AXIN2_MOUSE
ID AXIN2_MOUSE Reviewed; 840 AA.
AC O88566; Q6PFZ9; Q9QXJ6;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Axin-2;
DE AltName: Full=Axin-like protein;
DE Short=Axil;
DE AltName: Full=Axis inhibition protein 2;
DE AltName: Full=Conductin;
GN Name=Axin2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9554852; DOI=10.1126/science.280.5363.596;
RA Behrens J., Jerchow B.-A., Wuertele M., Grimm J., Asbrand C., Wirtz R.,
RA Kuehl M., Wedlich D., Birchmeier W.;
RT "Functional interaction of an axin homolog, conductin, with beta-catenin,
RT APC, and GSK3beta.";
RL Science 280:596-599(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Zhang T., Fagotto F., Hsu W., Zeng L., Gilbert D., Copeland N.G.,
RA Jenkins N.A., Warburton D., Costantini F.;
RT "Properties of mouse Axin2 and human AXIN2: chromosomal location,
RT expression pattern, interaction with Axin and effects on embryonic axis
RT formation.";
RL Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 [6]
RP INTERACTION WITH ANKRD6.
RX PubMed=12183362; DOI=10.1101/gad.230402;
RA Schwarz-Romond T., Asbrand C., Bakkers J., Kuehl M., Schaeffer H.J.,
RA Huelsken J., Behrens J., Hammerschmidt M., Birchmeier W.;
RT "The ankyrin repeat protein diversin recruits casein kinase Iepsilon to the
RT beta-catenin degradation complex and acts in both canonical Wnt and Wnt/JNK
RT signaling.";
RL Genes Dev. 16:2073-2084(2002).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=23562159; DOI=10.1016/j.immuni.2013.01.010;
RG Immunological Genome Project Consortium;
RA Malhotra N., Narayan K., Cho O.H., Sylvia K.E., Yin C., Melichar H.,
RA Rashighi M., Lefebvre V., Harris J.E., Berg L.J., Kang J.;
RT "A network of high-mobility group box transcription factors programs innate
RT interleukin-17 production.";
RL Immunity 38:681-693(2013).
CC -!- FUNCTION: Inhibitor of the Wnt signaling pathway. Down-regulates beta-
CC catenin. Probably facilitate the phosphorylation of beta-catenin and
CC APC by GSK3B. {ECO:0000250|UniProtKB:O15169}.
CC -!- SUBUNIT: Interacts with glycogen synthase kinase-3 beta (GSK3B) and
CC beta-catenin. The interaction between axin and beta-catenin occurs via
CC the armadillo repeats contained in beta-catenin. Interacts with SMAD7
CC and RNF111 (By similarity). Interacts with ANKRD6 (PubMed:12183362).
CC Interacts with SIAH1 (By similarity). Interacts with SIAH2 (By
CC similarity). {ECO:0000250|UniProtKB:Q9Y2T1,
CC ECO:0000269|PubMed:12183362}.
CC -!- INTERACTION:
CC O88566; Q8N944: AMER3; Xeno; NbExp=2; IntAct=EBI-7690990, EBI-8869590;
CC O88566; Q12834: CDC20; Xeno; NbExp=2; IntAct=EBI-7690990, EBI-367462;
CC O88566; Q9BV73: CEP250; Xeno; NbExp=3; IntAct=EBI-7690990, EBI-1053100;
CC O88566; Q15583: TGIF1; Xeno; NbExp=3; IntAct=EBI-7690990, EBI-714215;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9Y2T1}.
CC -!- TISSUE SPECIFICITY: Expressed in Tcf7-positive innate-like T-cells (at
CC protein level). {ECO:0000269|PubMed:23562159}.
CC -!- DOMAIN: The tankyrase-binding motif (also named TBD) is required for
CC interaction with tankyrase TNKS and TNKS2. {ECO:0000250}.
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:0000250|UniProtKB:Q9Y2T1}.
CC -!- PTM: Ubiquitinated by RNF146 when poly-ADP-ribosylated, leading to its
CC degradation and subsequent activation of the Wnt signaling pathway.
CC Deubiquitinated by USP34, deubiquitinated downstream of beta-catenin
CC stabilization step: deubiquitination is important Wnt signaling to
CC positively regulate beta-catenin (CTNBB1)-mediated transcription.
CC {ECO:0000250|UniProtKB:Q9Y2T1}.
CC -!- PTM: Probably phosphorylated by GSK3B and dephosphorylated by PP2A.
CC {ECO:0000250|UniProtKB:O15169}.
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DR EMBL; AF073788; AAC26047.1; -; mRNA.
DR EMBL; AF205889; AAF22800.1; -; mRNA.
DR EMBL; AL662893; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466558; EDL34346.1; -; Genomic_DNA.
DR EMBL; BC057338; AAH57338.1; -; mRNA.
DR CCDS; CCDS25575.1; -.
DR RefSeq; NP_056547.3; NM_015732.4.
DR RefSeq; XP_006532120.1; XM_006532057.3.
DR RefSeq; XP_006532121.1; XM_006532058.1.
DR RefSeq; XP_006532122.1; XM_006532059.3.
DR RefSeq; XP_006532123.1; XM_006532060.1.
DR AlphaFoldDB; O88566; -.
DR SMR; O88566; -.
DR BioGRID; 198288; 6.
DR ComplexPortal; CPX-449; Beta-catenin destruction core complex, variant 3.
DR ComplexPortal; CPX-452; Beta-catenin destruction core complex, variant 4.
DR ComplexPortal; CPX-457; Beta-catenin destruction core complex, variant 7.
DR ComplexPortal; CPX-458; Beta-catenin destruction core complex, variant 8.
DR CORUM; O88566; -.
DR DIP; DIP-42640N; -.
DR IntAct; O88566; 10.
DR MINT; O88566; -.
DR STRING; 10090.ENSMUSP00000051331; -.
DR ChEMBL; CHEMBL1255128; -.
DR iPTMnet; O88566; -.
DR PhosphoSitePlus; O88566; -.
DR MaxQB; O88566; -.
DR PaxDb; O88566; -.
DR PRIDE; O88566; -.
DR ProteomicsDB; 277234; -.
DR Antibodypedia; 31648; 425 antibodies from 38 providers.
DR DNASU; 12006; -.
DR Ensembl; ENSMUST00000052915; ENSMUSP00000051331; ENSMUSG00000000142.
DR GeneID; 12006; -.
DR KEGG; mmu:12006; -.
DR UCSC; uc007mbu.2; mouse.
DR CTD; 8313; -.
DR MGI; MGI:1270862; Axin2.
DR VEuPathDB; HostDB:ENSMUSG00000000142; -.
DR eggNOG; KOG3589; Eukaryota.
DR GeneTree; ENSGT00940000157338; -.
DR InParanoid; O88566; -.
DR OMA; TEPCLAL; -.
DR OrthoDB; 1481971at2759; -.
DR PhylomeDB; O88566; -.
DR TreeFam; TF315454; -.
DR Reactome; R-MMU-201681; TCF dependent signaling in response to WNT.
DR Reactome; R-MMU-4641257; Degradation of AXIN.
DR Reactome; R-MMU-5689880; Ub-specific processing proteases.
DR BioGRID-ORCS; 12006; 1 hit in 109 CRISPR screens.
DR ChiTaRS; Axin2; mouse.
DR PRO; PR:O88566; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; O88566; protein.
DR Bgee; ENSMUSG00000000142; Expressed in meninx of spinal cord and 299 other tissues.
DR ExpressionAtlas; O88566; baseline and differential.
DR Genevisible; O88566; MM.
DR GO; GO:0030877; C:beta-catenin destruction complex; IBA:GO_Central.
DR GO; GO:0005813; C:centrosome; IDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0008013; F:beta-catenin binding; ISO:MGI.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0070411; F:I-SMAD binding; IPI:MGI.
DR GO; GO:0060090; F:molecular adaptor activity; IBA:GO_Central.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:MGI.
DR GO; GO:0030282; P:bone mineralization; IMP:MGI.
DR GO; GO:0008219; P:cell death; ISO:MGI.
DR GO; GO:0048468; P:cell development; IBA:GO_Central.
DR GO; GO:0008283; P:cell population proliferation; IMP:MGI.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEA:Ensembl.
DR GO; GO:0003413; P:chondrocyte differentiation involved in endochondral bone morphogenesis; IMP:MGI.
DR GO; GO:0001957; P:intramembranous ossification; IMP:MGI.
DR GO; GO:0043570; P:maintenance of DNA repeat elements; ISO:MGI.
DR GO; GO:0048255; P:mRNA stabilization; ISO:MGI.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; ISO:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; IMP:MGI.
DR GO; GO:0033689; P:negative regulation of osteoblast proliferation; IMP:MGI.
DR GO; GO:2000054; P:negative regulation of Wnt signaling pathway involved in dorsal/ventral axis specification; ISO:MGI.
DR GO; GO:0042476; P:odontogenesis; ISO:MGI.
DR GO; GO:0001649; P:osteoblast differentiation; IMP:MGI.
DR GO; GO:0033687; P:osteoblast proliferation; IMP:MGI.
DR GO; GO:0010942; P:positive regulation of cell death; ISO:MGI.
DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; ISO:MGI.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; ISO: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; ISO:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IC:ComplexPortal.
DR GO; GO:0008104; P:protein localization; ISO:MGI.
DR GO; GO:0070602; P:regulation of centromeric sister chromatid cohesion; IMP:BHF-UCL.
DR GO; GO:0061181; P:regulation of chondrocyte development; IMP:MGI.
DR GO; GO:0032423; P:regulation of mismatch repair; ISO:MGI.
DR GO; GO:0030111; P:regulation of Wnt signaling pathway; IDA:MGI.
DR GO; GO:0003139; P:secondary heart field specification; IGI:MGI.
DR GO; GO:0001756; P:somitogenesis; IDA:MGI.
DR GO; GO:0072089; P:stem cell proliferation; IMP:MGI.
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; Phosphoprotein; Reference proteome;
KW Tumor suppressor; Ubl conjugation; Wnt signaling pathway.
FT CHAIN 1..840
FT /note="Axin-2"
FT /id="PRO_0000220896"
FT DOMAIN 81..200
FT /note="RGS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00171"
FT DOMAIN 758..840
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 300..363
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 327..413
FT /note="Interaction with GSK3B"
FT /evidence="ECO:0000250"
FT REGION 398..435
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 413..478
FT /note="Interaction with beta-catenin"
FT /evidence="ECO:0000250"
FT REGION 447..485
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 572..614
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 715..745
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 21..30
FT /note="Tankyrase-binding motif"
FT COMPBIAS 38..53
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 300..318
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 715..731
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 101
FT /note="R -> K (in Ref. 2; AAF22800)"
FT /evidence="ECO:0000305"
FT CONFLICT 474
FT /note="H -> Y (in Ref. 2; AAF22800)"
FT /evidence="ECO:0000305"
FT CONFLICT 484
FT /note="P -> S (in Ref. 1; AAC26047)"
FT /evidence="ECO:0000305"
FT CONFLICT 503
FT /note="F -> S (in Ref. 2; AAF22800)"
FT /evidence="ECO:0000305"
FT CONFLICT 603
FT /note="A -> G (in Ref. 1; AAC26047)"
FT /evidence="ECO:0000305"
FT CONFLICT 648
FT /note="C -> R (in Ref. 1; AAC26047 and 2; AAF22800)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 840 AA; 92906 MW; 53D7D33128879298 CRC64;
MSSAVLVTLL PDPSSSFRED APRPPVPGEE GETPPCQPSV GKVQSTKPMP VSSNARRNED
GLGEPEGRAS PDSPLTRWTK SLHSLLGDQD GAYLFRTFLE REKCVDTLDF WFACNGFRQM
NLKDTKTLRV AKAIYKRYIE NNSVVSKQLK PATKTYIRDG IKKQQIGSVM FDQAQTEIQA
VMEENAYQVF LTSDIYLEYV RSGGENTAYM SNGGLGSLKV LCGYLPTLNE EEEWTCADLK
CKLSPTVVGL SSKTLRATAS VRSTETAENG FRSFKRSDPV NPYHVGSGYV FAPATSANDS
ELSSDALTDD SMSMTDSSVD GVPPYRMGSK KQLQREMHRS VKANGQVSLP HFPRTHRLPK
EMTPVEPAAF AAELISRLEK LKLELESRHS LEERLQQIRE DEEKEGSEQA LSSRDGAPVQ
HPLALLPSGS YEEDPQTILD DHLSRVLKTP GCQSPGVGRY SPRSRSPDHH HQHHHHQQCH
TLLPTGGKLP PVAACPLLGG KSFLTKQTTK HVHHHYIHHH AVPKTKEEIE AEATQRVRCL
CPGGTDYYCY SKCKSHPKAP EPLPGEQFCG SRGGTLPKRN AKGTEPGLAL SARDGGMSSA
AGAPQLPGEE GDRSQDVWQW MLESERQSKS KPHSAQSIRK SYPLESACAA PGERVSRHHL
LGASGHSRSV ARAHPFTQDP AMPPLTPPNT LAQLEEACRR LAEVSKPQKQ RCCVASQQRD
RNHSAAGQAG ASPFANPSLA PEDHKEPKKL ASVHALQASE LVVTYFFCGE EIPYRRMLKA
QSLTLGHFKE QLSKKGNYRY YFKKASDEFA CGAVFEEIWD DETVLPMYEG RILGKVERID
