Pathway Human Homo sapiens

Transcriptional Regulation by E2F6

R-HSA-8953750 in Reactome release 97: under Generic Transcription Pathway, with 35 genes placed in it by the mapping files and 0 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-8953750 (mouse), R-RNO-8953750 (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-8953750.3
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2017-09-12
Events inside: 33, counted from the record

E2F6, similar to other E2F proteins, possesses the DNA binding domain, the dimerization domain and the marked box. E2F6, however, does not have a pocket protein binding domain and thus does not interact with the retinoblastoma family members RB1, RBL1 (p107) and RBL2 (p130) (Gaubatz et al. 1998, Trimarchi et al. 1998, Cartwright et al. 1998). E2F6 lacks the transactivation domain and acts as a transcriptional repressor (Gaubatz et al. 1998, Trimarchi et al. 1998, Cartwright et al. 1998). E2F6 forms a heterodimer with TFDP1 (DP-1) (Trimarchi et al. 1998, Ogawa et al. 2002, Cartwright et al. 1998) or TFDP2 (DP-2) (Gaubatz et al. 1998, Trimarchi et al. 1998, Cartwright et al. 1998).

E2f6 knockout mice are viable and embryonic fibroblasts derived from these mice proliferate normally. Although E2f6 knockout mice appear healthy, they are affected by homeotic transformations of the axial skeleton, involving vertebrae and ribs. Similar skeletal defects have been reported in mice harboring mutations in polycomb genes, suggesting that E2F6 may function in recruitment of polycomb repressor complex(es) to target promoters (Storre et al. 2002).

E2F6 mediates repression of E2F responsive genes. While E2F6 was suggested to maintain G0 state in quiescent cells (Gaubatz et al. 1998, Ogawa et al. 2002), this finding has been challenged (Giangrande et al. 2004, Bertoli et al. 2013, Bertoli et al. 2016). Instead, E2F6-mediated gene repression in proliferating (non-quiescent) cells is thought to repress E2F targets involved in G1/S transition during S phase of the cell cycle. E2F6 does not affect E2F targets involved in G2/M transition (Oberley et al. 2003, Giangrande et al. 2004, Attwooll et al. 2005, Trojer et al. 2011, Bertoli et al. 2013). In the context of the E2F6.com-1 complex, E2F6 was shown to bind to promoters of E2F1, MYC, CDC25A and TK1 genes (Ogawa et al. 2002). E2F6 also binds the promoters of CDC6, RRM1 (RR1), PCNA and TYMS (TS) genes (Giangrande et al. 2004), as well as the promoter of the DHFR gene (Gaubatz et al. 1998). While transcriptional repression by the E2F6.com 1 complex may be associated with histone methyltransferase activity (Ogawa et al. 2002), E2F6 can also repress transcription independently of H3K9 methylation (Oberley et al. 2003).

During S phase, E2F6 is involved in the DNA replication stress checkpoint (Bertoli et al. 2013, Bertoli et al. 2016). Under replication stress, CHEK1-mediated phosphorylation prevents association of E2F6 with its target promoters, allowing transcription of E2F target genes whose expression is needed for resolution of stalled replication forks and restart of DNA synthesis. Inability to induce transcription of E2F target genes (due to CHEK1 inhibition or E2F6 overexpression) leads to replication stress induced DNA damage (Bertoli et al. 2013, Bertoli et al. 2016). E2F6 represses transcription of a number of E2F targets involved in DNA synthesis and repair, such as RRM2, RAD51, BRCA1, and RBBP8 (Oberley et al. 2003, Bertoli et al. 2013).

Literature Reactome attaches

A complex with chromatin modifiers that occupies E2F- and Myc-responsive genes in G0 cellsScience, 2002, vol. 296, p. 1132-6PubMed 12004135
Unusual proliferation arrest and transcriptional control properties of a newly discovered E2F family member, E2F-6Proc. Natl. Acad. Sci. U.S.A., 1998, vol. 95, p. 9190-5PubMed 9689056
E2F-6, a member of the E2F family that can behave as a transcriptional repressorProc. Natl. Acad. Sci. U.S.A., 1998, vol. 95, p. 2850-5PubMed 9501179
E2F-6: a novel member of the E2F family is an inhibitor of E2F-dependent transcriptionOncogene, 1998, vol. 17, p. 611-23PubMed 9704927
A role for E2F6 in distinguishing G1/S- and G2/M-specific transcriptionGenes Dev., 2004, vol. 18, p. 2941-51PubMed 15574595
Homeotic transformations of the axial skeleton that accompany a targeted deletion of E2f6EMBO Rep., 2002, vol. 3, p. 695-700PubMed 12101104
L3MBTL2 protein acts in concert with PcG protein-mediated monoubiquitination of H2A to establish a repressive chromatin structure

Reactome's record lists 11 orthologous events, R-MMU-8953750 (Mus musculus), R-RNO-8953750 (Rattus norvegicus) among the species this site serves, and 9 in species this site opens no page for.

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-10-01 ET · Reactome pathway browser"Transcriptional Regulation by E2F6". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-8953750 with StableID: R-HSA-8953750.3 (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 35 genes in this human pathway; showing 1 to 35, 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
GeneAPAF1	AuthorityHGNC:576	Mapping file id317 NCBI file	EvidenceTAS
GeneBMI1	AuthorityHGNC:1066	Mapping file id648 NCBI file	EvidenceTAS
GeneBRCA1	AuthorityHGNC:1100	Mapping file id672 NCBI file	EvidenceTAS
GeneCBX3	AuthorityHGNC:1553	Mapping file id11335 NCBI file	EvidenceTAS
GeneCBX5	AuthorityHGNC:1555	Mapping file id23468 NCBI file	EvidenceTAS
GeneCDC7	AuthorityHGNC:1745	Mapping file id8317 NCBI file	EvidenceTAS
GeneCHEK1	AuthorityHGNC:1925	Mapping file id1111 NCBI file	EvidenceTAS
GeneCOMMD3-BMI1	AuthorityHGNC:48326	Mapping file id100532731 NCBI file	EvidenceTAS
GeneE2F1	AuthorityHGNC:3113	Mapping file id1869 NCBI file	EvidenceTAS
GeneE2F6	AuthorityHGNC:3120	Mapping file id1876 NCBI file	EvidenceTAS
GeneEED	AuthorityHGNC:3188	Mapping file id8726 NCBI file	EvidenceTAS
GeneEHMT1	AuthorityHGNC:24650	Mapping file id79813 NCBI file	EvidenceTAS
GeneEHMT2	AuthorityHGNC:14129	Mapping file id10919 NCBI file	EvidenceTAS
GeneEPC1	AuthorityHGNC:19876	Mapping file id80314 NCBI file	EvidenceTAS
GeneEZH2	AuthorityHGNC:3527	Mapping file id2146 NCBI file	EvidenceTAS
GeneL3MBTL2	AuthorityHGNC:18594	Mapping file id83746 NCBI file	EvidenceTAS
GeneMAX	AuthorityHGNC:6913	Mapping file id4149 NCBI file	EvidenceTAS
GeneMGA	AuthorityHGNC:14010	Mapping file id23269 NCBI file	EvidenceTAS
GenePCGF2	AuthorityHGNC:12929	Mapping file id7703 NCBI file	EvidenceTAS
GenePCGF6	AuthorityHGNC:21156	Mapping file id84108 NCBI file	EvidenceTAS
GenePHC1	AuthorityHGNC:3182	Mapping file id1911 NCBI file	EvidenceTAS
GenePHC3	AuthorityHGNC:15682	Mapping file id80012 NCBI file	EvidenceTAS
GeneRAD51	AuthorityHGNC:9817	Mapping file id5888 NCBI file	EvidenceTAS
GeneRBBP4	AuthorityHGNC:9887	Mapping file id5928 NCBI file	EvidenceTAS
GeneRBBP7	AuthorityHGNC:9890	Mapping file id5931 NCBI file	EvidenceTAS
GeneRBBP8	AuthorityHGNC:9891	Mapping file id5932 NCBI file	EvidenceTAS
GeneRING1	AuthorityHGNC:10018	Mapping file id6015 NCBI file	EvidenceTAS
GeneRNF2	AuthorityHGNC:10061	Mapping file id6045 NCBI file	EvidenceTAS
GeneRRM2	AuthorityHGNC:10452	Mapping file id6241 NCBI file	EvidenceTAS
GeneRYBP	AuthorityHGNC:10480	Mapping file id23429 NCBI file	EvidenceTAS
GeneSUZ12	AuthorityHGNC:17101	Mapping file id23512 NCBI file	EvidenceTAS
GeneTFDP1	AuthorityHGNC:11749	Mapping file id7027 NCBI file	EvidenceTAS
GeneTFDP2	AuthorityHGNC:11751	Mapping file id7029 NCBI file	EvidenceTAS
GeneUXT	AuthorityHGNC:12641	Mapping file id8409 NCBI file	EvidenceTAS
GeneYAF2	AuthorityHGNC:17363	Mapping file id10138 NCBI file	EvidenceTAS

Evidence codes on this page: 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

Generic Transcription PathwayR-HSA-2124361,251 genes

Children

None: no pathway of this release's list names this one as a parent.

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.