O70239 (AXIN1_RAT) Reviewed, UniProtKB/Swiss-Prot
Last modified November 13, 2013. Version 118. History...
Names and origin
|Protein names||Recommended name:|
Axis inhibition protein 1
|Organism||Rattus norvegicus (Rat) [Reference proteome]|
|Taxonomic identifier||10116 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus|
|Sequence length||827 AA.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
Component of the beta-catenin destruction complex required for regulating CTNNB1 levels through phosphorylation and ubiquitination, and modulating Wnt-signaling. Controls dorsoventral patterning via two opposing effects; down-regulates beta-catenin to inhibit the Wnt signaling pathway and ventralize embryos, but also dorsalizes embryos by activating a Wnt-independent JNK signaling pathway. Also facilitates the phosphorylation of APC by GSK3B. Facilitates the phosphorylation of TP53 by HIPK2 upon ultraviolet irradiation. Enhances TGF-beta signaling by recruiting the RNF111 E3 ubiquitin ligase and promoting the degradation of inhibitory SMAD7 By similarity.
Homodimer By similarity. Interacts with ZBED3; the interaction is direct, enhanced by protein kinase GSK3B and casein kinase CSNK1E activities and decreases GSK3B-induced beta-catenin serine and threonine phosphorylations By similarity. Component of the AXIN1-HIPK2-TP53 complex By similarity. Interacts directly in the complex with TP53 and HIPK2. Interacts with DAXX; the interaction stimulates the interaction of DAXX with TP53, stimulates 'Ser-46' phosphorylation of TP53 and induces cell death on UV irradiation. Also binds ANKRD6, PIAS1, PIAS2, PIAS4, MAP3K1, MAP3K4, SUMO1, SMAD6, SMAD7 and RNF111. Interacts with DIXDC1; the interaction prevents interaction with MAP3K1. Interacts with MDFI; the interaction decreases AXIN1-mediated JUN N-terminal kinase (JNK) activation. Interacts with MDFIC; the interaction inhibits beta-cateninin-mediated signaling and AXIN1-mediated JUN N-terminal kinase (JNK) activation. Interacts with LRP5 (via its phosphorylated PPPSP motifs); the interaction is stimulated by WNT1 and GSK3B and activates beta-catenin signaling. Interacts (via the C-terminal) with PPP1CA; the interaction dephosphorylates AXIN1 and regulates interaction with GSK3B. Interacts with PPP2CA; the interaction dephosphorylates AXIN1 By similarity. Component of the beta-catenin destruction complex, containing at least, CTNNB1, an axin and GSK3B, that regulates CTNNB1 protein levels through phosphorylation and ubiquitination. Interacts with CTNNB1 (via the armadillo repeats 2-7). Interacts with GSK3B; the interaction hyperphosphorylates CTNNB1 leading to its ubiquitination and destruction. Interacts with MACF1. Found in a complex composed of MACF1, APC, AXIN1, CTNNB1 and GSK3B. Interacts with TNKS. Interacts with DAB2; the interaction is mutually exclusive with the AXIN1:PPP1CA interaction By similarity. Ref.1 Ref.2
Cytoplasm By similarity. Nucleus By similarity. Cell membrane. Membrane By similarity. Note: On UV irradiation, translocates to the nucleus and colocalizes with DAAX By similarity. MACF1 is required for its translocation to cell membrane. Ref.2
Highly expressed in testis, thymus and lung. Less expression in cerebrum, cerebellum, heart, kidney, skeletal muscle, spleen and liver. Ref.1
The tankyrase-binding motif (also named TBD) is required for interaction with tankyrase TNKS and TNKS2 By similarity.
Phosphorylation and dephosphorylation of AXIN1 regulates assembly and function of the beta-catenin complex. Phosphorylated by CK1 and GSK3B. Dephosphorylated by PPP1CA and PPP2CA. Phosphorylation by CK1 enhances binding of GSK3B to AXIN1. Also phosphorylated by CDK2 which regulates interaction with CTNBB1 By similarity. Ref.1
ADP-ribosylated by tankyrase TNKS and TNKS2. Poly-ADP-ribosylated protein is recognized by RNF146, followed by ubiquitination and subsequent activation of the Wnt signaling pathway By similarity.
Ubiquitinated by RNF146 when poly-ADP-ribosylated, leading to its degradation and subsequent activation of the Wnt signaling pathway. Sumoylation at Lys-858 and Lys-861 prevents ubiquitination and degradation. Sumoylation is required for AXIN1-mediated JNK activation. Deubiquitinated by USP34, deubiquitinated downstream of beta-catenin stabilization step: deubiquitination is important for nuclear accumulation during Wnt signaling to positively regulate beta-catenin (CTNBB1)-mediated transcription By similarity.
Contains 1 DIX domain.
Contains 1 RGS domain.
The sequence AAC40066.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 827||827||Axin-1||PRO_0000220890|
|Domain||88 – 211||124||RGS|
|Domain||745 – 827||83||DIX|
|Region||209 – 338||130||Interaction with TP53 By similarity|
|Region||348 – 432||85||Interaction with GSK3B|
|Region||433 – 501||69||Interaction with CTNNB1|
|Motif||20 – 29||10||Tankyrase-binding motif|
Amino acid modifications
|Modified residue||75||1||Phosphoserine; by CK1 By similarity|
|Modified residue||77||1||Phosphoserine; by CK1 By similarity|
|Modified residue||217||1||Phosphoserine; by CK1 By similarity|
|Modified residue||468||1||Phosphoserine; by CK1 By similarity|
|Modified residue||480||1||Phosphothreonine; by GSK3-beta Probable|
|Modified residue||485||1||Phosphoserine; by GSK3-beta By similarity|
|Modified residue||492||1||Phosphoserine By similarity|
|Cross-link||822||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity|
|Cross-link||825||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity|
Helix Strand Turn
|Beta strand||748 – 754||7|
|Beta strand||761 – 768||8|
|Helix||772 – 778||7|
|Beta strand||785 – 792||8|
|Beta strand||799 – 805||7|
|Beta strand||818 – 825||8|
|||"Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK-3beta and beta-catenin and promotes GSK-3beta-dependent phosphorylation of beta-catenin."|
Ikeda S., Kishida S., Yamamoto H., Murai H., Koyama S., Kikuchi A.
EMBO J. 17:1371-1384(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PHOSPHORYLATION, INTERACTION WITH GSK3B AND CNNB1 IN THE BETA-CATENIN DESTRUCTION COMPLEX, TISSUE SPECIFICITY.
|||"The role of microtubule actin cross-linking factor 1 (MACF1) in the Wnt signaling pathway."|
Chen H.J., Lin C.M., Lin C.S., Perez-Olle R., Leung C.L., Liem R.K.
Genes Dev. 20:1933-1945(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, INTERACTION WITH MACF1, IDENTIFICATION IN A COMPLEX WITH MACF1; APC; GSK3B AND CTNNB1.
|+||Additional computationally mapped references.|
|AF017756 mRNA. Translation: AAC40066.1. Different initiation.|
|RefSeq||NP_077381.1. NM_024405.1. |
3D structure databases
|SMR||O70239. Positions 74-220, 744-827. |
Protein-protein interaction databases
|IntAct||O70239. 9 interactions.|
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSRNOT00000027705; ENSRNOP00000027705; ENSRNOG00000020414. |
|UCSC||RGD:620859. rat. |
|RGD||620859. Axin1. |
Gene expression databases
Family and domain databases
|Gene3D||22.214.171.124. 2 hits. |
|InterPro||IPR014936. Axin_b-cat-bd. |
|Pfam||PF08833. Axin_b-cat_bind. 1 hit. |
PF00778. DIX. 1 hit.
PF00615. RGS. 1 hit.
|PRINTS||PR01301. RGSPROTEIN. |
|SMART||SM00021. DAX. 1 hit. |
SM00315. RGS. 1 hit.
|SUPFAM||SSF48097. SSF48097. 1 hit. |
|PROSITE||PS50841. DIX. 1 hit. |
PS50132. RGS. 1 hit.
|Accession||Primary (citable) accession number: O70239|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|