AXIN2_RAT
ID AXIN2_RAT Reviewed; 838 AA.
AC O70240;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 153.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH CTNNB1 AND GSK3B, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=9566905; DOI=10.1128/mcb.18.5.2867;
RA Yamamoto H., Kishida S., Uochi T., Ikeda S., Koyama S., Asashima M.,
RA Kikuchi A.;
RT "Axil, a member of the Axin family, interacts with both glycogen synthase
RT kinase 3beta and beta-catenin and inhibits axis formation of Xenopus
RT embryos.";
RL Mol. Cell. Biol. 18:2867-2875(1998).
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 SMAD7 and RNF111. Interacts with ANKRD6 (By
CC similarity). Interacts with glycogen synthase kinase-3 beta (GSK3B) and
CC beta-catenin (PubMed:9566905). The interaction between axin and beta-
CC catenin occurs via the armadillo repeats contained in beta-catenin
CC (PubMed:9566905). Interacts with SIAH1 (By similarity). Interacts with
CC SIAH2 (By similarity). {ECO:0000250|UniProtKB:Q9Y2T1,
CC ECO:0000269|PubMed:9566905}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9Y2T1}.
CC -!- TISSUE SPECIFICITY: Expressed in lung and thymus.
CC {ECO:0000269|PubMed:9566905}.
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}.
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; AF017757; AAC40089.1; -; mRNA.
DR PIR; T08423; T08423.
DR RefSeq; NP_077331.1; NM_024355.1.
DR AlphaFoldDB; O70240; -.
DR SMR; O70240; -.
DR STRING; 10116.ENSRNOP00000004898; -.
DR PaxDb; O70240; -.
DR Ensembl; ENSRNOT00000088599; ENSRNOP00000073088; ENSRNOG00000055010.
DR GeneID; 29134; -.
DR KEGG; rno:29134; -.
DR CTD; 8313; -.
DR RGD; 69259; Axin2.
DR eggNOG; KOG3589; Eukaryota.
DR GeneTree; ENSGT00940000157338; -.
DR InParanoid; O70240; -.
DR OrthoDB; 1481971at2759; -.
DR PhylomeDB; O70240; -.
DR TreeFam; TF315454; -.
DR Reactome; R-RNO-201681; TCF dependent signaling in response to WNT.
DR Reactome; R-RNO-4641257; Degradation of AXIN.
DR Reactome; R-RNO-5689880; Ub-specific processing proteases.
DR PRO; PR:O70240; -.
DR Proteomes; UP000002494; Chromosome 10.
DR GO; GO:0030877; C:beta-catenin destruction complex; IBA:GO_Central.
DR GO; GO:0005813; C:centrosome; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0008013; F:beta-catenin binding; IDA:RGD.
DR GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR GO; GO:0070411; F:I-SMAD binding; ISO:RGD.
DR GO; GO:0060090; F:molecular adaptor activity; IBA:GO_Central.
DR GO; GO:0019901; F:protein kinase binding; IPI:RGD.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD.
DR GO; GO:0030282; P:bone mineralization; ISO:RGD.
DR GO; GO:0008219; P:cell death; IDA:RGD.
DR GO; GO:0048468; P:cell development; IBA:GO_Central.
DR GO; GO:0008283; P:cell population proliferation; ISO:RGD.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEP:RGD.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IEP:RGD.
DR GO; GO:0003413; P:chondrocyte differentiation involved in endochondral bone morphogenesis; ISO:RGD.
DR GO; GO:0001957; P:intramembranous ossification; ISO:RGD.
DR GO; GO:0043570; P:maintenance of DNA repeat elements; ISO:RGD.
DR GO; GO:0048255; P:mRNA stabilization; ISO:RGD.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; ISO:RGD.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:RGD.
DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; ISO:RGD.
DR GO; GO:0033689; P:negative regulation of osteoblast proliferation; IEA:Ensembl.
DR GO; GO:2000054; P:negative regulation of Wnt signaling pathway involved in dorsal/ventral axis specification; IDA:RGD.
DR GO; GO:0042476; P:odontogenesis; ISO:RGD.
DR GO; GO:0001649; P:osteoblast differentiation; IEA:Ensembl.
DR GO; GO:0033687; P:osteoblast proliferation; IEA:Ensembl.
DR GO; GO:0010942; P:positive regulation of cell death; ISO:RGD.
DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; ISO:RGD.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; IMP:RGD.
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; IDA:RGD.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:RGD.
DR GO; GO:0008104; P:protein localization; IEA:Ensembl.
DR GO; GO:0070602; P:regulation of centromeric sister chromatid cohesion; ISO:RGD.
DR GO; GO:0061181; P:regulation of chondrocyte development; ISO:RGD.
DR GO; GO:0032423; P:regulation of mismatch repair; ISO:RGD.
DR GO; GO:0030111; P:regulation of Wnt signaling pathway; ISO:RGD.
DR GO; GO:0048545; P:response to steroid hormone; IEP:RGD.
DR GO; GO:0003139; P:secondary heart field specification; ISO:RGD.
DR GO; GO:0001756; P:somitogenesis; ISO:RGD.
DR GO; GO:0072089; P:stem cell proliferation; IEA:Ensembl.
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..838
FT /note="Axin-2"
FT /id="PRO_0000220897"
FT DOMAIN 81..200
FT /note="RGS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00171"
FT DOMAIN 756..838
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..333
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..476
FT /note="Interaction with beta-catenin"
FT /evidence="ECO:0000250"
FT REGION 450..483
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 568..682
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 712..744
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 712..738
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 838 AA; 92948 MW; 45B825C13BA07F37 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 FRSFKRSEPV NPYHVGSGYV FAPATSANDS
ELSSDALTDD SMSMTDSSVD GIPPYRMGSK KQLQREMHRS VKANGQVSLP HFPRTHRLPK
EMTPVEPAAF AAELISRLEK LKLELESRHS LEERLQQIRE DEEKEGSEQA LSSRDGAPVQ
HPLALLPSGS YEEDPQTILD DHLSRVLKTP GCQSPGVGRY SPRSRSPDHH HHHHQQCHAL
LPTGGKLPPE AACPLLGGKS FLTKQTTKHV HHHYIHHHAV PKTKEEIEAE ATQRVRCLCP
GGTDYYCYSK CKSHSKPPEP LPGEQFCGSR GGTLPKRNTK GTEPGLALPA REGGMSSAAG
APQLPGEEGD RSQDVWQWML ESERQSKSKP HSTQSIRKSY PLESARAPPG ERVSRHHLLG
ASGHPRSAAR AHPFTQDPAM PPLTPPNTLA QLEEACRRLA EVSKPQKQRC CVASQQRDRN
HPATGQAGPT SFSNPSLASE DHKEPKRLAS VHALQASELI VTYFFCGEEI PYRRMLKAQS
LTLGHFKEQL SKKGNYRYYF KKASDEFACG AVFEEIWDDE TVLPMYEGRI LGKVERID
