AXIN1_HUMAN
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 03-AUG-2022, entry version 231.
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 VARIANTS HCC ARG-106; LEU-345; SER-425 AND SER-650, AND VARIANT
RP HEPATOBLASTOMA 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="http://atlasgeneticsoncology.org/Genes/AXIN1ID379ch16p13.html";
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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 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 AlphaFoldDB; O15169; -.
DR SMR; O15169; -.
DR BioGRID; 113909; 142.
DR ComplexPortal; CPX-107; Beta-catenin destruction core complex, variant 5.
DR ComplexPortal; CPX-109; Beta-catenin destruction core complex, variant 1.
DR ComplexPortal; CPX-442; Beta-catenin destruction core complex, variant 6.
DR ComplexPortal; CPX-99; Beta-catenin destruction core complex, variant 2.
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; O15169; -.
DR PeptideAtlas; O15169; -.
DR PRIDE; O15169; -.
DR ProteomicsDB; 48492; -. [O15169-1]
DR ProteomicsDB; 48493; -. [O15169-2]
DR Antibodypedia; 22635; 571 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 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; 1481971at2759; -.
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; 31 hits in 1084 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 100 other tissues.
DR ExpressionAtlas; O15169; baseline and differential.
DR Genevisible; O15169; HS.
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: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:0008022; F:protein C-terminus 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:0030159; F:signaling receptor complex adaptor activity; IMP:BHF-UCL.
DR GO; GO:0046332; F:SMAD binding; IPI: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:0071514; P:genomic imprinting; 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:0051248; P:negative regulation of protein metabolic process; IEA:Ensembl.
DR GO; GO:0034244; P:negative regulation of transcription elongation from RNA polymerase II promoter; 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:0043507; P:positive regulation of JUN kinase activity; IEA:Ensembl.
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:0045860; P:positive regulation of protein kinase activity; IBA:GO_Central.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:BHF-UCL.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; NAS:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; 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:0051443; P:positive regulation of ubiquitin-protein transferase activity; IMP: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; IC: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 DisProt; DP00959; -.
DR Gene3D; 1.10.167.10; -; 1.
DR Gene3D; 1.10.196.10; -; 2.
DR Gene3D; 2.40.240.130; -; 1.
DR IDEAL; IID00007; -.
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; 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)"
FT /evidence="ECO:0000269|PubMed:12101426"
FT /id="VAR_015589"
FT VARIANT 345
FT /note="P -> L (in HCC; dbSNP:rs779951904)"
FT /evidence="ECO:0000269|PubMed:12101426"
FT /id="VAR_015590"
FT VARIANT 425
FT /note="G -> S (in HCC; dbSNP:rs116350678)"
FT /evidence="ECO:0000269|PubMed:12101426"
FT /id="VAR_015591"
FT VARIANT 650
FT /note="G -> S (in HCC; also found in hepatoblastoma;
FT dbSNP:rs117208012)"
FT /evidence="ECO:0000269|PubMed:12101426"
FT /id="VAR_015592"
FT VARIANT 841
FT /note="R -> Q (in hepatoblastoma; 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
