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).

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 1,201 to 1,300, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 13 of 27
Gene	Authority id	Mapping file id	Evidence codes
GeneINSL5	AuthorityHGNC:6088	Mapping file id10022 NCBI file	EvidenceTAS
GeneINSR	AuthorityHGNC:6091	Mapping file id3643 NCBI file	EvidenceTAS
GeneINTU	AuthorityHGNC:29239	Mapping file id27152 NCBI file	EvidenceTAS
GeneIQCE	AuthorityHGNC:29171	Mapping file id23288 NCBI file	EvidenceTAS
GeneIQGAP1	AuthorityHGNC:6110	Mapping file id8826 NCBI file	EvidenceTAS
GeneIQGAP2	AuthorityHGNC:6111	Mapping file id10788 NCBI file	EvidenceTAS
GeneIQGAP3	AuthorityHGNC:20669	Mapping file id128239 NCBI file	EvidenceTAS
GeneIRAK1	AuthorityHGNC:6112	Mapping file id3654 NCBI file	EvidenceIEA, TAS
GeneIRAK4	AuthorityHGNC:17967	Mapping file id51135 NCBI file	EvidenceTAS
GeneIRS1	AuthorityHGNC:6125	Mapping file id3667 NCBI file	EvidenceIEA, TAS
GeneIRS2	AuthorityHGNC:6126	Mapping file id8660 NCBI file	EvidenceIEA, TAS
GeneIRS4	AuthorityHGNC:6128	Mapping file id8471 NCBI file	EvidenceTAS
GeneITCH	AuthorityHGNC:13890	Mapping file id83737 NCBI file	EvidenceIEA, TAS
GeneITGA2	AuthorityHGNC:6137	Mapping file id3673 NCBI file	EvidenceTAS
GeneITGA2B	AuthorityHGNC:6138	Mapping file id3674 NCBI file	EvidenceTAS
GeneITGA3	AuthorityHGNC:6139	Mapping file id3675 NCBI file	EvidenceTAS
GeneITGA5	AuthorityHGNC:6141	Mapping file id3678 NCBI file	EvidenceTAS
GeneITGA8	AuthorityHGNC:6144	Mapping file id8516 NCBI file	EvidenceTAS
GeneITGAV	AuthorityHGNC:6150	Mapping file id3685 NCBI file	EvidenceTAS
GeneITGB1	AuthorityHGNC:6153	Mapping file id3688 NCBI file	EvidenceTAS
GeneITGB3	AuthorityHGNC:6156	Mapping file id3690 NCBI file	EvidenceTAS
GeneITGB3BP	AuthorityHGNC:6157	Mapping file id23421 NCBI file	EvidenceIEA, TAS
GeneITGB5	AuthorityHGNC:6160	Mapping file id3693 NCBI file	EvidenceTAS
GeneITGB6	AuthorityHGNC:6161	Mapping file id3694 NCBI file	EvidenceTAS
GeneITGB8	AuthorityHGNC:6163	Mapping file id3696 NCBI file	EvidenceTAS
GeneITPR1	AuthorityHGNC:6180	Mapping file id3708 NCBI file	EvidenceIEA, TAS
GeneITPR2	AuthorityHGNC:6181	Mapping file id3709 NCBI file	EvidenceIEA, TAS
GeneITPR3	AuthorityHGNC:6182	Mapping file id3710 NCBI file	EvidenceIEA, TAS
GeneITSN1	AuthorityHGNC:6183	Mapping file id6453 NCBI file	EvidenceTAS
GeneITSN2	AuthorityHGNC:6184	Mapping file id50618 NCBI file	EvidenceTAS
GeneJAG1	AuthorityHGNC:6188	Mapping file id182 NCBI file	EvidenceIEA, TAS
GeneJAG2	AuthorityHGNC:6189	Mapping file id3714 NCBI file	EvidenceIEA, TAS
GeneJAK1	AuthorityHGNC:6190	Mapping file id3716 NCBI file	EvidenceTAS
GeneJAK2	AuthorityHGNC:6192	Mapping file id3717 NCBI file	EvidenceIEA, TAS
GeneJAK3	AuthorityHGNC:6193	Mapping file id3718 NCBI file	EvidenceTAS
GeneJUN	AuthorityHGNC:6204	Mapping file id3725 NCBI file	EvidenceIEA, TAS
GeneJUNB	AuthorityHGNC:6205	Mapping file id3726 NCBI file	EvidenceIEA, TAS
GeneJUND	AuthorityHGNC:6206	Mapping file id3727 NCBI file	EvidenceIEA, TAS
GeneJUP	AuthorityHGNC:6207	Mapping file id3728 NCBI file	EvidenceTAS
GeneKALRN	AuthorityHGNC:4814	Mapping file id8997 NCBI file	EvidenceTAS
GeneKANK1	AuthorityHGNC:19309	Mapping file id23189 NCBI file	EvidenceTAS
GeneKAT2A	AuthorityHGNC:4201	Mapping file id2648 NCBI file	EvidenceIEA, TAS
GeneKAT2B	AuthorityHGNC:8638	Mapping file id8850 NCBI file	EvidenceIEA, TAS
GeneKAT5	AuthorityHGNC:5275	Mapping file id10524 NCBI file	EvidenceIEA, TAS
GeneKBTBD7	AuthorityHGNC:25266	Mapping file id84078 NCBI file	EvidenceTAS
GeneKCTD13	AuthorityHGNC:22234	Mapping file id253980 NCBI file	EvidenceTAS
GeneKCTD3	AuthorityHGNC:21305	Mapping file id51133 NCBI file	EvidenceTAS
GeneKCTD6	AuthorityHGNC:22235	Mapping file id200845 NCBI file	EvidenceTAS
GeneKDM1A	AuthorityHGNC:29079	Mapping file id23028 NCBI file	EvidenceIEA, TAS
GeneKDM1B	AuthorityHGNC:21577	Mapping file id221656 NCBI file	EvidenceTAS
GeneKDM3A	AuthorityHGNC:20815	Mapping file id55818 NCBI file	EvidenceTAS
GeneKDM4A	AuthorityHGNC:22978	Mapping file id9682 NCBI file	EvidenceTAS
GeneKDM4B	AuthorityHGNC:29136	Mapping file id23030 NCBI file	EvidenceTAS
GeneKDM4C	AuthorityHGNC:17071	Mapping file id23081 NCBI file	EvidenceTAS
GeneKDR	AuthorityHGNC:6307	Mapping file id3791 NCBI file	EvidenceIEA, TAS
GeneKEL	AuthorityHGNC:6308	Mapping file id3792 NCBI file	EvidenceTAS
GeneKHDRBS1	AuthorityHGNC:18116	Mapping file id10657 NCBI file	EvidenceTAS
GeneKHDRBS2	AuthorityHGNC:18114	Mapping file id202559 NCBI file	EvidenceTAS
GeneKHDRBS3	AuthorityHGNC:18117	Mapping file id10656 NCBI file	EvidenceTAS
GeneKIDINS220	AuthorityHGNC:29508	Mapping file id57498 NCBI file	EvidenceIEA, TAS
GeneKIF14	AuthorityHGNC:19181	Mapping file id9928 NCBI file	EvidenceTAS
GeneKIF18A	AuthorityHGNC:29441	Mapping file id81930 NCBI file	EvidenceTAS
GeneKIF2A	AuthorityHGNC:6318	Mapping file id3796 NCBI file	EvidenceTAS
GeneKIF2B	AuthorityHGNC:29443	Mapping file id84643 NCBI file	EvidenceTAS
GeneKIF2C	AuthorityHGNC:6393	Mapping file id11004 NCBI file	EvidenceTAS
GeneKIF3A	AuthorityHGNC:6319	Mapping file id11127 NCBI file	EvidenceIEA, TAS
GeneKIF5A	AuthorityHGNC:6323	Mapping file id3798 NCBI file	EvidenceTAS
GeneKIF5B	AuthorityHGNC:6324	Mapping file id3799 NCBI file	EvidenceTAS
GeneKIF7	AuthorityHGNC:30497	Mapping file id374654 NCBI file	EvidenceTAS
GeneKISS1	AuthorityHGNC:6341	Mapping file id3814 NCBI file	EvidenceTAS
GeneKISS1R	AuthorityHGNC:4510	Mapping file id84634 NCBI file	EvidenceTAS
GeneKIT	AuthorityHGNC:6342	Mapping file id3815 NCBI file	EvidenceIEA, TAS
GeneKITLG	AuthorityHGNC:6343	Mapping file id4254 NCBI file	EvidenceIEA, TAS
GeneKL	AuthorityHGNC:6344	Mapping file id9365 NCBI file	EvidenceTAS
GeneKLB	AuthorityHGNC:15527	Mapping file id152831 NCBI file	EvidenceTAS
GeneKLC1	AuthorityHGNC:6387	Mapping file id3831 NCBI file	EvidenceTAS
GeneKLC2	AuthorityHGNC:20716	Mapping file id64837 NCBI file	EvidenceTAS
GeneKLC3	AuthorityHGNC:20717	Mapping file id147700 NCBI file	EvidenceTAS
GeneKLC4	AuthorityHGNC:21624	Mapping file id89953 NCBI file	EvidenceTAS
GeneKLF16	AuthorityHGNC:16857	Mapping file id83855 NCBI file	EvidenceTAS
GeneKLHL12	AuthorityHGNC:19360	Mapping file id59349 NCBI file	EvidenceTAS
GeneKLK2	AuthorityHGNC:6363	Mapping file id3817 NCBI file	EvidenceTAS
GeneKLK3	AuthorityHGNC:6364	Mapping file id354 NCBI file	EvidenceTAS
GeneKMT2B	AuthorityHGNC:15840	Mapping file id9757 NCBI file	EvidenceTAS
GeneKNG1	AuthorityHGNC:6383	Mapping file id3827 NCBI file	EvidenceTAS
GeneKNL1	AuthorityHGNC:24054	Mapping file id57082 NCBI file	EvidenceTAS
GeneKNTC1	AuthorityHGNC:17255	Mapping file id9735 NCBI file	EvidenceTAS
GeneKPNA2	AuthorityHGNC:6395	Mapping file id3838 NCBI file	EvidenceIEA, TAS
GeneKRAS	AuthorityHGNC:6407	Mapping file id3845 NCBI file	EvidenceIEA, TAS
GeneKREMEN1	AuthorityHGNC:17550	Mapping file id83999 NCBI file	EvidenceIEA, TAS
GeneKREMEN2	AuthorityHGNC:18797	Mapping file id79412 NCBI file	EvidenceIEA, TAS
GeneKSR1	AuthorityHGNC:6465	Mapping file id8844 NCBI file	EvidenceTAS
GeneKSR2	AuthorityHGNC:18610	Mapping file id283455 NCBI file	EvidenceTAS
GeneKTN1	AuthorityHGNC:6467	Mapping file id3895 NCBI file	EvidenceTAS
GeneLAMA1	AuthorityHGNC:6481	Mapping file id284217 NCBI file	EvidenceTAS
GeneLAMA2	AuthorityHGNC:6482	Mapping file id3908 NCBI file	EvidenceTAS
GeneLAMA3	AuthorityHGNC:6483	Mapping file id3909 NCBI file	EvidenceTAS
GeneLAMA4	AuthorityHGNC:6484	Mapping file id3910 NCBI file	EvidenceTAS
GeneLAMA5	AuthorityHGNC:6485	Mapping file id3911 NCBI file	EvidenceTAS
GeneLAMB1	AuthorityHGNC:6486	Mapping file id3912 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.