AXIN1_MOUSE
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 03-AUG-2022, entry version 203.
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};
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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, variant 1.
DR ComplexPortal; CPX-448; Beta-catenin destruction core complex, variant 2.
DR ComplexPortal; CPX-453; Beta-catenin destruction core complex, variant 5.
DR ComplexPortal; CPX-456; Beta-catenin destruction core complex, variant 6.
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; O35625; -.
DR PRIDE; O35625; -.
DR ProteomicsDB; 273638; -. [O35625-1]
DR ProteomicsDB; 273639; -. [O35625-2]
DR DNASU; 12005; -.
DR Ensembl; ENSMUST00000074370; ENSMUSP00000073974; ENSMUSG00000024182. [O35625-1]
DR Ensembl; ENSMUST00020183805; ENSMUSP00001091662; ENSMUSG00000024182. [O35625-2]
DR GeneID; 12005; -.
DR KEGG; mmu:12005; -.
DR CTD; 8312; -.
DR MGI; MGI:1096327; Axin1.
DR eggNOG; KOG3589; Eukaryota.
DR GeneTree; ENSGT00940000156947; -.
DR InParanoid; O35625; -.
DR OrthoDB; 1481971at2759; -.
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; 5 hits in 75 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:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0016328; C:lateral plasma membrane; ISO:MGI.
DR GO; GO:0015630; C:microtubule cytoskeleton; IDA: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:0014069; C:postsynaptic density; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; IDA: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; IMP:BHF-UCL.
DR GO; GO:0002039; F:p53 binding; IPI:MGI.
DR GO; GO:0008022; F:protein C-terminus binding; IDA: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:0030159; F:signaling receptor complex adaptor activity; ISO:MGI.
DR GO; GO:0046332; F:SMAD binding; ISO:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:BHF-UCL.
DR GO; GO:0032147; P:activation of protein kinase activity; ISO:MGI.
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:0071514; P:genomic imprinting; 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 from RNA polymerase II promoter; 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:0043507; P:positive regulation of JUN kinase activity; IDA:MGI.
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:0045893; P:positive regulation of transcription, DNA-templated; IDA:BHF-UCL.
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:0051443; P:positive regulation of ubiquitin-protein transferase activity; IMP:BHF-UCL.
DR GO; GO:0036342; P:post-anal tail morphogenesis; IMP:MGI.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IC: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 DisProt; DP02456; -.
DR Gene3D; 1.10.167.10; -; 1.
DR Gene3D; 1.10.196.10; -; 2.
DR Gene3D; 2.40.240.130; -; 1.
DR IDEAL; IID50192; -.
DR InterPro; IPR043581; Axin-like.
DR InterPro; IPR029797; AXIN1.
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; PTHR46102; 1.
DR PANTHER; PTHR46102:SF3; PTHR46102:SF3; 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; SSF48097; 1.
DR SUPFAM; SSF54236; SSF54236; 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 Wnt-
FT 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 Wnt-
FT 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 AXIN1-
FT mediated JNK activation. No effect on homodimerization nor
FT 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
