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 201 to 300, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 3 of 27
Gene	Authority id	Mapping file id	Evidence codes
GeneARHGEF4	AuthorityHGNC:684	Mapping file id50649 NCBI file	EvidenceTAS
GeneARHGEF40	AuthorityHGNC:25516	Mapping file id55701 NCBI file	EvidenceTAS
GeneARHGEF5	AuthorityHGNC:13209	Mapping file id7984 NCBI file	EvidenceTAS
GeneARHGEF6	AuthorityHGNC:685	Mapping file id9459 NCBI file	EvidenceTAS
GeneARHGEF7	AuthorityHGNC:15607	Mapping file id8874 NCBI file	EvidenceTAS
GeneARHGEF9	AuthorityHGNC:14561	Mapping file id23229 NCBI file	EvidenceTAS
GeneARL13B	AuthorityHGNC:25419	Mapping file id200894 NCBI file	EvidenceTAS
GeneARL2	AuthorityHGNC:693	Mapping file id402 NCBI file	EvidenceTAS
GeneARL4C	AuthorityHGNC:698	Mapping file id10123 NCBI file	EvidenceTAS
GeneARMCX3	AuthorityHGNC:24065	Mapping file id51566 NCBI file	EvidenceTAS
GeneARPC1A	AuthorityHGNC:703	Mapping file id10552 NCBI file	EvidenceIEA, TAS
GeneARPC1B	AuthorityHGNC:704	Mapping file id10095 NCBI file	EvidenceIEA, TAS
GeneARPC2	AuthorityHGNC:705	Mapping file id10109 NCBI file	EvidenceIEA, TAS
GeneARPC3	AuthorityHGNC:706	Mapping file id10094 NCBI file	EvidenceIEA, TAS
GeneARPC4	AuthorityHGNC:707	Mapping file id10093 NCBI file	EvidenceIEA, TAS
GeneARPC5	AuthorityHGNC:708	Mapping file id10092 NCBI file	EvidenceIEA, TAS
GeneARRB1	AuthorityHGNC:711	Mapping file id408 NCBI file	EvidenceIEA, TAS
GeneARRB2	AuthorityHGNC:712	Mapping file id409 NCBI file	EvidenceIEA, TAS
GeneARTN	AuthorityHGNC:727	Mapping file id9048 NCBI file	EvidenceTAS
GeneASCL1	AuthorityHGNC:738	Mapping file id429 NCBI file	EvidenceIEA, TAS
GeneASH2L	AuthorityHGNC:744	Mapping file id9070 NCBI file	EvidenceTAS
GeneATF1	AuthorityHGNC:783	Mapping file id466 NCBI file	EvidenceIEA, TAS
GeneATF2	AuthorityHGNC:784	Mapping file id1386 NCBI file	EvidenceIEA, TAS
GeneATN1	AuthorityHGNC:3033	Mapping file id1822 NCBI file	EvidenceIEA
GeneATP1B4	AuthorityHGNC:808	Mapping file id23439 NCBI file	EvidenceTAS
GeneATP2A1	AuthorityHGNC:811	Mapping file id487 NCBI file	EvidenceIEA
GeneATP2A2	AuthorityHGNC:812	Mapping file id488 NCBI file	EvidenceIEA
GeneATP2A3	AuthorityHGNC:813	Mapping file id489 NCBI file	EvidenceIEA
GeneATP6AP1	AuthorityHGNC:868	Mapping file id537 NCBI file	EvidenceTAS
GeneATP6V0A1	AuthorityHGNC:865	Mapping file id535 NCBI file	EvidenceTAS
GeneATP6V0A2	AuthorityHGNC:18481	Mapping file id23545 NCBI file	EvidenceTAS
GeneATP6V0A4	AuthorityHGNC:866	Mapping file id50617 NCBI file	EvidenceTAS
GeneATP6V0B	AuthorityHGNC:861	Mapping file id533 NCBI file	EvidenceTAS
GeneATP6V0C	AuthorityHGNC:855	Mapping file id527 NCBI file	EvidenceTAS
GeneATP6V0D1	AuthorityHGNC:13724	Mapping file id9114 NCBI file	EvidenceTAS
GeneATP6V0D2	AuthorityHGNC:18266	Mapping file id245972 NCBI file	EvidenceTAS
GeneATP6V0E1	AuthorityHGNC:863	Mapping file id8992 NCBI file	EvidenceTAS
GeneATP6V0E2	AuthorityHGNC:21723	Mapping file id155066 NCBI file	EvidenceTAS
GeneATP6V1A	AuthorityHGNC:851	Mapping file id523 NCBI file	EvidenceTAS
GeneATP6V1B1	AuthorityHGNC:853	Mapping file id525 NCBI file	EvidenceTAS
GeneATP6V1B2	AuthorityHGNC:854	Mapping file id526 NCBI file	EvidenceTAS
GeneATP6V1C1	AuthorityHGNC:856	Mapping file id528 NCBI file	EvidenceTAS
GeneATP6V1C2	AuthorityHGNC:18264	Mapping file id245973 NCBI file	EvidenceTAS
GeneATP6V1D	AuthorityHGNC:13527	Mapping file id51382 NCBI file	EvidenceTAS
GeneATP6V1E1	AuthorityHGNC:857	Mapping file id529 NCBI file	EvidenceTAS
GeneATP6V1E2	AuthorityHGNC:18125	Mapping file id90423 NCBI file	EvidenceTAS
GeneATP6V1F	AuthorityHGNC:16832	Mapping file id9296 NCBI file	EvidenceTAS
GeneATP6V1G1	AuthorityHGNC:864	Mapping file id9550 NCBI file	EvidenceTAS
GeneATP6V1G2	AuthorityHGNC:862	Mapping file id534 NCBI file	EvidenceTAS
GeneATP6V1G3	AuthorityHGNC:18265	Mapping file id127124 NCBI file	EvidenceTAS
GeneATP6V1H	AuthorityHGNC:18303	Mapping file id51606 NCBI file	EvidenceTAS
GeneAURKB	AuthorityHGNC:11390	Mapping file id9212 NCBI file	EvidenceTAS
GeneAVP	AuthorityHGNC:894	Mapping file id551 NCBI file	EvidenceTAS
GeneAVPR1A	AuthorityHGNC:895	Mapping file id552 NCBI file	EvidenceTAS
GeneAVPR1B	AuthorityHGNC:896	Mapping file id553 NCBI file	EvidenceTAS
GeneAVPR2	AuthorityHGNC:897	Mapping file id554 NCBI file	EvidenceTAS
GeneAXIN1	AuthorityHGNC:903	Mapping file id8312 NCBI file	EvidenceIEA, TAS
GeneAXIN2	AuthorityHGNC:904	Mapping file id8313 NCBI file	EvidenceTAS
GeneAXL	AuthorityHGNC:905	Mapping file id558 NCBI file	EvidenceTAS
GeneB4GALT1	AuthorityHGNC:924	Mapping file id2683 NCBI file	EvidenceIEA
GeneB9D2	AuthorityHGNC:28636	Mapping file id80776 NCBI file	EvidenceTAS
GeneBAD	AuthorityHGNC:936	Mapping file id572 NCBI file	EvidenceIEA, TAS
GeneBAG4	AuthorityHGNC:940	Mapping file id9530 NCBI file	EvidenceTAS
GeneBAIAP2	AuthorityHGNC:947	Mapping file id10458 NCBI file	EvidenceIEA, TAS
GeneBAIAP2L1	AuthorityHGNC:21649	Mapping file id55971 NCBI file	EvidenceTAS
GeneBAIAP2L2	AuthorityHGNC:26203	Mapping file id80115 NCBI file	EvidenceTAS
GeneBAMBI	AuthorityHGNC:30251	Mapping file id25805 NCBI file	EvidenceTAS
GeneBASP1	AuthorityHGNC:957	Mapping file id10409 NCBI file	EvidenceTAS
GeneBAX	AuthorityHGNC:959	Mapping file id581 NCBI file	EvidenceIEA
GeneBCAP31	AuthorityHGNC:16695	Mapping file id10134 NCBI file	EvidenceTAS
GeneBCAR1	AuthorityHGNC:971	Mapping file id9564 NCBI file	EvidenceIEA, TAS
GeneBCL2	AuthorityHGNC:990	Mapping file id596 NCBI file	EvidenceTAS
GeneBCL2L1	AuthorityHGNC:992	Mapping file id598 NCBI file	EvidenceTAS
GeneBCL2L11	AuthorityHGNC:994	Mapping file id10018 NCBI file	EvidenceTAS
GeneBCL9	AuthorityHGNC:1008	Mapping file id607 NCBI file	EvidenceTAS
GeneBCL9L	AuthorityHGNC:23688	Mapping file id283149 NCBI file	EvidenceTAS
GeneBCR	AuthorityHGNC:1014	Mapping file id613 NCBI file	EvidenceTAS
GeneBDKRB1	AuthorityHGNC:1029	Mapping file id623 NCBI file	EvidenceTAS
GeneBDKRB2	AuthorityHGNC:1030	Mapping file id624 NCBI file	EvidenceTAS
GeneBDNF	AuthorityHGNC:1033	Mapping file id627 NCBI file	EvidenceIEA, TAS
GeneBEX3	AuthorityHGNC:13388	Mapping file id27018 NCBI file	EvidenceTAS
GeneBIRC2	AuthorityHGNC:590	Mapping file id329 NCBI file	EvidenceTAS
GeneBIRC3	AuthorityHGNC:591	Mapping file id330 NCBI file	EvidenceTAS
GeneBIRC5	AuthorityHGNC:593	Mapping file id332 NCBI file	EvidenceTAS
GeneBLTP3B	AuthorityHGNC:29102	Mapping file id23074 NCBI file	EvidenceTAS
GeneBMI1	AuthorityHGNC:1066	Mapping file id648 NCBI file	EvidenceIEA, TAS
GeneBMP10	AuthorityHGNC:20869	Mapping file id27302 NCBI file	EvidenceTAS
GeneBMP2	AuthorityHGNC:1069	Mapping file id650 NCBI file	EvidenceTAS
GeneBMPR1A	AuthorityHGNC:1076	Mapping file id657 NCBI file	EvidenceTAS
GeneBMPR1B	AuthorityHGNC:1077	Mapping file id658 NCBI file	EvidenceTAS
GeneBMPR2	AuthorityHGNC:1078	Mapping file id659 NCBI file	EvidenceTAS
GeneBOC	AuthorityHGNC:17173	Mapping file id91653 NCBI file	EvidenceIEA, TAS
GeneBRAF	AuthorityHGNC:1097	Mapping file id673 NCBI file	EvidenceIEA, TAS
GeneBRAP	AuthorityHGNC:1099	Mapping file id8315 NCBI file	EvidenceTAS
GeneBRK1	AuthorityHGNC:23057	Mapping file id55845 NCBI file	EvidenceIEA, TAS
GeneBRS3	AuthorityHGNC:1113	Mapping file id680 NCBI file	EvidenceTAS
GeneBTC	AuthorityHGNC:1121	Mapping file id685 NCBI file	EvidenceIEA, TAS
GeneBTK	AuthorityHGNC:1133	Mapping file id695 NCBI file	EvidenceTAS
GeneBTRC	AuthorityHGNC:1144	Mapping file id8945 NCBI file	EvidenceIEA, TAS
GeneBUB1	AuthorityHGNC:1148	Mapping file id699 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.