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 2,001 to 2,100, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 21 of 27
Gene	Authority id	Mapping file id	Evidence codes
GeneRASGRP3	AuthorityHGNC:14545	Mapping file id25780 NCBI file	EvidenceTAS
GeneRASGRP4	AuthorityHGNC:18958	Mapping file id115727 NCBI file	EvidenceTAS
GeneRBBP4	AuthorityHGNC:9887	Mapping file id5928 NCBI file	EvidenceIEA, TAS
GeneRBBP5	AuthorityHGNC:9888	Mapping file id5929 NCBI file	EvidenceTAS
GeneRBBP6	AuthorityHGNC:9889	Mapping file id5930 NCBI file	EvidenceTAS
GeneRBBP7	AuthorityHGNC:9890	Mapping file id5931 NCBI file	EvidenceIEA, TAS
GeneRBCK1	AuthorityHGNC:15864	Mapping file id10616 NCBI file	EvidenceTAS
GeneRBFOX2	AuthorityHGNC:9906	Mapping file id23543 NCBI file	EvidenceTAS
GeneRBL1	AuthorityHGNC:9893	Mapping file id5933 NCBI file	EvidenceTAS
GeneRBMX	AuthorityHGNC:9910	Mapping file id27316 NCBI file	EvidenceTAS
GeneRBPJ	AuthorityHGNC:5724	Mapping file id3516 NCBI file	EvidenceIEA, TAS
GeneRBX1	AuthorityHGNC:9928	Mapping file id9978 NCBI file	EvidenceIEA, TAS
GeneRCC2	AuthorityHGNC:30297	Mapping file id55920 NCBI file	EvidenceTAS
GeneRCE1	AuthorityHGNC:13721	Mapping file id9986 NCBI file	EvidenceTAS
GeneRCOR1	AuthorityHGNC:17441	Mapping file id23186 NCBI file	EvidenceIEA
GeneRDH10	AuthorityHGNC:19975	Mapping file id157506 NCBI file	EvidenceTAS
GeneRDH11	AuthorityHGNC:17964	Mapping file id51109 NCBI file	EvidenceTAS
GeneRDH13	AuthorityHGNC:19978	Mapping file id112724 NCBI file	EvidenceTAS
GeneRDH14	AuthorityHGNC:19979	Mapping file id57665 NCBI file	EvidenceTAS
GeneRDH16	AuthorityHGNC:29674	Mapping file id8608 NCBI file	EvidenceTAS
GeneRDH5	AuthorityHGNC:9940	Mapping file id5959 NCBI file	EvidenceTAS
GeneRELA	AuthorityHGNC:9955	Mapping file id5970 NCBI file	EvidenceTAS
GeneREST	AuthorityHGNC:9966	Mapping file id5978 NCBI file	EvidenceIEA, TAS
GeneRET	AuthorityHGNC:9967	Mapping file id5979 NCBI file	EvidenceTAS
GeneRFNG	AuthorityHGNC:9974	Mapping file id5986 NCBI file	EvidenceIEA
GeneRGL1	AuthorityHGNC:30281	Mapping file id23179 NCBI file	EvidenceTAS
GeneRGL2	AuthorityHGNC:9769	Mapping file id5863 NCBI file	EvidenceTAS
GeneRGL3	AuthorityHGNC:30282	Mapping file id57139 NCBI file	EvidenceTAS
GeneRGR	AuthorityHGNC:9990	Mapping file id5995 NCBI file	EvidenceTAS
GeneRGS1	AuthorityHGNC:9991	Mapping file id5996 NCBI file	EvidenceIEA, TAS
GeneRGS10	AuthorityHGNC:9992	Mapping file id6001 NCBI file	EvidenceIEA, TAS
GeneRGS11	AuthorityHGNC:9993	Mapping file id8786 NCBI file	EvidenceIEA, TAS
GeneRGS12	AuthorityHGNC:9994	Mapping file id6002 NCBI file	EvidenceIEA, TAS
GeneRGS13	AuthorityHGNC:9995	Mapping file id6003 NCBI file	EvidenceIEA, TAS
GeneRGS14	AuthorityHGNC:9996	Mapping file id10636 NCBI file	EvidenceIEA, TAS
GeneRGS16	AuthorityHGNC:9997	Mapping file id6004 NCBI file	EvidenceIEA, TAS
GeneRGS17	AuthorityHGNC:14088	Mapping file id26575 NCBI file	EvidenceIEA, TAS
GeneRGS18	AuthorityHGNC:14261	Mapping file id64407 NCBI file	EvidenceIEA, TAS
GeneRGS19	AuthorityHGNC:13735	Mapping file id10287 NCBI file	EvidenceIEA, TAS
GeneRGS2	AuthorityHGNC:9998	Mapping file id5997 NCBI file	EvidenceTAS
GeneRGS20	AuthorityHGNC:14600	Mapping file id8601 NCBI file	EvidenceIEA, TAS
GeneRGS21	AuthorityHGNC:26839	Mapping file id431704 NCBI file	EvidenceIEA, TAS
GeneRGS22	AuthorityHGNC:24499	Mapping file id26166 NCBI file	EvidenceIEA
GeneRGS3	AuthorityHGNC:9999	Mapping file id5998 NCBI file	EvidenceTAS
GeneRGS4	AuthorityHGNC:10000	Mapping file id5999 NCBI file	EvidenceIEA, TAS
GeneRGS5	AuthorityHGNC:10001	Mapping file id8490 NCBI file	EvidenceIEA, TAS
GeneRGS6	AuthorityHGNC:10002	Mapping file id9628 NCBI file	EvidenceIEA, TAS
GeneRGS7	AuthorityHGNC:10003	Mapping file id6000 NCBI file	EvidenceIEA, TAS
GeneRGS8	AuthorityHGNC:16810	Mapping file id85397 NCBI file	EvidenceIEA, TAS
GeneRGS9	AuthorityHGNC:10004	Mapping file id8787 NCBI file	EvidenceIEA, TAS
GeneRGSL1	AuthorityHGNC:18636	Mapping file id353299 NCBI file	EvidenceIEA, TAS
GeneRHEB	AuthorityHGNC:10011	Mapping file id6009 NCBI file	EvidenceTAS
GeneRHO	AuthorityHGNC:10012	Mapping file id6010 NCBI file	EvidenceTAS
GeneRHOA	AuthorityHGNC:667	Mapping file id387 NCBI file	EvidenceIEA, TAS
GeneRHOB	AuthorityHGNC:668	Mapping file id388 NCBI file	EvidenceIEA, TAS
GeneRHOBTB1	AuthorityHGNC:18738	Mapping file id9886 NCBI file	EvidenceTAS
GeneRHOBTB2	AuthorityHGNC:18756	Mapping file id23221 NCBI file	EvidenceTAS
GeneRHOBTB3	AuthorityHGNC:18757	Mapping file id22836 NCBI file	EvidenceTAS
GeneRHOC	AuthorityHGNC:669	Mapping file id389 NCBI file	EvidenceIEA, TAS
GeneRHOD	AuthorityHGNC:670	Mapping file id29984 NCBI file	EvidenceTAS
GeneRHOF	AuthorityHGNC:15703	Mapping file id54509 NCBI file	EvidenceTAS
GeneRHOG	AuthorityHGNC:672	Mapping file id391 NCBI file	EvidenceTAS
GeneRHOH	AuthorityHGNC:686	Mapping file id399 NCBI file	EvidenceTAS
GeneRHOJ	AuthorityHGNC:688	Mapping file id57381 NCBI file	EvidenceTAS
GeneRHOQ	AuthorityHGNC:17736	Mapping file id23433 NCBI file	EvidenceTAS
GeneRHOT1	AuthorityHGNC:21168	Mapping file id55288 NCBI file	EvidenceIEA, TAS
GeneRHOT2	AuthorityHGNC:21169	Mapping file id89941 NCBI file	EvidenceIEA, TAS
GeneRHOU	AuthorityHGNC:17794	Mapping file id58480 NCBI file	EvidenceIEA, TAS
GeneRHOV	AuthorityHGNC:18313	Mapping file id171177 NCBI file	EvidenceTAS
GeneRHPN1	AuthorityHGNC:19973	Mapping file id114822 NCBI file	EvidenceIEA, TAS
GeneRHPN2	AuthorityHGNC:19974	Mapping file id85415 NCBI file	EvidenceIEA, TAS
GeneRICTOR	AuthorityHGNC:28611	Mapping file id253260 NCBI file	EvidenceTAS
GeneRING1	AuthorityHGNC:10018	Mapping file id6015 NCBI file	EvidenceIEA, TAS
GeneRIPK1	AuthorityHGNC:10019	Mapping file id8737 NCBI file	EvidenceTAS
GeneRIPK2	AuthorityHGNC:10020	Mapping file id8767 NCBI file	EvidenceTAS
GeneRIT1	AuthorityHGNC:10023	Mapping file id6016 NCBI file	EvidenceIEA
GeneRIT2	AuthorityHGNC:10017	Mapping file id6014 NCBI file	EvidenceIEA
GeneRLN2	AuthorityHGNC:10027	Mapping file id6019 NCBI file	EvidenceTAS
GeneRLN3	AuthorityHGNC:17135	Mapping file id117579 NCBI file	EvidenceTAS
GeneRND1	AuthorityHGNC:18314	Mapping file id27289 NCBI file	EvidenceTAS
GeneRND2	AuthorityHGNC:18315	Mapping file id8153 NCBI file	EvidenceTAS
GeneRND3	AuthorityHGNC:671	Mapping file id390 NCBI file	EvidenceTAS
GeneRNF111	AuthorityHGNC:17384	Mapping file id54778 NCBI file	EvidenceIEA, TAS
GeneRNF146	AuthorityHGNC:21336	Mapping file id81847 NCBI file	EvidenceTAS
GeneRNF2	AuthorityHGNC:10061	Mapping file id6045 NCBI file	EvidenceIEA, TAS
GeneRNF20	AuthorityHGNC:10062	Mapping file id56254 NCBI file	EvidenceTAS
GeneRNF31	AuthorityHGNC:16031	Mapping file id55072 NCBI file	EvidenceTAS
GeneRNF41	AuthorityHGNC:18401	Mapping file id10193 NCBI file	EvidenceTAS
GeneRNF43	AuthorityHGNC:18505	Mapping file id54894 NCBI file	EvidenceTAS
GeneROCK1	AuthorityHGNC:10251	Mapping file id6093 NCBI file	EvidenceIEA, TAS
GeneROCK2	AuthorityHGNC:10252	Mapping file id9475 NCBI file	EvidenceIEA, TAS
GeneROPN1	AuthorityHGNC:17692	Mapping file id54763 NCBI file	EvidenceIEA
GeneROR1	AuthorityHGNC:10256	Mapping file id4919 NCBI file	EvidenceTAS
GeneROR2	AuthorityHGNC:10257	Mapping file id4920 NCBI file	EvidenceIEA, TAS
GeneRPGRIP1L	AuthorityHGNC:29168	Mapping file id23322 NCBI file	EvidenceTAS
GeneRPS27	AuthorityHGNC:10416	Mapping file id6232 NCBI file	EvidenceTAS
GeneRPS27A	AuthorityHGNC:10417	Mapping file id6233 NCBI file	EvidenceIEA, TAS
GeneRPS6	AuthorityHGNC:10429	Mapping file id6194 NCBI file	EvidenceTAS
GeneRPS6KA1	AuthorityHGNC:10430	Mapping file id6195 NCBI file	EvidenceTAS
GeneRPS6KA2	AuthorityHGNC:10431	Mapping file id6196 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.