ID   AXIN1_XENLA             Reviewed;         842 AA.
AC   Q9YGY0;
DT   01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1999, sequence version 1.
DT   27-MAR-2024, entry version 142.
DE   RecName: Full=Axin-1;
DE   AltName: Full=Axis inhibition protein 1;
DE            Short=xAxin;
GN   Name=axin1; Synonyms=axin, axn;
OS   Xenopus laevis (African clawed frog).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC   Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX   NCBI_TaxID=8355;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND DEVELOPMENTAL STAGE.
RX   PubMed=10072781; DOI=10.1016/s0925-4773(98)00203-2;
RA   Hedgepeth C.M., Deardorff M.A., Klein P.S.;
RT   "Xenopus axin interacts with glycogen synthase kinase-3 beta and is
RT   expressed in the anterior midbrain.";
RL   Mech. Dev. 80:147-151(1999).
RN   [2]
RP   X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 435-504 IN COMPLEX WITH HUMAN
RP   BETA-CATENIN.
RX   PubMed=14600025; DOI=10.1101/gad.1142603;
RA   Xing Y., Clements W.K., Kimelman D., Xu W.;
RT   "Crystal structure of a beta-catenin/axin complex suggests a mechanism for
RT   the beta-catenin destruction complex.";
RL   Genes Dev. 17:2753-2764(2003).
CC   -!- FUNCTION: Component of the beta-catenin destruction complex required
CC       for regulating ctnnb1 levels through phosphorylation and
CC       ubiquitination, and modulating Wnt-signaling. Controls dorsoventral
CC       patterning via two opposing effects; down-regulates ctnnb1 to inhibit
CC       the Wnt signaling pathway and ventralize embryos, but also dorsalizes
CC       embryos by activating a Wnt-independent JNK signaling pathway.
CC       {ECO:0000250|UniProtKB:O15169}.
CC   -!- SUBUNIT: Homodimer (By similarity). Interacts with hwa; leading to
CC       promote the tankyrase-mediated degradation of axin1 (By similarity).
CC       {ECO:0000250|UniProtKB:O35625, ECO:0000250|UniProtKB:P57094}.
CC   -!- INTERACTION:
CC       Q9YGY0; P70039: apc; NbExp=2; IntAct=EBI-1037449, EBI-8069633;
CC       Q9YGY0; A0A0H5BJW1: wdr26.L; NbExp=3; IntAct=EBI-1037449, EBI-11786127;
CC       Q9YGY0; P35222: CTNNB1; Xeno; NbExp=2; IntAct=EBI-1037449, EBI-491549;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O15169}. Nucleus
CC       {ECO:0000250|UniProtKB:O15169}. Membrane
CC       {ECO:0000250|UniProtKB:O35625}. Cell membrane
CC       {ECO:0000250|UniProtKB:O35625}.
CC   -!- DEVELOPMENTAL STAGE: Weakly and ubiquitously expressed throughout early
CC       development, and highly expressed in the anterior mesencephalon
CC       adjacent to the forebrain-midbrain boundary.
CC       {ECO:0000269|PubMed:10072781}.
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:0000250|UniProtKB:O15169}.
CC   -!- PTM: Ubiquitinated by rnf146 when poly-ADP-ribosylated, leading to its
CC       degradation and subsequent activation of the Wnt signaling pathway.
CC       {ECO:0000250|UniProtKB:O15169}.
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DR   EMBL; AF097313; AAC71036.1; -; mRNA.
DR   RefSeq; NP_001081874.1; NM_001088405.1.
DR   PDB; 1QZ7; X-ray; 2.20 A; B=435-504.
DR   PDBsum; 1QZ7; -.
DR   AlphaFoldDB; Q9YGY0; -.
DR   SMR; Q9YGY0; -.
DR   BioGRID; 99432; 1.
DR   DIP; DIP-36387N; -.
DR   ELM; Q9YGY0; -.
DR   IntAct; Q9YGY0; 3.
DR   MINT; Q9YGY0; -.
DR   GeneID; 398097; -.
DR   KEGG; xla:398097; -.
DR   AGR; Xenbase:XB-GENE-17339457; -.
DR   CTD; 398097; -.
DR   Xenbase; XB-GENE-17339457; axin1.L.
DR   OrthoDB; 4256282at2759; -.
DR   EvolutionaryTrace; Q9YGY0; -.
DR   PRO; PR:Q9YGY0; -.
DR   Proteomes; UP000186698; Chromosome 9_10L.
DR   GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR   GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IEA:InterPro.
DR   GO; GO:2000054; P:negative regulation of Wnt signaling pathway involved in dorsal/ventral axis specification; ISS:UniProtKB.
DR   GO; GO:0046330; P:positive regulation of JNK cascade; ISS:UniProtKB.
DR   GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR   CDD; cd11582; Axin_TNKS_binding; 1.
DR   CDD; cd08707; RGS_Axin; 1.
DR   DisProt; DP00954; -.
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; IID50017; -.
DR   InterPro; IPR043581; Axin-like.
DR   InterPro; IPR014936; Axin_b-cat-bd.
DR   InterPro; IPR032101; Axin_TNKS-bd.
DR   InterPro; IPR001158; DIX.
DR   InterPro; IPR038207; DIX_dom_sf.
DR   InterPro; IPR016137; RGS.
DR   InterPro; IPR036305; RGS_sf.
DR   InterPro; IPR024066; RGS_subdom1/3.
DR   InterPro; IPR044926; RGS_subdomain_2.
DR   InterPro; IPR029071; Ubiquitin-like_domsf.
DR   PANTHER; PTHR46102; AXIN; 1.
DR   PANTHER; PTHR46102:SF3; AXIN-1; 1.
DR   Pfam; PF16646; AXIN1_TNKS_BD; 1.
DR   Pfam; PF08833; Axin_b-cat_bind; 1.
DR   Pfam; PF00778; DIX; 1.
DR   Pfam; PF00615; RGS; 1.
DR   PRINTS; PR01301; RGSPROTEIN.
DR   SMART; SM00021; DAX; 1.
DR   SMART; SM00315; RGS; 1.
DR   SUPFAM; SSF48097; Regulator of G-protein signaling, RGS; 1.
DR   SUPFAM; SSF54236; Ubiquitin-like; 1.
DR   PROSITE; PS50841; DIX; 1.
DR   PROSITE; PS50132; RGS; 1.
PE   1: Evidence at protein level;
KW   3D-structure; ADP-ribosylation; Cell membrane; Cytoplasm;
KW   Developmental protein; Membrane; Nucleus; Phosphoprotein;
KW   Reference proteome; Ubl conjugation; Wnt signaling pathway.
FT   CHAIN           1..842
FT                   /note="Axin-1"
FT                   /id="PRO_0000220892"
FT   DOMAIN          88..211
FT                   /note="RGS"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00171"
FT   DOMAIN          760..842
FT                   /note="DIX"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00069"
FT   REGION          1..75
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          218..242
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          277..297
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"
FT   REGION          414..451
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          434..508
FT                   /note="Interaction with beta-catenin"
FT   REGION          482..532
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          543..562
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          615..637
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          656..675
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          729..754
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        36..61
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        218..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   COMPBIAS        510..531
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   HELIX           471..480
FT                   /evidence="ECO:0007829|PDB:1QZ7"
SQ   SEQUENCE   842 AA;  94460 MW;  BDA152734C97191E CRC64;
     MSVKGKGFPL DLGGSFTEDA PRPPVPGEEG ELITTDQRPF SHTYYSLKND GIKNETSTAT
     PRRPDLDLGY EPEGSASPTP PYLKWAESLH SLLDDQDGIH LFRTFLQQEN CADLLDFWFA
     CSGFRKLEPN DSKVEKRLKL AKAIYKKYVL DSNGIVSRQI KPATKSFIKD CVLRQQIDPA
     MFDQAQMEIQ SMMEDNTYPV FLKSDIYLEY TTIGGESPKN YSDQSSGSGT GKGPSGYLPT
     LNEDEEWRCD QGGEHERERE CIPSSLFSQK LALDSSSHCA GSNRRLSDGR EFRPGTWREP
     VNPYYVNTGY AGAPVTSAND SEQQSMSSDA DTMSLTDSSV DGIPPYRLRK HYRREMQESA
     NANGRGPLPH IPRTYHMPKD IHVDPEKFAA ELISRLEGVL RDREAEQKLE ERLKRVRAEE
     EGDDGDVSSG PSVISHKLPS GPPMHHFNSR YSETGCVGMQ IRDAHEENPE SILDEHVQRV
     MKTPGCQSPG TGRHSPKSRS PDGHLSKTLP GSLGTMQTGH GKHSSKSTAK VDSGNLHHHK
     HVYHHVHHHG GVKPKEQIDG ESTQRVQTNF PWNVESHNYA TKSRNYAESM GMAPNPMDSL
     AYSGKVSMLS KRNAKKADLG KSESASHEMP VVPEDSERHQ KILQWIMEGE KEIIRHKKSN
     HSSSSAKKQP PTELARPLSI ERPGAVHPWV SAQLRNVVQP SHPFIQDPTM PPNPAPNPLT
     QLVSKPGARL EEEEKKAAKM PQKQRLKPQK KNVSAPSQPC DNIVVAYYFC GEPIPYRTMV
     KGRVVTLGQF KELLTKKGNY RYYFKKVSDE FDCGVVFEEV REDDMILPIY EEKIIGQVEK
     ID
//