ID AXIN1_HUMAN Reviewed; 862 AA. AC O15169; Q4TT26; Q4TT27; Q86YA7; Q8WVW6; Q96S28; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 10-MAY-2002, sequence version 2. DT 27-MAR-2024, entry version 240. DE RecName: Full=Axin-1; DE AltName: Full=Axis inhibition protein 1; DE Short=hAxin; GN Name=AXIN1; Synonyms=AXIN; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). 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]. RX PubMed=11157797; DOI=10.1093/hmg/10.4.339; RA Daniels R.J., Peden J.F., Lloyd C., Horsley S.W., Clark K., Tufarelli C., RA Kearney L., Buckle V.J., Doggett N.A., Flint J., Higgs D.R.; RT "Sequence, structure and pathology of the fully annotated terminal 2 Mb of RT the short arm of human chromosome 16."; RL Hum. Mol. Genet. 10:339-352(2001). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15616553; DOI=10.1038/nature03187; RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M., RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., RA Myers R.M., Rubin E.M., Pennacchio L.A.; RT "The sequence and analysis of duplication-rich human chromosome 16."; RL Nature 432:988-994(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE RP [LARGE SCALE MRNA] OF 471-862 (ISOFORM 1). RC TISSUE=Lymphoma, and Renal cell carcinoma; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP INTERACTION WITH GSK3B AND PPP2CA, PHOSPHORYLATION, AND DEPHOSPHORYLATION. RX PubMed=9920888; DOI=10.1074/jbc.274.6.3439; RA Hsu W., Zeng L., Costantini F.; RT "Identification of a domain of Axin that binds to the serine/threonine RT protein phosphatase 2A and a self-binding domain."; RL J. Biol. Chem. 274:3439-3445(1999). RN [6] RP DISEASE. RX PubMed=10700176; DOI=10.1038/73448; RA Satoh S., Daigo Y., Furukawa Y., Kato T., Miwa N., Nishiwaki T., RA Kawasoe T., Ishiguro H., Fujita M., Tokino T., Sasaki Y., Imaoka S., RA Murata M., Shimano T., Yamaoka Y., Nakamura Y.; RT "AXIN1 mutations in hepatocellular carcinomas, and growth suppression in RT cancer cells by virus-mediated transfer of AXIN1."; RL Nat. Genet. 24:245-250(2000). RN [7] 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 [8] RP INTERACTION WITH MDFI AND MDFIC, AND FUNCTION. RX PubMed=12192039; DOI=10.1128/mcb.22.18.6393-6405.2002; RA Kusano S., Raab-Traub N.; RT "I-mfa domain proteins interact with Axin and affect its regulation of the RT Wnt and c-Jun N-terminal kinase signaling pathways."; RL Mol. Cell. Biol. 22:6393-6405(2002). RN [9] RP INTERACTION WITH DAB2. RX PubMed=12805222; DOI=10.1093/emboj/cdg286; RA Howe P.H.; RT "Regulation of the Wnt signaling pathway by disabled-2 (Dab2)."; RL EMBO J. 22:3084-3094(2003). RN [10] 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 [11] RP INVOLVEMENT IN CAUDAL DUPLICATION ANOMALY. RX PubMed=16773576; DOI=10.1086/505031; RA Oates N.A., van Vliet J., Duffy D.L., Kroes H.Y., Martin N.G., RA Boomsma D.I., Campbell M., Coulthard M.G., Whitelaw E., Chong S.; RT "Increased DNA methylation at the AXIN1 gene in a monozygotic twin from a RT pair discordant for a caudal duplication anomaly."; RL Am. J. Hum. Genet. 79:155-162(2006). RN [12] RP INTERACTION WITH SMAD6; SMAD7 AND RNF111, FUNCTION, AND SUBCELLULAR RP LOCATION. RX PubMed=16601693; DOI=10.1038/sj.emboj.7601057; RA Liu W., Rui H., Wang J., Lin S., He Y., Chen M., Li Q., Ye Z., Zhang S., RA Chan S.C., Chen Y.-G., Han J., Lin S.-C.; RT "Axin is a scaffold protein in TGF-beta signaling that promotes degradation RT of Smad7 by Arkadia."; RL EMBO J. 25:1646-1658(2006). RN [13] RP INTERACTION WITH DAXX, IDENTIFICATION AS A COMPONENT OF THE RP AXIN1-HIPK2-TP53 COMPLEX, SUBCELLULAR LOCATION, AND FUNCTION. RX PubMed=17210684; DOI=10.1158/0008-5472.can-06-1671; RA Li Q., Wang X., Wu X., Rui Y., Liu W., Wang J., Wang X., Liou Y.C., Ye Z., RA Lin S.C.; RT "Daxx cooperates with the Axin/HIPK2/p53 complex to induce cell death."; RL Cancer Res. 67:66-74(2007). RN [14] RP PHOSPHORYLATION AT SER-75; SER-77; SER-217 AND SER-469, INTERACTION WITH RP GSK3B AND PPP1CA, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=17318175; DOI=10.1038/sj.emboj.7601607; RA Luo W., Peterson A., Garcia B.A., Coombs G., Kofahl B., Heinrich R., RA Shabanowitz J., Hunt D.F., Yost H.J., Virshup D.M.; RT "Protein phosphatase 1 regulates assembly and function of the beta-catenin RT degradation complex."; RL EMBO J. 26:1511-1521(2007). RN [15] RP SUMOYLATION. 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 [16] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [17] RP ADP-RIBOSYLATION, UBIQUITINATION, DOMAIN TANKYRASE-BINDING MOTIF, AND RP INTERACTION WITH TNKS AND TNKS2. RX PubMed=19759537; DOI=10.1038/nature08356; RA Huang S.M., Mishina Y.M., Liu S., Cheung A., Stegmeier F., Michaud G.A., RA Charlat O., Wiellette E., Zhang Y., Wiessner S., Hild M., Shi X., RA Wilson C.J., Mickanin C., Myer V., Fazal A., Tomlinson R., Serluca F., RA Shao W., Cheng H., Shultz M., Rau C., Schirle M., Schlegl J., Ghidelli S., RA Fawell S., Lu C., Curtis D., Kirschner M.W., Lengauer C., Finan P.M., RA Tallarico J.A., Bouwmeester T., Porter J.A., Bauer A., Cong F.; RT "Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling."; RL Nature 461:614-620(2009). RN [18] RP UBIQUITINATION, DEUBIQUITINATION BY USP34, AND SUBCELLULAR LOCATION. RX PubMed=21383061; DOI=10.1128/mcb.01094-10; RA Lui T.T., Lacroix C., Ahmed S.M., Goldenberg S.J., Leach C.A., Daulat A.M., RA Angers S.; RT "The Ubiquitin specific protease USP34 regulates Axin stability and RT Wnt/beta-catenin signaling."; RL Mol. Cell. Biol. 31:2053-2065(2011). RN [19] RP ADP-RIBOSYLATION, UBIQUITINATION, AND INTERACTION WITH RNF146; TNKS AND RP TNKS2. RX PubMed=21478859; DOI=10.1038/ncb2222; RA Zhang Y., Liu S., Mickanin C., Feng Y., Charlat O., Michaud G.A., RA Schirle M., Shi X., Hild M., Bauer A., Myer V.E., Finan P.M., Porter J.A., RA Huang S.M., Cong F.; RT "RNF146 is a poly(ADP-ribose)-directed E3 ligase that regulates axin RT degradation and Wnt signalling."; RL Nat. Cell Biol. 13:623-629(2011). RN [20] RP INTERACTION WITH TNKS, AND UBIQUITINATION. RX PubMed=21799911; DOI=10.1371/journal.pone.0022595; RA Callow M.G., Tran H., Phu L., Lau T., Lee J., Sandoval W.N., Liu P.S., RA Bheddah S., Tao J., Lill J.R., Hongo J.A., Davis D., Kirkpatrick D.S., RA Polakis P., Costa M.; RT "Ubiquitin ligase RNF146 regulates tankyrase and Axin to promote Wnt RT signaling."; RL PLoS ONE 6:E22595-E22595(2011). RN [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-77; SER-486; SER-511 AND RP SER-581, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [22] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [23] RP INTERACTION WITH WDR26, AND FUNCTION. RX PubMed=27098453; DOI=10.1002/1873-3468.12180; RA Goto T., Matsuzawa J., Iemura S., Natsume T., Shibuya H.; RT "WDR26 is a new partner of Axin1 in the canonical Wnt signaling pathway."; RL FEBS Lett. 590:1291-1303(2016). RN [24] RP INTERACTION WITH GID8; GSK3B AND CTNNB1. RX PubMed=28829046; DOI=10.1038/cr.2017.107; RA Lu Y., Xie S., Zhang W., Zhang C., Gao C., Sun Q., Cai Y., Xu Z., Xiao M., RA Xu Y., Huang X., Wu X., Liu W., Wang F., Kang Y., Zhou T.; RT "Twa1/Gid8 is a beta-catenin nuclear retention factor in Wnt signaling and RT colorectal tumorigenesis."; RL Cell Res. 27:1422-1440(2017). RN [25] RP FUNCTION, INTERACTION WITH GSK3B; SIAH1 AND SIAH2, UBIQUITINATION, AND RP MUTAGENESIS OF VAL-383 AND PRO-385. RX PubMed=28546513; DOI=10.1101/gad.300053.117; RA Ji L., Jiang B., Jiang X., Charlat O., Chen A., Mickanin C., Bauer A., RA Xu W., Yan X., Cong F.; RT "The SIAH E3 ubiquitin ligases promote Wnt/beta-catenin signaling through RT mediating Wnt-induced Axin degradation."; RL Genes Dev. 31:904-915(2017). RN [26] RP X-RAY CRYSTALLOGRAPHY (1.57 ANGSTROMS) OF 74-220 IN COMPLEX WITH APC. RX PubMed=10811618; DOI=10.1093/emboj/19.10.2270; RA Spink K.E., Polakis P., Weis W.I.; RT "Structural basis of the axin-adenomatous polyposis coli interaction."; RL EMBO J. 19:2270-2279(2000). RN [27] RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 383-400 IN COMPLEX WITH GSK3B. RX PubMed=12554650; DOI=10.1093/emboj/cdg068; RA Dajani R., Fraser E., Roe S.M., Yeo M., Good V.M., Thompson V., Dale T.C., RA Pearl L.H.; RT "Structural basis for recruitment of glycogen synthase kinase 3beta to the RT axin-APC scaffold complex."; RL EMBO J. 22:494-501(2003). RN [28] RP INVOLVEMENT IN HCC, VARIANTS HCC ARG-106; LEU-345 AND SER-425, AND VARIANTS RP SER-650 AND GLN-841. RX PubMed=12101426; DOI=10.1038/sj.onc.1205591; RA Taniguchi K., Roberts L.R., Aderca I.N., Dong X., Qian C., Murphy L.M., RA Nagorney D.M., Burgart L.J., Roche P.C., Smith D.I., Ross J.A., Liu W.; RT "Mutational spectrum of beta-catenin, AXIN1, and AXIN2 in hepatocellular RT carcinomas and hepatoblastomas."; RL Oncogene 21:4863-4871(2002). CC -!- FUNCTION: Component of the beta-catenin destruction complex required CC for regulating CTNNB1 levels through phosphorylation and CC ubiquitination, and modulating Wnt-signaling (PubMed:12192039, CC PubMed:27098453, PubMed:28829046). Controls dorsoventral patterning via CC two opposing effects; down-regulates CTNNB1 to inhibit the Wnt CC signaling pathway and ventralize embryos, but also dorsalizes embryos CC by activating a Wnt-independent JNK signaling pathway CC (PubMed:12192039). In Wnt signaling, probably facilitates the CC phosphorylation of CTNNB1 and APC by GSK3B (PubMed:12192039). Likely to CC function as a tumor suppressor. Enhances TGF-beta signaling by CC recruiting the RNF111 E3 ubiquitin ligase and promoting the degradation CC of inhibitory SMAD7 (PubMed:16601693). Also a component of the AXIN1- CC HIPK2-TP53 complex which controls cell growth, apoptosis and CC development (PubMed:17210684). Facilitates the phosphorylation of TP53 CC by HIPK2 upon ultraviolet irradiation (PubMed:17210684). CC {ECO:0000269|PubMed:12192039, ECO:0000269|PubMed:16601693, CC ECO:0000269|PubMed:17210684, ECO:0000269|PubMed:27098453, CC ECO:0000269|PubMed:28546513}. CC -!- SUBUNIT: Homodimer (By similarity). Interacts with ZBED3; the CC interaction is direct, enhanced by protein kinase GSK3B and casein CC kinase CSNK1E activities and decreases GSK3B-induced beta-catenin CC serine and threonine phosphorylations (By similarity). Component of the CC beta-catenin destruction complex, containing at least, CTNNB1, an axin CC and GSK3B, that regulates CTNNB1 protein levels through phosphorylation CC and ubiquitination. Interacts with CTNNB1 (via the armadillo repeats 2- CC 7). Interacts with GSK3B; the interaction hyperphosphorylates CTNNB1 CC leading to its ubiquitination and destruction (PubMed:17318175, CC PubMed:12554650, PubMed:28546513). Component of the AXIN1-HIPK2-TP53 CC complex (PubMed:17210684). Interacts directly in the complex with TP53 CC and HIPK2 (PubMed:17210684). 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 CC (PubMed:17210684). Also binds APC, SMAD6, SMAD7 and RNF111 CC (PubMed:16601693, PubMed:10811618). Interacts with DIXDC1; prevents CC interaction with MAP3K1 (PubMed:15262978). Interacts with MAP3K4 CC (PubMed:15262978). Interacts with ANKRD6 and AIDA (By similarity). CC Interacts with MDFI; the interaction decreases AXIN1-mediated JUN N- CC terminal kinase (JNK) activation (PubMed:12192039). Interacts with CC MDFIC; the interaction inhibits beta-cateninin-mediated signaling and CC AXIN1-mediated JUN N-terminal kinase (JNK) activation CC (PubMed:12192039). Interacts with LRP5 (via its phosphorylated PPPSP CC motifs); the interaction is stimulated by WNT1 and GSK3B and activates CC beta-catenin signaling (PubMed:11336703). Interacts (via the C- CC terminal) with PPP1CA; the interaction dephosphorylates AXIN1 and CC regulates interaction with GSK3B (PubMed:9920888). Interacts with CC PPP2CA; the interaction dephosphorylates AXIN1 (PubMed:9920888). CC Interacts with MACF1 (By similarity). Found in a complex composed of CC MACF1, APC, AXIN1, CTNNB1 and GSK3B (By similarity). Interacts with CC TNKS (PubMed:19759537, PubMed:21478859, PubMed:21799911). Interacts CC with DAB2; the interaction is mutually exclusive with the AXIN1:PPP1CA CC interaction (PubMed:12805222). Interacts with WDR26 (PubMed:27098453). CC Interacts with GID8 (PubMed:28829046). Interacts with SIAH1 and SIAH2; CC both probably catalyze AXIN1 ubiquitination and subsequent proteasome- CC mediated ubiquitin-dependent degradation (PubMed:28546513). Interaction CC with GSK3B and AXIN1 is competitive (PubMed:28546513). CC {ECO:0000250|UniProtKB:O35625, ECO:0000250|UniProtKB:O70239, CC ECO:0000269|PubMed:10811618, ECO:0000269|PubMed:11336703, CC ECO:0000269|PubMed:12192039, ECO:0000269|PubMed:12554650, CC ECO:0000269|PubMed:12805222, ECO:0000269|PubMed:15262978, CC ECO:0000269|PubMed:16601693, ECO:0000269|PubMed:17210684, CC ECO:0000269|PubMed:17318175, ECO:0000269|PubMed:19759537, CC ECO:0000269|PubMed:21478859, ECO:0000269|PubMed:21799911, CC ECO:0000269|PubMed:27098453, ECO:0000269|PubMed:28546513, CC ECO:0000269|PubMed:28829046, ECO:0000269|PubMed:9920888}. CC -!- INTERACTION: CC O15169; Q5JTC6: AMER1; NbExp=7; IntAct=EBI-710484, EBI-6169747; CC O15169; P39687: ANP32A; NbExp=2; IntAct=EBI-710484, EBI-359234; CC O15169; P25054: APC; NbExp=17; IntAct=EBI-710484, EBI-727707; CC O15169; P49407: ARRB1; NbExp=2; IntAct=EBI-710484, EBI-743313; CC O15169; O15169: AXIN1; NbExp=5; IntAct=EBI-710484, EBI-710484; CC O15169; Q13137: CALCOCO2; NbExp=3; IntAct=EBI-710484, EBI-739580; CC O15169; Q9H257-2: CARD9; NbExp=3; IntAct=EBI-710484, EBI-11530605; CC O15169; Q2TAC2-2: CCDC57; NbExp=3; IntAct=EBI-710484, EBI-10961624; CC O15169; Q14194: CRMP1; NbExp=2; IntAct=EBI-710484, EBI-473101; CC O15169; P49674: CSNK1E; NbExp=5; IntAct=EBI-710484, EBI-749343; CC O15169; P35222: CTNNB1; NbExp=44; IntAct=EBI-710484, EBI-491549; CC O15169; Q5VWQ8-2: DAB2IP; NbExp=2; IntAct=EBI-710484, EBI-9543020; CC O15169; O14641: DVL2; NbExp=3; IntAct=EBI-710484, EBI-740850; CC O15169; Q9UKB1: FBXW11; NbExp=4; IntAct=EBI-710484, EBI-355189; CC O15169; Q08379: GOLGA2; NbExp=3; IntAct=EBI-710484, EBI-618309; CC O15169; P49840: GSK3A; NbExp=3; IntAct=EBI-710484, EBI-1044067; CC O15169; P49841: GSK3B; NbExp=51; IntAct=EBI-710484, EBI-373586; CC O15169; P14923: JUP; NbExp=4; IntAct=EBI-710484, EBI-702484; CC O15169; Q6A162: KRT40; NbExp=3; IntAct=EBI-710484, EBI-10171697; CC O15169; Q9BQ66: KRTAP4-12; NbExp=3; IntAct=EBI-710484, EBI-739863; CC O15169; Q9BYR5: KRTAP4-2; NbExp=3; IntAct=EBI-710484, EBI-10172511; CC O15169; Q969G2: LHX4; NbExp=3; IntAct=EBI-710484, EBI-2865388; CC O15169; Q99750: MDFI; NbExp=3; IntAct=EBI-710484, EBI-724076; CC O15169; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-710484, EBI-16439278; CC O15169; Q9UJV3-2: MID2; NbExp=3; IntAct=EBI-710484, EBI-10172526; CC O15169; Q5JR59-3: MTUS2; NbExp=3; IntAct=EBI-710484, EBI-11522433; CC O15169; P01106: MYC; NbExp=10; IntAct=EBI-710484, EBI-447544; CC O15169; P35813: PPM1A; NbExp=2; IntAct=EBI-710484, EBI-989143; CC O15169; P62136: PPP1CA; NbExp=4; IntAct=EBI-710484, EBI-357253; CC O15169; O43586: PSTPIP1; NbExp=3; IntAct=EBI-710484, EBI-1050964; CC O15169; Q6ZNA4: RNF111; NbExp=2; IntAct=EBI-710484, EBI-2129175; CC O15169; Q96KG9-4: SCYL1; NbExp=3; IntAct=EBI-710484, EBI-12023020; CC O15169; O15105: SMAD7; NbExp=8; IntAct=EBI-710484, EBI-3861591; CC O15169; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-710484, EBI-5235340; CC O15169; O75558: STX11; NbExp=3; IntAct=EBI-710484, EBI-714135; CC O15169; P63165: SUMO1; NbExp=3; IntAct=EBI-710484, EBI-80140; CC O15169; G2XKQ0: SUMO1P1; NbExp=3; IntAct=EBI-710484, EBI-10175576; CC O15169; Q9UBB9: TFIP11; NbExp=3; IntAct=EBI-710484, EBI-1105213; CC O15169; Q15583: TGIF1; NbExp=4; IntAct=EBI-710484, EBI-714215; CC O15169; Q9H2K2: TNKS2; NbExp=2; IntAct=EBI-710484, EBI-4398527; CC O15169; P04637: TP53; NbExp=4; IntAct=EBI-710484, EBI-366083; CC O15169; Q12933: TRAF2; NbExp=3; IntAct=EBI-710484, EBI-355744; CC O15169; Q9C019: TRIM15; NbExp=3; IntAct=EBI-710484, EBI-2342111; CC O15169; P14373: TRIM27; NbExp=3; IntAct=EBI-710484, EBI-719493; CC O15169; Q14134: TRIM29; NbExp=2; IntAct=EBI-710484, EBI-702370; CC O15169; O94972: TRIM37; NbExp=3; IntAct=EBI-710484, EBI-741602; CC O15169; Q15654: TRIP6; NbExp=6; IntAct=EBI-710484, EBI-742327; CC O15169; P23258: TUBG1; NbExp=4; IntAct=EBI-710484, EBI-302589; CC O15169; Q9H7D7: WDR26; NbExp=4; IntAct=EBI-710484, EBI-1046864; CC O15169; P46937: YAP1; NbExp=11; IntAct=EBI-710484, EBI-1044059; CC O15169; Q9HCK0: ZBTB26; NbExp=3; IntAct=EBI-710484, EBI-3918996; CC O15169; Q96K21-3: ZFYVE19; NbExp=3; IntAct=EBI-710484, EBI-10187928; CC O15169; P70039: apc; Xeno; NbExp=2; IntAct=EBI-710484, EBI-8069633; CC O15169; Q02248: Ctnnb1; Xeno; NbExp=5; IntAct=EBI-710484, EBI-397872; CC O15169; G1T8E2: GSK3B; Xeno; NbExp=2; IntAct=EBI-710484, EBI-3833365; CC O15169; Q99ML9: Rnf111; Xeno; NbExp=5; IntAct=EBI-710484, EBI-646015; CC O15169-2; O75581: LRP6; NbExp=3; IntAct=EBI-10987526, EBI-910915; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16601693}. Nucleus CC {ECO:0000269|PubMed:17210684}. Membrane {ECO:0000250|UniProtKB:O35625}. CC Cell membrane {ECO:0000250|UniProtKB:O35625}. Note=MACF1 is required CC for its translocation to cell membrane (By similarity). On UV CC irradiation, translocates to the nucleus and colocalizes with DAAX CC (PubMed:17210684). {ECO:0000250|UniProtKB:O35625, CC ECO:0000269|PubMed:17210684}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O15169-1; Sequence=Displayed; CC Name=2; CC IsoId=O15169-2; Sequence=VSP_019398; CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. CC -!- DOMAIN: The tankyrase-binding motif (also named TBD) is required for CC interaction with tankyrase TNKS and TNKS2. CC {ECO:0000269|PubMed:19759537}. 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. {ECO:0000269|PubMed:17318175, CC ECO:0000269|PubMed:9920888}. CC -!- PTM: ADP-ribosylated by tankyrase TNKS and TNKS2. Poly-ADP-ribosylated CC protein is recognized by RNF146, followed by ubiquitination at 'Lys-48' CC and subsequent activation of the Wnt signaling pathway. CC {ECO:0000269|PubMed:21383061}. CC -!- PTM: Ubiquitinated by RNF146 when poly-ADP-ribosylated, leading to its CC degradation and subsequent activation of the Wnt signaling pathway. CC Sumoylation at Lys-857 and Lys-860 prevents ubiquitination and CC degradation. Sumoylation is required for AXIN1-mediated JNK activation. 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. Ubiquitination by SIAH1 and SIAH2 CC induces its proteasomal degradation as part of the activation of the CC Wnt signaling pathway (PubMed:28546513). {ECO:0000269|PubMed:18632848, CC ECO:0000269|PubMed:21383061, ECO:0000269|PubMed:28546513}. CC -!- DISEASE: Hepatocellular carcinoma (HCC) [MIM:114550]: A primary CC malignant neoplasm of epithelial liver cells. The major risk factors CC for HCC are chronic hepatitis B virus (HBV) infection, chronic CC hepatitis C virus (HCV) infection, prolonged dietary aflatoxin CC exposure, alcoholic cirrhosis, and cirrhosis due to other causes. CC {ECO:0000269|PubMed:12101426}. Note=The gene represented in this entry CC is involved in disease pathogenesis. CC -!- DISEASE: Caudal duplication anomaly (CADUA) [MIM:607864]: A condition CC characterized by the occurrence of duplications of different organs in CC the caudal region. {ECO:0000269|PubMed:16773576}. Note=The disease is CC caused by variants affecting the gene represented in this entry. Caudal CC duplication anomaly is associated with hypermethylation of the AXIN1 CC promoter. CC -!- SEQUENCE CAUTION: CC Sequence=AAC51624.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/379/AXIN1"; 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; AF009674; AAC51624.1; ALT_INIT; mRNA. DR EMBL; AE006463; AAK61224.1; -; Genomic_DNA. DR EMBL; Z69667; CAI95589.2; -; Genomic_DNA. DR EMBL; AC005202; CAI95589.2; JOINED; Genomic_DNA. DR EMBL; Z99754; CAI95589.2; JOINED; Genomic_DNA. DR EMBL; Z69667; CAI95590.2; -; Genomic_DNA. DR EMBL; AC005202; CAI95590.2; JOINED; Genomic_DNA. DR EMBL; Z99754; CAI95590.2; JOINED; Genomic_DNA. DR EMBL; Z99754; CAI95600.2; -; Genomic_DNA. DR EMBL; AC005202; CAI95600.2; JOINED; Genomic_DNA. DR EMBL; Z69667; CAI95600.2; JOINED; Genomic_DNA. DR EMBL; Z99754; CAI95601.2; -; Genomic_DNA. DR EMBL; AC005202; CAI95601.2; JOINED; Genomic_DNA. DR EMBL; Z69667; CAI95601.2; JOINED; Genomic_DNA. DR EMBL; BC017447; AAH17447.1; -; mRNA. DR EMBL; BC044648; AAH44648.1; -; mRNA. DR CCDS; CCDS10405.1; -. [O15169-1] DR CCDS; CCDS10406.1; -. [O15169-2] DR RefSeq; NP_003493.1; NM_003502.3. [O15169-1] DR RefSeq; NP_851393.1; NM_181050.2. [O15169-2] DR PDB; 1DK8; X-ray; 1.57 A; A=74-220. DR PDB; 1EMU; X-ray; 1.90 A; A=80-211. DR PDB; 1O9U; X-ray; 2.40 A; B=383-400. DR PDB; 3ZDI; X-ray; 2.64 A; B=383-400. DR PDB; 4B7T; X-ray; 2.77 A; B=383-400. DR PDB; 4NM0; X-ray; 2.50 A; B=383-402. DR PDB; 4NM3; X-ray; 2.10 A; B=383-402. DR PDB; 4NM5; X-ray; 2.30 A; B=383-402. DR PDB; 4NM7; X-ray; 2.30 A; B=383-402. DR PDB; 4NU1; X-ray; 2.50 A; B=383-402. DR PDB; 5WZZ; X-ray; 2.10 A; E/F/G/H=375-394. DR PDB; 6JCK; X-ray; 3.09 A; A=781-862. DR PDB; 7SXF; X-ray; 1.94 A; B=385-399. DR PDB; 7SXG; X-ray; 2.40 A; B=385-400. DR PDB; 7SXH; X-ray; 2.09 A; B=385-400. DR PDB; 7SXJ; X-ray; 1.85 A; B=384-400. DR PDBsum; 1DK8; -. DR PDBsum; 1EMU; -. DR PDBsum; 1O9U; -. DR PDBsum; 3ZDI; -. DR PDBsum; 4B7T; -. DR PDBsum; 4NM0; -. DR PDBsum; 4NM3; -. DR PDBsum; 4NM5; -. DR PDBsum; 4NM7; -. DR PDBsum; 4NU1; -. DR PDBsum; 5WZZ; -. DR PDBsum; 6JCK; -. DR PDBsum; 7SXF; -. DR PDBsum; 7SXG; -. DR PDBsum; 7SXH; -. DR PDBsum; 7SXJ; -. DR AlphaFoldDB; O15169; -. DR SMR; O15169; -. DR BioGRID; 113909; 152. DR ComplexPortal; CPX-107; Beta-catenin destruction core complex, APC-AXIN1-GSK3A variant. DR ComplexPortal; CPX-109; Beta-catenin destruction core complex, APC-AXIN1-GSK3B variant. DR ComplexPortal; CPX-442; Beta-catenin destruction core complex, APC2-AXIN1-GSK3A variant. DR ComplexPortal; CPX-99; Beta-catenin destruction core complex, APC2-AXIN1-GSK3B variant. DR CORUM; O15169; -. DR DIP; DIP-34630N; -. DR IntAct; O15169; 133. DR MINT; O15169; -. DR STRING; 9606.ENSP00000262320; -. DR ChEMBL; CHEMBL1255127; -. DR DrugBank; DB04447; 1,4-Dithiothreitol. DR iPTMnet; O15169; -. DR PhosphoSitePlus; O15169; -. DR BioMuta; AXIN1; -. DR EPD; O15169; -. DR jPOST; O15169; -. DR MassIVE; O15169; -. DR MaxQB; O15169; -. DR PaxDb; 9606-ENSP00000262320; -. DR PeptideAtlas; O15169; -. DR ProteomicsDB; 48492; -. [O15169-1] DR ProteomicsDB; 48493; -. [O15169-2] DR Pumba; O15169; -. DR Antibodypedia; 22635; 635 antibodies from 40 providers. DR DNASU; 8312; -. DR Ensembl; ENST00000262320.8; ENSP00000262320.3; ENSG00000103126.15. [O15169-1] DR Ensembl; ENST00000354866.7; ENSP00000346935.3; ENSG00000103126.15. [O15169-2] DR GeneID; 8312; -. DR KEGG; hsa:8312; -. DR MANE-Select; ENST00000262320.8; ENSP00000262320.3; NM_003502.4; NP_003493.1. DR UCSC; uc002cgp.3; human. [O15169-1] DR AGR; HGNC:903; -. DR CTD; 8312; -. DR DisGeNET; 8312; -. DR GeneCards; AXIN1; -. DR HGNC; HGNC:903; AXIN1. DR HPA; ENSG00000103126; Low tissue specificity. DR MalaCards; AXIN1; -. DR MIM; 114550; phenotype. DR MIM; 603816; gene. DR MIM; 607864; phenotype. DR neXtProt; NX_O15169; -. DR OpenTargets; ENSG00000103126; -. DR Orphanet; 210159; Adult hepatocellular carcinoma. DR PharmGKB; PA25195; -. DR VEuPathDB; HostDB:ENSG00000103126; -. DR eggNOG; KOG3589; Eukaryota. DR GeneTree; ENSGT00940000156947; -. DR HOGENOM; CLU_016422_0_0_1; -. DR InParanoid; O15169; -. DR OMA; YVYTAST; -. DR OrthoDB; 4256282at2759; -. DR PhylomeDB; O15169; -. DR TreeFam; TF315454; -. DR PathwayCommons; O15169; -. DR Reactome; R-HSA-195253; Degradation of beta-catenin by the destruction complex. DR Reactome; R-HSA-196299; Beta-catenin phosphorylation cascade. DR Reactome; R-HSA-201681; TCF dependent signaling in response to WNT. DR Reactome; R-HSA-4641257; Degradation of AXIN. DR Reactome; R-HSA-4641262; Disassembly of the destruction complex and recruitment of AXIN to the membrane. DR Reactome; R-HSA-5339716; Signaling by GSK3beta mutants. DR Reactome; R-HSA-5358747; CTNNB1 S33 mutants aren't phosphorylated. DR Reactome; R-HSA-5358749; CTNNB1 S37 mutants aren't phosphorylated. DR Reactome; R-HSA-5358751; CTNNB1 S45 mutants aren't phosphorylated. DR Reactome; R-HSA-5358752; CTNNB1 T41 mutants aren't phosphorylated. DR Reactome; R-HSA-5467337; APC truncation mutants have impaired AXIN binding. DR Reactome; R-HSA-5467340; AXIN missense mutants destabilize the destruction complex. DR Reactome; R-HSA-5467348; Truncations of AMER1 destabilize the destruction complex. DR Reactome; R-HSA-5689880; Ub-specific processing proteases. DR Reactome; R-HSA-8931987; RUNX1 regulates estrogen receptor mediated transcription. DR Reactome; R-HSA-8939256; RUNX1 regulates transcription of genes involved in WNT signaling. DR Reactome; R-HSA-9018519; Estrogen-dependent gene expression. DR SignaLink; O15169; -. DR SIGNOR; O15169; -. DR BioGRID-ORCS; 8312; 42 hits in 1179 CRISPR screens. DR ChiTaRS; AXIN1; human. DR EvolutionaryTrace; O15169; -. DR GeneWiki; AXIN1; -. DR GenomeRNAi; 8312; -. DR Pharos; O15169; Tbio. DR PRO; PR:O15169; -. DR Proteomes; UP000005640; Chromosome 16. DR RNAct; O15169; Protein. DR Bgee; ENSG00000103126; Expressed in granulocyte and 102 other cell types or tissues. DR ExpressionAtlas; O15169; baseline and differential. DR GO; GO:0030877; C:beta-catenin destruction complex; IDA:UniProtKB. DR GO; GO:0005938; C:cell cortex; IEA:Ensembl. DR GO; GO:0071944; C:cell periphery; IDA:BHF-UCL. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0031410; C:cytoplasmic vesicle; ISS:BHF-UCL. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0016328; C:lateral plasma membrane; IDA:MGI. DR GO; GO:0015630; C:microtubule cytoskeleton; IEA:Ensembl. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:BHF-UCL. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:1990909; C:Wnt signalosome; IEA:Ensembl. DR GO; GO:0070016; F:armadillo repeat domain binding; ISS:BHF-UCL. DR GO; GO:0008013; F:beta-catenin binding; IDA:BHF-UCL. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0070411; F:I-SMAD binding; IPI:BHF-UCL. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0060090; F:molecular adaptor activity; IDA:BHF-UCL. DR GO; GO:0002039; F:p53 binding; IEA:Ensembl. DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; ISS:BHF-UCL. DR GO; GO:0043621; F:protein self-association; IEA:Ensembl. DR GO; GO:0070412; F:R-SMAD binding; IEA:Ensembl. DR GO; GO:0035591; F:signaling adaptor activity; TAS:BHF-UCL. DR GO; GO:0046332; F:SMAD binding; IPI:BHF-UCL. DR GO; GO:1990756; F:ubiquitin ligase-substrate adaptor activity; IMP:BHF-UCL. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB. DR GO; GO:0032147; P:activation of protein kinase activity; IDA:BHF-UCL. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0048320; P:axial mesoderm formation; IEA:Ensembl. DR GO; GO:0060070; P:canonical Wnt signaling pathway; IEA:Ensembl. DR GO; GO:0048468; P:cell development; IBA:GO_Central. DR GO; GO:0031122; P:cytoplasmic microtubule organization; IEA:Ensembl. DR GO; GO:0009950; P:dorsal/ventral axis specification; IEA:Ensembl. DR GO; GO:0044725; P:epigenetic programming in the zygotic pronuclei; IEA:Ensembl. DR GO; GO:0060322; P:head development; IEA:Ensembl. DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl. DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IDA:BHF-UCL. DR GO; GO:0045599; P:negative regulation of fat cell differentiation; IEA:Ensembl. DR GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl. DR GO; GO:0051248; P:negative regulation of protein metabolic process; IEA:Ensembl. DR GO; GO:0034244; P:negative regulation of transcription elongation by RNA polymerase II; IEA:Ensembl. DR GO; GO:0006913; P:nucleocytoplasmic transport; IEA:Ensembl. DR GO; GO:0046330; P:positive regulation of JNK cascade; ISS:UniProtKB. DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; NAS:BHF-UCL. DR GO; GO:0010800; P:positive regulation of peptidyl-threonine phosphorylation; NAS:BHF-UCL. DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IBA:GO_Central. DR GO; GO:0045732; P:positive regulation of protein catabolic process; IDA:BHF-UCL. DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:BHF-UCL. DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IMP:BHF-UCL. DR GO; GO:0030511; P:positive regulation of transforming growth factor beta receptor signaling pathway; IEA:Ensembl. DR GO; GO:2000060; P:positive regulation of ubiquitin-dependent protein catabolic process; ISS:BHF-UCL. DR GO; GO:0036342; P:post-anal tail morphogenesis; IEA:Ensembl. DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; NAS:ComplexPortal. DR GO; GO:0000209; P:protein polyubiquitination; IEA:Ensembl. DR GO; GO:0065003; P:protein-containing complex assembly; IDA:BHF-UCL. DR GO; GO:0007605; P:sensory perception of sound; IEA:Ensembl. DR CDD; cd11582; Axin_TNKS_binding; 1. DR CDD; cd08707; RGS_Axin; 1. DR DisProt; DP00959; -. 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; IID00007; -. 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. DR Genevisible; O15169; HS. PE 1: Evidence at protein level; KW 3D-structure; ADP-ribosylation; Alternative splicing; Apoptosis; KW Cell membrane; Cytoplasm; Developmental protein; Disease variant; KW Isopeptide bond; Membrane; Nucleus; Phosphoprotein; Reference proteome; KW Tumor suppressor; Ubl conjugation; Wnt signaling pathway. FT CHAIN 1..862 FT /note="Axin-1" FT /id="PRO_0000220888" FT DOMAIN 88..211 FT /note="RGS" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00171" FT DOMAIN 780..862 FT /note="DIX" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00069" FT REGION 1..78 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 209..338 FT /note="Interaction with TP53" FT /evidence="ECO:0000250" FT REGION 215..289 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 316..344 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 348..433 FT /note="Interaction with GSK3B" FT /evidence="ECO:0000250|UniProtKB:O70239" FT REGION 353..411 FT /note="Interaction with SIAH1 and SIAH2" FT /evidence="ECO:0000269|PubMed:28546513" FT REGION 413..441 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 434..502 FT /note="Interaction with CTNNB1" FT /evidence="ECO:0000250" FT REGION 480..500 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 507..757 FT /note="Interaction with RNF111" FT /evidence="ECO:0000269|PubMed:16601693" FT REGION 531..629 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 575..789 FT /note="Interaction with PPP2CA" FT /evidence="ECO:0000269|PubMed:9920888" FT REGION 641..679 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 677..752 FT /note="Interaction with HIPK2" FT /evidence="ECO:0000250" FT MOTIF 20..29 FT /note="Tankyrase-binding motif" FT COMPBIAS 215..235 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 316..339 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 75 FT /note="Phosphoserine; by CK1" FT /evidence="ECO:0000269|PubMed:17318175" FT MOD_RES 77 FT /note="Phosphoserine; by CK1" FT /evidence="ECO:0000269|PubMed:17318175, FT ECO:0007744|PubMed:23186163" FT MOD_RES 217 FT /note="Phosphoserine; by CK1" FT /evidence="ECO:0000269|PubMed:17318175" FT MOD_RES 469 FT /note="Phosphoserine; by CK1" FT /evidence="ECO:0000269|PubMed:17318175" FT MOD_RES 481 FT /note="Phosphothreonine; by GSK3-beta" FT /evidence="ECO:0000250|UniProtKB:O35625" FT MOD_RES 486 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 493 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O35625" FT MOD_RES 511 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 581 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT CROSSLNK 857 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT /evidence="ECO:0000250" FT CROSSLNK 860 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT /evidence="ECO:0000250" FT VAR_SEQ 730..765 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_019398" FT VARIANT 106 FT /note="L -> R (in HCC; uncertain significance; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:12101426" FT /id="VAR_015589" FT VARIANT 345 FT /note="P -> L (in HCC; uncertain significance; somatic FT mutation; dbSNP:rs779951904)" FT /evidence="ECO:0000269|PubMed:12101426" FT /id="VAR_015590" FT VARIANT 425 FT /note="G -> S (in HCC; uncertain significance; somatic FT mutation; dbSNP:rs116350678)" FT /evidence="ECO:0000269|PubMed:12101426" FT /id="VAR_015591" FT VARIANT 650 FT /note="G -> S (in dbSNP:rs117208012)" FT /evidence="ECO:0000269|PubMed:12101426" FT /id="VAR_015592" FT VARIANT 841 FT /note="R -> Q (in dbSNP:rs34015754)" FT /evidence="ECO:0000269|PubMed:12101426" FT /id="VAR_015593" FT MUTAGEN 383 FT /note="V->A: Loss of interaction with SIAH1. Decreased FT SIAH1-induced proteasome-mediated ubiquitin-dependent FT degradation of AXIN1. No effect on interaction with GSK3B." FT /evidence="ECO:0000269|PubMed:28546513" FT MUTAGEN 385 FT /note="P->A: Loss of interaction with SIAH1. Decreased FT SIAH1-induced proteasome-mediated ubiquitin-dependent FT degradation of AXIN1. No effect on interaction with GSK3B." FT /evidence="ECO:0000269|PubMed:28546513" FT CONFLICT 360 FT /note="V -> A (in Ref. 1; AAC51624)" FT /evidence="ECO:0000305" FT CONFLICT 451..455 FT /note="CVDMG -> LCWTWA (in Ref. 1; AAC51624)" FT /evidence="ECO:0000305" FT CONFLICT 482 FT /note="P -> T (in Ref. 1; AAC51624)" FT /evidence="ECO:0000305" FT HELIX 81..87 FT /evidence="ECO:0007829|PDB:1DK8" FT HELIX 89..92 FT /evidence="ECO:0007829|PDB:1DK8" FT HELIX 96..107 FT /evidence="ECO:0007829|PDB:1DK8" FT TURN 108..110 FT /evidence="ECO:0007829|PDB:1DK8" FT HELIX 112..126 FT /evidence="ECO:0007829|PDB:1DK8" FT HELIX 131..133 FT /evidence="ECO:0007829|PDB:1EMU" FT HELIX 134..148 FT /evidence="ECO:0007829|PDB:1DK8" FT HELIX 155..159 FT /evidence="ECO:0007829|PDB:1DK8" FT HELIX 162..174 FT /evidence="ECO:0007829|PDB:1DK8" FT TURN 179..182 FT /evidence="ECO:0007829|PDB:1DK8" FT HELIX 183..195 FT /evidence="ECO:0007829|PDB:1DK8" FT HELIX 197..201 FT /evidence="ECO:0007829|PDB:1DK8" FT HELIX 205..208 FT /evidence="ECO:0007829|PDB:1DK8" FT TURN 209..212 FT /evidence="ECO:0007829|PDB:1DK8" FT STRAND 379..383 FT /evidence="ECO:0007829|PDB:5WZZ" FT HELIX 385..400 FT /evidence="ECO:0007829|PDB:4NM3" FT STRAND 782..786 FT /evidence="ECO:0007829|PDB:6JCK" FT STRAND 798..801 FT /evidence="ECO:0007829|PDB:6JCK" FT HELIX 807..811 FT /evidence="ECO:0007829|PDB:6JCK" FT STRAND 818..826 FT /evidence="ECO:0007829|PDB:6JCK" FT STRAND 836..839 FT /evidence="ECO:0007829|PDB:6JCK" FT STRAND 853..860 FT /evidence="ECO:0007829|PDB:6JCK" SQ SEQUENCE 862 AA; 95635 MW; 10779173F5092F3F CRC64; MNIQEQGFPL DLGASFTEDA PRPPVPGEEG ELVSTDPRPA SYSFCSGKGV GIKGETSTAT PRRSDLDLGY EPEGSASPTP PYLKWAESLH SLLDDQDGIS LFRTFLKQEG CADLLDFWFA CTGFRKLEPC DSNEEKRLKL ARAIYRKYIL DNNGIVSRQT KPATKSFIKG CIMKQLIDPA MFDQAQTEIQ ATMEENTYPS FLKSDIYLEY TRTGSESPKV CSDQSSGSGT GKGISGYLPT LNEDEEWKCD QDMDEDDGRD AAPPGRLPQK LLLETAAPRV SSSRRYSEGR EFRYGSWREP VNPYYVNAGY ALAPATSAND SEQQSLSSDA DTLSLTDSSV DGIPPYRIRK QHRREMQESV QVNGRVPLPH IPRTYRVPKE VRVEPQKFAE ELIHRLEAVQ RTREAEEKLE ERLKRVRMEE EGEDGDPSSG PPGPCHKLPP APAWHHFPPR CVDMGCAGLR DAHEENPESI LDEHVQRVLR TPGRQSPGPG HRSPDSGHVA KMPVALGGAA SGHGKHVPKS GAKLDAAGLH HHRHVHHHVH HSTARPKEQV EAEATRRAQS SFAWGLEPHS HGARSRGYSE SVGAAPNASD GLAHSGKVGV ACKRNAKKAE SGKSASTEVP GASEDAEKNQ KIMQWIIEGE KEISRHRRTG HGSSGTRKPQ PHENSRPLSL EHPWAGPQLR TSVQPSHLFI QDPTMPPHPA PNPLTQLEEA RRRLEEEEKR ASRAPSKQRY VQEVMRRGRA CVRPACAPVL HVVPAVSDME LSETETRSQR KVGGGSAQPC DSIVVAYYFC GEPIPYRTLV RGRAVTLGQF KELLTKKGSY RYYFKKVSDE FDCGVVFEEV REDEAVLPVF EEKIIGKVEK VD //