Pathway Human Homo sapiens

Disassembly of the destruction complex and recruitment of AXIN to the membrane

R-HSA-4641262 in Reactome release 97: under TCF dependent signaling in response to WNT, with 31 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-4641262 (mouse), R-RNO-4641262 (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-4641262.6
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2014-03-12
Last updated: 2017-09-27
Events inside: 7, counted from the record

Upon stimulation with WNT ligand, AXIN and GSK3beta are recruited to the plasma membrane through interaction with DVL (Tamai et al, 2004; Mao et al, 2001; reviewed in He et al, 2004). Polymerization of membrane-associated DVL and GSK3beta- and CSNK1-mediated phosphorylation of LRP5/6 establish a feed-forward mechanism for enhanced membrane recruitment of AXIN upon WNT signaling (Tamai et al, 2004; Cong et al, 2004; Zeng et al, 2005; Bilic et al, 2007). In Xenopus oocytes, but not necessarily all sytems, AXIN is present in limiting concentrations and is considered rate limiting for the assembly of the destruction complex (Lee et al, 2003; Benchabane et al, 2008; Tan et al, 2012; reviewed in MacDonald et al, 2009). The recruitment of AXIN away from the destruction complex upon WNT stimulation effectively destabilizes the destruction complex and contributes to the accumulation of free beta-catenin (Kikuchi, 1999; Lee et al, 2003). AXIN association with the destruction complex is also regulated by phosphorylation. In the active destruction complex, AXIN is phosphorylated by GSK3beta; dephosphorylation by protein phosphatase 1 (PP1) or protein phosphatase 2A (PP2A) destabilizes the interaction of AXIN with the other components of the destruction complex and promotes its disassembly (Luo et al, 2007; Willert et al, 1999; Jho et al, 1999). Free AXIN is also subject to degradation by the 26S proteasome in a manner that depends on the poly-ADP-ribosylating enzymes tankyrase 1 and 2 (Huang et al, 2009).

Literature Reactome attaches

A dual-kinase mechanism for Wnt co-receptor phosphorylation and activationNature, 2005, vol. 438, p. 873-7PubMed 16341017
A mechanism for Wnt coreceptor activationMol Cell, 2004, vol. 13, p. 149-56PubMed 14731402
Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signaling pathwayMol Cell, 2001, vol. 7, p. 801-9PubMed 11336703
LDL receptor-related proteins 5 and 6 in Wnt/beta-catenin signaling: arrows point the wayDevelopment, 2004, vol. 131, p. 1663-77PubMed 15084453
Wnt-induced dephosphorylation of axin releases beta-catenin from the axin complexGenes Dev, 1999, vol. 13, p. 1768-73PubMed 10421629
A GSK3beta phosphorylation site in axin modulates interaction with beta-catenin and Tcf-mediated gene expressionBiochem Biophys Res Commun, 1999, vol. 266, p. 28-35PubMed 10581160
Tankyrase inhibition stabilizes axin and antagonizes Wnt signallingNature, 2009, vol. 461, p. 614-20PubMed 19759537
Wnt signals across the plasma membrane to activate the beta-catenin pathway by forming oligomers containing its receptors, Frizzled and LRPDevelopment, 2004, vol. 131, p. 5103-15PubMed 15459103
Wnt induces LRP6 signalosomes and promotes dishevelled-dependent LRP6 phosphorylationScience, 2007, vol. 316, p. 1619-22PubMed 17569865
Protein phosphatase 1 regulates assembly and function of the beta-catenin degradation complexEMBO J., 2007, vol. 26, p. 1511-21PubMed 17318175
Modulation of Wnt signaling by Axin and AxilCytokine Growth Factor Rev., 1999, vol. 10, p. 255-65PubMed 10647780
The roles of APC and Axin derived from experimental and theoretical analysis of the Wnt pathwayPLoS Biol, 2003, vol. 1, p. E10PubMed 14551908
Wnt signalling pathway parameters for mammalian cellsPLoS ONE, 2012, vol. 7, p. e31882PubMed 22363759
Adenomatous polyposis coli is present near the minimal level required for accurate graded responses to the Wingless morphogenDevelopment, 2008, vol. 135, p. 963-71PubMed 18234723
Wnt/beta-catenin signaling: components, mechanisms, and diseasesDev Cell, 2009, vol. 17, p. 9-26PubMed 19619488

Reactome's record lists 9 orthologous events, R-MMU-4641262 (Mus musculus), R-RNO-4641262 (Rattus norvegicus) among the species this site serves, and 7 in species this site opens no page for.

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-10-01 ET · Reactome pathway browser"Disassembly of the destruction complex and recruitment of AXIN to the membrane". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-4641262 with StableID: R-HSA-4641262.6 (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 31 genes in this human pathway; showing 1 to 31, 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
GeneAMER1	AuthorityHGNC:26837	Mapping file id139285 NCBI file	EvidenceIEA, TAS
GeneAPC	AuthorityHGNC:583	Mapping file id324 NCBI file	EvidenceIEA, TAS
GeneAXIN1	AuthorityHGNC:903	Mapping file id8312 NCBI file	EvidenceIEA, TAS
GeneCAV1	AuthorityHGNC:1527	Mapping file id857 NCBI file	EvidenceTAS
GeneCSNK1A1	AuthorityHGNC:2451	Mapping file id1452 NCBI file	EvidenceIEA, TAS
GeneCSNK1G2	AuthorityHGNC:2455	Mapping file id1455 NCBI file	EvidenceIEA
GeneCTNNB1	AuthorityHGNC:2514	Mapping file id1499 NCBI file	EvidenceIEA, TAS
GeneDVL1	AuthorityHGNC:3084	Mapping file id1855 NCBI file	EvidenceIEA, TAS
GeneDVL2	AuthorityHGNC:3086	Mapping file id1856 NCBI file	EvidenceIEA, TAS
GeneDVL3	AuthorityHGNC:3087	Mapping file id1857 NCBI file	EvidenceIEA, TAS
GeneFRAT1	AuthorityHGNC:3944	Mapping file id10023 NCBI file	EvidenceTAS
GeneFRAT2	AuthorityHGNC:16048	Mapping file id23401 NCBI file	EvidenceTAS
GeneFZD1	AuthorityHGNC:4038	Mapping file id8321 NCBI file	EvidenceIEA, TAS
GeneFZD2	AuthorityHGNC:4040	Mapping file id2535 NCBI file	EvidenceIEA, TAS
GeneFZD5	AuthorityHGNC:4043	Mapping file id7855 NCBI file	EvidenceTAS
GeneGSK3B	AuthorityHGNC:4617	Mapping file id2932 NCBI file	EvidenceIEA, TAS
GeneLRP5	AuthorityHGNC:6697	Mapping file id4041 NCBI file	EvidenceIEA, TAS
GeneLRP6	AuthorityHGNC:6698	Mapping file id4040 NCBI file	EvidenceIEA, TAS
GenePPP2CA	AuthorityHGNC:9299	Mapping file id5515 NCBI file	EvidenceIEA, TAS
GenePPP2CB	AuthorityHGNC:9300	Mapping file id5516 NCBI file	EvidenceIEA, TAS
GenePPP2R1A	AuthorityHGNC:9302	Mapping file id5518 NCBI file	EvidenceIEA, TAS
GenePPP2R1B	AuthorityHGNC:9303	Mapping file id5519 NCBI file	EvidenceIEA, TAS
GenePPP2R5A	AuthorityHGNC:9309	Mapping file id5525 NCBI file	EvidenceIEA, TAS
GenePPP2R5B	AuthorityHGNC:9310	Mapping file id5526 NCBI file	EvidenceIEA, TAS
GenePPP2R5C	AuthorityHGNC:9311	Mapping file id5527 NCBI file	EvidenceIEA, TAS
GenePPP2R5D	AuthorityHGNC:9312	Mapping file id5528 NCBI file	EvidenceIEA, TAS
GenePPP2R5E	AuthorityHGNC:9313	Mapping file id5529 NCBI file	EvidenceIEA, TAS
GeneWNT1	AuthorityHGNC:12774	Mapping file id7471 NCBI file	EvidenceIEA, TAS
GeneWNT3A	AuthorityHGNC:15983	Mapping file id89780 NCBI file	EvidenceIEA, TAS
GeneWNT8A	AuthorityHGNC:12788	Mapping file id7478 NCBI file	EvidenceIEA, TAS
GeneWNT8B	AuthorityHGNC:12789	Mapping file id7479 NCBI file	EvidenceIEA, TAS

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

TCF dependent signaling in response to WNTR-HSA-201681222 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.