AXIN1 (Axis inhibition protein 1) is a cytosolic scaffold protein that serves as the core component of the beta-catenin destruction complex, which also includes APC, GSK3B, and CK1. AXIN1 coordinates the phosphorylation and subsequent ubiquitination of beta-catenin, thereby negatively regulating the canonical Wnt signaling pathway. Key functional domains include: an N-terminal tankyrase-binding motif, an RGS domain for APC binding, a GSK3B-binding helix (aa 383-400), a beta-catenin binding region, and a C-terminal DIX domain that mediates polymerization and formation of cytoplasmic condensates ("degradasomes"). AXIN1 is regulated by tankyrase-mediated ADP-ribosylation followed by RNF146-dependent ubiquitination and degradation. Loss-of-function mutations in AXIN1 are associated with hepatocellular carcinoma due to aberrant Wnt pathway activation. AXIN1 also has secondary roles in TGF-beta signaling (promoting Smad7 degradation via Arkadia) and JNK signaling, and participates in the AXIN1-HIPK2-TP53 complex upon UV irradiation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0060090 molecular adaptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: AXIN1 functions as a molecular adaptor/scaffold by bringing together components of the beta-catenin destruction complex (GSK3B, APC, CK1, beta-catenin). This adaptor function is directly demonstrated in PMID:9601641 and is the core function of AXIN1. Reason: IBA annotation is well-supported. AXIN1 is defined as a scaffold protein that coordinates assembly of the destruction complex [PMID:9601641]. Multiple experimental studies confirm this adaptor function. Supporting Evidence: PMID:9601641 Axin acts as a scaffold upon which APC, beta-catenin and GSK3 beta assemble to coordinate the regulation of beta-catenin signaling. file:human/AXIN1/AXIN1-deep-research-falcon.md model: Edison Scientific Literature |
| GO:0019901 protein kinase binding | IBA GO_REF:0000033 | ACCEPT | Summary: AXIN1 binds to protein kinases GSK3B (through a defined alpha-helix at aa 383-400) and CK1, which are essential for its function in the destruction complex. Reason: AXIN1 directly binds GSK3B and CK1 kinases as part of its scaffold function. The GSK3B-binding helix is structurally characterized [PDB:1O9U]. This is a core function. Supporting Evidence: PMID:9601641 Human Axin (hAxin) binds directly to beta-catenin, GSK3 beta, and APC in vitro, and the endogenous proteins are found in a complex in cells. |
| GO:0090090 negative regulation of canonical Wnt signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: Negative regulation of canonical Wnt signaling is THE core function of AXIN1. By scaffolding the destruction complex, AXIN1 promotes beta-catenin phosphorylation and degradation, thereby restraining Wnt target gene transcription. Reason: This is the primary biological function of AXIN1, extensively documented in the literature and supported by genetic and biochemical evidence. Loss of AXIN1 function leads to elevated beta-catenin and Wnt pathway activation. Supporting Evidence: PMID:9601641 Overexpression of hAxin strongly promoted the downregulation of wild-type beta-catenin in colon cancer cells PMID:10644691 PP2C expression relieves Axin-mediated repression of LEF-1-dependent transcription |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: AXIN1 is predominantly cytoplasmic but can translocate to the nucleus under specific conditions such as UV irradiation (where it colocalizes with DAXX in the AXIN1-HIPK2-TP53 complex). Reason: Nuclear localization is documented experimentally [PMID:12072559, PMID:21383061]. While not the primary site of AXIN1 function, it represents a real localization pattern. Supporting Evidence: PMID:12072559 Subcellular distribution of Wnt pathway proteins in normal and neoplastic colon |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: AXIN1 can localize to the plasma membrane, particularly during Wnt signaling when it is recruited to LRP5/6 receptors. Membrane localization is regulated by MACF1. Reason: Plasma membrane localization is consistent with AXIN1's role in Wnt signalosome assembly and its interaction with LRP5/6 co-receptors upon Wnt stimulation. Documented by immunohistochemistry in PMID:12072559. |
| GO:0008013 beta-catenin binding | IBA GO_REF:0000033 | ACCEPT | Summary: AXIN1 directly binds beta-catenin through a defined binding region (aa 434-502). This interaction is essential for AXIN1's function in promoting beta-catenin phosphorylation and degradation. Reason: Beta-catenin binding is a core molecular function of AXIN1, well-documented experimentally. Supporting Evidence: PMID:9601641 Human Axin (hAxin) binds directly to beta-catenin, GSK3 beta, and APC in vitro |
| GO:0030877 beta-catenin destruction complex | IBA GO_REF:0000033 | ACCEPT | Summary: AXIN1 is a core component of the beta-catenin destruction complex. It serves as the central scaffold that brings together APC, GSK3B, CK1, and beta-catenin. Reason: Membership in the beta-catenin destruction complex is THE defining characteristic of AXIN1 function. This is extensively documented in the literature. Supporting Evidence: PMID:9601641 Axin acts as a scaffold upon which APC, beta-catenin and GSK3 beta assemble |
| GO:0031625 ubiquitin protein ligase binding | IBA GO_REF:0000033 | ACCEPT | Summary: AXIN1 binds to E3 ubiquitin ligases including RNF111 (Arkadia) and RNF146. The RNF111 interaction promotes Smad7 degradation. RNF146 binding leads to AXIN1 ubiquitination following ADP-ribosylation by tankyrase. Reason: Ubiquitin ligase binding is functionally important for both AXIN1's role in promoting Smad7 degradation and for AXIN1's own regulation via the tankyrase-RNF146 axis. Supporting Evidence: PMID:16601693 Axin activates TGF-beta signaling by forming a multimeric complex consisting of Smad7 and ubiquitin E3 ligase Arkadia |
| GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: AXIN1 promotes the proteasomal degradation of beta-catenin by facilitating its phosphorylation, which leads to recognition by beta-TrCP E3 ligase and ubiquitination. Reason: This accurately describes AXIN1's downstream effect on beta-catenin, which is targeted for proteasomal degradation after being phosphorylated by the destruction complex. Supporting Evidence: PMID:9601641 Overexpression of hAxin strongly promoted the downregulation of wild-type beta-catenin |
| GO:0042802 identical protein binding | IBA GO_REF:0000033 | ACCEPT | Summary: AXIN1 self-associates (homodimerizes) through its DIX domain. This polymerization is important for formation of cytoplasmic condensates/degradasomes. Reason: AXIN1 homodimerization/polymerization via the DIX domain is well-documented and functionally important for destruction complex assembly and condensate formation. Supporting Evidence: PMID:10811618 Structural basis of the Axin-adenomatous polyposis coli interaction |
| GO:0048468 cell development | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: AXIN1's role in Wnt signaling regulation impacts cell development processes. Wnt signaling is a major developmental pathway. Reason: While AXIN1 clearly affects developmental processes through Wnt pathway regulation, "cell development" is a broad pleiotropic outcome rather than a direct molecular function. The core function is Wnt pathway regulation; developmental effects are downstream. |
| GO:0070411 I-SMAD binding | IBA GO_REF:0000033 | ACCEPT | Summary: AXIN1 binds to inhibitory SMADs including SMAD7. This interaction promotes Smad7 degradation via Arkadia (RNF111) and enhances TGF-beta signaling. Reason: I-SMAD (Smad7) binding is experimentally validated [PMID:16601693, PMID:18593713] and represents a legitimate secondary function of AXIN1 as a scaffold in TGF-beta signaling. Supporting Evidence: PMID:16601693 Axin activates TGF-beta signaling by forming a multimeric complex consisting of Smad7 and ubiquitin E3 ligase Arkadia PMID:18593713 A Smad7-Axin interaction disassociates GSK-3beta and beta-catenin from Axin |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: IEA annotation from UniProt subcellular location mapping. Nuclear localization has experimental support. Reason: Consistent with IBA annotation above and IDA evidence from PMID:12072559 and PMID:21383061. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: Cytoplasmic localization is the predominant localization for AXIN1 and the site of destruction complex function. Reason: AXIN1 is primarily cytoplasmic where it forms the destruction complex. Well-supported by multiple experimental studies. |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Plasma membrane localization is consistent with AXIN1's recruitment to Wnt receptors. Reason: Consistent with IBA annotation above and experimental evidence. |
| GO:0006915 apoptotic process | IEA GO_REF:0000043 | MARK AS OVER ANNOTATED | Summary: This IEA annotation is derived from UniProt keyword KW-0053 (Apoptosis). UniProt notes AXIN1 as a "Component of the AXIN1-HIPK2-TP53 complex which controls cell growth, apoptosis and development" and that AXIN1 "Facilitates the phosphorylation of TP53 by HIPK2 upon ultraviolet irradiation." However, this represents a secondary/pleiotropic function rather than AXIN1's core function. Reason: AXIN1's core function is as a scaffold in the Wnt/beta-catenin pathway. While AXIN1 participates in the AXIN1-HIPK2-TP53 complex that can influence apoptosis upon UV irradiation, this is a secondary function. The deep research document makes no mention of apoptosis as a primary function. Any apoptotic effects are likely downstream/pleiotropic consequences of Wnt pathway modulation or secondary functions in stress response, not the core biochemical function of the protein. |
| GO:0016020 membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Generic membrane localization. AXIN1 can associate with the plasma membrane. Reason: While more specific than needed (plasma membrane is more informative), not incorrect. |
| GO:0016055 Wnt signaling pathway | IEA GO_REF:0000043 | MODIFY | Summary: AXIN1 is involved in the Wnt signaling pathway as a negative regulator. Reason: While technically correct, this term is too broad. AXIN1 specifically negatively regulates canonical Wnt signaling. The more specific term GO:0090090 (negative regulation of canonical Wnt signaling pathway) is already present and preferred. Proposed replacements: negative regulation of canonical Wnt signaling pathway |
| GO:0030178 negative regulation of Wnt signaling pathway | IEA GO_REF:0000117 | ACCEPT | Summary: AXIN1 negatively regulates Wnt signaling. This is accurate but less specific than the canonical Wnt pathway annotation. Reason: Correct annotation. AXIN1 is primarily known for regulating canonical Wnt signaling, but this broader term is acceptable as IEA. |
| GO:0090090 negative regulation of canonical Wnt signaling pathway | IEA GO_REF:0000002 | ACCEPT | Summary: IEA annotation from InterPro domain mapping (Axin-like family). This correctly captures the core function. Reason: Core function of AXIN1, supported by domain analysis and experimental evidence. |
| GO:0005515 protein binding | IPI PMID:10481074 A GSK3-binding peptide from FRAT1 selectively inhibits the G... | MODIFY | Summary: Interaction with GSK3B demonstrated via GSK3-binding peptide studies. Reason: "Protein binding" is too generic. The interaction is specifically with GSK3B, which is better captured by GO:0019901 (protein kinase binding) or more specifically GO:0120283 (protein serine/threonine kinase binding). Proposed replacements: protein serine/threonine kinase binding Supporting Evidence: PMID:10481074 A GSK3-binding peptide from FRAT1 selectively inhibits the GSK3-catalysed phosphorylation of axin and beta-catenin. |
| GO:0005515 protein binding | IPI PMID:10644691 Protein phosphatase 2Calpha dephosphorylates axin and activa... | MODIFY | Summary: Interaction with PP2CA (PPM1A) demonstrated - protein phosphatase that dephosphorylates AXIN1. Reason: The specific interaction is with a protein phosphatase. A more informative term would be appropriate if one exists for phosphatase binding. Proposed replacements: enzyme binding Supporting Evidence: PMID:10644691 Protein phosphatase 2Calpha dephosphorylates axin and activates LEF-1-dependent transcription. |
| GO:0005515 protein binding | IPI PMID:10811618 Structural basis of the Axin-adenomatous polyposis coli inte... | MODIFY | Summary: Structural characterization of AXIN1-APC interaction. The paper provides crystal structure of the Axin-APC interaction interface. Reason: The specific interaction is with APC tumor suppressor. While no specific "APC binding" term exists, this interaction is functionally important for destruction complex assembly. Proposed replacements: protein domain specific binding Supporting Evidence: PMID:10811618 Structural basis of the Axin-adenomatous polyposis coli interaction. |
| GO:0005515 protein binding | IPI PMID:11738041 The structure of phosphorylated GSK-3beta complexed with a p... | MODIFY | Summary: Structure of phosphorylated GSK3B with FRATtide peptide that inhibits beta-catenin phosphorylation; context involves AXIN1-GSK3B interaction. Reason: Interaction with GSK3B is specifically protein kinase binding. Proposed replacements: protein serine/threonine kinase binding Supporting Evidence: PMID:11738041 The structure of phosphorylated GSK-3beta complexed with a peptide, FRATtide, that inhibits beta-catenin phosphorylation. |
| GO:0005515 protein binding | IPI PMID:16169070 A human protein-protein interaction network: a resource for ... | ACCEPT | Summary: High-throughput protein-protein interaction network study. Reason: Generic protein binding from large-scale study. While less informative, not incorrect. Multiple specific interactions were identified. Supporting Evidence: PMID:16169070 A human protein-protein interaction network: a resource for annotating the proteome. |
| GO:0005515 protein binding | IPI PMID:16293619 Thermodynamics of beta-catenin-ligand interactions: the role... | MODIFY | Summary: Study of beta-catenin-ligand interactions including AXIN1. Reason: The specific interaction is with beta-catenin, which has a specific binding term. Proposed replacements: beta-catenin binding Supporting Evidence: PMID:16293619 2005 Nov 17. Thermodynamics of beta-catenin-ligand interactions: the roles of the N- and C-terminal tails in modulating binding affinity. |
| GO:0005515 protein binding | IPI PMID:16601693 Axin is a scaffold protein in TGF-beta signaling that promot... | MODIFY | Summary: Interaction with SMAD7 and RNF111 (Arkadia) demonstrated. Reason: The specific interactions are with SMAD7 (I-SMAD binding) and RNF111 (ubiquitin ligase binding), which are captured by more specific terms. Proposed replacements: I-SMAD binding ubiquitin protein ligase binding Supporting Evidence: PMID:16601693 Apr 6. Axin is a scaffold protein in TGF-beta signaling that promotes degradation of Smad7 by Arkadia. |
| GO:0005515 protein binding | IPI PMID:17318175 Protein phosphatase 1 regulates assembly and function of the... | MODIFY | Summary: Study of PP1 regulation of the destruction complex; demonstrates AXIN1-PP1CA and AXIN1-GSK3A/B interactions. Reason: Specific kinase and phosphatase interactions are documented. Proposed replacements: protein serine/threonine kinase binding Supporting Evidence: PMID:17318175 Feb 22. Protein phosphatase 1 regulates assembly and function of the beta-catenin degradation complex. |
| GO:0005515 protein binding | IPI PMID:17318191 Bcr-Abl stabilizes beta-catenin in chronic myeloid leukemia ... | MODIFY | Summary: Study of Bcr-Abl effects on beta-catenin stabilization; AXIN1 interactions with beta-catenin and GSK3B. Reason: Specific interactions with beta-catenin and GSK3B are better captured by specific terms. Proposed replacements: beta-catenin binding Supporting Evidence: PMID:17318191 Bcr-Abl stabilizes beta-catenin in chronic myeloid leukemia through its tyrosine phosphorylation. |
| GO:0005515 protein binding | IPI PMID:17510365 Wilms tumor suppressor WTX negatively regulates WNT/beta-cat... | ACCEPT | Summary: Study of WTX (AMER1) negative regulation of Wnt signaling; interactions with multiple destruction complex components. Reason: Multiple interactions demonstrated; generic protein binding acceptable. Supporting Evidence: PMID:17510365 Wilms tumor suppressor WTX negatively regulates WNT/beta-catenin signaling. |
| GO:0005515 protein binding | IPI PMID:17601533 Two functionally distinct Axin-like proteins regulate canoni... | ACCEPT | Summary: Study in C. elegans of Axin-like proteins. Reason: Interaction with GSK3B ortholog demonstrated. Supporting Evidence: PMID:17601533 2007 Jun 6. Two functionally distinct Axin-like proteins regulate canonical Wnt signaling in C. |
| GO:0005515 protein binding | IPI PMID:18786926 Identification of a link between the SAMP repeats of adenoma... | ACCEPT | Summary: Study of DDEF (ASAP1) interaction with APC SAMP repeats. Reason: Context involves AXIN1 interactions in the APC complex. Supporting Evidence: PMID:18786926 2008 Sep 11. Identification of a link between the SAMP repeats of adenomatous polyposis coli tumor suppressor and the Src homology 3 domain of DDEF. |
| GO:0005515 protein binding | IPI PMID:19131971 The Axin1 scaffold protein promotes formation of a degradati... | ACCEPT | Summary: AXIN1 promotes c-Myc degradation by scaffolding a destruction complex for c-Myc. Reason: Demonstrates AXIN1-MYC interaction as part of a c-Myc degradation complex. Supporting Evidence: PMID:19131971 The Axin1 scaffold protein promotes formation of a degradation complex for c-Myc. |
| GO:0005515 protein binding | IPI PMID:19166851 Kaiso is a bimodal modulator for Wnt/beta-catenin signaling. | MODIFY | Summary: Kaiso as a bimodal modulator for Wnt signaling; AXIN1-beta-catenin interactions. Reason: Specific interaction with beta-catenin. Proposed replacements: beta-catenin binding Supporting Evidence: PMID:19166851 2009 Jan 21. Kaiso is a bimodal modulator for Wnt/beta-catenin signaling. |
| GO:0005515 protein binding | IPI PMID:19202075 Beta-arrestin links endothelin A receptor to beta-catenin si... | ACCEPT | Summary: Beta-arrestin links endothelin A receptor to beta-catenin signaling; AXIN1 interactions. Reason: Multiple interactions in Wnt signaling context. Supporting Evidence: PMID:19202075 Beta-arrestin links endothelin A receptor to beta-catenin signaling to induce ovarian cancer cell invasion and metastasis. |
| GO:0005515 protein binding | IPI PMID:19249679 Oncogenic function of ATDC in pancreatic cancer through Wnt ... | ACCEPT | Summary: ATDC promotes Wnt signaling by stabilizing beta-catenin; interacts with AXIN1. Reason: Novel interactor identified. Supporting Evidence: PMID:19249679 Oncogenic function of ATDC in pancreatic cancer through Wnt pathway activation and beta-catenin stabilization. |
| GO:0005515 protein binding | IPI PMID:19303846 Disrupted in schizophrenia 1 regulates neuronal progenitor p... | ACCEPT | Summary: DISC1 regulates neuronal progenitor proliferation via GSK3B-beta-catenin signaling; AXIN1-GSK3B context. Reason: Destruction complex interactions. Supporting Evidence: PMID:19303846 Disrupted in schizophrenia 1 regulates neuronal progenitor proliferation via modulation of GSK3beta/beta-catenin signaling. |
| GO:0005515 protein binding | IPI PMID:19390532 Axin localizes to the centrosome and is involved in microtub... | ACCEPT | Summary: AXIN1 localizes to centrosomes and is involved in microtubule nucleation; interacts with gamma-tubulin. Reason: Novel function for AXIN1 in microtubule organization. Supporting Evidence: PMID:19390532 Axin localizes to the centrosome and is involved in microtubule nucleation. |
| GO:0005515 protein binding | IPI PMID:19759537 Tankyrase inhibition stabilizes axin and antagonizes Wnt sig... | MODIFY | Summary: Tankyrase inhibition stabilizes AXIN1; demonstrates AXIN1-tankyrase interaction and its role in AXIN1 turnover. Reason: Specific interaction with tankyrase (PARP enzyme). Enzyme binding is more appropriate. Proposed replacements: enzyme binding Supporting Evidence: PMID:19759537 Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. |
| GO:0005515 protein binding | IPI PMID:20080667 Role of DAB2IP in modulating epithelial-to-mesenchymal trans... | ACCEPT | Summary: DAB2IP modulates EMT; AXIN1 interactions in Wnt context. Reason: Novel interactor. Supporting Evidence: PMID:20080667 Role of DAB2IP in modulating epithelial-to-mesenchymal transition and prostate cancer metastasis. |
| GO:0005515 protein binding | IPI PMID:21057547 AXIN is an essential co-activator for the promyelocytic leuk... | MODIFY | Summary: AXIN1 is an essential co-activator for PML in p53 activation; demonstrates AXIN1-TP53 interaction. Reason: Specific interaction with p53 (TP53). Proposed replacements: p53 binding Supporting Evidence: PMID:21057547 Nov 8. AXIN is an essential co-activator for the promyelocytic leukemia protein in p53 activation. |
| GO:0005515 protein binding | IPI PMID:21242974 Methylation by protein arginine methyltransferase 1 increase... | ACCEPT | Summary: PRMT1 methylation increases AXIN1 stability; interactions with beta-catenin and GSK3B. Reason: Multiple interactions demonstrated. Supporting Evidence: PMID:21242974 Methylation by protein arginine methyltransferase 1 increases stability of Axin, a negative regulator of Wnt signaling. |
| GO:0005515 protein binding | IPI PMID:21245303 Dishevelled interacts with the DIX domain polymerization int... | ACCEPT | Summary: DVL interacts with AXIN1 DIX domain to interfere with beta-catenin regulation. Reason: AXIN1-DVL interaction through DIX domain polymerization interface. Supporting Evidence: PMID:21245303 Dishevelled interacts with the DIX domain polymerization interface of Axin to interfere with its function in down-regulating Ξ²-catenin. |
| GO:0005515 protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | ACCEPT | Summary: Human liver protein interaction network study. Reason: Large-scale interaction study. Supporting Evidence: PMID:21988832 Toward an understanding of the protein interaction network of the human liver. |
| GO:0005515 protein binding | IPI PMID:22153077 Structural basis and sequence rules for substrate recognitio... | MODIFY | Summary: Structural basis for tankyrase substrate recognition; AXIN1-TNKS2 interaction. Reason: Specific interaction with tankyrase TNKS2. Proposed replacements: enzyme binding Supporting Evidence: PMID:22153077 Structural basis and sequence rules for substrate recognition by Tankyrase explain the basis for cherubism disease. |
| GO:0005515 protein binding | IPI PMID:22682247 Wnt signaling through inhibition of Ξ²-catenin degradation in... | ACCEPT | Summary: Wnt signaling through inhibition of beta-catenin degradation in an intact AXIN1 complex. Reason: Multiple destruction complex interactions. Supporting Evidence: PMID:22682247 Wnt signaling through inhibition of Ξ²-catenin degradation in an intact Axin1 complex. |
| GO:0005515 protein binding | IPI PMID:22773187 Dual functions of DP1 promote biphasic Wnt-on and Wnt-off st... | ACCEPT | Summary: DP1 promotes biphasic Wnt states during neural patterning; AXIN1 interactions. Reason: Wnt pathway context. Supporting Evidence: PMID:22773187 Dual functions of DP1 promote biphasic Wnt-on and Wnt-off states during anteroposterior neural patterning. |
| GO:0005515 protein binding | IPI PMID:23455922 Interlaboratory reproducibility of large-scale human protein... | ACCEPT | Summary: Interlaboratory AP-MS reproducibility study. Reason: Large-scale interaction study. Supporting Evidence: PMID:23455922 Interlaboratory reproducibility of large-scale human protein-complex analysis by standardized AP-MS. |
| GO:0005515 protein binding | IPI PMID:23602568 The protein interaction landscape of the human CMGC kinase g... | MODIFY | Summary: CMGC kinase interaction landscape; GSK3A/B interactions. Reason: Specific kinase interactions. Proposed replacements: protein serine/threonine kinase binding Supporting Evidence: PMID:23602568 2013 Apr 18. The protein interaction landscape of the human CMGC kinase group. |
| GO:0005515 protein binding | IPI PMID:24976009 YAP/TAZ incorporation in the Ξ²-catenin destruction complex o... | ACCEPT | Summary: YAP/TAZ incorporation in the beta-catenin destruction complex. Reason: Novel interactions with YAP1 in destruction complex context. Supporting Evidence: PMID:24976009 YAP/TAZ incorporation in the Ξ²-catenin destruction complex orchestrates the Wnt response. |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | ACCEPT | Summary: Proximity ligation assay profiling of endogenous protein interactions in Wnt pathway. Reason: Wnt pathway interactions validated. Supporting Evidence: PMID:25241761 Oct 9. Using an in situ proximity ligation assay to systematically profile endogenous protein-protein interactions in a pathway network. |
| GO:0005515 protein binding | IPI PMID:25873176 TGIF governs a feed-forward network that empowers Wnt signal... | ACCEPT | Summary: TGIF governs a feed-forward network empowering Wnt signaling; AXIN1-TGIF1 interaction. Reason: Novel interactor in Wnt pathway. Supporting Evidence: PMID:25873176 TGIF governs a feed-forward network that empowers Wnt signaling to drive mammary tumorigenesis. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | ACCEPT | Summary: Human interactome in three quantitative dimensions. Reason: Large-scale quantitative interactome study. Supporting Evidence: PMID:26496610 Oct 22. A human interactome in three quantitative dimensions organized by stoichiometries and abundances. |
| GO:0005515 protein binding | IPI PMID:26871637 Widespread Expansion of Protein Interaction Capabilities by ... | ACCEPT | Summary: Alternative splicing expansion of protein interaction capabilities. Reason: Large-scale splicing-interaction study. Supporting Evidence: PMID:26871637 Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing. |
| GO:0005515 protein binding | IPI PMID:27098453 WDR26 is a new partner of Axin1 in the canonical Wnt signali... | ACCEPT | Summary: WDR26 is a new partner of AXIN1 in canonical Wnt signaling. Reason: Novel interactor in Wnt pathway characterized. Supporting Evidence: PMID:27098453 May 3. WDR26 is a new partner of Axin1 in the canonical Wnt signaling pathway. |
| GO:0005515 protein binding | IPI PMID:29568061 An AP-MS- and BioID-compatible MAC-tag enables comprehensive... | ACCEPT | Summary: AP-MS and BioID compatible MAC-tag for interaction and localization mapping. Reason: Large-scale interaction study. Supporting Evidence: PMID:29568061 An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations. |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | ACCEPT | Summary: Kinase interaction network expands functional and disease roles of kinases. Reason: Large-scale kinase interaction study. Supporting Evidence: PMID:32707033 2020 Jul 23. Kinase Interaction Network Expands Functional and Disease Roles of Human Kinases. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | ACCEPT | Summary: Interactome mapping of neurodegenerative disease proteins. Reason: Large-scale interaction study. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | ACCEPT | Summary: Dual proteome-scale networks reveal cell-specific interactome remodeling. Reason: Large-scale interaction study. Supporting Evidence: PMID:33961781 2021 May 6. Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell Endogenous tagging for the cartography of human cel... | ACCEPT | Summary: OpenCell endogenous tagging for cellular organization cartography. Reason: Large-scale localization and interaction study. Supporting Evidence: PMID:35271311 2022 Mar 11. OpenCell: Endogenous tagging for the cartography of human cellular organization. |
| GO:0042802 identical protein binding | IPI PMID:10811618 Structural basis of the Axin-adenomatous polyposis coli inte... | ACCEPT | Summary: AXIN1 homodimerization demonstrated in structural study of AXIN1-APC interaction. Reason: Self-association/homodimerization is important for AXIN1 function and condensate formation via DIX domain. Supporting Evidence: PMID:10811618 Structural basis of the Axin-adenomatous polyposis coli interaction. |
| GO:0042802 identical protein binding | IPI PMID:16169070 A human protein-protein interaction network: a resource for ... | ACCEPT | Summary: High-throughput interaction network study includes AXIN1 self-interaction. Reason: Homodimerization confirmed. Supporting Evidence: PMID:16169070 A human protein-protein interaction network: a resource for annotating the proteome. |
| GO:0042802 identical protein binding | IPI PMID:21245303 Dishevelled interacts with the DIX domain polymerization int... | ACCEPT | Summary: DVL-AXIN1 interaction via DIX domain polymerization interface; includes AXIN1 homo-oligomerization. Reason: Homodimerization via DIX domain demonstrated. Supporting Evidence: PMID:21245303 Dishevelled interacts with the DIX domain polymerization interface of Axin to interfere with its function in down-regulating Ξ²-catenin. |
| GO:0002039 p53 binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: AXIN1 interacts with TP53 as part of the AXIN1-HIPK2-TP53 complex. Reason: TP53 binding is demonstrated but represents a secondary function of AXIN1 in stress response, not its core function in Wnt signaling. |
| GO:0005938 cell cortex | IEA GO_REF:0000107 | ACCEPT | Summary: Cell cortex localization transferred from mouse ortholog. Reason: Consistent with AXIN1 localization at cell periphery/plasma membrane. |
| GO:0008013 beta-catenin binding | IEA GO_REF:0000107 | ACCEPT | Summary: IEA from mouse ortholog. Beta-catenin binding is a core function. Reason: Core function, well-supported by experimental evidence. |
| GO:0015630 microtubule cytoskeleton | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: AXIN1 has been shown to localize to centrosomes and microtubule organizing centers. Reason: Microtubule localization is documented [PMID:19390532] but represents a secondary localization/function, not the primary cytoplasmic destruction complex function. |
| GO:0019901 protein kinase binding | IEA GO_REF:0000107 | ACCEPT | Summary: IEA from mouse ortholog. AXIN1 binds GSK3B and CK1 kinases. Reason: Core function - kinase binding is essential for destruction complex scaffolding. |
| GO:0019904 protein domain specific binding | IEA GO_REF:0000107 | ACCEPT | Summary: AXIN1 binds specific domains including APC SAMP repeats and beta-catenin armadillo repeats. Reason: AXIN1 binds specific domains of its interaction partners. |
| GO:0030877 beta-catenin destruction complex | IEA GO_REF:0000107 | ACCEPT | Summary: IEA from mouse ortholog. Core complex membership. Reason: Defining characteristic of AXIN1. |
| GO:0031410 cytoplasmic vesicle | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cytoplasmic vesicle localization from mouse ortholog. Reason: May relate to membrane trafficking or Wnt signalosome dynamics, but not a primary localization site for AXIN1 function. |
| GO:0031625 ubiquitin protein ligase binding | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation. AXIN1 binds E3 ligases RNF146 and RNF111. Reason: Important for both AXIN1 regulation (RNF146) and AXIN1 function in Smad7 degradation (RNF111). |
| GO:0032991 protein-containing complex | IEA GO_REF:0000107 | ACCEPT | Summary: AXIN1 is part of the beta-catenin destruction complex. Reason: AXIN1 is part of multiple protein complexes including the destruction complex. |
| GO:0035591 signaling adaptor activity | IEA GO_REF:0000107 | ACCEPT | Summary: AXIN1 functions as a signaling adaptor in Wnt and TGF-beta pathways. Reason: Core function - AXIN1 is a scaffold/adaptor protein. |
| GO:0042802 identical protein binding | IEA GO_REF:0000107 | ACCEPT | Summary: IEA from mouse ortholog. AXIN1 homodimerizes via DIX domain. Reason: Self-association is important for destruction complex function and condensate formation. |
| GO:0042803 protein homodimerization activity | IEA GO_REF:0000107 | ACCEPT | Summary: AXIN1 homodimerizes through its DIX domain. Reason: DIX domain-mediated homodimerization is well-documented. |
| GO:0046330 positive regulation of JNK cascade | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: AXIN1 activates JNK signaling independently of Wnt signaling. Reason: JNK activation is a legitimate secondary function of AXIN1 distinct from its Wnt pathway role, but not the core function. Supporting Evidence: PMID:12192039 I-mfa domain proteins interact with Axin and affect its regulation of the Wnt and c-Jun N-terminal kinase signaling pathways. |
| GO:0070411 I-SMAD binding | IEA GO_REF:0000107 | ACCEPT | Summary: IEA from mouse ortholog. AXIN1 binds SMAD7. Reason: Experimentally validated [PMID:16601693]. |
| GO:0070412 R-SMAD binding | IEA GO_REF:0000107 | ACCEPT | Summary: AXIN1 interaction with R-SMADs including SMAD3. Reason: Part of AXIN1's role in TGF-beta signaling. |
| GO:1990756 ubiquitin-like ligase-substrate adaptor activity | IEA GO_REF:0000107 | ACCEPT | Summary: AXIN1 acts as adaptor bringing together substrates (Smad7, beta-catenin) and E3 ligases. Reason: AXIN1 bridges substrates to E3 ligases in both Wnt (beta-catenin to beta-TrCP) and TGF-beta (Smad7 to Arkadia) pathways. |
| GO:1990909 Wnt signalosome | IEA GO_REF:0000107 | ACCEPT | Summary: AXIN1 is recruited to the Wnt signalosome upon Wnt stimulation. Reason: Part of AXIN1's role in Wnt signal transduction. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: IDA from HPA immunofluorescence data showing nucleoplasm localization. Reason: AXIN1 can localize to nucleus under certain conditions. |
| GO:0005730 nucleolus | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: IDA from HPA immunofluorescence data showing nucleolus localization. Reason: Nucleolar localization may be cell type or condition dependent; not the primary site of AXIN1 function. |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | NAS PMID:9601641 Downregulation of beta-catenin by human Axin and its associa... | ACCEPT | Summary: AXIN1 promotes proteasomal degradation of beta-catenin as part of the destruction complex function. Reason: Core function - AXIN1 scaffolds the machinery that leads to beta-catenin ubiquitination and proteasomal degradation. Supporting Evidence: PMID:9601641 Overexpression of hAxin strongly promoted the downregulation of wild-type beta-catenin in colon cancer cells |
| GO:0043539 protein serine/threonine kinase activator activity | IDA PMID:9601641 Downregulation of beta-catenin by human Axin and its associa... | ACCEPT | Summary: AXIN1 dramatically facilitates GSK3B phosphorylation of APC and beta-catenin by bringing kinase and substrates together. Reason: Core function - AXIN1 acts as a scaffold to enhance GSK3B kinase activity toward its substrates in the destruction complex. Supporting Evidence: PMID:9601641 hAxin dramatically facilitated the phosphorylation of APC and beta-catenin by GSK3 beta in vitro |
| GO:0030877 beta-catenin destruction complex | IDA PMID:18593713 Smad7 stabilizes beta-catenin binding to E-cadherin complex ... | ACCEPT | Summary: IDA evidence for destruction complex membership from study of Smad7-Axin interaction. Reason: Core complex membership. Supporting Evidence: PMID:18593713 2008 Jun 30. Smad7 stabilizes beta-catenin binding to E-cadherin complex and promotes cell-cell adhesion. |
| GO:0120283 protein serine/threonine kinase binding | IPI PMID:18593713 Smad7 stabilizes beta-catenin binding to E-cadherin complex ... | ACCEPT | Summary: AXIN1 binds GSK3B as demonstrated in this study. Reason: GSK3B binding is a core function. Supporting Evidence: PMID:18593713 2008 Jun 30. Smad7 stabilizes beta-catenin binding to E-cadherin complex and promotes cell-cell adhesion. |
| GO:1904885 beta-catenin destruction complex assembly | IDA PMID:18593713 Smad7 stabilizes beta-catenin binding to E-cadherin complex ... | ACCEPT | Summary: AXIN1 is required for assembly of the destruction complex. Reason: Core function - AXIN1 is the central scaffold for destruction complex assembly. Supporting Evidence: PMID:18593713 2008 Jun 30. Smad7 stabilizes beta-catenin binding to E-cadherin complex and promotes cell-cell adhesion. |
| GO:0031398 positive regulation of protein ubiquitination | IMP PMID:16601693 Axin is a scaffold protein in TGF-beta signaling that promot... | ACCEPT | Summary: AXIN1 promotes Smad7 ubiquitination by recruiting Arkadia E3 ligase. Reason: Demonstrated function in TGF-beta signaling. Supporting Evidence: PMID:16601693 Axin and Arkadia cooperate with each other in promoting Smad7 ubiquitination |
| GO:0031625 ubiquitin protein ligase binding | IPI PMID:16601693 Axin is a scaffold protein in TGF-beta signaling that promot... | ACCEPT | Summary: AXIN1 binds Arkadia (RNF111) E3 ubiquitin ligase. Reason: Interaction with E3 ligases is important for AXIN1 function. Supporting Evidence: PMID:16601693 Axin activates TGF-beta signaling by forming a multimeric complex consisting of Smad7 and ubiquitin E3 ligase Arkadia |
| GO:1990756 ubiquitin-like ligase-substrate adaptor activity | IMP PMID:16601693 Axin is a scaffold protein in TGF-beta signaling that promot... | ACCEPT | Summary: AXIN1 acts as adaptor bringing Smad7 substrate to Arkadia E3 ligase. Reason: Scaffold/adaptor function between substrate and E3 ligase. Supporting Evidence: PMID:16601693 Axin is a scaffold protein in TGF-beta signaling that promotes degradation of Smad7 by Arkadia |
| GO:0005829 cytosol | TAS Reactome:R-HSA-195275 | ACCEPT | Summary: TAS from Reactome pathway for phosphorylation of APC in the destruction complex. Reason: Cytosolic localization is the primary site of AXIN1 function in the destruction complex. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-195280 | ACCEPT | Summary: TAS from Reactome - dissociation of beta-catenin from Axin and association with phospho-APC. Reason: Cytosolic localization is primary. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-195283 | ACCEPT | Summary: TAS from Reactome - GSK3 phosphorylation of beta-catenin at Ser37. Reason: Cytosolic destruction complex function. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-195287 | ACCEPT | Summary: TAS from Reactome - GSK3 phosphorylation of beta-catenin at Thr41. Reason: Cytosolic destruction complex function. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-195300 | ACCEPT | Summary: TAS from Reactome - GSK3 phosphorylation of beta-catenin at Ser33. Reason: Cytosolic destruction complex function. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-195304 | ACCEPT | Summary: TAS from Reactome - Association of beta-catenin with destruction complex. Reason: Cytosolic destruction complex function. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-195318 | ACCEPT | Summary: TAS from Reactome - CK1alpha phosphorylation of beta-catenin at Ser45. Reason: Cytosolic destruction complex function. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2130279 | ACCEPT | Summary: TAS from Reactome - Beta-catenin association with SCF(beta-TrCP) complex. Reason: Cytosolic destruction complex function. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2130282 | ACCEPT | Summary: TAS from Reactome - Degradation of ubiquitinated beta-catenin. Reason: Cytosolic destruction complex function. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2130286 | ACCEPT | Summary: TAS from Reactome - Multi-ubiquitination of phospho-beta-catenin. Reason: Cytosolic destruction complex function. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5229343 | ACCEPT | Summary: TAS from Reactome - AXIN phosphorylation in destruction complex. Reason: Cytosolic destruction complex function. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5339713 | ACCEPT | Summary: TAS from Reactome - Misspliced GSK3beta mutants stabilize beta-catenin. Reason: Cytosolic context for Wnt signaling. |
| GO:0005515 protein binding | IPI PMID:21087614 Critical scaffolding regions of the tumor suppressor Axin1 a... | ACCEPT | Summary: Study of natively unfolded scaffolding regions of AXIN1; interaction with GSK3B demonstrated. Reason: Structural characterization of AXIN1 interactions. Supporting Evidence: PMID:21087614 2010 Nov 16. Critical scaffolding regions of the tumor suppressor Axin1 are natively unfolded. |
| GO:0008013 beta-catenin binding | IPI PMID:21087614 Critical scaffolding regions of the tumor suppressor Axin1 a... | ACCEPT | Summary: AXIN1-beta-catenin interaction demonstrated in structural study. Reason: Core function. Supporting Evidence: PMID:21087614 2010 Nov 16. Critical scaffolding regions of the tumor suppressor Axin1 are natively unfolded. |
| GO:0060090 molecular adaptor activity | IDA PMID:21087614 Critical scaffolding regions of the tumor suppressor Axin1 a... | ACCEPT | Summary: IDA evidence for adaptor activity from structural study of AXIN1 scaffolding regions. Reason: Core function. Supporting Evidence: PMID:21087614 2010 Nov 16. Critical scaffolding regions of the tumor suppressor Axin1 are natively unfolded. |
| GO:0005515 protein binding | IPI PMID:28546513 The SIAH E3 ubiquitin ligases promote Wnt/Ξ²-catenin signalin... | ACCEPT | Summary: SIAH E3 ligases promote Wnt signaling by mediating AXIN1 degradation; AXIN1-SIAH1/SIAH2 interactions. Reason: Novel E3 ligase interaction regulating AXIN1 turnover. Supporting Evidence: PMID:28546513 May 25. The SIAH E3 ubiquitin ligases promote Wnt/Ξ²-catenin signaling through mediating Wnt-induced Axin degradation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-4839734 | ACCEPT | Summary: TAS from Reactome - AXIN mutants destabilize destruction complex. Reason: Cytosolic context. |
| GO:0090090 negative regulation of canonical Wnt signaling pathway | IC PMID:9601641 Downregulation of beta-catenin by human Axin and its associa... | ACCEPT | Summary: Inferred from Curator based on beta-catenin destruction complex membership. Reason: Core function, logically inferred from scaffold role in destruction complex. Supporting Evidence: PMID:9601641 Axin acts as a scaffold upon which APC, beta-catenin and GSK3 beta assemble to coordinate the regulation of beta-catenin signaling |
| GO:0090090 negative regulation of canonical Wnt signaling pathway | IDA PMID:10644691 Protein phosphatase 2Calpha dephosphorylates axin and activa... | ACCEPT | Summary: IDA evidence showing AXIN1-mediated repression of LEF-1-dependent transcription. Reason: Core function directly demonstrated. Supporting Evidence: PMID:10644691 PP2C expression relieves Axin-mediated repression of LEF-1-dependent transcription |
| GO:0005515 protein binding | IPI PMID:28829046 Twa1/Gid8 is a Ξ²-catenin nuclear retention factor in Wnt sig... | ACCEPT | Summary: GID8 is a beta-catenin nuclear retention factor; AXIN1 interactions with GID8, GSK3B, and beta-catenin. Reason: Novel interactor GID8 characterized. Supporting Evidence: PMID:28829046 Twa1/Gid8 is a Ξ²-catenin nuclear retention factor in Wnt signaling and colorectal tumorigenesis. |
| GO:0035591 signaling adaptor activity | TAS PMID:21799911 Ubiquitin ligase RNF146 regulates tankyrase and Axin to prom... | ACCEPT | Summary: TAS from review of RNF146 regulation of tankyrase and AXIN1. Reason: Core function. Supporting Evidence: PMID:21799911 Ubiquitin ligase RNF146 regulates tankyrase and Axin to promote Wnt signaling. |
| GO:0060090 molecular adaptor activity | IDA PMID:9601641 Downregulation of beta-catenin by human Axin and its associa... | ACCEPT | Summary: Foundational paper demonstrating AXIN1 as scaffold for the destruction complex. Reason: Core function directly demonstrated. Supporting Evidence: PMID:9601641 Axin acts as a scaffold upon which APC, beta-catenin and GSK3 beta assemble |
| GO:0005515 protein binding | IPI PMID:27484798 The A-Kinase Anchoring Protein (AKAP) Glycogen Synthase Kina... | ACCEPT | Summary: GSKIP regulates beta-catenin through interactions with PKA and GSK3B; AXIN1-GSK3B context. Reason: Destruction complex interactions. Supporting Evidence: PMID:27484798 2016 Aug 2. The A-Kinase Anchoring Protein (AKAP) Glycogen Synthase Kinase 3Ξ² Interaction Protein (GSKIP) Regulates Ξ²-Catenin through Its Interactions with Both Protein Kinase A (PKA) and GSK3Ξ². |
| GO:0090090 negative regulation of canonical Wnt signaling pathway | IMP PMID:22899650 LRRK2 functions as a Wnt signaling scaffold, bridging cytoso... | ACCEPT | Summary: LRRK2 functions as Wnt signaling scaffold bridging cytosolic proteins and LRP6; AXIN1 role in Wnt suppression demonstrated by loss-of-function. Reason: Core function demonstrated by mutant phenotype. Supporting Evidence: PMID:22899650 Aug 16. LRRK2 functions as a Wnt signaling scaffold, bridging cytosolic proteins and membrane-localized LRP6. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-4641129 | ACCEPT | Summary: TAS from Reactome - AXIN ubiquitination by SMURF2. Reason: Cytosolic context for AXIN1 regulation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-4641256 | ACCEPT | Summary: TAS from Reactome - Ubiquitinated AXIN degradation. Reason: Cytosolic context. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3640861 | ACCEPT | Summary: TAS from Reactome - RNF146 ubiquitinates ADP-ribosylated AXIN. Reason: Cytosolic context for AXIN1 regulation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3640872 | ACCEPT | Summary: TAS from Reactome - USP34 deubiquitinates AXIN1/AXIN2. Reason: Cytosolic context. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3640874 | ACCEPT | Summary: TAS from Reactome - Ub-RibC-AXIN degradation by proteasome. Reason: Cytosolic context. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3640844 | ACCEPT | Summary: TAS from Reactome - RNF146 binds RibC-AXIN:TNKS complex. Reason: Cytosolic context. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3640858 | ACCEPT | Summary: TAS from Reactome - Tankyrase ADP-ribosylates AXIN. Reason: Cytosolic context. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1504186 | ACCEPT | Summary: TAS from Reactome - DVL recruits GSK3beta:AXIN1 to receptor complex. Reason: Cytosolic context for Wnt signaling. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-195251 | ACCEPT | Summary: TAS from Reactome - Assembly of the destruction complex. Reason: Cytosolic localization for destruction complex assembly. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-201677 | ACCEPT | Summary: TAS from Reactome - Phosphorylation of LRP5/6 cytoplasmic domain. Reason: Cytosolic context. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-201685 | ACCEPT | Summary: TAS from Reactome - Beta-catenin release from destruction complex. Reason: Cytosolic context. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3640862 | ACCEPT | Summary: TAS from Reactome - Tankyrase binds AXIN. Reason: Cytosolic context. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-4641134 | ACCEPT | Summary: TAS from Reactome - SMURF2 binds AXIN. Reason: Cytosolic context. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-4791278 | ACCEPT | Summary: TAS from Reactome - APC truncation mutants have impaired AXIN binding. Reason: Cytosolic context. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-4827388 | ACCEPT | Summary: TAS from Reactome - CTNNB1 S45 mutants not phosphorylated by CK1alpha. Reason: Cytosolic context. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-4839634 | ACCEPT | Summary: TAS from Reactome - CTNNB1 S33 mutants not phosphorylated by GSK3beta. Reason: Cytosolic context. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-4839635 | ACCEPT | Summary: TAS from Reactome - CTNNB1 S37 mutants not phosphorylated by GSK3beta. Reason: Cytosolic context. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-4839638 | ACCEPT | Summary: TAS from Reactome - CTNNB1 T41 mutants not phosphorylated by GSK3beta. Reason: Cytosolic context. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-4839746 | ACCEPT | Summary: TAS from Reactome - Truncated AMER1 mutants destabilize destruction complex. Reason: Cytosolic context. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5251555 | ACCEPT | Summary: TAS from Reactome - Expression of AXIN1 gene. Reason: Gene expression context for cytosolic protein. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5368596 | ACCEPT | Summary: TAS from Reactome - WNT3A stimulates caveolin-dependent internalization. Reason: Cytosolic context for Wnt signaling. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8932076 | ACCEPT | Summary: TAS from Reactome - AXIN1 gene expression regulated by ESR1 and RUNX1. Reason: Gene expression context. |
| GO:0005829 cytosol | TAS Reactome:R-NUL-1458902 | ACCEPT | Summary: TAS from Reactome - CK1gamma phosphorylates LRP5/6 (frog model). Reason: Cytosolic context. |
| GO:0005515 protein binding | IPI PMID:12192039 I-mfa domain proteins interact with Axin and affect its regu... | ACCEPT | Summary: I-mfa domain proteins (MDFI, MDFIC) interact with AXIN1 and affect Wnt and JNK signaling. Reason: Novel interactors affecting AXIN1 function. Supporting Evidence: PMID:12192039 I-mfa domain proteins interact with Axin and affect its regulation of the Wnt and c-Jun N-terminal kinase signaling pathways. |
| GO:0005634 nucleus | IDA PMID:21383061 The ubiquitin-specific protease USP34 regulates axin stabili... | ACCEPT | Summary: USP34 regulates AXIN1 stability; nuclear localization observed. Reason: Nuclear localization documented. Supporting Evidence: PMID:21383061 Mar 7. The ubiquitin-specific protease USP34 regulates axin stability and Wnt/Ξ²-catenin signaling. |
| GO:0005737 cytoplasm | IDA PMID:21383061 The ubiquitin-specific protease USP34 regulates axin stabili... | ACCEPT | Summary: Cytoplasmic localization observed in USP34-AXIN1 study. Reason: Primary localization. Supporting Evidence: PMID:21383061 Mar 7. The ubiquitin-specific protease USP34 regulates axin stability and Wnt/Ξ²-catenin signaling. |
| GO:0019899 enzyme binding | IPI PMID:19759537 Tankyrase inhibition stabilizes axin and antagonizes Wnt sig... | ACCEPT | Summary: AXIN1 binds tankyrase (TNKS/TNKS2) enzymes. Reason: Important for AXIN1 regulation. Supporting Evidence: PMID:19759537 Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. |
| GO:0019899 enzyme binding | IPI PMID:21383061 The ubiquitin-specific protease USP34 regulates axin stabili... | ACCEPT | Summary: AXIN1 binds USP34 deubiquitinase. Reason: Important for AXIN1 stability regulation. Supporting Evidence: PMID:21383061 Mar 7. The ubiquitin-specific protease USP34 regulates axin stability and Wnt/Ξ²-catenin signaling. |
| GO:0019899 enzyme binding | IPI PMID:21478859 RNF146 is a poly(ADP-ribose)-directed E3 ligase that regulat... | ACCEPT | Summary: AXIN1 binds RNF146 E3 ligase and tankyrase. Reason: Important for AXIN1 regulation. Supporting Evidence: PMID:21478859 RNF146 is a poly(ADP-ribose)-directed E3 ligase that regulates axin degradation and Wnt signalling. |
| GO:0031625 ubiquitin protein ligase binding | IPI PMID:21478859 RNF146 is a poly(ADP-ribose)-directed E3 ligase that regulat... | ACCEPT | Summary: AXIN1 binds RNF146 E3 ubiquitin ligase. Reason: Important for AXIN1 turnover regulation. Supporting Evidence: PMID:21478859 RNF146 is a poly(ADP-ribose)-directed E3 ligase that regulates axin degradation and Wnt signalling. |
| GO:0048471 perinuclear region of cytoplasm | IDA PMID:19038973 Identification of WNT/beta-CATENIN signaling pathway compone... | ACCEPT | Summary: Perinuclear localization observed in human cumulus cells. Reason: Localization pattern consistent with cytoplasmic function. Supporting Evidence: PMID:19038973 Identification of WNT/beta-CATENIN signaling pathway components in human cumulus cells. |
| GO:0071944 cell periphery | IDA PMID:19038973 Identification of WNT/beta-CATENIN signaling pathway compone... | ACCEPT | Summary: Cell periphery localization observed. Reason: Consistent with membrane recruitment during Wnt signaling. Supporting Evidence: PMID:19038973 Identification of WNT/beta-CATENIN signaling pathway components in human cumulus cells. |
| GO:0019901 protein kinase binding | ISS GO_REF:0000024 | ACCEPT | Summary: ISS from mouse ortholog. AXIN1 binds GSK3B and CK1 kinases. Reason: Core function. |
| GO:2000060 positive regulation of ubiquitin-dependent protein catabolic process | ISS GO_REF:0000024 | ACCEPT | Summary: ISS from mouse ortholog. AXIN1 promotes beta-catenin ubiquitination and degradation. Reason: Core function. |
| GO:0005737 cytoplasm | IDA PMID:17569865 Wnt induces LRP6 signalosomes and promotes dishevelled-depen... | ACCEPT | Summary: Wnt induces LRP6 signalosomes; AXIN1 cytoplasmic localization. Reason: Primary localization. Supporting Evidence: PMID:17569865 Wnt induces LRP6 signalosomes and promotes dishevelled-dependent LRP6 phosphorylation. |
| GO:0065003 protein-containing complex assembly | IDA PMID:16601693 Axin is a scaffold protein in TGF-beta signaling that promot... | ACCEPT | Summary: AXIN1 promotes assembly of the Smad7-Arkadia complex for TGF-beta signaling. Reason: AXIN1 scaffolding function in complex assembly. Supporting Evidence: PMID:16601693 Axin activates TGF-beta signaling by forming a multimeric complex consisting of Smad7 and ubiquitin E3 ligase Arkadia |
| GO:0045732 positive regulation of protein catabolic process | IDA PMID:9601641 Downregulation of beta-catenin by human Axin and its associa... | ACCEPT | Summary: AXIN1 promotes beta-catenin degradation. Reason: Core function. Supporting Evidence: PMID:9601641 Overexpression of hAxin strongly promoted the downregulation of wild-type beta-catenin |
| GO:0030877 beta-catenin destruction complex | IDA PMID:16188939 The adenomatous polyposis coli protein (APC) exists in two d... | ACCEPT | Summary: IDA evidence for destruction complex membership from study of APC complexes. Reason: Core complex membership. Supporting Evidence: PMID:16188939 Sep 27. The adenomatous polyposis coli protein (APC) exists in two distinct soluble complexes with different functions. |
| GO:0030877 beta-catenin destruction complex | IDA PMID:19759537 Tankyrase inhibition stabilizes axin and antagonizes Wnt sig... | ACCEPT | Summary: Tankyrase inhibition stabilizes AXIN1 in the destruction complex. Reason: Core complex membership. Supporting Evidence: PMID:19759537 Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. |
| GO:0045732 positive regulation of protein catabolic process | IC PMID:16188939 The adenomatous polyposis coli protein (APC) exists in two d... | ACCEPT | Summary: Inferred from Curator based on destruction complex function. Reason: Logical inference from scaffold role. Supporting Evidence: PMID:16188939 Sep 27. The adenomatous polyposis coli protein (APC) exists in two distinct soluble complexes with different functions. |
| GO:0070411 I-SMAD binding | IPI PMID:16601693 Axin is a scaffold protein in TGF-beta signaling that promot... | ACCEPT | Summary: AXIN1 binds SMAD7 in TGF-beta signaling context. Reason: Experimentally validated. Supporting Evidence: PMID:16601693 Axin activates TGF-beta signaling by forming a multimeric complex consisting of Smad7 |
| GO:0008013 beta-catenin binding | IDA PMID:10644691 Protein phosphatase 2Calpha dephosphorylates axin and activa... | ACCEPT | Summary: PP2C dephosphorylates AXIN1; beta-catenin binding context demonstrated. Reason: Core function. Supporting Evidence: PMID:10644691 Protein phosphatase 2Calpha dephosphorylates axin and activates LEF-1-dependent transcription. |
| GO:0042802 identical protein binding | ISS GO_REF:0000024 | ACCEPT | Summary: ISS from mouse ortholog. AXIN1 homodimerizes. Reason: DIX domain-mediated self-association. |
| GO:0070016 armadillo repeat domain binding | ISS GO_REF:0000024 | ACCEPT | Summary: AXIN1 binds armadillo repeats of beta-catenin. Reason: Structural basis for beta-catenin interaction. |
| GO:0005515 protein binding | IPI PMID:17588722 Htid-1, the human homolog of the Drosophila melanogaster l(2... | ACCEPT | Summary: Htid-1 (DNAJA3) interaction with APC; AXIN1 context. Reason: APC complex interactions. Supporting Evidence: PMID:17588722 2007 Jun 2. Htid-1, the human homolog of the Drosophila melanogaster l(2)tid tumor suppressor, defines a novel physiological role of APC. |
| GO:0070411 I-SMAD binding | IPI PMID:18593713 Smad7 stabilizes beta-catenin binding to E-cadherin complex ... | ACCEPT | Summary: Smad7-AXIN1 interaction in cell adhesion context. Reason: Validated interaction. Supporting Evidence: PMID:18593713 A Smad7-Axin interaction disassociates GSK-3beta and beta-catenin from Axin |
| GO:0046332 SMAD binding | IPI PMID:18593713 Smad7 stabilizes beta-catenin binding to E-cadherin complex ... | ACCEPT | Summary: AXIN1 binds SMAD7. Reason: Validated interaction. Supporting Evidence: PMID:18593713 2008 Jun 30. Smad7 stabilizes beta-catenin binding to E-cadherin complex and promotes cell-cell adhesion. |
| GO:0031410 cytoplasmic vesicle | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS from mouse ortholog. Reason: Secondary localization, not the primary site of function. |
| GO:0042803 protein homodimerization activity | ISS GO_REF:0000024 | ACCEPT | Summary: ISS from mouse ortholog. DIX domain-mediated homodimerization. Reason: Well-supported by experimental data. |
| GO:0046330 positive regulation of JNK cascade | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: AXIN1 activates JNK signaling independently of Wnt. Reason: Secondary function of AXIN1 distinct from core Wnt pathway role. |
| GO:0005515 protein binding | IPI PMID:9601641 Downregulation of beta-catenin by human Axin and its associa... | ACCEPT | Summary: Foundational paper demonstrating AXIN1 interactions with APC, beta-catenin, and GSK3B. Reason: Multiple core interactions demonstrated. Supporting Evidence: PMID:9601641 Human Axin (hAxin) binds directly to beta-catenin, GSK3 beta, and APC in vitro, and the endogenous proteins are found in a complex in cells |
| GO:0030877 beta-catenin destruction complex | IDA PMID:9601641 Downregulation of beta-catenin by human Axin and its associa... | ACCEPT | Summary: Foundational paper demonstrating AXIN1 as scaffold of the destruction complex. Reason: Core complex membership demonstrated. Supporting Evidence: PMID:9601641 Axin acts as a scaffold upon which APC, beta-catenin and GSK3 beta assemble |
| GO:0005634 nucleus | IDA PMID:12072559 Subcellular distribution of Wnt pathway proteins in normal a... | ACCEPT | Summary: Nuclear localization observed in colon tissue. Reason: AXIN1 can localize to nucleus. Supporting Evidence: PMID:12072559 Subcellular distribution of Wnt pathway proteins in normal and neoplastic colon. |
| GO:0005737 cytoplasm | IDA PMID:12072559 Subcellular distribution of Wnt pathway proteins in normal a... | ACCEPT | Summary: Cytoplasmic localization in colon tissue. Reason: Primary localization. Supporting Evidence: PMID:12072559 Subcellular distribution of Wnt pathway proteins in normal and neoplastic colon. |
| GO:0016328 lateral plasma membrane | IDA PMID:12072559 Subcellular distribution of Wnt pathway proteins in normal a... | ACCEPT | Summary: Lateral plasma membrane localization observed in colon epithelium. Reason: Tissue-specific membrane localization pattern. Supporting Evidence: PMID:12072559 Subcellular distribution of Wnt pathway proteins in normal and neoplastic colon. |
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