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

Scripts are off

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 1,001 to 1,100, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 11 of 27
Gene	Authority id	Mapping file id	Evidence codes
GeneGPSM2	AuthorityHGNC:29501	Mapping file id29899 NCBI file	EvidenceTAS
GeneGPSM3	AuthorityHGNC:13945	Mapping file id63940 NCBI file	EvidenceTAS
GeneGRAP	AuthorityHGNC:4562	Mapping file id10750 NCBI file	EvidenceTAS
GeneGRAP2	AuthorityHGNC:4563	Mapping file id9402 NCBI file	EvidenceTAS
GeneGRB10	AuthorityHGNC:4564	Mapping file id2887 NCBI file	EvidenceTAS
GeneGRB2	AuthorityHGNC:4566	Mapping file id2885 NCBI file	EvidenceIEA, TAS
GeneGRB7	AuthorityHGNC:4567	Mapping file id2886 NCBI file	EvidenceTAS
GeneGREB1	AuthorityHGNC:24885	Mapping file id9687 NCBI file	EvidenceTAS
GeneGREM2	AuthorityHGNC:17655	Mapping file id64388 NCBI file	EvidenceTAS
GeneGRIN1	AuthorityHGNC:4584	Mapping file id2902 NCBI file	EvidenceTAS
GeneGRIN2B	AuthorityHGNC:4586	Mapping file id2904 NCBI file	EvidenceIEA, TAS
GeneGRIN2D	AuthorityHGNC:4588	Mapping file id2906 NCBI file	EvidenceTAS
GeneGRK2	AuthorityHGNC:289	Mapping file id156 NCBI file	EvidenceIEA, TAS
GeneGRK3	AuthorityHGNC:290	Mapping file id157 NCBI file	EvidenceTAS
GeneGRK5	AuthorityHGNC:4544	Mapping file id2869 NCBI file	EvidenceIEA, TAS
GeneGRK6	AuthorityHGNC:4545	Mapping file id2870 NCBI file	EvidenceTAS
GeneGRM1	AuthorityHGNC:4593	Mapping file id2911 NCBI file	EvidenceTAS
GeneGRM2	AuthorityHGNC:4594	Mapping file id2912 NCBI file	EvidenceTAS
GeneGRM3	AuthorityHGNC:4595	Mapping file id2913 NCBI file	EvidenceTAS
GeneGRM4	AuthorityHGNC:4596	Mapping file id2914 NCBI file	EvidenceTAS
GeneGRM5	AuthorityHGNC:4597	Mapping file id2915 NCBI file	EvidenceTAS
GeneGRM6	AuthorityHGNC:4598	Mapping file id2916 NCBI file	EvidenceTAS
GeneGRM7	AuthorityHGNC:4599	Mapping file id2917 NCBI file	EvidenceTAS
GeneGRM8	AuthorityHGNC:4600	Mapping file id2918 NCBI file	EvidenceTAS
GeneGRP	AuthorityHGNC:4605	Mapping file id2922 NCBI file	EvidenceTAS
GeneGRPR	AuthorityHGNC:4609	Mapping file id2925 NCBI file	EvidenceTAS
GeneGSK3A	AuthorityHGNC:4616	Mapping file id2931 NCBI file	EvidenceIEA
GeneGSK3B	AuthorityHGNC:4617	Mapping file id2932 NCBI file	EvidenceIEA, TAS
GeneGTF2A1	AuthorityHGNC:4646	Mapping file id2957 NCBI file	EvidenceTAS
GeneGTF2A2	AuthorityHGNC:4647	Mapping file id2958 NCBI file	EvidenceTAS
GeneGTF2F1	AuthorityHGNC:4652	Mapping file id2962 NCBI file	EvidenceTAS
GeneGTF2F2	AuthorityHGNC:4653	Mapping file id2963 NCBI file	EvidenceTAS
GeneGZMB	AuthorityHGNC:4709	Mapping file id3002 NCBI file	EvidenceIEA
GeneH2AB1	AuthorityHGNC:22516	Mapping file id474382 NCBI file	EvidenceIEA, TAS
GeneH2AC14	AuthorityHGNC:4727	Mapping file id8331 NCBI file	EvidenceIEA, TAS
GeneH2AC18	AuthorityHGNC:4736	Mapping file id8337 NCBI file	EvidenceIEA, TAS
GeneH2AC19	AuthorityHGNC:29668	Mapping file id723790 NCBI file	EvidenceIEA, TAS
GeneH2AC20	AuthorityHGNC:4738	Mapping file id8338 NCBI file	EvidenceIEA, TAS
GeneH2AC4	AuthorityHGNC:4734	Mapping file id8335 NCBI file	EvidenceIEA, TAS
GeneH2AC6	AuthorityHGNC:4733	Mapping file id8334 NCBI file	EvidenceIEA, TAS
GeneH2AC7	AuthorityHGNC:4729	Mapping file id3013 NCBI file	EvidenceIEA, TAS
GeneH2AC8	AuthorityHGNC:4724	Mapping file id3012 NCBI file	EvidenceIEA, TAS
GeneH2AJ	AuthorityHGNC:14456	Mapping file id55766 NCBI file	EvidenceIEA, TAS
GeneH2AX	AuthorityHGNC:4739	Mapping file id3014 NCBI file	EvidenceIEA, TAS
GeneH2AZ2	AuthorityHGNC:20664	Mapping file id94239 NCBI file	EvidenceIEA, TAS
GeneH2BC1	AuthorityHGNC:18730	Mapping file id255626 NCBI file	EvidenceIEA, TAS
GeneH2BC10	AuthorityHGNC:4756	Mapping file id8346 NCBI file	EvidenceIEA, TAS
GeneH2BC11	AuthorityHGNC:4761	Mapping file id8970 NCBI file	EvidenceIEA, TAS
GeneH2BC12	AuthorityHGNC:13954	Mapping file id85236 NCBI file	EvidenceIEA, TAS
GeneH2BC12L	AuthorityHGNC:4762	Mapping file id54145 NCBI file	EvidenceIEA, TAS
GeneH2BC13	AuthorityHGNC:4748	Mapping file id8340 NCBI file	EvidenceIEA, TAS
GeneH2BC14	AuthorityHGNC:4750	Mapping file id8342 NCBI file	EvidenceIEA, TAS
GeneH2BC15	AuthorityHGNC:4749	Mapping file id8341 NCBI file	EvidenceIEA, TAS
GeneH2BC17	AuthorityHGNC:4758	Mapping file id8348 NCBI file	EvidenceIEA, TAS
GeneH2BC21	AuthorityHGNC:4760	Mapping file id8349 NCBI file	EvidenceIEA, TAS
GeneH2BC26	AuthorityHGNC:20514	Mapping file id128312 NCBI file	EvidenceIEA, TAS
GeneH2BC3	AuthorityHGNC:4751	Mapping file id3018 NCBI file	EvidenceIEA, TAS
GeneH2BC4	AuthorityHGNC:4757	Mapping file id8347 NCBI file	EvidenceIEA, TAS
GeneH2BC5	AuthorityHGNC:4747	Mapping file id3017 NCBI file	EvidenceIEA, TAS
GeneH2BC6	AuthorityHGNC:4753	Mapping file id8344 NCBI file	EvidenceIEA, TAS
GeneH2BC7	AuthorityHGNC:4752	Mapping file id8343 NCBI file	EvidenceIEA, TAS
GeneH2BC8	AuthorityHGNC:4746	Mapping file id8339 NCBI file	EvidenceIEA, TAS
GeneH2BC9	AuthorityHGNC:4755	Mapping file id8345 NCBI file	EvidenceIEA, TAS
GeneH3-3A	AuthorityHGNC:4764	Mapping file id3020 NCBI file	EvidenceIEA, TAS
GeneH3-3B	AuthorityHGNC:4765	Mapping file id3021 NCBI file	EvidenceIEA, TAS
GeneH3-4	AuthorityHGNC:4778	Mapping file id8290 NCBI file	EvidenceIEA, TAS
GeneH3C1	AuthorityHGNC:4766	Mapping file id8350 NCBI file	EvidenceIEA, TAS
GeneH3C10	AuthorityHGNC:4775	Mapping file id8357 NCBI file	EvidenceIEA, TAS
GeneH3C11	AuthorityHGNC:4771	Mapping file id8354 NCBI file	EvidenceIEA, TAS
GeneH3C12	AuthorityHGNC:4774	Mapping file id8356 NCBI file	EvidenceIEA, TAS
GeneH3C13	AuthorityHGNC:25311	Mapping file id653604 NCBI file	EvidenceIEA, TAS
GeneH3C14	AuthorityHGNC:20503	Mapping file id126961 NCBI file	EvidenceIEA, TAS
GeneH3C15	AuthorityHGNC:20505	Mapping file id333932 NCBI file	EvidenceIEA, TAS
GeneH3C2	AuthorityHGNC:4776	Mapping file id8358 NCBI file	EvidenceIEA, TAS
GeneH3C3	AuthorityHGNC:4768	Mapping file id8352 NCBI file	EvidenceIEA, TAS
GeneH3C4	AuthorityHGNC:4767	Mapping file id8351 NCBI file	EvidenceIEA, TAS
GeneH3C6	AuthorityHGNC:4769	Mapping file id8353 NCBI file	EvidenceIEA, TAS
GeneH3C7	AuthorityHGNC:4773	Mapping file id8968 NCBI file	EvidenceIEA, TAS
GeneH3C8	AuthorityHGNC:4772	Mapping file id8355 NCBI file	EvidenceIEA, TAS
GeneH4C1	AuthorityHGNC:4781	Mapping file id8359 NCBI file	EvidenceIEA, TAS
GeneH4C11	AuthorityHGNC:4785	Mapping file id8363 NCBI file	EvidenceIEA, TAS
GeneH4C12	AuthorityHGNC:4784	Mapping file id8362 NCBI file	EvidenceIEA, TAS
GeneH4C13	AuthorityHGNC:4791	Mapping file id8368 NCBI file	EvidenceIEA, TAS
GeneH4C14	AuthorityHGNC:4794	Mapping file id8370 NCBI file	EvidenceIEA, TAS
GeneH4C15	AuthorityHGNC:29607	Mapping file id554313 NCBI file	EvidenceIEA, TAS
GeneH4C16	AuthorityHGNC:20510	Mapping file id121504 NCBI file	EvidenceIEA, TAS
GeneH4C2	AuthorityHGNC:4789	Mapping file id8366 NCBI file	EvidenceIEA, TAS
GeneH4C3	AuthorityHGNC:4787	Mapping file id8364 NCBI file	EvidenceIEA, TAS
GeneH4C4	AuthorityHGNC:4782	Mapping file id8360 NCBI file	EvidenceIEA, TAS
GeneH4C5	AuthorityHGNC:4790	Mapping file id8367 NCBI file	EvidenceIEA, TAS
GeneH4C6	AuthorityHGNC:4783	Mapping file id8361 NCBI file	EvidenceIEA, TAS
GeneH4C8	AuthorityHGNC:4788	Mapping file id8365 NCBI file	EvidenceIEA, TAS
GeneH4C9	AuthorityHGNC:4793	Mapping file id8294 NCBI file	EvidenceIEA, TAS
GeneHBEGF	AuthorityHGNC:3059	Mapping file id1839 NCBI file	EvidenceIEA, TAS
GeneHCAR1	AuthorityHGNC:4532	Mapping file id27198 NCBI file	EvidenceTAS
GeneHCAR2	AuthorityHGNC:24827	Mapping file id338442 NCBI file	EvidenceTAS
GeneHCAR3	AuthorityHGNC:16824	Mapping file id8843 NCBI file	EvidenceTAS
GeneHCRT	AuthorityHGNC:4847	Mapping file id3060 NCBI file	EvidenceTAS
GeneHCRTR1	AuthorityHGNC:4848	Mapping file id3061 NCBI file	EvidenceTAS
GeneHCRTR2	AuthorityHGNC:4849	Mapping file id3062 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.