Linked Life Data

CPATH-132762

Source:http://cbio.mskcc.org/cpath#CPATH-132762

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SubjectPredicateObjectContext
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cpath:CPATH-132762http://www.biopax.org/relea...FUNCTION: Component of the beta-catenin destruction complex required for regulating CTNNB1 levels through phosphorylation and ubiquitination, and modulating Wnt-signaling (By similarity). Controls dorsoventral patterning via two opposing effects; down- regulates CTNNB1 to inhibit the Wnt signaling pathway and ventralize embryos, but also dorsalizes embryos by activating a Wnt-independent JNK signaling pathway. In Wnt signaling, probably facilitates the phosphorylation of CTNNB1 and APC by GSK3B. Likely to function as a tumor suppressor. Facilitates the phosphorylation of TP53 by HIPK2 upon ultraviolet irradiation. Enhances TGF-beta signaling by recruiting the RNF111 E3 ubiquitin ligase and promoting the degradation of inhibitory SMAD7 (By similarity). Also component of the AXIN1-HIPK2-TP53 complex which controls cell growth, apoptosis and development. SUBUNIT: Homodimer. Component of the beta-catenin destruction complex, containing at least CTNNB1, an axin and GSK3B, that regulates CTNNB1 protein levels through phosphorylation and ubiquitination (By similarity). Interacts with GSK3B; the interaction hyperphosphorylates CTNNB1 leading to its ubiquitination and destruction. Interacts with DAXX; the interaction stimulates the interaction of DAXX with TP53, stimulates 'Ser-46' phosphorylation of TP53 and induces cell death on UV irradiation. Also interacts with APC, RNF111, SMAD6 and SMAD7. Interacts (via the C-terminal) with PPP1CA; the interaction dephosphorylates AXIN1 and regulates interaction with GSK3B. Interacts with PPP2CA; the interaction dephosphorylates AXIN1. Interacts with MDFI; the interaction decreases AXIN1-mediated JUN N-terminal kinase (JNK) activation. Interacts with MDFIC; the interaction inhibits beta-cateninin-mediated signaling and AXIN1- mediated JUN N-terminal kinase (JNK) activation (By similarity). Binds ANKRD6, PIAS1, PIAS2, PIAS4, SUMO1, MAP3K1 and MAP3K4. Component of the AXIN1-HIPK2-TP53 complex. Interacts directly in the complex with TP53 and HIPK2. Interacts with DIXDC1; the interaction prevents interaction with MAP3K1. Interacts with AIDA; the interaction blocks the AXIN1-mediated JNK activation through disrupting AXIN1 homodimerization and Wnt signaling. Interacts with LRP5 (via its phosphorylated PPPSP motifs); the interaction is stimulated by WNT1 and GSK3B and activates beta-catenin signaling. Interacts with CTNNB1 (via the armadillo repeats 2-7). Interacts with MACF1 (By similarity). Found in a complex composed of MACF1, APC, AXIN1, CTNNB1 and GSK3B (By similarity). SUBCELLULAR LOCATION: Cytoplasm (By similarity). Nucleus (By similarity). Cell membrane. Note=On UV irradiation, translocates to the nucleus and colocalizes with DAAX (By similarity). MACF1 is required for its translocation to cell membrane. ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=O35625-1; Sequence=Displayed; Name=2; IsoId=O35625-2; Sequence=VSP_000452; TISSUE SPECIFICITY: Expressed in embryonic stem cells. DEVELOPMENTAL STAGE: Widely expressed at E10.5 to E16.5 day. DOMAIN: The tankyrase-binding motif (also named TBD) is required for interaction with tankyrase TNKS and TNKS2 (By similarity). PTM: Phosphorylation and dephosphorylation of AXIN1 regulates assembly and function of the beta-catenin complex. Phosphorylated by CK1 and GSK3B. Dephosphorylated by PPP1CA and PPP2CA. Phosphorylation by CK1 enhances binding of GSK3B to AXIN1 (By similarity). Also phosphorylated by CDK2 which regulates interaction with CTNBB1. PTM: ADP-ribosylated by tankyrase TNKS and TNKS2. Poly-ADP- ribosylated protein is recognized by RNF146, followed by ubiquitination and subsequent activation of the Wnt signaling pathway (By similarity). PTM: Ubiquitinated by RNF146 when poly-ADP-ribosylated, leading to its degradation and subsequent activation of the Wnt signaling pathway. Deubiquitinated by USP34, deubiquitinated downstream of beta-catenin stabilization step: deubiquitination is important for nuclear accumulation during Wnt signaling to positively regulate beta-catenin (CTNBB1)-mediated transcription (By similarity). Sumoylation at Lys-858 and Lys-861 prevents ubiquitination and degradation. Sumoylation is required for AXIN1-mediated JNK activation. SIMILARITY: Contains 1 DIX domain. SIMILARITY: Contains 1 RGS domain. SEQUENCE CAUTION: Sequence=AAC53285.1; Type=Erroneous initiation; GENE SYNONYMS: Axin Fu. COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License.lld:biogrid
cpath:CPATH-132762http://www.biopax.org/relea...FUNCTION: Component of the beta-catenin destruction complex required for regulating CTNNB1 levels through phosphorylation and ubiquitination, and modulating Wnt-signaling (By similarity). Controls dorsoventral patterning via two opposing effects; down- regulates CTNNB1 to inhibit the Wnt signaling pathway and ventralize embryos, but also dorsalizes embryos by activating a Wnt-independent JNK signaling pathway. In Wnt signaling, probably facilitates the phosphorylation of CTNNB1 and APC by GSK3B. Likely to function as a tumor suppressor. Facilitates the phosphorylation of TP53 by HIPK2 upon ultraviolet irradiation. Enhances TGF-beta signaling by recruiting the RNF111 E3 ubiquitin ligase and promoting the degradation of inhibitory SMAD7 (By similarity). Also component of the AXIN1-HIPK2-TP53 complex which controls cell growth, apoptosis and development. SUBUNIT: Homodimer. Component of the beta-catenin destruction complex, containing at least CTNNB1, an axin and GSK3B, that regulates CTNNB1 protein levels through phosphorylation and ubiquitination (By similarity). Interacts with GSK3B; the interaction hyperphosphorylates CTNNB1 leading to its ubiquitination and destruction. Interacts with DAXX; the interaction stimulates the interaction of DAXX with TP53, stimulates 'Ser-46' phosphorylation of TP53 and induces cell death on UV irradiation. Also interacts with APC, RNF111, SMAD6 and SMAD7. Interacts (via the C-terminal) with PPP1CA; the interaction dephosphorylates AXIN1 and regulates interaction with GSK3B. Interacts with PPP2CA; the interaction dephosphorylates AXIN1. Interacts with MDFI; the interaction decreases AXIN1-mediated JUN N-terminal kinase (JNK) activation. Interacts with MDFIC; the interaction inhibits beta-cateninin-mediated signaling and AXIN1- mediated JUN N-terminal kinase (JNK) activation (By similarity). Binds ANKRD6, PIAS1, PIAS2, PIAS4, SUMO1, MAP3K1 and MAP3K4. Component of the AXIN1-HIPK2-TP53 complex. Interacts directly in the complex with TP53 and HIPK2. Interacts with DIXDC1; the interaction prevents interaction with MAP3K1. Interacts with AIDA; the interaction blocks the AXIN1-mediated JNK activation through disrupting AXIN1 homodimerization and Wnt signaling. Interacts with LRP5 (via its phosphorylated PPPSP motifs); the interaction is stimulated by WNT1 and GSK3B and activates beta-catenin signaling. Interacts with CTNNB1 (via the armadillo repeats 2-7). Interacts with MACF1 (By similarity). Found in a complex composed of MACF1, APC, AXIN1, CTNNB1 and GSK3B (By similarity). SUBCELLULAR LOCATION: Cytoplasm (By similarity). Nucleus (By similarity). Cell membrane. Note=On UV irradiation, translocates to the nucleus and colocalizes with DAAX (By similarity). MACF1 is required for its translocation to cell membrane. ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=O35625-1; Sequence=Displayed; Name=2; IsoId=O35625-2; Sequence=VSP_000452; TISSUE SPECIFICITY: Expressed in embryonic stem cells. DEVELOPMENTAL STAGE: Widely expressed at E10.5 to E16.5 day. DOMAIN: The tankyrase-binding motif (also named TBD) is required for interaction with tankyrase TNKS and TNKS2 (By similarity). PTM: Phosphorylation and dephosphorylation of AXIN1 regulates assembly and function of the beta-catenin complex. Phosphorylated by CK1 and GSK3B. Dephosphorylated by PPP1CA and PPP2CA. Phosphorylation by CK1 enhances binding of GSK3B to AXIN1 (By similarity). Also phosphorylated by CDK2 which regulates interaction with CTNBB1. PTM: ADP-ribosylated by tankyrase TNKS and TNKS2. Poly-ADP- ribosylated protein is recognized by RNF146, followed by ubiquitination and subsequent activation of the Wnt signaling pathway (By similarity). PTM: Ubiquitinated by RNF146 when poly-ADP-ribosylated, leading to its degradation and subsequent activation of the Wnt signaling pathway. Deubiquitinated by USP34, deubiquitinated downstream of beta-catenin stabilization step: deubiquitination is important for nuclear accumulation during Wnt signaling to positively regulate beta-catenin (CTNBB1)-mediated transcription (By similarity). Sumoylation at Lys-858 and Lys-861 prevents ubiquitination and degradation. Sumoylation is required for AXIN1-mediated JNK activation. SIMILARITY: Contains 1 DIX domain. SIMILARITY: Contains 1 RGS domain. SEQUENCE CAUTION: Sequence=AAC53285.1; Type=Erroneous initiation; GENE SYNONYMS: Axin Fu. COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License.lld:cellmap
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