ID   AXIN1_DANRE             Reviewed;         835 AA.
AC   P57094; Q499B7;
DT   01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT   22-JUL-2008, sequence version 2.
DT   27-MAR-2024, entry version 156.
DE   RecName: Full=Axin-1;
DE   AltName: Full=Axis inhibition protein 1;
GN   Name=axin1; Synonyms=axin;
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 [LARGE SCALE MRNA].
RC   STRAIN=AB;
RG   NIH - Zebrafish Gene Collection (ZGC) project;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   INTERACTION WITH DIXDC1.
RX   PubMed=12526749; DOI=10.1016/s0960-9822(02)01398-2;
RA   Shiomi K., Uchida H., Keino-Masu K., Masu M.;
RT   "Ccd1, a novel protein with a DIX domain, is a positive regulator in the
RT   Wnt signaling during zebrafish neural patterning.";
RL   Curr. Biol. 13:73-77(2003).
RN   [4]
RP   FUNCTION.
RX   PubMed=17681137; DOI=10.1016/j.devcel.2007.07.006;
RA   Rui Y., Xu Z., Xiong B., Cao Y., Lin S., Zhang M., Chan S.-C., Luo W.,
RA   Han Y., Lu Z., Ye Z., Zhou H.-M., Han J., Meng A., Lin S.-C.;
RT   "A beta-catenin-independent dorsalization pathway activated by Axin/JNK
RT   signaling and antagonized by aida.";
RL   Dev. Cell 13:268-282(2007).
RN   [5]
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 (PubMed:17681137).
CC       Controls dorsoventral patterning via two opposing effects: down-
CC       regulates ctnnb1 to inhibit the Wnt signaling pathway and ventralize
CC       embryos, but also dorsalizes embryos by activating a Wnt-independent
CC       JNK signaling pathway (PubMed:17681137, PubMed:30467143).
CC       {ECO:0000269|PubMed:17681137, ECO:0000269|PubMed:30467143}.
CC   -!- SUBUNIT: Homodimer (By similarity). Interacts with dixdc1
CC       (PubMed:12526749). Interacts with hwa; leading to promote the
CC       tankyrase-mediated degradation of axin1 (PubMed:30467143).
CC       {ECO:0000250|UniProtKB:O35625, ECO:0000269|PubMed:12526749,
CC       ECO:0000269|PubMed:30467143}.
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   -!- DOMAIN: The DIX domain mediates interaction with dixdc1.
CC       {ECO:0000269|PubMed:12526749}.
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: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; AB032262; BAA92439.1; -; mRNA.
DR   EMBL; BC099991; AAH99991.1; -; mRNA.
DR   RefSeq; NP_571578.2; NM_131503.2.
DR   AlphaFoldDB; P57094; -.
DR   SMR; P57094; -.
DR   BioGRID; 78941; 3.
DR   ELM; P57094; -.
DR   STRING; 7955.ENSDARP00000135613; -.
DR   PaxDb; 7955-ENSDARP00000036978; -.
DR   GeneID; 57931; -.
DR   KEGG; dre:57931; -.
DR   AGR; ZFIN:ZDB-GENE-000403-1; -.
DR   CTD; 8312; -.
DR   ZFIN; ZDB-GENE-000403-1; axin1.
DR   eggNOG; KOG3589; Eukaryota.
DR   InParanoid; P57094; -.
DR   OrthoDB; 4256282at2759; -.
DR   PhylomeDB; P57094; -.
DR   Reactome; R-DRE-195253; Degradation of beta-catenin by the destruction complex.
DR   Reactome; R-DRE-196299; Beta-catenin phosphorylation cascade.
DR   Reactome; R-DRE-201681; TCF dependent signaling in response to WNT.
DR   Reactome; R-DRE-4641257; Degradation of AXIN.
DR   Reactome; R-DRE-4641262; Disassembly of the destruction complex and recruitment of AXIN to the membrane.
DR   Reactome; R-DRE-5689880; Ub-specific processing proteases.
DR   PRO; PR:P57094; -.
DR   Proteomes; UP000000437; Chromosome 3.
DR   GO; GO:0030877; C:beta-catenin destruction complex; IDA:ZFIN.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
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:0042802; F:identical protein binding; IBA:GO_Central.
DR   GO; GO:0060090; F:molecular adaptor activity; IBA:GO_Central.
DR   GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
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:0007368; P:determination of left/right symmetry; IMP:ZFIN.
DR   GO; GO:0009950; P:dorsal/ventral axis specification; IDA:MGI.
DR   GO; GO:0009953; P:dorsal/ventral pattern formation; IDA:MGI.
DR   GO; GO:0048048; P:embryonic eye morphogenesis; IMP:ZFIN.
DR   GO; GO:0001654; P:eye development; IMP:ZFIN.
DR   GO; GO:0031101; P:fin regeneration; IMP:ZFIN.
DR   GO; GO:0021797; P:forebrain anterior/posterior pattern specification; IMP:ZFIN.
DR   GO; GO:0030900; P:forebrain development; IMP:ZFIN.
DR   GO; GO:0021877; P:forebrain neuron fate commitment; IMP:ZFIN.
DR   GO; GO:0001743; P:lens placode formation; IMP:ZFIN.
DR   GO; GO:0055001; P:muscle cell development; IGI:ZFIN.
DR   GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IMP:ZFIN.
DR   GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IMP:ZFIN.
DR   GO; GO:2000054; P:negative regulation of Wnt signaling pathway involved in dorsal/ventral axis specification; IDA:UniProtKB.
DR   GO; GO:0021999; P:neural plate anterior/posterior regionalization; IMP:ZFIN.
DR   GO; GO:0060896; P:neural plate pattern specification; IMP:ZFIN.
DR   GO; GO:0030910; P:olfactory placode formation; IMP:ZFIN.
DR   GO; GO:0046330; P:positive regulation of JNK cascade; IMP:UniProtKB.
DR   GO; GO:0043507; P:positive regulation of JUN kinase activity; IDA:MGI.
DR   GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR   GO; GO:0046328; P:regulation of JNK cascade; IDA:ZFIN.
DR   GO; GO:0001756; P:somitogenesis; IGI:ZFIN.
DR   GO; GO:0090244; P:Wnt signaling pathway involved in somitogenesis; IGI:ZFIN.
DR   CDD; cd11582; Axin_TNKS_binding; 1.
DR   CDD; cd08707; RGS_Axin; 1.
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   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   ADP-ribosylation; Cell membrane; Cytoplasm; Developmental protein;
KW   Membrane; Nucleus; Phosphoprotein; Reference proteome; Ubl conjugation;
KW   Wnt signaling pathway.
FT   CHAIN           1..835
FT                   /note="Axin-1"
FT                   /id="PRO_0000220893"
FT   DOMAIN          92..214
FT                   /note="RGS"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00171"
FT   DOMAIN          753..835
FT                   /note="DIX"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00069"
FT   REGION          16..60
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          318..349
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          351..436
FT                   /note="Interaction with GSK3B"
FT                   /evidence="ECO:0000250"
FT   REGION          437..512
FT                   /note="Interaction with beta-catenin"
FT                   /evidence="ECO:0000250"
FT   REGION          485..530
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          602..627
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        40..60
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        318..342
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        612..627
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CONFLICT        176
FT                   /note="T -> M (in Ref. 1; BAA92439)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        275
FT                   /note="P -> L (in Ref. 1; BAA92439)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        658
FT                   /note="G -> S (in Ref. 1; BAA92439)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        763
FT                   /note="R -> C (in Ref. 1; BAA92439)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   835 AA;  94329 MW;  7ABEE52E1DE2FAB6 CRC64;
     MSMSVNEKGI CYLPDLGSSF TEDAPRPPVP GEEGDLVSSD GRQYNHSFYS SKSDSLKNEA
     SIATPRRPDL DLGYEPEGSA SPTPPYLKWA ESLHSLLDDQ DGIHLFRTFL KQEECADMLD
     FWFACSGFRK QEANDGNEKM LKLAKAIYKK YILDNNGIVS RQIKPATKSF IKDCVTKLHI
     DPAMFDQAQT EIQTMMEENT YPLFLKSDIY LEYTRTGGES PKLFSDQSSV SGNGKVLPGY
     LPTVIEDVEW RCDQEEEQIA ESDPTPSNRL TQKLPLETVP QRVANSKRYQ DNREYRHASW
     REPVNPYYVN SGYALAPATS ANDSEQQSMS SDADTLSLTD SSVDGVPPYR YRKPHRREIH
     ESAKVNGRVP LPHIPRTNRI PKDIHVEPEK FAAELISRLE GVLREREAQE KLEERLKRVR
     LEEEGDDADI STGPSLANHR VPPAVHVQHY GGRYSEMSYN GLQLRDAHEE NPESILDEHV
     QRVMKTPGCQ SPGTGRHSPK SRSPDGLPAG KIPGLMMPLS GGQGKHQARQ GPKGEAAHLH
     HHKHIHHTHY AAAGKPKEQA EAEAARMHGG FAWNTEQHHY GPKSRNYADG MSVGPNTMDP
     MGYSSKGSTL SKRPVRKGED GRNFEMREPL PADDMERNQK ILQWMMEGEK EAGRYKRGPY
     GSISGPKKAQ GHEPARPSSV ERLGAVHPWV TAQLRNNVQP SHPFIQDPTM PPNPAPNPLT
     QLEEARRRLE EERRKSGTLQ AKQRHKNMKK QPCENITVAY YFRGEPIPYR TSVKGRIVTL
     GQFKELLTKK GSYKYYFKKV SYEFDCGVVF EEVREDDAIL PIFEEKIIGK VEKVD
//