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O70239 (AXIN1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 123. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Axin-1
Alternative name(s):
Axis inhibition protein 1
Short name=rAxin
Gene names
Name:Axin1
Synonyms:Axin
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length827 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subunit structure

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

Subcellular location

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

Tissue specificity

Highly expressed in testis, thymus and lung. Less expression in cerebrum, cerebellum, heart, kidney, skeletal muscle, spleen and liver. Ref.1

Domain

The tankyrase-binding motif (also named TBD) is required for interaction with tankyrase TNKS and TNKS2 By similarity.

Post-translational modification

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.

Sequence similarities

Contains 1 DIX domain.

Contains 1 RGS domain.

Sequence caution

The sequence AAC40066.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
   Biological processApoptosis
Wnt signaling pathway
   Cellular componentCell membrane
Cytoplasm
Membrane
Nucleus
   Molecular functionDevelopmental protein
   PTMADP-ribosylation
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processWnt signaling pathway

Inferred from direct assay Ref.1. Source: RGD

Wnt signaling pathway involved in somitogenesis

Inferred from Biological aspect of Ancestor. Source: RefGenome

Wnt-activated signaling pathway involved in forebrain neuron fate commitment

Inferred from Biological aspect of Ancestor. Source: RefGenome

activation of JUN kinase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

apoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

axial mesoderm formation

Inferred from Biological aspect of Ancestor. Source: RefGenome

canonical Wnt signaling pathway

Traceable author statement Ref.1. Source: BHF-UCL

canonical Wnt signaling pathway involved in neural plate anterior/posterior pattern formation

Inferred from Biological aspect of Ancestor. Source: RefGenome

cell death

Inferred from Biological aspect of Ancestor. Source: RefGenome

cellular protein complex assembly

Inferred from electronic annotation. Source: Ensembl

cellular response to organic cyclic compound

Inferred from Biological aspect of Ancestor. Source: RefGenome

cytoplasmic microtubule organization

Inferred from Biological aspect of Ancestor. Source: RefGenome

determination of left/right symmetry

Inferred from Biological aspect of Ancestor. Source: RefGenome

dorsal/ventral axis specification

Inferred from Biological aspect of Ancestor. Source: RefGenome

embryonic eye morphogenesis

Inferred from Biological aspect of Ancestor. Source: RefGenome

embryonic skeletal joint morphogenesis

Inferred from Biological aspect of Ancestor. Source: RefGenome

forebrain anterior/posterior pattern specification

Inferred from Biological aspect of Ancestor. Source: RefGenome

genetic imprinting

Inferred from electronic annotation. Source: Ensembl

in utero embryonic development

Inferred from electronic annotation. Source: Ensembl

muscle cell development

Inferred from Biological aspect of Ancestor. Source: RefGenome

negative regulation of Wnt signaling pathway

Traceable author statement Ref.1. Source: BHF-UCL

negative regulation of canonical Wnt signaling pathway

Inferred from Biological aspect of Ancestor. Source: RefGenome

negative regulation of fat cell differentiation

Inferred from Biological aspect of Ancestor. Source: RefGenome

negative regulation of protein metabolic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription elongation from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

nucleocytoplasmic transport

Inferred from electronic annotation. Source: Ensembl

olfactory placode formation

Inferred from Biological aspect of Ancestor. Source: RefGenome

optic placode formation

Inferred from Biological aspect of Ancestor. Source: RefGenome

positive regulation of GTPase activity

Inferred from Biological aspect of Ancestor. Source: GOC

positive regulation of JNK cascade

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of peptidyl-serine phosphorylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of peptidyl-threonine phosphorylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of proteasomal ubiquitin-dependent protein catabolic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein kinase activity

Inferred from direct assay PubMed 15228590. Source: RGD

positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process

Inferred from direct assay PubMed 10228155. Source: BHF-UCL

positive regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: Ensembl

positive regulation of transforming growth factor beta receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of ubiquitin-protein transferase activity

Inferred from electronic annotation. Source: Ensembl

post-anal tail morphogenesis

Inferred from electronic annotation. Source: Ensembl

protein catabolic process

Inferred from electronic annotation. Source: Ensembl

protein homooligomerization

Inferred from direct assay PubMed 10330181. Source: RGD

protein polyubiquitination

Inferred from electronic annotation. Source: Ensembl

regulation of catenin import into nucleus

Inferred from Biological aspect of Ancestor. Source: RefGenome

sensory perception of sound

Inferred from electronic annotation. Source: Ensembl

termination of G-protein coupled receptor signaling pathway

Inferred from electronic annotation. Source: InterPro

   Cellular_componentbeta-catenin destruction complex

Inferred from direct assay PubMed 10228155. Source: BHF-UCL

cell cortex

Inferred from Biological aspect of Ancestor. Source: RefGenome

cytoplasmic membrane-bounded vesicle

Inferred from Biological aspect of Ancestor. Source: RefGenome

cytoplasmic microtubule

Inferred from Biological aspect of Ancestor. Source: RefGenome

cytoplasmic vesicle

Inferred from direct assay PubMed 11113207. Source: BHF-UCL

lateral plasma membrane

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Inferred from direct assay Ref.2. Source: UniProtKB

postsynaptic density

Inferred from direct assay PubMed 15228590. Source: RGD

   Molecular_functionGTPase activator activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

armadillo repeat domain binding

Inferred from direct assay Ref.1. Source: BHF-UCL

beta-catenin binding

Inferred from direct assay Ref.1. Source: BHF-UCL

identical protein binding

Inferred from physical interaction PubMed 10330181. Source: IntAct

protein binding

Inferred from physical interaction Ref.2. Source: UniProtKB

protein domain specific binding

Inferred from physical interaction PubMed 10944533. Source: RGD

protein homodimerization activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein kinase binding

Inferred from physical interaction PubMed 10228155. Source: BHF-UCL

receptor binding

Inferred from physical interaction PubMed 16890161. Source: BHF-UCL

signal transducer activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

itself4EBI-6857773,EBI-6857773
AMMECR1Q9Y4X03EBI-6857773,EBI-8583355From a different organism.
CAV1Q031355EBI-6857773,EBI-603614From a different organism.
CSNK1EP496747EBI-6857773,EBI-749343From a different organism.
DVL1O1464012EBI-6857773,EBI-723489From a different organism.
LRP6O7558112EBI-6857773,EBI-910915From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 827827Axin-1
PRO_0000220890

Regions

Domain88 – 211124RGS
Domain745 – 82783DIX
Region209 – 338130Interaction with TP53 By similarity
Region348 – 43285Interaction with GSK3B
Region433 – 50169Interaction with CTNNB1
Motif20 – 2910Tankyrase-binding motif

Amino acid modifications

Modified residue751Phosphoserine; by CK1 By similarity
Modified residue771Phosphoserine; by CK1 By similarity
Modified residue2171Phosphoserine; by CK1 By similarity
Modified residue4681Phosphoserine; by CK1 By similarity
Modified residue4801Phosphothreonine; by GSK3-beta Probable
Modified residue4851Phosphoserine; by GSK3-beta By similarity
Modified residue4921Phosphoserine By similarity
Cross-link822Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
Cross-link825Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Secondary structure

............. 827
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O70239 [UniParc].

Last modified May 10, 2002. Version 3.
Checksum: BB1EE9CCECF6D487

FASTA82792,285
        10         20         30         40         50         60 
MNVQEQGFPL DLGASFTEDA PRPPVPGEEG ELVSTDSRPV NHSFCSGKGT SIKSETSTAT 

        70         80         90        100        110        120 
PRRSDLDLGY EPEGSASPTP PYLRWAESLH SLLDDQDGIS LFRTFLKQEG CADLLDFWFA 

       130        140        150        160        170        180 
CSGFRKLEPC DSNEEKRLKL ARAIYRKYIL DSNGIVSRQT KPATKSFIKD CVMKQQIDPA 

       190        200        210        220        230        240 
MFDQAQTEIQ STMEENTYPS FLKSDIYLEY TRTGSESPKV CSDQSSGSGT GKGMSGYLPT 

       250        260        270        280        290        300 
LNEDEEWKCD QDADEDDGRD SVPPSRLTQK LLLETAAPRA PSSRRYNEGR ELRYGSWREP 

       310        320        330        340        350        360 
VNPYYVNSGY ALAPATSAND SEQQSLSSDA DTLSLTDSSV DGIPPYRIRK QHRREMQESV 

       370        380        390        400        410        420 
QVNGRVPLPH IPRTYRMPKE IRVEPQKFAE ELIHRLEAVQ RTREAEEKLE ERLKRVRMEE 

       430        440        450        460        470        480 
EGEDGEMPSG PMASHKLPSV PAWHHFPPRY VDMGCSGLRD AHEENPESIL DEHVQRVMRT 

       490        500        510        520        530        540 
PGCQSPGPGH RSPDSGHVAK TAVLGGTASG HGKHAPKLGL KLDSAGLHHH RHVHHHVHHN 

       550        560        570        580        590        600 
SARPKEQMEA EAARRVQSSF SWGPETHGHA KPRSYSESTG TNPSAGDLAF GGKASAPSKR 

       610        620        630        640        650        660 
NTKKAESGKN ASAEVPSTTE DAEKNQKIMQ WIIEGEKEIS RHRKAGHGSS GMRKQQAHES 

       670        680        690        700        710        720 
SRPLSIERPG AVHPWVSAQL RNSVQPSHLF IQDPTMPPNP APNPLTQLEE ARRRLEEEEK 

       730        740        750        760        770        780 
RANKLPSKQR TKSQRKAGGG SAPPCDSIVV AYYFCGEPIP YRTLVRGRAV TLGQFKELLT 

       790        800        810        820 
KKGSYRYYFK KVSDEFDCGV VFEEVREDEA ILPVFEEKII GKVEKVD 

« Hide

References

[1]"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.
Tissue: Brain.
[2]"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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF017756 mRNA. Translation: AAC40066.1. Different initiation.
PIRT08422.
RefSeqNP_077381.1. NM_024405.1.
UniGeneRn.31781.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1WSPX-ray2.90A/B/C744-827[»]
2D5GX-ray3.20A/B/C/D/E/F743-827[»]
ProteinModelPortalO70239.
SMRO70239. Positions 74-220, 744-827.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid249455. 9 interactions.
IntActO70239. 10 interactions.
MINTMINT-1532436.
STRING10116.ENSRNOP00000044336.

PTM databases

PhosphoSiteO70239.

Proteomic databases

PRIDEO70239.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000027705; ENSRNOP00000027705; ENSRNOG00000020414.
GeneID79257.
KEGGrno:79257.
UCSCRGD:620859. rat.

Organism-specific databases

CTD8312.
RGD620859. Axin1.

Phylogenomic databases

eggNOGNOG238205.
GeneTreeENSGT00390000010011.
HOVERGENHBG004324.
KOK02157.
OrthoDBEOG79PJQ0.

Gene expression databases

GenevestigatorO70239.

Family and domain databases

Gene3D1.10.196.10. 2 hits.
InterProIPR014936. Axin_b-cat-bd.
IPR001158. DIX.
IPR024066. Regulat_G_prot_signal_dom1.
IPR016137. Regulat_G_prot_signal_superfam.
IPR000342. RGS_dom.
IPR029071. Ubiquitin-rel_dom.
[Graphical view]
PfamPF08833. Axin_b-cat_bind. 1 hit.
PF00778. DIX. 1 hit.
PF00615. RGS. 1 hit.
[Graphical view]
PRINTSPR01301. RGSPROTEIN.
SMARTSM00021. DAX. 1 hit.
SM00315. RGS. 1 hit.
[Graphical view]
SUPFAMSSF48097. SSF48097. 1 hit.
SSF54236. SSF54236. 1 hit.
PROSITEPS50841. DIX. 1 hit.
PS50132. RGS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceO70239.
NextBio614758.
PROO70239.

Entry information

Entry nameAXIN1_RAT
AccessionPrimary (citable) accession number: O70239
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: May 10, 2002
Last modified: June 11, 2014
This is version 123 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references