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).

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 2,601 to 2,631, in pages of 100, sorted by symbol for reading. The order carries no ranking. 4 of the rows shown carry an id the identity file does not name, kept as the source wrote it.

Genes Reactome places in this human pathway, page 27 of 27
Gene	Authority id	Mapping file id	Evidence codes
GeneXIAP	AuthorityHGNC:592	Mapping file id331 NCBI file	EvidenceTAS
GeneXK	AuthorityHGNC:12811	Mapping file id7504 NCBI file	EvidenceTAS
GeneXPO1	AuthorityHGNC:12825	Mapping file id7514 NCBI file	EvidenceIEA, TAS
GeneYAP1	AuthorityHGNC:16262	Mapping file id10413 NCBI file	EvidenceTAS
GeneYBX1	AuthorityHGNC:8014	Mapping file id4904 NCBI file	EvidenceTAS
GeneYES1	AuthorityHGNC:12841	Mapping file id7525 NCBI file	EvidenceIEA, TAS
GeneYKT6	AuthorityHGNC:16959	Mapping file id10652 NCBI file	EvidenceTAS
GeneYWHAB	AuthorityHGNC:12849	Mapping file id7529 NCBI file	EvidenceIEA, TAS
GeneYWHAE	AuthorityHGNC:12851	Mapping file id7531 NCBI file	EvidenceTAS
GeneYWHAG	AuthorityHGNC:12852	Mapping file id7532 NCBI file	EvidenceTAS
GeneYWHAH	AuthorityHGNC:12853	Mapping file id7533 NCBI file	EvidenceTAS
GeneYWHAQ	AuthorityHGNC:12854	Mapping file id10971 NCBI file	EvidenceTAS
GeneYWHAZ	AuthorityHGNC:12855	Mapping file id7534 NCBI file	EvidenceIEA, TAS
GeneYY1	AuthorityHGNC:12856	Mapping file id7528 NCBI file	EvidenceTAS
GeneZAP70	AuthorityHGNC:12858	Mapping file id7535 NCBI file	EvidenceTAS
GeneZDHHC21	AuthorityHGNC:20750	Mapping file id340481 NCBI file	EvidenceTAS
GeneZDHHC7	AuthorityHGNC:18459	Mapping file id55625 NCBI file	EvidenceTAS
GeneZDHHC9	AuthorityHGNC:18475	Mapping file id51114 NCBI file	EvidenceTAS
GeneZFYVE16	AuthorityHGNC:20756	Mapping file id9765 NCBI file	EvidenceTAS
GeneZFYVE9	AuthorityHGNC:6775	Mapping file id9372 NCBI file	EvidenceIEA, TAS
GeneZNF217	AuthorityHGNC:13009	Mapping file id7764 NCBI file	EvidenceTAS
GeneZNF512B	AuthorityHGNC:29212	Mapping file id57473 NCBI file	EvidenceTAS
GeneZNRF3	AuthorityHGNC:18126	Mapping file id84133 NCBI file	EvidenceTAS
GeneZRANB1	AuthorityHGNC:18224	Mapping file id54764 NCBI file	EvidenceTAS
GeneZW10	AuthorityHGNC:13194	Mapping file id9183 NCBI file	EvidenceTAS
GeneZWILCH	AuthorityHGNC:25468	Mapping file id55055 NCBI file	EvidenceTAS
GeneZWINT	AuthorityHGNC:13195	Mapping file id11130 NCBI file	EvidenceTAS
Geneno symbol in the identity file	Authoritynone	Mapping file id1486086 NCBI file	EvidenceTAS
Geneno symbol in the identity file	Authoritynone	Mapping file id3707572 NCBI file	EvidenceTAS
Geneno symbol in the identity file	Authoritynone	Mapping file id43740571 NCBI file	EvidenceTAS
Geneno symbol in the identity file	Authoritynone	Mapping file id43740575 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.