Pathway Human Homo sapiens

Signaling by EGFR

R-HSA-177929 in Reactome release 97: under Signaling by Receptor Tyrosine Kinases, with 53 genes placed in it by the mapping files and 5 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-177929 (mouse), R-RNO-177929 (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-177929.6
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2007-02-20
Last updated: 2023-03-29
Events inside: 12, counted from the record
Also named: Epidermal Growth Factor Receptor (EGFR) signaling

The epidermal growth factor receptor (EGFR) is one member of the ERBB family of transmembrane glycoprotein tyrosine receptor kinases (RTK). Binding of EGFR to its ligands induces conformational change that unmasks the dimerization interface in the extracellular domain of EGFR, leading to receptor homo- or heterodimerization at the cell surface. Dimerization of the extracellular regions of EGFR triggers additional conformational change of the cytoplasmic EGFR regions, enabling the kinase domains of two EGFR molecules to achieve the catalytically active conformation. Ligand activated EGFR dimers trans-autophosphorylate on tyrosine residues in the cytoplasmic tail of the receptor. Phosphorylated tyrosines serve as binding sites for the recruitment of signal transducers and activators of intracellular substrates, which then stimulate intracellular signal transduction cascades that are involved in regulating cellular proliferation, differentiation, and survival. Recruitment of complexes containing GRB2 and SOS1 to phosphorylated EGFR dimers either directly, through phosphotyrosine residues that serve as GRB2 docking sites, or indirectly, through SHC1 recruitment, promotes GDP to GTP exchange on RAS, resulting in the activation of RAF/MAP kinase cascade. Binding of complexes of GRB2 and GAB1 to phosphorylated EGFR dimers leads to formation of the active PI3K complex, conversion of PIP2 into PIP3, and activation of AKT signaling. Phospholipase C-gamma1 (PLCG1) can also be recruited directly, through EGFR phosphotyrosine residues that serve as PLCG1 docking sites, which leads to PLCG1 phosphorylation by EGFR and activation of DAG and IP3 signaling. EGFR signaling is downregulated by the action of ubiquitin ligase CBL. CBL binds directly to the phosphorylated EGFR dimer through the phosphotyrosine Y1069 (i.e. Y1045 in the mature protein) in the C-tail of EGFR, and after CBL is phosphorylated by EGFR, it becomes active and ubiquitinates phosphorylated EGFR dimers, targeting them for degradation. Positive regulation of EGFR signaling by direct association of EGFR with accessory proteins such as AAMP and FAM83B is being investigated. For review of EGFR signaling, please refer to Carpenter 1999, Wells 1999, Schlessinger 2002, Herbst 2004, Avraham and Yarden, 2011, Bartel et al. 2016, Uribe et al. 2021, Keflee et al. 2022.

Literature Reactome attaches

Review of epidermal growth factor receptor biologyInt J Radiat Oncol Biol Phys, 2004, vol. 59, p. 21-6PubMed 15142631
EGF receptorInt J Biochem Cell Biol, 1999, vol. 31, p. 637-43PubMed 10404636
Employment of the epidermal growth factor receptor in growth factor-independent signaling pathwaysJ Cell Biol, 1999, vol. 146, p. 697-702PubMed 10459005
Ligand-induced, receptor-mediated dimerization and activation of EGF receptorCell, 2002, vol. 110, p. 669-72PubMed 12297041
Feedback regulation of EGFR signalling: decision making by early and delayed loopsNat Rev Mol Cell Biol, 2011, vol. 12, p. 104-17PubMed 21252999
Overview of the multifaceted resistances toward EGFR-TKIs and new chemotherapeutic strategies in non-small cell lung cancerBiochem Pharmacol, 2022, vol. 205, p. 115262PubMed 36191627
EGFR in Cancer: Signaling Mechanisms, Drugs, and Acquired ResistanceCancers (Basel), 2021, vol. 13PubMed 34206026

Reactome's record lists 10 orthologous events, R-RNO-177929 (Rattus norvegicus), R-MMU-177929 (Mus musculus) among the species this site serves, and 8 in species this site opens no page for.

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-10-01 ET · Reactome pathway browser"Signaling by EGFR". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-177929 with StableID: R-HSA-177929.6 (accessed 2026-10-01 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 53 genes in this human pathway; showing 1 to 53, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 1 of 1
Gene	Authority id	Mapping file id	Evidence codes
GeneAAMP	AuthorityHGNC:18	Mapping file id14 NCBI file	EvidenceTAS
GeneADAM10	AuthorityHGNC:188	Mapping file id102 NCBI file	EvidenceIEA
GeneADAM12	AuthorityHGNC:190	Mapping file id8038 NCBI file	EvidenceIEA
GeneADAM17	AuthorityHGNC:195	Mapping file id6868 NCBI file	EvidenceIEA
GeneAREG	AuthorityHGNC:651	Mapping file id374 NCBI file	EvidenceTAS
GeneARHGEF7	AuthorityHGNC:15607	Mapping file id8874 NCBI file	EvidenceTAS
GeneBTC	AuthorityHGNC:1121	Mapping file id685 NCBI file	EvidenceTAS
GeneCBL	AuthorityHGNC:1541	Mapping file id867 NCBI file	EvidenceTAS
GeneCDC42	AuthorityHGNC:1736	Mapping file id998 NCBI file	EvidenceTAS
GeneCSK	AuthorityHGNC:2444	Mapping file id1445 NCBI file	EvidenceTAS
GeneEGF	AuthorityHGNC:3229	Mapping file id1950 NCBI file	EvidenceIEA, TAS
GeneEGFR	AuthorityHGNC:3236	Mapping file id1956 NCBI file	EvidenceTAS
GeneEPGN	AuthorityHGNC:17470	Mapping file id255324 NCBI file	EvidenceTAS
GeneEPN1	AuthorityHGNC:21604	Mapping file id29924 NCBI file	EvidenceTAS
GeneEPS15	AuthorityHGNC:3419	Mapping file id2060 NCBI file	EvidenceTAS
GeneEPS15L1	AuthorityHGNC:24634	Mapping file id58513 NCBI file	EvidenceTAS
GeneEREG	AuthorityHGNC:3443	Mapping file id2069 NCBI file	EvidenceTAS
GeneGAB1	AuthorityHGNC:4066	Mapping file id2549 NCBI file	EvidenceTAS
GeneGRB2	AuthorityHGNC:4566	Mapping file id2885 NCBI file	EvidenceTAS
GeneHBEGF	AuthorityHGNC:3059	Mapping file id1839 NCBI file	EvidenceTAS
GeneHGS	AuthorityHGNC:4897	Mapping file id9146 NCBI file	EvidenceTAS
GeneHRAS	AuthorityHGNC:5173	Mapping file id3265 NCBI file	EvidenceTAS
GeneKRAS	AuthorityHGNC:6407	Mapping file id3845 NCBI file	EvidenceTAS
GeneLRIG1	AuthorityHGNC:17360	Mapping file id26018 NCBI file	EvidenceTAS
GeneNRAS	AuthorityHGNC:7989	Mapping file id4893 NCBI file	EvidenceTAS
GenePAG1	AuthorityHGNC:30043	Mapping file id55824 NCBI file	EvidenceTAS
GenePIK3CA	AuthorityHGNC:8975	Mapping file id5290 NCBI file	EvidenceTAS
GenePIK3R1	AuthorityHGNC:8979	Mapping file id5295 NCBI file	EvidenceTAS
GenePLCG1	AuthorityHGNC:9065	Mapping file id5335 NCBI file	EvidenceTAS
GenePTPN11	AuthorityHGNC:9644	Mapping file id5781 NCBI file	EvidenceTAS
GenePTPN12	AuthorityHGNC:9645	Mapping file id5782 NCBI file	EvidenceTAS
GenePTPN3	AuthorityHGNC:9655	Mapping file id5774 NCBI file	EvidenceTAS
GenePTPRK	AuthorityHGNC:9674	Mapping file id5796 NCBI file	EvidenceTAS
GenePXN	AuthorityHGNC:9718	Mapping file id5829 NCBI file	EvidenceTAS
GeneRPS27A	AuthorityHGNC:10417	Mapping file id6233 NCBI file	EvidenceTAS
GeneSACK1A	AuthorityHGNC:28210	Mapping file id84985 NCBI file	EvidenceTAS
GeneSACK1B	AuthorityHGNC:21357	Mapping file id222584 NCBI file	EvidenceTAS
GeneSACK1D	AuthorityHGNC:16122	Mapping file id81610 NCBI file	EvidenceTAS
GeneSH3GL1	AuthorityHGNC:10830	Mapping file id6455 NCBI file	EvidenceTAS
GeneSH3GL2	AuthorityHGNC:10831	Mapping file id6456 NCBI file	EvidenceTAS
GeneSH3GL3	AuthorityHGNC:10832	Mapping file id6457 NCBI file	EvidenceTAS
GeneSH3KBP1	AuthorityHGNC:13867	Mapping file id30011 NCBI file	EvidenceTAS
GeneSHC1	AuthorityHGNC:10840	Mapping file id6464 NCBI file	EvidenceTAS
GeneSOS1	AuthorityHGNC:11187	Mapping file id6654 NCBI file	EvidenceTAS
GeneSPRY1	AuthorityHGNC:11269	Mapping file id10252 NCBI file	EvidenceTAS
GeneSPRY2	AuthorityHGNC:11270	Mapping file id10253 NCBI file	EvidenceTAS
GeneSRC	AuthorityHGNC:11283	Mapping file id6714 NCBI file	EvidenceTAS
GeneSTAM	AuthorityHGNC:11357	Mapping file id8027 NCBI file	EvidenceTAS
GeneSTAM2	AuthorityHGNC:11358	Mapping file id10254 NCBI file	EvidenceTAS
GeneTGFA	AuthorityHGNC:11765	Mapping file id7039 NCBI file	EvidenceTAS
GeneUBA52	AuthorityHGNC:12458	Mapping file id7311 NCBI file	EvidenceTAS
GeneUBB	AuthorityHGNC:12463	Mapping file id7314 NCBI file	EvidenceTAS
GeneUBC	AuthorityHGNC:12468	Mapping file id7316 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

Signaling by Receptor Tyrosine KinasesR-HSA-9006934536 genes

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.