ID AXIN1_MOUSE Reviewed; 863 AA. AC O35625; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 03-OCT-2012, sequence version 3. DT 24-JAN-2024, entry version 211. DE RecName: Full=Axin-1; DE AltName: Full=Axis inhibition protein 1; DE AltName: Full=Protein Fused; GN Name=Axin1; Synonyms=Axin, Fu; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). RX PubMed=9230313; DOI=10.1016/s0092-8674(00)80324-4; RA Zeng L., Fagotto F., Zhang T., Hsu W., Vasicek T.J., Perry W.L. III, RA Lee J.J., Tilghman S.M., Gumbiner B.M., Costantini F.; RT "The mouse Fused locus encodes Axin, an inhibitor of the Wnt signaling RT pathway that regulates embryonic axis formation."; RL Cell 90:181-192(1997). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [3] RP PHOSPHORYLATION AT THR-480; SER-485 AND SER-492, INTERACTION WITH CTNNB1, RP AND MUTAGENESIS OF THR-480; SER-485; SER-492 AND SER-495. RX PubMed=10581160; DOI=10.1006/bbrc.1999.1760; RA Jho E., Lomvardas S., Costantini F.; RT "A GSK3beta phosphorylation site in axin modulates interaction with beta- RT catenin and Tcf-mediated gene expression."; RL Biochem. Biophys. Res. Commun. 266:28-35(1999). RN [4] RP INTERACTION WITH LRP5. RX PubMed=11336703; DOI=10.1016/s1097-2765(01)00224-6; RA Mao J., Wang J., Liu B., Pan W., Farr G.H. III, Flynn C., Yuan H., RA Takada S., Kimelman D., Li L., Wu D.; RT "Low-density lipoprotein receptor-related protein-5 binds to Axin and RT regulates the canonical Wnt signaling pathway."; RL Mol. Cell 7:801-809(2001). RN [5] RP INTERACTION WITH ANKRD6. RX PubMed=12183362; DOI=10.1101/gad.230402; RA Schwarz-Romond T., Asbrand C., Bakkers J., Kuehl M., Schaeffer H.J., RA Huelsken J., Behrens J., Hammerschmidt M., Birchmeier W.; RT "The ankyrin repeat protein diversin recruits casein kinase Iepsilon to the RT beta-catenin degradation complex and acts in both canonical Wnt and Wnt/JNK RT signaling."; RL Genes Dev. 16:2073-2084(2002). RN [6] RP SUMOYLATION AT LYS-858 AND LYS-861, INTERACTION WITH MAP3K1; SUMO1; PIAS1; RP PIAS2 AND PIAS4, FUNCTION, HOMODIMERIZATION, AND MUTAGENESIS OF RP 858-LYS--ASP-863. RX PubMed=12223491; DOI=10.1074/jbc.m208099200; RA Rui H.L., Fan E., Zhou H.M., Xu Z., Zhang Y., Lin S.C.; RT "SUMO-1 modification of the C-terminal KVEKVD of Axin is required for JNK RT activation but has no effect on Wnt signaling."; RL J. Biol. Chem. 277:42981-42986(2002). RN [7] RP PHOSPHORYLATION, AND INTERACTION WITH CTNNB1. RX PubMed=15063782; DOI=10.1016/j.bbrc.2004.03.065; RA Kim S.I., Park C.S., Lee M.S., Kwon M.S., Jho E.H., Song W.K.; RT "Cyclin-dependent kinase 2 regulates the interaction of Axin with beta- RT catenin."; RL Biochem. Biophys. Res. Commun. 317:478-483(2004). RN [8] RP FUNCTION, INTERACTION WITH TP53 AND HIPK2, AND IDENTIFICATION IN A COMPLEX RP WITH TP53 AND HIPK2. RX PubMed=15526030; DOI=10.1038/sj.emboj.7600475; RA Rui Y., Xu Z., Lin S., Li Q., Rui H., Luo W., Zhou H.-M., Cheung P.-Y., RA Wu Z., Ye Z., Li P., Han J., Lin S.-C.; RT "Axin stimulates p53 functions by activation of HIPK2 kinase through RT multimeric complex formation."; RL EMBO J. 23:4583-4594(2004). RN [9] RP INTERACTION WITH DIXDC1; MAP3K1 AND MAP3K4. RX PubMed=15262978; DOI=10.1074/jbc.m404598200; RA Wong C.K., Luo W., Deng Y., Zou H., Ye Z., Lin S.-C.; RT "The DIX domain protein coiled-coil-DIX1 inhibits c-Jun N-terminal kinase RT activation by Axin and dishevelled through distinct mechanisms."; RL J. Biol. Chem. 279:39366-39373(2004). RN [10] RP SUBCELLULAR LOCATION. RX PubMed=16815997; DOI=10.1101/gad.1411206; RA Chen H.J., Lin C.M., Lin C.S., Perez-Olle R., Leung C.L., Liem R.K.; RT "The role of microtubule actin cross-linking factor 1 (MACF1) in the Wnt RT signaling pathway."; RL Genes Dev. 20:1933-1945(2006). RN [11] RP FUNCTION, HOMODIMERIZATION, AND INTERACTION WITH AIDA. RX PubMed=17681137; DOI=10.1016/j.devcel.2007.07.006; RA Rui Y., Xu Z., Xiong B., Cao Y., Lin S., Zhang M., Chan S.-C., Luo W., RA Han Y., Lu Z., Ye Z., Zhou H.-M., Han J., Meng A., Lin S.-C.; RT "A beta-catenin-independent dorsalization pathway activated by Axin/JNK RT signaling and antagonized by aida."; RL Dev. Cell 13:268-282(2007). RN [12] RP SUMOYLATION AT LYS-858 AND LYS-861, AND MUTAGENESIS OF LYS-858 AND LYS-861. RX PubMed=18632848; DOI=10.1096/fj.08-113910; RA Kim M.J., Chia I.V., Costantini F.; RT "SUMOylation target sites at the C terminus protect Axin from RT ubiquitination and confer protein stability."; RL FASEB J. 22:3785-3794(2008). RN [13] RP INTERACTION WITH ZBED3, AND SUBCELLULAR LOCATION. RX PubMed=19141611; DOI=10.1074/jbc.m807753200; RA Chen T., Li M., Ding Y., Zhang L.S., Xi Y., Pan W.J., Tao D.L., Wang J.Y., RA Li L.; RT "Identification of zinc-finger BED domain-containing 3 (Zbed3) as a novel RT Axin-interacting protein that activates Wnt/beta-catenin signaling."; RL J. Biol. Chem. 284:6683-6689(2009). RN [14] RP INTERACTION WITH DAB2. RX PubMed=19581931; DOI=10.1038/onc.2009.157; RA Jiang Y., Luo W., Howe P.H.; RT "Dab2 stabilizes Axin and attenuates Wnt/beta-catenin signaling by RT preventing protein phosphatase 1 (PP1)-Axin interactions."; RL Oncogene 28:2999-3007(2009). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-75 AND SER-217, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Kidney, Liver, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). CC -!- FUNCTION: Component of the beta-catenin destruction complex required CC for regulating CTNNB1 levels through phosphorylation and CC ubiquitination, and modulating Wnt-signaling (By similarity). Controls CC dorsoventral patterning via two opposing effects; down-regulates CTNNB1 CC to inhibit the Wnt signaling pathway and ventralize embryos, but also CC dorsalizes embryos by activating a Wnt-independent JNK signaling CC pathway. In Wnt signaling, probably facilitates the phosphorylation of CC CTNNB1 and APC by GSK3B. Likely to function as a tumor suppressor. CC Facilitates the phosphorylation of TP53 by HIPK2 upon ultraviolet CC irradiation. Enhances TGF-beta signaling by recruiting the RNF111 E3 CC ubiquitin ligase and promoting the degradation of inhibitory SMAD7 (By CC similarity). Also a component of the AXIN1-HIPK2-TP53 complex which CC controls cell growth, apoptosis and development. CC {ECO:0000250|UniProtKB:O15169, ECO:0000269|PubMed:12223491, CC ECO:0000269|PubMed:15526030, ECO:0000269|PubMed:17681137}. CC -!- SUBUNIT: Homodimer (PubMed:17681137). Component of the beta-catenin CC destruction complex, containing at least CTNNB1, an axin and GSK3B, CC that regulates CTNNB1 protein levels through phosphorylation and CC ubiquitination (By similarity). Interacts with GSK3B; the interaction CC hyperphosphorylates CTNNB1 leading to its ubiquitination and CC destruction (By similarity). Interacts with DAXX; the interaction CC stimulates the interaction of DAXX with TP53, stimulates 'Ser-46' CC phosphorylation of TP53 and induces cell death on UV irradiation (By CC similarity). Also interacts with APC, RNF111, SMAD6 and SMAD7 (By CC similarity). Interacts (via the C-terminal) with PPP1CA; the CC interaction dephosphorylates AXIN1 and regulates interaction with GSK3B CC (By similarity). Interacts with PPP2CA; the interaction CC dephosphorylates AXIN1 (By similarity). Interacts with MDFI; the CC interaction decreases AXIN1-mediated JUN N-terminal kinase (JNK) CC activation (By similarity). Interacts with MDFIC; the interaction CC inhibits beta-cateninin-mediated signaling and AXIN1-mediated JUN N- CC terminal kinase (JNK) activation (By similarity). Binds ANKRD6, PIAS1, CC PIAS2, PIAS4, SUMO1, MAP3K1 and MAP3K4 (PubMed:12183362, CC PubMed:12223491). Component of the AXIN1-HIPK2-TP53 complex CC (PubMed:15526030). Interacts directly in the complex with TP53 and CC HIPK2 (PubMed:15526030). Interacts with DIXDC1; the interaction CC prevents interaction with MAP3K1 (PubMed:15262978). Interacts with CC AIDA; the interaction blocks the AXIN1-mediated JNK activation through CC disrupting AXIN1 homodimerization and Wnt signaling (PubMed:17681137). CC Interacts with LRP5 (via its phosphorylated PPPSP motifs); the CC interaction is stimulated by WNT1 and GSK3B and activates beta-catenin CC signaling (PubMed:11336703). Interacts with CTNNB1 (via the armadillo CC repeats 2-7) (PubMed:10581160, PubMed:15063782). Interacts with MACF1 CC (By similarity). Found in a complex composed of MACF1, APC, AXIN1, CC CTNNB1 and GSK3B (By similarity). Interacts with TNKS (By similarity). CC Interacts with DAB2; the interaction is mutually exclusive with the CC AXIN1:PPP1CA interaction (PubMed:19581931). Interacts with ZBED3 (via CC PPPSP motif); the interaction is direct, enhanced by protein kinase CC GSK3B and casein kinase CSNK1E activities and decreases GSK3B-induced CC beta-catenin serine and threonine phosphorylations (PubMed:19141611). CC Interacts with WDR26 (By similarity). Interacts with GID8 (By CC similarity). Interacts with SIAH1 and SIAH2; both probably catalyze CC AXIN1 ubiquitination and subsequent proteasome-mediated ubiquitin- CC dependent degradation. Interaction with GSK3B and AXIN1 is competitive CC (By similarity). {ECO:0000250|UniProtKB:O15169, CC ECO:0000250|UniProtKB:O70239, ECO:0000269|PubMed:10581160, CC ECO:0000269|PubMed:11336703, ECO:0000269|PubMed:12183362, CC ECO:0000269|PubMed:12223491, ECO:0000269|PubMed:15063782, CC ECO:0000269|PubMed:15262978, ECO:0000269|PubMed:15526030, CC ECO:0000269|PubMed:17681137, ECO:0000269|PubMed:19141611, CC ECO:0000269|PubMed:19581931}. CC -!- INTERACTION: CC O35625; P98078: Dab2; NbExp=4; IntAct=EBI-2365912, EBI-1391846; CC O35625; Q61062: Dvl3; NbExp=2; IntAct=EBI-2365912, EBI-1538450; CC O35625; P62137: Ppp1ca; NbExp=2; IntAct=EBI-2365912, EBI-357187; CC O35625; Q99ML9: Rnf111; NbExp=4; IntAct=EBI-2365912, EBI-646015; CC O35625; Q8BUN5: Smad3; NbExp=2; IntAct=EBI-2365912, EBI-2337983; CC O35625; O35182: Smad6; NbExp=2; IntAct=EBI-2365912, EBI-4321242; CC O35625; O35253: Smad7; NbExp=2; IntAct=EBI-2365912, EBI-5274835; CC O35625; Q9EPK5: Wwtr1; NbExp=4; IntAct=EBI-2365912, EBI-1211920; CC O35625; P35222: CTNNB1; Xeno; NbExp=4; IntAct=EBI-2365912, EBI-491549; CC O35625; P49841: GSK3B; Xeno; NbExp=5; IntAct=EBI-2365912, EBI-373586; CC O35625; O75581: LRP6; Xeno; NbExp=2; IntAct=EBI-2365912, EBI-910915; CC O35625; Q15583: TGIF1; Xeno; NbExp=2; IntAct=EBI-2365912, EBI-714215; CC O35625; O95271: TNKS; Xeno; NbExp=4; IntAct=EBI-2365912, EBI-1105254; CC O35625; P46937: YAP1; Xeno; NbExp=3; IntAct=EBI-2365912, EBI-1044059; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16815997, CC ECO:0000269|PubMed:19141611}. Nucleus {ECO:0000250|UniProtKB:O15169}. CC Cell membrane {ECO:0000269|PubMed:16815997}. Membrane CC {ECO:0000269|PubMed:19141611}. Note=On UV irradiation, translocates to CC the nucleus and colocalizes with DAAX (By similarity). MACF1 is CC required for its translocation to cell membrane (PubMed:16815997). CC {ECO:0000250|UniProtKB:O15169, ECO:0000269|PubMed:16815997}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O35625-1; Sequence=Displayed; CC Name=2; CC IsoId=O35625-2; Sequence=VSP_000452; CC -!- TISSUE SPECIFICITY: Expressed in embryonic stem cells. CC -!- DEVELOPMENTAL STAGE: Widely expressed at 10.5 dpc to 16.5 dpc. CC -!- DOMAIN: The tankyrase-binding motif (also named TBD) is required for CC interaction with tankyrase TNKS and TNKS2. {ECO:0000250}. CC -!- PTM: Phosphorylation and dephosphorylation of AXIN1 regulates assembly CC and function of the beta-catenin complex. Phosphorylated by CK1 and CC GSK3B. Dephosphorylated by PPP1CA and PPP2CA. Phosphorylation by CK1 CC enhances binding of GSK3B to AXIN1 (By similarity). Also phosphorylated CC by CDK2 which regulates interaction with CTNBB1. {ECO:0000250, CC ECO:0000269|PubMed:10581160, ECO:0000269|PubMed:15063782}. CC -!- PTM: ADP-ribosylated by tankyrase TNKS and TNKS2. Poly-ADP-ribosylated CC protein is recognized by RNF146, followed by ubiquitination and CC subsequent activation of the Wnt signaling pathway (By similarity). CC {ECO:0000250}. CC -!- PTM: Ubiquitinated by RNF146 when poly-ADP-ribosylated, leading to its CC degradation and subsequent activation of the Wnt signaling pathway. CC Deubiquitinated by USP34, deubiquitinated downstream of beta-catenin CC stabilization step: deubiquitination is important for nuclear CC accumulation during Wnt signaling to positively regulate beta-catenin CC (CTNBB1)-mediated transcription (By similarity). Sumoylation at Lys-858 CC and Lys-861 prevents ubiquitination and degradation. Sumoylation is CC required for AXIN1-mediated JNK activation. Ubiquitination by SIAH1 and CC SIAH2 induces its proteasomal degradation as part of the activation of CC the Wnt signaling pathway (By similarity). {ECO:0000250, CC ECO:0000250|UniProtKB:O15169, ECO:0000269|PubMed:12223491, CC ECO:0000269|PubMed:18632848}. CC -!- SEQUENCE CAUTION: CC Sequence=AAC53285.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF009011; AAC53285.1; ALT_INIT; mRNA. DR EMBL; AC126438; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC140047; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS28547.2; -. [O35625-1] DR CCDS; CCDS50042.1; -. [O35625-2] DR RefSeq; NP_033863.2; NM_009733.2. [O35625-1] DR PDB; 3UTM; X-ray; 2.00 A; C=1-80. DR PDBsum; 3UTM; -. DR AlphaFoldDB; O35625; -. DR SMR; O35625; -. DR BioGRID; 198287; 36. DR ComplexPortal; CPX-103; Beta-catenin destruction core complex, Apc-Axin1-Gsk3b variant. DR ComplexPortal; CPX-448; Beta-catenin destruction core complex, Apc2-Axin1-Gsk3b variant. DR ComplexPortal; CPX-453; Beta-catenin destruction core complex, Apc-Axin1-Gsk3a variant. DR ComplexPortal; CPX-456; Beta-catenin destruction core complex, Apc2-Axin1-Gsk3a variant. DR CORUM; O35625; -. DR DIP; DIP-42637N; -. DR ELM; O35625; -. DR IntAct; O35625; 29. DR MINT; O35625; -. DR STRING; 10090.ENSMUSP00000073974; -. DR ChEMBL; CHEMBL4295996; -. DR iPTMnet; O35625; -. DR PhosphoSitePlus; O35625; -. DR EPD; O35625; -. DR MaxQB; O35625; -. DR PaxDb; 10090-ENSMUSP00000073974; -. DR ProteomicsDB; 273638; -. [O35625-1] DR ProteomicsDB; 273639; -. [O35625-2] DR Pumba; O35625; -. DR DNASU; 12005; -. DR Ensembl; ENSMUST00000074370.11; ENSMUSP00000073974.5; ENSMUSG00000024182.18. [O35625-1] DR Ensembl; ENSMUST00020183805.1; ENSMUSP00001091662.1; ENSMUSG00000024182.18. [O35625-2] DR GeneID; 12005; -. DR KEGG; mmu:12005; -. DR AGR; MGI:1096327; -. DR CTD; 8312; -. DR MGI; MGI:1096327; Axin1. DR eggNOG; KOG3589; Eukaryota. DR GeneTree; ENSGT00940000156947; -. DR InParanoid; O35625; -. DR OrthoDB; 4256282at2759; -. DR Reactome; R-MMU-195253; Degradation of beta-catenin by the destruction complex. DR Reactome; R-MMU-196299; Beta-catenin phosphorylation cascade. DR Reactome; R-MMU-201681; TCF dependent signaling in response to WNT. DR Reactome; R-MMU-4641257; Degradation of AXIN. DR Reactome; R-MMU-4641262; Disassembly of the destruction complex and recruitment of AXIN to the membrane. DR Reactome; R-MMU-5689880; Ub-specific processing proteases. DR BioGRID-ORCS; 12005; 6 hits in 80 CRISPR screens. DR ChiTaRS; Axin1; mouse. DR PRO; PR:O35625; -. DR Proteomes; UP000000589; Chromosome 17. DR RNAct; O35625; Protein. DR GO; GO:0030877; C:beta-catenin destruction complex; IDA:MGI. DR GO; GO:0005938; C:cell cortex; IDA:MGI. DR GO; GO:0071944; C:cell periphery; ISO:MGI. DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL. DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:MGI. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0016328; C:lateral plasma membrane; ISO:MGI. DR GO; GO:0015630; C:microtubule cytoskeleton; IDA:MGI. DR GO; GO:0005730; C:nucleolus; ISO:MGI. DR GO; GO:0005634; C:nucleus; ISO:MGI. DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; IDA:MGI. DR GO; GO:0045202; C:synapse; ISO:MGI. DR GO; GO:1990909; C:Wnt signalosome; IDA:ParkinsonsUK-UCL. DR GO; GO:0070016; F:armadillo repeat domain binding; ISO:MGI. DR GO; GO:0008013; F:beta-catenin binding; IPI:MGI. DR GO; GO:0019899; F:enzyme binding; ISO:MGI. DR GO; GO:0070411; F:I-SMAD binding; IDA:BHF-UCL. DR GO; GO:0042802; F:identical protein binding; IPI:MGI. DR GO; GO:0060090; F:molecular adaptor activity; ISO:MGI. DR GO; GO:0002039; F:p53 binding; IPI:MGI. DR GO; GO:0019904; F:protein domain specific binding; IPI:MGI. DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; IPI:ParkinsonsUK-UCL. DR GO; GO:0043621; F:protein self-association; IPI:MGI. DR GO; GO:0070412; F:R-SMAD binding; IPI:MGI. DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI. DR GO; GO:0046332; F:SMAD binding; ISO:MGI. DR GO; GO:1990756; F:ubiquitin ligase-substrate adaptor activity; IMP:BHF-UCL. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:BHF-UCL. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0048318; P:axial mesoderm development; IMP:MGI. DR GO; GO:0048320; P:axial mesoderm formation; IMP:MGI. DR GO; GO:0060070; P:canonical Wnt signaling pathway; IDA:MGI. DR GO; GO:0048468; P:cell development; IBA:GO_Central. DR GO; GO:0031122; P:cytoplasmic microtubule organization; IGI:MGI. DR GO; GO:0009950; P:dorsal/ventral axis specification; IDA:MGI. DR GO; GO:0009953; P:dorsal/ventral pattern formation; IMP:MGI. DR GO; GO:0044725; P:epigenetic programming in the zygotic pronuclei; IMP:MGI. DR GO; GO:0060322; P:head development; IMP:MGI. DR GO; GO:0001701; P:in utero embryonic development; IMP:MGI. DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IDA:MGI. DR GO; GO:0045599; P:negative regulation of fat cell differentiation; IDA:MGI. DR GO; GO:0010629; P:negative regulation of gene expression; IDA:MGI. DR GO; GO:0051248; P:negative regulation of protein metabolic process; IDA:MGI. DR GO; GO:0034244; P:negative regulation of transcription elongation by RNA polymerase II; IDA:MGI. DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IDA:MGI. DR GO; GO:0006913; P:nucleocytoplasmic transport; IDA:MGI. DR GO; GO:0046330; P:positive regulation of JNK cascade; IMP:UniProtKB. DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IDA:ParkinsonsUK-UCL. DR GO; GO:0010800; P:positive regulation of peptidyl-threonine phosphorylation; IDA:ParkinsonsUK-UCL. DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IDA:MGI. DR GO; GO:0045732; P:positive regulation of protein catabolic process; ISO:MGI. DR GO; GO:0045860; P:positive regulation of protein kinase activity; IDA:CACAO. DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:MGI. DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IDA:MGI. DR GO; GO:0030511; P:positive regulation of transforming growth factor beta receptor signaling pathway; IDA:MGI. DR GO; GO:2000060; P:positive regulation of ubiquitin-dependent protein catabolic process; IDA:MGI. DR GO; GO:0036342; P:post-anal tail morphogenesis; IMP:MGI. DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; NAS:ComplexPortal. DR GO; GO:0030163; P:protein catabolic process; IDA:MGI. DR GO; GO:0000209; P:protein polyubiquitination; IDA:MGI. DR GO; GO:0065003; P:protein-containing complex assembly; ISO:MGI. DR GO; GO:0060828; P:regulation of canonical Wnt signaling pathway; IDA:MGI. DR GO; GO:0001932; P:regulation of protein phosphorylation; IGI:MGI. DR GO; GO:0007605; P:sensory perception of sound; IMP:MGI. DR GO; GO:0016055; P:Wnt signaling pathway; IDA:MGI. DR CDD; cd11582; Axin_TNKS_binding; 1. DR CDD; cd08707; RGS_Axin; 1. DR DisProt; DP02456; -. DR Gene3D; 1.10.196.10; -; 2. DR Gene3D; 2.40.240.130; -; 1. DR Gene3D; 1.10.167.10; Regulator of G-protein Signalling 4, domain 2; 1. DR IDEAL; IID50192; -. DR InterPro; IPR043581; Axin-like. DR InterPro; IPR014936; Axin_b-cat-bd. DR InterPro; IPR032101; Axin_TNKS-bd. DR InterPro; IPR001158; DIX. DR InterPro; IPR038207; DIX_dom_sf. DR InterPro; IPR016137; RGS. DR InterPro; IPR036305; RGS_sf. DR InterPro; IPR024066; RGS_subdom1/3. DR InterPro; IPR044926; RGS_subdomain_2. DR InterPro; IPR029071; Ubiquitin-like_domsf. DR PANTHER; PTHR46102; AXIN; 1. DR PANTHER; PTHR46102:SF3; AXIN-1; 1. DR Pfam; PF16646; AXIN1_TNKS_BD; 1. DR Pfam; PF08833; Axin_b-cat_bind; 1. DR Pfam; PF00778; DIX; 1. DR Pfam; PF00615; RGS; 1. DR PRINTS; PR01301; RGSPROTEIN. DR SMART; SM00021; DAX; 1. DR SMART; SM00315; RGS; 1. DR SUPFAM; SSF48097; Regulator of G-protein signaling, RGS; 1. DR SUPFAM; SSF54236; Ubiquitin-like; 1. DR PROSITE; PS50841; DIX; 1. DR PROSITE; PS50132; RGS; 1. PE 1: Evidence at protein level; KW 3D-structure; ADP-ribosylation; Alternative splicing; Apoptosis; KW Cell membrane; Cytoplasm; Developmental protein; Isopeptide bond; Membrane; KW Nucleus; Phosphoprotein; Reference proteome; Tumor suppressor; KW Ubl conjugation; Wnt signaling pathway. FT CHAIN 1..863 FT /note="Axin-1" FT /id="PRO_0000220889" FT DOMAIN 88..211 FT /note="RGS" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00171" FT DOMAIN 781..863 FT /note="DIX" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00069" FT REGION 1..81 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 209..338 FT /note="Interaction with TP53" FT /evidence="ECO:0000269|PubMed:15526030" FT REGION 215..240 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 249..268 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 315..344 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 348..432 FT /note="Interaction with GSK3B" FT /evidence="ECO:0000250|UniProtKB:O70239" FT REGION 353..411 FT /note="Interaction with SIAH1" FT /evidence="ECO:0000250|UniProtKB:O15169" FT REGION 433..501 FT /note="Interaction with beta-catenin" FT /evidence="ECO:0000250" FT REGION 505..758 FT /note="Interaction with RNF111" FT /evidence="ECO:0000250" FT REGION 529..624 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 572..790 FT /note="Interaction with PPP2CA" FT /evidence="ECO:0000250" FT REGION 642..664 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 678..753 FT /note="Interaction with HIPK2" FT /evidence="ECO:0000269|PubMed:15526030" FT MOTIF 20..29 FT /note="Tankyrase-binding motif" FT COMPBIAS 36..63 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 215..235 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 315..339 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 75 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 77 FT /note="Phosphoserine; by CK1" FT /evidence="ECO:0000250|UniProtKB:O15169" FT MOD_RES 217 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 468 FT /note="Phosphoserine; by CK1" FT /evidence="ECO:0000250|UniProtKB:O15169" FT MOD_RES 480 FT /note="Phosphothreonine; by GSK3-beta" FT /evidence="ECO:0000305|PubMed:10581160" FT MOD_RES 485 FT /note="Phosphoserine; by GSK3-beta" FT /evidence="ECO:0000269|PubMed:10581160" FT MOD_RES 492 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:10581160" FT MOD_RES 509 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O15169" FT CROSSLNK 858 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT /evidence="ECO:0000269|PubMed:12223491, FT ECO:0000269|PubMed:18632848" FT CROSSLNK 861 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT /evidence="ECO:0000269|PubMed:12223491, FT ECO:0000269|PubMed:18632848" FT VAR_SEQ 731..766 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:9230313" FT /id="VSP_000452" FT MUTAGEN 480 FT /note="T->A: Greatly reduced GSK3B-mediated FT phosphorylation; when associated with A-485 and A-492." FT /evidence="ECO:0000269|PubMed:10581160" FT MUTAGEN 485 FT /note="S->A: Greatly reduced GSK3B-mediated phosphorylation FT and large effect on the inhibitory activity in FT Wnt-signaling; when associated with A-480 and A-492." FT /evidence="ECO:0000269|PubMed:10581160" FT MUTAGEN 492 FT /note="S->A: Greatly reduced GSK3B-mediated FT phosphorylation; when associated with A-480 and A-485." FT /evidence="ECO:0000269|PubMed:10581160" FT MUTAGEN 492 FT /note="S->I: Little effect on inhibitory activity on FT Wnt-signaling." FT /evidence="ECO:0000269|PubMed:10581160" FT MUTAGEN 495 FT /note="S->A: No effect on phosphorylation. Little effect on FT inhibitory activity on Wnt-signaling." FT /evidence="ECO:0000269|PubMed:10581160" FT MUTAGEN 858..863 FT /note="Missing: Abolishes binding of PIAS1 and PIAS2. FT Dramatically reduces sumoylation and abolishes FT AXIN1-mediated JNK activation. No effect on FT homodimerization nor on Wnt-signaling." FT /evidence="ECO:0000269|PubMed:12223491" FT MUTAGEN 858 FT /note="K->A: Decreased sumoylation followed by increased FT ubiquitination; when associated with A-861." FT /evidence="ECO:0000269|PubMed:18632848" FT MUTAGEN 861 FT /note="K->A: Decreased sumoylation followed by increased FT ubiquitination; when associated with A-858." FT /evidence="ECO:0000269|PubMed:18632848" FT CONFLICT 589 FT /note="A -> P (in Ref. 1; AAC53285)" FT /evidence="ECO:0000305" FT CONFLICT 787 FT /note="A -> G (in Ref. 1; AAC53285)" FT /evidence="ECO:0000305" FT CONFLICT 846 FT /note="A -> P (in Ref. 1; AAC53285)" FT /evidence="ECO:0000305" FT STRAND 64..66 FT /evidence="ECO:0007829|PDB:3UTM" SQ SEQUENCE 863 AA; 96276 MW; 2216D66E92387B81 CRC64; MNVQEQGFPL DLGASFTEDA PRPPVPGEEG ELVSTDSRPV NHSFCSGKGT SIKSETSTAT PRRSDLDLGY EPEGSASPTP PYLRWAESLH SLLDDQDGIS LFRTFLKQEG CADLLDFWFA CSGFRKLEPC DSNEEKRLKL ARAIYRKYIL DSNGIVSRQT KPATKSFIKD CVMKQQIDPA MFDQAQTEIQ STMEENTYPS FLKSDIYLEY TRTGSESPKV CSDQSSGSGT GKGMSGYLPT LNEDEEWKCD QDADEDDGRD PLPPSRLTQK LLLETAAPRA PSSRRYNEGR ELRYGSWREP VNPYYVNSGY ALAPATSAND SEQQSLSSDA DTLSLTDSSV DGIPPYRIRK QHRREMQESI QVNGRVPLPH IPRTYRMPKE IRVEPQKFAE ELIHRLEAVQ RTREAEEKLE ERLKRVRMEE EGEDGEMPSG PMASHKLPSV PAWHHFPPRY VDMGCSGLRD AHEENPESIL DEHVQRVMRT PGCQSPGPGH RSPDSGHVAK TAVLGGTASG HGKHVPKLGL KLDTAGLHHH RHVHHHVHHN SARPKEQMEA EVARRVQSSF SWGPETHGHA KPRSYSENAG TTLSAGDLAF GGKTSAPSKR NTKKAESGKN ANAEVPSTTE DAEKNQKIMQ WIIEGEKEIS RHRKAGHGSS GLRKQQAHES SRPLSIERPG AVHPWVSAQL RNSVQPSHLF IQDPTMPPNP APNPLTQLEE ARRRLEEEEK RANKLPSKQR YVQAVMQRGR TCVRPACAPV LSVVPAVSDL ELSETETKSQ RKAGGGSAPP CDSIVVAYYF CGEPIPYRTL VRGRAVTLGQ FKELLTKKGS YRYYFKKVSD EFDCGVVFEE VREDEAVLPV FEEKIIGKVE KVD //