ID   AXIN2_DANRE             Reviewed;         812 AA.
AC   P57095; Q335M5;
DT   01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2000, sequence version 1.
DT   03-AUG-2022, entry version 148.
DE   RecName: Full=Axin-2;
DE   AltName: Full=Axis inhibition protein 2;
GN   Name=axin2;
OS   Danio rerio (Zebrafish) (Brachydanio rerio).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC   Danionidae; Danioninae; Danio.
OX   NCBI_TaxID=7955;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=10704853; DOI=10.1016/s0925-4773(99)00319-6;
RA   Shimizu T., Yamanaka Y., Ryu S.-L., Hashimoto H., Yabe T., Hirata T.,
RA   Bae Y.-K., Hibi M., Hirano T.;
RT   "Cooperative roles of Bozozok/Dharma and Nodal-related proteins in the
RT   formation of the dorsal organizer in zebrafish.";
RL   Mech. Dev. 91:293-303(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Pogoda H.-M., Meyer D.;
RT   "Cloning of zebrafish axin2.";
RL   Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Tsai J.N., Chang W.C.;
RT   "Functional Analysis of Zebrafish axin2 during embryogenesis.";
RL   Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   FUNCTION, AND INTERACTION WITH HWA.
RX   PubMed=30467143; DOI=10.1126/science.aat1045;
RA   Yan L., Chen J., Zhu X., Sun J., Wu X., Shen W., Zhang W., Tao Q., Meng A.;
RT   "Maternal Huluwa dictates the embryonic body axis through beta-catenin in
RT   vertebrates.";
RL   Science 362:0-0(2018).
CC   -!- FUNCTION: Component of the beta-catenin destruction complex required
CC       for regulating ctnnb1 levels through phosphorylation and
CC       ubiquitination, and modulating Wnt-signaling (By similarity). Controls
CC       dorsoventral patterning by down-regulating ctnnb1 to inhibit the Wnt
CC       signaling pathway and ventralize embryos (PubMed:30467143).
CC       {ECO:0000250|UniProtKB:O15169, ECO:0000269|PubMed:30467143}.
CC   -!- SUBUNIT: Interacts with hwa; leading to promote the tankyrase-mediated
CC       degradation of axin1. {ECO:0000269|PubMed:30467143}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9Y2T1}.
CC   -!- PTM: ADP-ribosylated by tankyrase tnks and tnks2. Poly-ADP-ribosylated
CC       protein is recognized by rnf146, followed by ubiquitination and
CC       subsequent activation of the Wnt signaling pathway.
CC       {ECO:0000305|PubMed:30467143}.
CC   -!- PTM: Ubiquitinated by rnf146 when poly-ADP-ribosylated, leading to its
CC       degradation and subsequent activation of the Wnt signaling pathway.
CC       {ECO:0000305|PubMed:30467143}.
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DR   EMBL; AB032263; BAA92440.1; -; mRNA.
DR   EMBL; AF387812; AAK70877.1; -; mRNA.
DR   EMBL; AJ854187; CAH69531.1; -; mRNA.
DR   RefSeq; NP_571636.1; NM_131561.1.
DR   AlphaFoldDB; P57095; -.
DR   SMR; P57095; -.
DR   STRING; 7955.ENSDARP00000003845; -.
DR   PaxDb; P57095; -.
DR   Ensembl; ENSDART00000162413; ENSDARP00000132477; ENSDARG00000100149.
DR   Ensembl; ENSDART00000176127; ENSDARP00000143690; ENSDARG00000100149.
DR   GeneID; 58080; -.
DR   KEGG; dre:58080; -.
DR   CTD; 8313; -.
DR   ZFIN; ZDB-GENE-000403-2; axin2.
DR   eggNOG; KOG3589; Eukaryota.
DR   GeneTree; ENSGT00940000157338; -.
DR   HOGENOM; CLU_016422_0_0_1; -.
DR   InParanoid; P57095; -.
DR   OMA; FACKGFR; -.
DR   OrthoDB; 1481971at2759; -.
DR   PhylomeDB; P57095; -.
DR   TreeFam; TF315454; -.
DR   Reactome; R-DRE-201681; TCF dependent signaling in response to WNT.
DR   Reactome; R-DRE-4641257; Degradation of AXIN.
DR   Reactome; R-DRE-5689880; Ub-specific processing proteases.
DR   PRO; PR:P57095; -.
DR   Proteomes; UP000000437; Genome assembly.
DR   Proteomes; UP000814640; Chromosome 3.
DR   Bgee; ENSDARG00000100149; Expressed in blastodisc and 55 other tissues.
DR   ExpressionAtlas; P57095; baseline and differential.
DR   GO; GO:0030877; C:beta-catenin destruction complex; IBA:GO_Central.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0008013; F:beta-catenin binding; IBA:GO_Central.
DR   GO; GO:0070411; F:I-SMAD binding; IBA:GO_Central.
DR   GO; GO:0060090; F:molecular adaptor activity; IBA:GO_Central.
DR   GO; GO:0019901; F:protein kinase binding; IBA:GO_Central.
DR   GO; GO:0031625; F:ubiquitin protein ligase binding; IBA:GO_Central.
DR   GO; GO:0048468; P:cell development; IBA:GO_Central.
DR   GO; GO:0009950; P:dorsal/ventral axis specification; IGI:ZFIN.
DR   GO; GO:0009953; P:dorsal/ventral pattern formation; IDA:ZFIN.
DR   GO; GO:0007507; P:heart development; IMP:ZFIN.
DR   GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IBA:GO_Central.
DR   GO; GO:2000054; P:negative regulation of Wnt signaling pathway involved in dorsal/ventral axis specification; IDA:UniProtKB.
DR   GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR   GO; GO:0045860; P:positive regulation of protein kinase activity; IBA:GO_Central.
DR   GO; GO:0070602; P:regulation of centromeric sister chromatid cohesion; IBA:GO_Central.
DR   GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR   CDD; cd11582; Axin_TNKS_binding; 1.
DR   Gene3D; 1.10.167.10; -; 1.
DR   Gene3D; 1.10.196.10; -; 1.
DR   Gene3D; 2.40.240.130; -; 1.
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; PTHR46102; 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   ADP-ribosylation; Cytoplasm; Developmental protein; Phosphoprotein;
KW   Reference proteome; Ubl conjugation; Wnt signaling pathway.
FT   CHAIN           1..812
FT                   /note="Axin-2"
FT                   /id="PRO_0000220898"
FT   DOMAIN          84..203
FT                   /note="RGS"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00171"
FT   DOMAIN          730..812
FT                   /note="DIX"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00069"
FT   REGION          1..43
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          275..326
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          329..415
FT                   /note="Interaction with GSK3B"
FT                   /evidence="ECO:0000250"
FT   REGION          388..430
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          415..467
FT                   /note="Interaction with beta-catenin"
FT                   /evidence="ECO:0000250"
FT   REGION          446..484
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          609..726
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        281..320
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        388..403
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        622..637
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        672..695
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   812 AA;  91497 MW;  46E5ADA6DE2240CC CRC64;
     MNRTLTDPMV SSFREDDPRP PVPGEEGETT CHHPSKLAMM RPKDPVKTIM ADLRCSTARR
     DEDGLGEPEG SASPDSPLAR WTKSLHFLLG DQDGAQLFRA YLEREKCVDT LDFWFACNGF
     RQMDLKDTKT HRVAKAIYKR YIENNSIVAK QLKPATKTFI RDNIKRQQID SAMFDQAQME
     IQTAMEENAY QMFLTSDIYL EYVRTGCENP SHVNPNGLGG LKLVCGYLPT LNEEEEWSCN
     DFKAKALATV VGLSAKTLRS PPLRAVEALE KGYRSYRRSD PGNPNRFTSG YSFAPATSAN
     DSEVSSDALT DDSMSMTDSS VDAIPPYKLG SKKQLQREMQ RNMRMNGQVS LPPFPRTRRP
     PKEMTPVEPA AFAAQLIARL ERLKREQETM SSLEERLQQI QEEEERDESE MSSSSASHSL
     PLLPPGTCEE DPQAILDEHL SRVLKTPGCQ SPGLLRHSPR SRSPEQRPLP RGGLSTRSQS
     SSMNGYVPAK TFISRQSTKH IHHHYIHHHA GPKSKEQIEV EATQRVQCLC HGTSECCTAP
     YIRSRSLGRD QCASPAEVAL GHSSTLSKRL CKSGEEVNME GLENSLLQLP ADSTDRSQNV
     WQWILESDRQ TKHKPHSTQN VKKSHSLEPT RTHTWGGGGS SGHLRAHQPA HPFVQDPAMP
     PLPPPNTLAQ LEEARRRLEE VSKPSKQRHS TSSLQRDKSH PVPVQNGSSA FPMDERKDPK
     KMSGCHSSLG SETVVTYFFC GEEIPYRRMM KTHSLTLGHF KEQLRKKGNY RYFFKRASDE
     FECGAVFEEV WDDCTVLPMY EGKILGKVDR MD