AXIN1_DANRE
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 03-AUG-2022, entry version 149.
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}.
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; 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.ENSDARP00000036978; -.
DR PaxDb; P57094; -.
DR GeneID; 57931; -.
DR KEGG; dre:57931; -.
DR CTD; 8312; -.
DR ZFIN; ZDB-GENE-000403-1; axin1.
DR eggNOG; KOG3589; Eukaryota.
DR InParanoid; P57094; -.
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; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0030877; C:beta-catenin destruction complex; IDA:ZFIN.
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:ZFIN.
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: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:0045860; P:positive regulation of protein kinase activity; IBA:GO_Central.
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 Gene3D; 1.10.167.10; -; 1.
DR Gene3D; 1.10.196.10; -; 2.
DR Gene3D; 2.40.240.130; -; 1.
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 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
