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 2026-10-02 ET · Reactome pathway browser"Signal Transduction". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-162582 with StableID: R-HSA-162582.13 (accessed 2026-10-02 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 101 to 200, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 2 of 27
Gene	Authority id	Mapping file id	Evidence codes
GeneALS2	AuthorityHGNC:443	Mapping file id57679 NCBI file	EvidenceTAS
GeneAMER1	AuthorityHGNC:26837	Mapping file id139285 NCBI file	EvidenceIEA, TAS
GeneAMH	AuthorityHGNC:464	Mapping file id268 NCBI file	EvidenceTAS
GeneAMHR2	AuthorityHGNC:465	Mapping file id269 NCBI file	EvidenceTAS
GeneAMIGO2	AuthorityHGNC:24073	Mapping file id347902 NCBI file	EvidenceTAS
GeneAMOT	AuthorityHGNC:17810	Mapping file id154796 NCBI file	EvidenceTAS
GeneAMOTL1	AuthorityHGNC:17811	Mapping file id154810 NCBI file	EvidenceTAS
GeneAMOTL2	AuthorityHGNC:17812	Mapping file id51421 NCBI file	EvidenceTAS
GeneANGPT1	AuthorityHGNC:484	Mapping file id284 NCBI file	EvidenceTAS
GeneANGPTL3	AuthorityHGNC:491	Mapping file id27329 NCBI file	EvidenceTAS
GeneANKFY1	AuthorityHGNC:20763	Mapping file id51479 NCBI file	EvidenceTAS
GeneANKLE2	AuthorityHGNC:29101	Mapping file id23141 NCBI file	EvidenceTAS
GeneANKRD26	AuthorityHGNC:29186	Mapping file id22852 NCBI file	EvidenceTAS
GeneANLN	AuthorityHGNC:14082	Mapping file id54443 NCBI file	EvidenceTAS
GeneANOS1	AuthorityHGNC:6211	Mapping file id3730 NCBI file	EvidenceTAS
GeneANXA1	AuthorityHGNC:533	Mapping file id301 NCBI file	EvidenceTAS
GeneAP2A1	AuthorityHGNC:561	Mapping file id160 NCBI file	EvidenceIEA, TAS
GeneAP2A2	AuthorityHGNC:562	Mapping file id161 NCBI file	EvidenceIEA, TAS
GeneAP2B1	AuthorityHGNC:563	Mapping file id163 NCBI file	EvidenceIEA, TAS
GeneAP2M1	AuthorityHGNC:564	Mapping file id1173 NCBI file	EvidenceIEA, TAS
GeneAP2S1	AuthorityHGNC:565	Mapping file id1175 NCBI file	EvidenceIEA, TAS
GeneAPBB1IP	AuthorityHGNC:17379	Mapping file id54518 NCBI file	EvidenceTAS
GeneAPC	AuthorityHGNC:583	Mapping file id324 NCBI file	EvidenceIEA, TAS
GeneAPH1A	AuthorityHGNC:29509	Mapping file id51107 NCBI file	EvidenceIEA, TAS
GeneAPH1B	AuthorityHGNC:24080	Mapping file id83464 NCBI file	EvidenceIEA, TAS
GeneAPLN	AuthorityHGNC:16665	Mapping file id8862 NCBI file	EvidenceTAS
GeneAPLNR	AuthorityHGNC:339	Mapping file id187 NCBI file	EvidenceTAS
GeneAPOC1	AuthorityHGNC:607	Mapping file id341 NCBI file	EvidenceTAS
GeneAPOC2	AuthorityHGNC:609	Mapping file id344 NCBI file	EvidenceTAS
GeneAPOC4	AuthorityHGNC:611	Mapping file id346 NCBI file	EvidenceTAS
GeneAPOD	AuthorityHGNC:612	Mapping file id347 NCBI file	EvidenceTAS
GeneAPOE	AuthorityHGNC:613	Mapping file id348 NCBI file	EvidenceTAS
GeneAPP	AuthorityHGNC:620	Mapping file id351 NCBI file	EvidenceTAS
GeneAR	AuthorityHGNC:644	Mapping file id367 NCBI file	EvidenceTAS
GeneARAF	AuthorityHGNC:646	Mapping file id369 NCBI file	EvidenceTAS
GeneARAP1	AuthorityHGNC:16925	Mapping file id116985 NCBI file	EvidenceTAS
GeneARAP2	AuthorityHGNC:16924	Mapping file id116984 NCBI file	EvidenceTAS
GeneARAP3	AuthorityHGNC:24097	Mapping file id64411 NCBI file	EvidenceTAS
GeneARC	AuthorityHGNC:648	Mapping file id23237 NCBI file	EvidenceIEA, TAS
GeneAREG	AuthorityHGNC:651	Mapping file id374 NCBI file	EvidenceTAS
GeneARF6	AuthorityHGNC:659	Mapping file id382 NCBI file	EvidenceTAS
GeneARFGAP2	AuthorityHGNC:13504	Mapping file id84364 NCBI file	EvidenceTAS
GeneARFGAP3	AuthorityHGNC:661	Mapping file id26286 NCBI file	EvidenceTAS
GeneARHGAP1	AuthorityHGNC:673	Mapping file id392 NCBI file	EvidenceTAS
GeneARHGAP10	AuthorityHGNC:26099	Mapping file id79658 NCBI file	EvidenceTAS
GeneARHGAP11A	AuthorityHGNC:15783	Mapping file id9824 NCBI file	EvidenceTAS
GeneARHGAP11B	AuthorityHGNC:15782	Mapping file id89839 NCBI file	EvidenceTAS
GeneARHGAP12	AuthorityHGNC:16348	Mapping file id94134 NCBI file	EvidenceTAS
GeneARHGAP15	AuthorityHGNC:21030	Mapping file id55843 NCBI file	EvidenceTAS
GeneARHGAP17	AuthorityHGNC:18239	Mapping file id55114 NCBI file	EvidenceTAS
GeneARHGAP18	AuthorityHGNC:21035	Mapping file id93663 NCBI file	EvidenceTAS
GeneARHGAP19	AuthorityHGNC:23724	Mapping file id84986 NCBI file	EvidenceTAS
GeneARHGAP20	AuthorityHGNC:18357	Mapping file id57569 NCBI file	EvidenceTAS
GeneARHGAP21	AuthorityHGNC:23725	Mapping file id57584 NCBI file	EvidenceTAS
GeneARHGAP22	AuthorityHGNC:30320	Mapping file id58504 NCBI file	EvidenceTAS
GeneARHGAP23	AuthorityHGNC:29293	Mapping file id57636 NCBI file	EvidenceTAS
GeneARHGAP24	AuthorityHGNC:25361	Mapping file id83478 NCBI file	EvidenceTAS
GeneARHGAP25	AuthorityHGNC:28951	Mapping file id9938 NCBI file	EvidenceTAS
GeneARHGAP26	AuthorityHGNC:17073	Mapping file id23092 NCBI file	EvidenceTAS
GeneARHGAP27	AuthorityHGNC:31813	Mapping file id201176 NCBI file	EvidenceTAS
GeneARHGAP28	AuthorityHGNC:25509	Mapping file id79822 NCBI file	EvidenceTAS
GeneARHGAP29	AuthorityHGNC:30207	Mapping file id9411 NCBI file	EvidenceTAS
GeneARHGAP30	AuthorityHGNC:27414	Mapping file id257106 NCBI file	EvidenceTAS
GeneARHGAP31	AuthorityHGNC:29216	Mapping file id57514 NCBI file	EvidenceTAS
GeneARHGAP32	AuthorityHGNC:17399	Mapping file id9743 NCBI file	EvidenceTAS
GeneARHGAP33	AuthorityHGNC:23085	Mapping file id115703 NCBI file	EvidenceTAS
GeneARHGAP35	AuthorityHGNC:4591	Mapping file id2909 NCBI file	EvidenceTAS
GeneARHGAP39	AuthorityHGNC:29351	Mapping file id80728 NCBI file	EvidenceTAS
GeneARHGAP4	AuthorityHGNC:674	Mapping file id393 NCBI file	EvidenceTAS
GeneARHGAP40	AuthorityHGNC:16226	Mapping file id343578 NCBI file	EvidenceTAS
GeneARHGAP42	AuthorityHGNC:26545	Mapping file id143872 NCBI file	EvidenceTAS
GeneARHGAP44	AuthorityHGNC:29096	Mapping file id9912 NCBI file	EvidenceTAS
GeneARHGAP45	AuthorityHGNC:17102	Mapping file id23526 NCBI file	EvidenceTAS
GeneARHGAP5	AuthorityHGNC:675	Mapping file id394 NCBI file	EvidenceTAS
GeneARHGAP6	AuthorityHGNC:676	Mapping file id395 NCBI file	EvidenceTAS
GeneARHGAP8	AuthorityHGNC:677	Mapping file id23779 NCBI file	EvidenceTAS
GeneARHGAP9	AuthorityHGNC:14130	Mapping file id64333 NCBI file	EvidenceTAS
GeneARHGDIA	AuthorityHGNC:678	Mapping file id396 NCBI file	EvidenceTAS
GeneARHGDIB	AuthorityHGNC:679	Mapping file id397 NCBI file	EvidenceTAS
GeneARHGDIG	AuthorityHGNC:680	Mapping file id398 NCBI file	EvidenceTAS
GeneARHGEF1	AuthorityHGNC:681	Mapping file id9138 NCBI file	EvidenceTAS
GeneARHGEF10	AuthorityHGNC:14103	Mapping file id9639 NCBI file	EvidenceTAS
GeneARHGEF10L	AuthorityHGNC:25540	Mapping file id55160 NCBI file	EvidenceTAS
GeneARHGEF11	AuthorityHGNC:14580	Mapping file id9826 NCBI file	EvidenceTAS
GeneARHGEF12	AuthorityHGNC:14193	Mapping file id23365 NCBI file	EvidenceTAS
GeneARHGEF15	AuthorityHGNC:15590	Mapping file id22899 NCBI file	EvidenceTAS
GeneARHGEF16	AuthorityHGNC:15515	Mapping file id27237 NCBI file	EvidenceTAS
GeneARHGEF17	AuthorityHGNC:21726	Mapping file id9828 NCBI file	EvidenceTAS
GeneARHGEF18	AuthorityHGNC:17090	Mapping file id23370 NCBI file	EvidenceIEA, TAS
GeneARHGEF19	AuthorityHGNC:26604	Mapping file id128272 NCBI file	EvidenceTAS
GeneARHGEF2	AuthorityHGNC:682	Mapping file id9181 NCBI file	EvidenceTAS
GeneARHGEF25	AuthorityHGNC:30275	Mapping file id115557 NCBI file	EvidenceTAS
GeneARHGEF26	AuthorityHGNC:24490	Mapping file id26084 NCBI file	EvidenceTAS
GeneARHGEF28	AuthorityHGNC:30322	Mapping file id64283 NCBI file	EvidenceTAS
GeneARHGEF3	AuthorityHGNC:683	Mapping file id50650 NCBI file	EvidenceTAS
GeneARHGEF33	AuthorityHGNC:37252	Mapping file id100271715 NCBI file	EvidenceTAS
GeneARHGEF35	AuthorityHGNC:33846	Mapping file id445328 NCBI file	EvidenceTAS
GeneARHGEF37	AuthorityHGNC:34430	Mapping file id389337 NCBI file	EvidenceTAS
GeneARHGEF38	AuthorityHGNC:25968	Mapping file id54848 NCBI file	EvidenceTAS
GeneARHGEF39	AuthorityHGNC:25909	Mapping file id84904 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.