEA, TAS
GeneFZD7	AuthorityHGNC:4045	Mapping file id8324 NCBI file	EvidenceIEA, TAS
GeneFZD8	AuthorityHGNC:4046	Mapping file id8325 NCBI file	EvidenceIEA, TAS
GeneFZD9	AuthorityHGNC:4047	Mapping file id8326 NCBI file	EvidenceIEA
GeneGAB1	AuthorityHGNC:4066	Mapping file id2549 NCBI file	EvidenceIEA, TAS
GeneGAB2	AuthorityHGNC:14458	Mapping file id9846 NCBI file	EvidenceTAS
GeneGABBR1	AuthorityHGNC:4070	Mapping file id2550 NCBI file	EvidenceTAS
GeneGABBR2	AuthorityHGNC:4507	Mapping file id9568 NCBI file	EvidenceTAS
GeneGABRA1	AuthorityHGNC:4075	Mapping file id2554 NCBI file	EvidenceIEA
GeneGABRB1	AuthorityHGNC:4081	Mapping file id2560 NCBI file	EvidenceIEA
GeneGABRB2	AuthorityHGNC:4082	Mapping file id2561 NCBI file	EvidenceIEA
GeneGABRB3	AuthorityHGNC:4083	Mapping file id2562 NCBI file	EvidenceIEA
GeneGABRG2	AuthorityHGNC:4087	Mapping file id2566 NCBI file	EvidenceIEA
GeneGABRG3	AuthorityHGNC:4088	Mapping file id2567 NCBI file	EvidenceIEA
GeneGABRQ	AuthorityHGNC:14454	Mapping file id55879 NCBI file	EvidenceIEA
GeneGAL	AuthorityHGNC:4114	Mapping file id51083 NCBI file	EvidenceTAS
GeneGALNT3	AuthorityHGNC:4125	Mapping file id2591 NCBI file	EvidenceTAS
GeneGALR1	AuthorityHGNC:4132	Mapping file id2587 NCBI file	EvidenceTAS
GeneGALR2	AuthorityHGNC:4133	Mapping file id8811 NCBI file	EvidenceTAS
GeneGALR3	AuthorityHGNC:4134	Mapping file id8484 NCBI file	EvidenceTAS
GeneGARRE1	AuthorityHGNC:29016	Mapping file id9710 NCBI file	EvidenceTAS
GeneGAS1	AuthorityHGNC:4165	Mapping file id2619 NCBI file	EvidenceTAS
GeneGAST	AuthorityHGNC:4164	Mapping file id2520 NCBI file	EvidenceTAS
GeneGATA3	AuthorityHGNC:4172	Mapping file id2625 NCBI file	EvidenceTAS
GeneGATAD2A	AuthorityHGNC:29989	Mapping file id54815 NCBI file	EvidenceIEA, TAS
GeneGATAD2B	AuthorityHGNC:30778	Mapping file id57459 NCBI file	EvidenceIEA, TAS
GeneGCG	AuthorityHGNC:4191	Mapping file id2641 NCBI file	EvidenceTAS
GeneGCGR	AuthorityHGNC:4192	Mapping file id2642 NCBI file	EvidenceTAS
GeneGDF2	AuthorityHGNC:4217	Mapping file id2658 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.