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O70239

- AXIN1_RAT

UniProt

O70239 - AXIN1_RAT

Protein

Axin-1

Gene

Axin1

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 125 (01 Oct 2014)
      Sequence version 3 (10 May 2002)
      Previous versions | rss
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    Functioni

    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.By similarity

    GO - Molecular functioni

    1. armadillo repeat domain binding Source: BHF-UCL
    2. beta-catenin binding Source: BHF-UCL
    3. GTPase activator activity Source: RefGenome
    4. identical protein binding Source: IntAct
    5. protein binding Source: UniProtKB
    6. protein domain specific binding Source: RGD
    7. protein homodimerization activity Source: UniProtKB
    8. protein kinase binding Source: BHF-UCL
    9. receptor binding Source: BHF-UCL
    10. signal transducer activity Source: Ensembl

    GO - Biological processi

    1. activation of JUN kinase activity Source: RefGenome
    2. apoptotic process Source: UniProtKB-KW
    3. axial mesoderm formation Source: RefGenome
    4. canonical Wnt signaling pathway Source: BHF-UCL
    5. canonical Wnt signaling pathway involved in neural plate anterior/posterior pattern formation Source: RefGenome
    6. cell death Source: RefGenome
    7. cellular protein complex assembly Source: Ensembl
    8. cellular response to organic cyclic compound Source: RefGenome
    9. cytoplasmic microtubule organization Source: RefGenome
    10. determination of left/right symmetry Source: RefGenome
    11. dorsal/ventral axis specification Source: RefGenome
    12. embryonic eye morphogenesis Source: RefGenome
    13. embryonic skeletal joint morphogenesis Source: RefGenome
    14. forebrain anterior/posterior pattern specification Source: RefGenome
    15. genetic imprinting Source: Ensembl
    16. in utero embryonic development Source: Ensembl
    17. muscle cell development Source: RefGenome
    18. negative regulation of canonical Wnt signaling pathway Source: RefGenome
    19. negative regulation of fat cell differentiation Source: RefGenome
    20. negative regulation of protein metabolic process Source: Ensembl
    21. negative regulation of transcription elongation from RNA polymerase II promoter Source: Ensembl
    22. negative regulation of Wnt signaling pathway Source: BHF-UCL
    23. nucleocytoplasmic transport Source: Ensembl
    24. olfactory placode formation Source: RefGenome
    25. optic placode formation Source: RefGenome
    26. positive regulation of GTPase activity Source: GOC
    27. positive regulation of JNK cascade Source: UniProtKB
    28. positive regulation of peptidyl-serine phosphorylation Source: Ensembl
    29. positive regulation of peptidyl-threonine phosphorylation Source: Ensembl
    30. positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: Ensembl
    31. positive regulation of protein kinase activity Source: RGD
    32. positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: BHF-UCL
    33. positive regulation of transcription, DNA-templated Source: Ensembl
    34. positive regulation of transforming growth factor beta receptor signaling pathway Source: Ensembl
    35. positive regulation of ubiquitin-protein transferase activity Source: Ensembl
    36. post-anal tail morphogenesis Source: Ensembl
    37. protein catabolic process Source: Ensembl
    38. protein homooligomerization Source: RGD
    39. protein polyubiquitination Source: Ensembl
    40. regulation of catenin import into nucleus Source: RefGenome
    41. sensory perception of sound Source: Ensembl
    42. termination of G-protein coupled receptor signaling pathway Source: InterPro
    43. Wnt-activated signaling pathway involved in forebrain neuron fate commitment Source: RefGenome
    44. Wnt signaling pathway Source: RGD
    45. Wnt signaling pathway involved in somitogenesis Source: RefGenome

    Keywords - Molecular functioni

    Developmental protein

    Keywords - Biological processi

    Apoptosis, Wnt signaling pathway

    Enzyme and pathway databases

    ReactomeiREACT_212065. TCF dependent signaling in response to WNT.
    REACT_216976. disassembly of the destruction complex and recruitment of AXIN to the membrane.
    REACT_227706. degradation of AXIN.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Axin-1
    Alternative name(s):
    Axis inhibition protein 1
    Short name:
    rAxin
    Gene namesi
    Name:Axin1
    Synonyms:Axin
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Chromosome 10

    Organism-specific databases

    RGDi620859. Axin1.

    Subcellular locationi

    Cytoplasm By similarity. Nucleus By similarity. Cell membrane 1 Publication. 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.By similarity

    GO - Cellular componenti

    1. beta-catenin destruction complex Source: BHF-UCL
    2. cell cortex Source: RefGenome
    3. cytoplasmic membrane-bounded vesicle Source: RefGenome
    4. cytoplasmic microtubule Source: RefGenome
    5. cytoplasmic vesicle Source: BHF-UCL
    6. lateral plasma membrane Source: Ensembl
    7. nucleus Source: UniProtKB-SubCell
    8. perinuclear region of cytoplasm Source: Ensembl
    9. plasma membrane Source: UniProtKB
    10. postsynaptic density Source: RGD

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 827827Axin-1PRO_0000220890Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei75 – 751Phosphoserine; by CK1By similarity
    Modified residuei77 – 771Phosphoserine; by CK1By similarity
    Modified residuei217 – 2171Phosphoserine; by CK1By similarity
    Modified residuei468 – 4681Phosphoserine; by CK1By similarity
    Modified residuei480 – 4801Phosphothreonine; by GSK3-beta1 Publication
    Modified residuei485 – 4851Phosphoserine; by GSK3-betaBy similarity
    Modified residuei492 – 4921PhosphoserineBy similarity
    Cross-linki822 – 822Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
    Cross-linki825 – 825Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity

    Post-translational modificationi

    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.By similarity
    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.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.By similarity

    Keywords - PTMi

    ADP-ribosylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    PRIDEiO70239.

    PTM databases

    PhosphoSiteiO70239.

    Expressioni

    Tissue specificityi

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

    Gene expression databases

    GenevestigatoriO70239.

    Interactioni

    Subunit structurei

    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.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    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.

    Protein-protein interaction databases

    BioGridi249455. 9 interactions.
    IntActiO70239. 10 interactions.
    MINTiMINT-1532436.
    STRINGi10116.ENSRNOP00000044336.

    Structurei

    Secondary structure

    1
    827
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi748 – 7547
    Beta strandi761 – 7688
    Helixi772 – 7787
    Beta strandi785 – 7928
    Beta strandi799 – 8057
    Beta strandi818 – 8258

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1WSPX-ray2.90A/B/C744-827[»]
    2D5GX-ray3.20A/B/C/D/E/F743-827[»]
    ProteinModelPortaliO70239.
    SMRiO70239. Positions 74-220, 744-827.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiO70239.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini88 – 211124RGSPROSITE-ProRule annotationAdd
    BLAST
    Domaini745 – 82783DIXPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni209 – 338130Interaction with TP53By similarityAdd
    BLAST
    Regioni348 – 43285Interaction with GSK3BAdd
    BLAST
    Regioni433 – 50169Interaction with CTNNB1Add
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi20 – 2910Tankyrase-binding motif

    Domaini

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

    Sequence similaritiesi

    Contains 1 DIX domain.PROSITE-ProRule annotation
    Contains 1 RGS domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiNOG238205.
    GeneTreeiENSGT00390000010011.
    HOVERGENiHBG004324.
    KOiK02157.
    OrthoDBiEOG79PJQ0.

    Family and domain databases

    Gene3Di1.10.196.10. 2 hits.
    InterProiIPR014936. 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]
    PfamiPF08833. Axin_b-cat_bind. 1 hit.
    PF00778. DIX. 1 hit.
    PF00615. RGS. 1 hit.
    [Graphical view]
    PRINTSiPR01301. RGSPROTEIN.
    SMARTiSM00021. DAX. 1 hit.
    SM00315. RGS. 1 hit.
    [Graphical view]
    SUPFAMiSSF48097. SSF48097. 1 hit.
    SSF54236. SSF54236. 1 hit.
    PROSITEiPS50841. DIX. 1 hit.
    PS50132. RGS. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    O70239-1 [UniParc]FASTAAdd to Basket

    « Hide

    MNVQEQGFPL DLGASFTEDA PRPPVPGEEG ELVSTDSRPV NHSFCSGKGT    50
    SIKSETSTAT PRRSDLDLGY EPEGSASPTP PYLRWAESLH SLLDDQDGIS 100
    LFRTFLKQEG CADLLDFWFA CSGFRKLEPC DSNEEKRLKL ARAIYRKYIL 150
    DSNGIVSRQT KPATKSFIKD CVMKQQIDPA MFDQAQTEIQ STMEENTYPS 200
    FLKSDIYLEY TRTGSESPKV CSDQSSGSGT GKGMSGYLPT LNEDEEWKCD 250
    QDADEDDGRD SVPPSRLTQK LLLETAAPRA PSSRRYNEGR ELRYGSWREP 300
    VNPYYVNSGY ALAPATSAND SEQQSLSSDA DTLSLTDSSV DGIPPYRIRK 350
    QHRREMQESV QVNGRVPLPH IPRTYRMPKE IRVEPQKFAE ELIHRLEAVQ 400
    RTREAEEKLE ERLKRVRMEE EGEDGEMPSG PMASHKLPSV PAWHHFPPRY 450
    VDMGCSGLRD AHEENPESIL DEHVQRVMRT PGCQSPGPGH RSPDSGHVAK 500
    TAVLGGTASG HGKHAPKLGL KLDSAGLHHH RHVHHHVHHN SARPKEQMEA 550
    EAARRVQSSF SWGPETHGHA KPRSYSESTG TNPSAGDLAF GGKASAPSKR 600
    NTKKAESGKN ASAEVPSTTE DAEKNQKIMQ WIIEGEKEIS RHRKAGHGSS 650
    GMRKQQAHES SRPLSIERPG AVHPWVSAQL RNSVQPSHLF IQDPTMPPNP 700
    APNPLTQLEE ARRRLEEEEK RANKLPSKQR TKSQRKAGGG SAPPCDSIVV 750
    AYYFCGEPIP YRTLVRGRAV TLGQFKELLT KKGSYRYYFK KVSDEFDCGV 800
    VFEEVREDEA ILPVFEEKII GKVEKVD 827
    Length:827
    Mass (Da):92,285
    Last modified:May 10, 2002 - v3
    Checksum:iBB1EE9CCECF6D487
    GO

    Sequence cautioni

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

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF017756 mRNA. Translation: AAC40066.1. Different initiation.
    PIRiT08422.
    RefSeqiNP_077381.1. NM_024405.1.
    UniGeneiRn.31781.

    Genome annotation databases

    EnsembliENSRNOT00000027705; ENSRNOP00000027705; ENSRNOG00000020414.
    GeneIDi79257.
    KEGGirno:79257.
    UCSCiRGD:620859. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF017756 mRNA. Translation: AAC40066.1 . Different initiation.
    PIRi T08422.
    RefSeqi NP_077381.1. NM_024405.1.
    UniGenei Rn.31781.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1WSP X-ray 2.90 A/B/C 744-827 [» ]
    2D5G X-ray 3.20 A/B/C/D/E/F 743-827 [» ]
    ProteinModelPortali O70239.
    SMRi O70239. Positions 74-220, 744-827.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 249455. 9 interactions.
    IntActi O70239. 10 interactions.
    MINTi MINT-1532436.
    STRINGi 10116.ENSRNOP00000044336.

    PTM databases

    PhosphoSitei O70239.

    Proteomic databases

    PRIDEi O70239.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSRNOT00000027705 ; ENSRNOP00000027705 ; ENSRNOG00000020414 .
    GeneIDi 79257.
    KEGGi rno:79257.
    UCSCi RGD:620859. rat.

    Organism-specific databases

    CTDi 8312.
    RGDi 620859. Axin1.

    Phylogenomic databases

    eggNOGi NOG238205.
    GeneTreei ENSGT00390000010011.
    HOVERGENi HBG004324.
    KOi K02157.
    OrthoDBi EOG79PJQ0.

    Enzyme and pathway databases

    Reactomei REACT_212065. TCF dependent signaling in response to WNT.
    REACT_216976. disassembly of the destruction complex and recruitment of AXIN to the membrane.
    REACT_227706. degradation of AXIN.

    Miscellaneous databases

    EvolutionaryTracei O70239.
    NextBioi 614758.
    PROi O70239.

    Gene expression databases

    Genevestigatori O70239.

    Family and domain databases

    Gene3Di 1.10.196.10. 2 hits.
    InterProi IPR014936. 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 ]
    Pfami PF08833. Axin_b-cat_bind. 1 hit.
    PF00778. DIX. 1 hit.
    PF00615. RGS. 1 hit.
    [Graphical view ]
    PRINTSi PR01301. RGSPROTEIN.
    SMARTi SM00021. DAX. 1 hit.
    SM00315. RGS. 1 hit.
    [Graphical view ]
    SUPFAMi SSF48097. SSF48097. 1 hit.
    SSF54236. SSF54236. 1 hit.
    PROSITEi PS50841. DIX. 1 hit.
    PS50132. RGS. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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.

    Entry informationi

    Entry nameiAXIN1_RAT
    AccessioniPrimary (citable) accession number: O70239
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 1, 2000
    Last sequence update: May 10, 2002
    Last modified: October 1, 2014
    This is version 125 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3