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 901 to 1,000, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 10 of 27
Gene	Authority id	Mapping file id	Evidence codes
GeneGDNF	AuthorityHGNC:4232	Mapping file id2668 NCBI file	EvidenceTAS
GeneGFAP	AuthorityHGNC:4235	Mapping file id2670 NCBI file	EvidenceTAS
GeneGFOD1	AuthorityHGNC:21096	Mapping file id54438 NCBI file	EvidenceTAS
GeneGFRA1	AuthorityHGNC:4243	Mapping file id2674 NCBI file	EvidenceTAS
GeneGFRA2	AuthorityHGNC:4244	Mapping file id2675 NCBI file	EvidenceTAS
GeneGFRA3	AuthorityHGNC:4245	Mapping file id2676 NCBI file	EvidenceTAS
GeneGFRA4	AuthorityHGNC:13821	Mapping file id64096 NCBI file	EvidenceTAS
GeneGGA3	AuthorityHGNC:17079	Mapping file id23163 NCBI file	EvidenceTAS
GeneGHRH	AuthorityHGNC:4265	Mapping file id2691 NCBI file	EvidenceTAS
GeneGHRHR	AuthorityHGNC:4266	Mapping file id2692 NCBI file	EvidenceTAS
GeneGHRL	AuthorityHGNC:18129	Mapping file id51738 NCBI file	EvidenceIEA, TAS
GeneGHSR	AuthorityHGNC:4267	Mapping file id2693 NCBI file	EvidenceIEA, TAS
GeneGIP	AuthorityHGNC:4270	Mapping file id2695 NCBI file	EvidenceTAS
GeneGIPC1	AuthorityHGNC:1226	Mapping file id10755 NCBI file	EvidenceTAS
GeneGIPR	AuthorityHGNC:4271	Mapping file id2696 NCBI file	EvidenceTAS
GeneGIT1	AuthorityHGNC:4272	Mapping file id28964 NCBI file	EvidenceTAS
GeneGIT2	AuthorityHGNC:4273	Mapping file id9815 NCBI file	EvidenceTAS
GeneGJA1	AuthorityHGNC:4274	Mapping file id2697 NCBI file	EvidenceTAS
GeneGLI1	AuthorityHGNC:4317	Mapping file id2735 NCBI file	EvidenceIEA, TAS
GeneGLI2	AuthorityHGNC:4318	Mapping file id2736 NCBI file	EvidenceIEA, TAS
GeneGLI3	AuthorityHGNC:4319	Mapping file id2737 NCBI file	EvidenceTAS
GeneGLP1R	AuthorityHGNC:4324	Mapping file id2740 NCBI file	EvidenceTAS
GeneGLP2R	AuthorityHGNC:4325	Mapping file id9340 NCBI file	EvidenceTAS
GeneGMIP	AuthorityHGNC:24852	Mapping file id51291 NCBI file	EvidenceTAS
GeneGNA11	AuthorityHGNC:4379	Mapping file id2767 NCBI file	EvidenceIEA, TAS
GeneGNA12	AuthorityHGNC:4380	Mapping file id2768 NCBI file	EvidenceTAS
GeneGNA13	AuthorityHGNC:4381	Mapping file id10672 NCBI file	EvidenceTAS
GeneGNA14	AuthorityHGNC:4382	Mapping file id9630 NCBI file	EvidenceIEA, TAS
GeneGNA15	AuthorityHGNC:4383	Mapping file id2769 NCBI file	EvidenceIEA, TAS
GeneGNAI1	AuthorityHGNC:4384	Mapping file id2770 NCBI file	EvidenceIEA, TAS
GeneGNAI2	AuthorityHGNC:4385	Mapping file id2771 NCBI file	EvidenceIEA, TAS
GeneGNAI3	AuthorityHGNC:4387	Mapping file id2773 NCBI file	EvidenceIEA, TAS
GeneGNAL	AuthorityHGNC:4388	Mapping file id2774 NCBI file	EvidenceTAS
GeneGNAO1	AuthorityHGNC:4389	Mapping file id2775 NCBI file	EvidenceIEA, TAS
GeneGNAQ	AuthorityHGNC:4390	Mapping file id2776 NCBI file	EvidenceIEA, TAS
GeneGNAS	AuthorityHGNC:4392	Mapping file id2778 NCBI file	EvidenceIEA, TAS
GeneGNAT1	AuthorityHGNC:4393	Mapping file id2779 NCBI file	EvidenceTAS
GeneGNAT2	AuthorityHGNC:4394	Mapping file id2780 NCBI file	EvidenceIEA, TAS
GeneGNAT3	AuthorityHGNC:22800	Mapping file id346562 NCBI file	EvidenceIEA, TAS
GeneGNAZ	AuthorityHGNC:4395	Mapping file id2781 NCBI file	EvidenceIEA, TAS
GeneGNB1	AuthorityHGNC:4396	Mapping file id2782 NCBI file	EvidenceIEA, TAS
GeneGNB2	AuthorityHGNC:4398	Mapping file id2783 NCBI file	EvidenceIEA, TAS
GeneGNB3	AuthorityHGNC:4400	Mapping file id2784 NCBI file	EvidenceIEA, TAS
GeneGNB4	AuthorityHGNC:20731	Mapping file id59345 NCBI file	EvidenceIEA, TAS
GeneGNB5	AuthorityHGNC:4401	Mapping file id10681 NCBI file	EvidenceIEA, TAS
GeneGNG10	AuthorityHGNC:4402	Mapping file id2790 NCBI file	EvidenceIEA, TAS
GeneGNG11	AuthorityHGNC:4403	Mapping file id2791 NCBI file	EvidenceIEA, TAS
GeneGNG12	AuthorityHGNC:19663	Mapping file id55970 NCBI file	EvidenceIEA, TAS
GeneGNG13	AuthorityHGNC:14131	Mapping file id51764 NCBI file	EvidenceIEA, TAS
GeneGNG2	AuthorityHGNC:4404	Mapping file id54331 NCBI file	EvidenceIEA, TAS
GeneGNG3	AuthorityHGNC:4405	Mapping file id2785 NCBI file	EvidenceIEA, TAS
GeneGNG4	AuthorityHGNC:4407	Mapping file id2786 NCBI file	EvidenceIEA, TAS
GeneGNG5	AuthorityHGNC:4408	Mapping file id2787 NCBI file	EvidenceIEA, TAS
GeneGNG7	AuthorityHGNC:4410	Mapping file id2788 NCBI file	EvidenceIEA, TAS
GeneGNG8	AuthorityHGNC:19664	Mapping file id94235 NCBI file	EvidenceIEA, TAS
GeneGNGT1	AuthorityHGNC:4411	Mapping file id2792 NCBI file	EvidenceIEA, TAS
GeneGNGT2	AuthorityHGNC:4412	Mapping file id2793 NCBI file	EvidenceIEA, TAS
GeneGNRH1	AuthorityHGNC:4419	Mapping file id2796 NCBI file	EvidenceTAS
GeneGNRH2	AuthorityHGNC:4420	Mapping file id2797 NCBI file	EvidenceTAS
GeneGNRHR	AuthorityHGNC:4421	Mapping file id2798 NCBI file	EvidenceTAS
GeneGOLGA3	AuthorityHGNC:4426	Mapping file id2802 NCBI file	EvidenceTAS
GeneGOLGA7	AuthorityHGNC:24876	Mapping file id51125 NCBI file	EvidenceTAS
GeneGOLGA8R	AuthorityHGNC:44407	Mapping file id101059918 NCBI file	EvidenceTAS
GeneGOPC	AuthorityHGNC:17643	Mapping file id57120 NCBI file	EvidenceTAS
GeneGPAM	AuthorityHGNC:24865	Mapping file id57678 NCBI file	EvidenceTAS
GeneGPBAR1	AuthorityHGNC:19680	Mapping file id151306 NCBI file	EvidenceTAS
GeneGPC5	AuthorityHGNC:4453	Mapping file id2262 NCBI file	EvidenceTAS
GeneGPER1	AuthorityHGNC:4485	Mapping file id2852 NCBI file	EvidenceTAS
GeneGPHA2	AuthorityHGNC:18054	Mapping file id170589 NCBI file	EvidenceTAS
GeneGPHB5	AuthorityHGNC:18055	Mapping file id122876 NCBI file	EvidenceTAS
GeneGPNMB	AuthorityHGNC:4462	Mapping file id10457 NCBI file	EvidenceTAS
GeneGPR132	AuthorityHGNC:17482	Mapping file id29933 NCBI file	EvidenceTAS
GeneGPR143	AuthorityHGNC:20145	Mapping file id4935 NCBI file	EvidenceTAS
GeneGPR15	AuthorityHGNC:4469	Mapping file id2838 NCBI file	EvidenceTAS
GeneGPR150	AuthorityHGNC:23628	Mapping file id285601 NCBI file	EvidenceTAS
GeneGPR161	AuthorityHGNC:23694	Mapping file id23432 NCBI file	EvidenceTAS
GeneGPR17	AuthorityHGNC:4471	Mapping file id2840 NCBI file	EvidenceTAS
GeneGPR176	AuthorityHGNC:32370	Mapping file id11245 NCBI file	EvidenceTAS
GeneGPR18	AuthorityHGNC:4472	Mapping file id2841 NCBI file	EvidenceTAS
GeneGPR183	AuthorityHGNC:3128	Mapping file id1880 NCBI file	EvidenceTAS
GeneGPR20	AuthorityHGNC:4475	Mapping file id2843 NCBI file	EvidenceTAS
GeneGPR25	AuthorityHGNC:4480	Mapping file id2848 NCBI file	EvidenceTAS
GeneGPR27	AuthorityHGNC:4482	Mapping file id2850 NCBI file	EvidenceTAS
GeneGPR31	AuthorityHGNC:4486	Mapping file id2853 NCBI file	EvidenceTAS
GeneGPR32	AuthorityHGNC:4487	Mapping file id2854 NCBI file	EvidenceTAS
GeneGPR35	AuthorityHGNC:4492	Mapping file id2859 NCBI file	EvidenceTAS
GeneGPR37	AuthorityHGNC:4494	Mapping file id2861 NCBI file	EvidenceTAS
GeneGPR37L1	AuthorityHGNC:14923	Mapping file id9283 NCBI file	EvidenceTAS
GeneGPR39	AuthorityHGNC:4496	Mapping file id2863 NCBI file	EvidenceTAS
GeneGPR4	AuthorityHGNC:4497	Mapping file id2828 NCBI file	EvidenceTAS
GeneGPR45	AuthorityHGNC:4503	Mapping file id11250 NCBI file	EvidenceTAS
GeneGPR55	AuthorityHGNC:4511	Mapping file id9290 NCBI file	EvidenceTAS
GeneGPR65	AuthorityHGNC:4517	Mapping file id8477 NCBI file	EvidenceTAS
GeneGPR68	AuthorityHGNC:4519	Mapping file id8111 NCBI file	EvidenceTAS
GeneGPR83	AuthorityHGNC:4523	Mapping file id10888 NCBI file	EvidenceTAS
GeneGPR84	AuthorityHGNC:4535	Mapping file id53831 NCBI file	EvidenceTAS
GeneGPRC6A	AuthorityHGNC:18510	Mapping file id222545 NCBI file	EvidenceTAS
GeneGPS1	AuthorityHGNC:4549	Mapping file id2873 NCBI file	EvidenceTAS
GeneGPS2	AuthorityHGNC:4550	Mapping file id2874 NCBI file	EvidenceTAS
GeneGPSM1	AuthorityHGNC:17858	Mapping file id26086 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.