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 601 to 700, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 7 of 27
Gene	Authority id	Mapping file id	Evidence codes
GeneDGKD	AuthorityHGNC:2851	Mapping file id8527 NCBI file	EvidenceTAS
GeneDGKE	AuthorityHGNC:2852	Mapping file id8526 NCBI file	EvidenceTAS
GeneDGKG	AuthorityHGNC:2853	Mapping file id1608 NCBI file	EvidenceTAS
GeneDGKH	AuthorityHGNC:2854	Mapping file id160851 NCBI file	EvidenceTAS
GeneDGKI	AuthorityHGNC:2855	Mapping file id9162 NCBI file	EvidenceTAS
GeneDGKK	AuthorityHGNC:32395	Mapping file id139189 NCBI file	EvidenceTAS
GeneDGKQ	AuthorityHGNC:2856	Mapping file id1609 NCBI file	EvidenceTAS
GeneDGKZ	AuthorityHGNC:2857	Mapping file id8525 NCBI file	EvidenceTAS
GeneDHH	AuthorityHGNC:2865	Mapping file id50846 NCBI file	EvidenceIEA, TAS
GeneDHRS3	AuthorityHGNC:17693	Mapping file id9249 NCBI file	EvidenceTAS
GeneDHRS4	AuthorityHGNC:16985	Mapping file id10901 NCBI file	EvidenceTAS
GeneDHRS9	AuthorityHGNC:16888	Mapping file id10170 NCBI file	EvidenceTAS
GeneDIAPH1	AuthorityHGNC:2876	Mapping file id1729 NCBI file	EvidenceTAS
GeneDIAPH2	AuthorityHGNC:2877	Mapping file id1730 NCBI file	EvidenceTAS
GeneDIAPH3	AuthorityHGNC:15480	Mapping file id81624 NCBI file	EvidenceTAS
GeneDISP2	AuthorityHGNC:19712	Mapping file id85455 NCBI file	EvidenceIEA, TAS
GeneDKK1	AuthorityHGNC:2891	Mapping file id22943 NCBI file	EvidenceIEA, TAS
GeneDKK2	AuthorityHGNC:2892	Mapping file id27123 NCBI file	EvidenceIEA, TAS
GeneDKK4	AuthorityHGNC:2894	Mapping file id27121 NCBI file	EvidenceIEA, TAS
GeneDLAT	AuthorityHGNC:2896	Mapping file id1737 NCBI file	EvidenceTAS
GeneDLC1	AuthorityHGNC:2897	Mapping file id10395 NCBI file	EvidenceTAS
GeneDLD	AuthorityHGNC:2898	Mapping file id1738 NCBI file	EvidenceTAS
GeneDLG1	AuthorityHGNC:2900	Mapping file id1739 NCBI file	EvidenceTAS
GeneDLG2	AuthorityHGNC:2901	Mapping file id1740 NCBI file	EvidenceTAS
GeneDLG3	AuthorityHGNC:2902	Mapping file id1741 NCBI file	EvidenceTAS
GeneDLG4	AuthorityHGNC:2903	Mapping file id1742 NCBI file	EvidenceIEA, TAS
GeneDLG5	AuthorityHGNC:2904	Mapping file id9231 NCBI file	EvidenceTAS
GeneDLGAP5	AuthorityHGNC:16864	Mapping file id9787 NCBI file	EvidenceTAS
GeneDLK1	AuthorityHGNC:2907	Mapping file id8788 NCBI file	EvidenceIEA
GeneDLL1	AuthorityHGNC:2908	Mapping file id28514 NCBI file	EvidenceIEA, TAS
GeneDLL4	AuthorityHGNC:2910	Mapping file id54567 NCBI file	EvidenceIEA, TAS
GeneDNAJB1	AuthorityHGNC:5270	Mapping file id3337 NCBI file	EvidenceTAS
GeneDNAL4	AuthorityHGNC:2955	Mapping file id10126 NCBI file	EvidenceTAS
GeneDNER	AuthorityHGNC:24456	Mapping file id92737 NCBI file	EvidenceIEA
GeneDNM1	AuthorityHGNC:2972	Mapping file id1759 NCBI file	EvidenceIEA
GeneDNM2	AuthorityHGNC:2974	Mapping file id1785 NCBI file	EvidenceIEA
GeneDNM3	AuthorityHGNC:29125	Mapping file id26052 NCBI file	EvidenceIEA
GeneDNMBP	AuthorityHGNC:30373	Mapping file id23268 NCBI file	EvidenceTAS
GeneDNMT1	AuthorityHGNC:2976	Mapping file id1786 NCBI file	EvidenceTAS
GeneDOCK1	AuthorityHGNC:2987	Mapping file id1793 NCBI file	EvidenceTAS
GeneDOCK10	AuthorityHGNC:23479	Mapping file id55619 NCBI file	EvidenceTAS
GeneDOCK11	AuthorityHGNC:23483	Mapping file id139818 NCBI file	EvidenceTAS
GeneDOCK2	AuthorityHGNC:2988	Mapping file id1794 NCBI file	EvidenceTAS
GeneDOCK3	AuthorityHGNC:2989	Mapping file id1795 NCBI file	EvidenceIEA, TAS
GeneDOCK4	AuthorityHGNC:19192	Mapping file id9732 NCBI file	EvidenceTAS
GeneDOCK5	AuthorityHGNC:23476	Mapping file id80005 NCBI file	EvidenceTAS
GeneDOCK6	AuthorityHGNC:19189	Mapping file id57572 NCBI file	EvidenceTAS
GeneDOCK7	AuthorityHGNC:19190	Mapping file id85440 NCBI file	EvidenceTAS
GeneDOCK8	AuthorityHGNC:19191	Mapping file id81704 NCBI file	EvidenceTAS
GeneDOCK9	AuthorityHGNC:14132	Mapping file id23348 NCBI file	EvidenceTAS
GeneDOK1	AuthorityHGNC:2990	Mapping file id1796 NCBI file	EvidenceTAS
GeneDPY30	AuthorityHGNC:24590	Mapping file id84661 NCBI file	EvidenceTAS
GeneDRAP1	AuthorityHGNC:3019	Mapping file id10589 NCBI file	EvidenceIEA
GeneDRC4	AuthorityHGNC:4166	Mapping file id2622 NCBI file	EvidenceTAS
GeneDRD1	AuthorityHGNC:3020	Mapping file id1812 NCBI file	EvidenceTAS
GeneDRD2	AuthorityHGNC:3023	Mapping file id1813 NCBI file	EvidenceTAS
GeneDRD3	AuthorityHGNC:3024	Mapping file id1814 NCBI file	EvidenceTAS
GeneDRD4	AuthorityHGNC:3025	Mapping file id1815 NCBI file	EvidenceTAS
GeneDRD5	AuthorityHGNC:3026	Mapping file id1816 NCBI file	EvidenceTAS
GeneDSG1	AuthorityHGNC:3048	Mapping file id1828 NCBI file	EvidenceTAS
GeneDSG2	AuthorityHGNC:3049	Mapping file id1829 NCBI file	EvidenceTAS
GeneDSN1	AuthorityHGNC:16165	Mapping file id79980 NCBI file	EvidenceTAS
GeneDSP	AuthorityHGNC:3052	Mapping file id1832 NCBI file	EvidenceTAS
GeneDST	AuthorityHGNC:1090	Mapping file id667 NCBI file	EvidenceTAS
GeneDTX1	AuthorityHGNC:3060	Mapping file id1840 NCBI file	EvidenceIEA, TAS
GeneDTX2	AuthorityHGNC:15973	Mapping file id113878 NCBI file	EvidenceIEA, TAS
GeneDTX4	AuthorityHGNC:29151	Mapping file id23220 NCBI file	EvidenceIEA, TAS
GeneDUSP1	AuthorityHGNC:3064	Mapping file id1843 NCBI file	EvidenceTAS
GeneDUSP10	AuthorityHGNC:3065	Mapping file id11221 NCBI file	EvidenceTAS
GeneDUSP16	AuthorityHGNC:17909	Mapping file id80824 NCBI file	EvidenceTAS
GeneDUSP2	AuthorityHGNC:3068	Mapping file id1844 NCBI file	EvidenceTAS
GeneDUSP3	AuthorityHGNC:3069	Mapping file id1845 NCBI file	EvidenceTAS
GeneDUSP4	AuthorityHGNC:3070	Mapping file id1846 NCBI file	EvidenceTAS
GeneDUSP5	AuthorityHGNC:3071	Mapping file id1847 NCBI file	EvidenceTAS
GeneDUSP6	AuthorityHGNC:3072	Mapping file id1848 NCBI file	EvidenceTAS
GeneDUSP7	AuthorityHGNC:3073	Mapping file id1849 NCBI file	EvidenceTAS
GeneDUSP8	AuthorityHGNC:3074	Mapping file id1850 NCBI file	EvidenceTAS
GeneDUSP9	AuthorityHGNC:3076	Mapping file id1852 NCBI file	EvidenceTAS
GeneDVL1	AuthorityHGNC:3084	Mapping file id1855 NCBI file	EvidenceIEA, TAS
GeneDVL2	AuthorityHGNC:3086	Mapping file id1856 NCBI file	EvidenceIEA, TAS
GeneDVL3	AuthorityHGNC:3087	Mapping file id1857 NCBI file	EvidenceIEA, TAS
GeneDYNC1H1	AuthorityHGNC:2961	Mapping file id1778 NCBI file	EvidenceTAS
GeneDYNC1I1	AuthorityHGNC:2963	Mapping file id1780 NCBI file	EvidenceTAS
GeneDYNC1I2	AuthorityHGNC:2964	Mapping file id1781 NCBI file	EvidenceTAS
GeneDYNC1LI1	AuthorityHGNC:18745	Mapping file id51143 NCBI file	EvidenceTAS
GeneDYNC1LI2	AuthorityHGNC:2966	Mapping file id1783 NCBI file	EvidenceTAS
GeneDYNC2H1	AuthorityHGNC:2962	Mapping file id79659 NCBI file	EvidenceTAS
GeneDYNLL1	AuthorityHGNC:15476	Mapping file id8655 NCBI file	EvidenceTAS
GeneDYNLL2	AuthorityHGNC:24596	Mapping file id140735 NCBI file	EvidenceTAS
GeneDZIP1	AuthorityHGNC:20908	Mapping file id22873 NCBI file	EvidenceTAS
GeneE2F1	AuthorityHGNC:3113	Mapping file id1869 NCBI file	EvidenceIEA, TAS
GeneE2F3	AuthorityHGNC:3115	Mapping file id1871 NCBI file	EvidenceIEA, TAS
GeneE2F4	AuthorityHGNC:3118	Mapping file id1874 NCBI file	EvidenceTAS
GeneE2F5	AuthorityHGNC:3119	Mapping file id1875 NCBI file	EvidenceTAS
GeneEBAG9	AuthorityHGNC:3123	Mapping file id9166 NCBI file	EvidenceTAS
GeneECE1	AuthorityHGNC:3146	Mapping file id1889 NCBI file	EvidenceTAS
GeneECE2	AuthorityHGNC:13275	Mapping file id9718 NCBI file	EvidenceTAS
GeneECT2	AuthorityHGNC:3155	Mapping file id1894 NCBI file	EvidenceTAS
GeneEDN1	AuthorityHGNC:3176	Mapping file id1906 NCBI file	EvidenceTAS
GeneEDN2	AuthorityHGNC:3177	Mapping file id1907 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.