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O70239

- AXIN1_RAT

UniProt

O70239 - AXIN1_RAT

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Protein

Axin-1

Gene
Axin1, Axin
Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

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.

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
Complete GO annotation...

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. 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.1 Publication

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
Complete GO annotation...

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 CK1 By similarity
Modified residuei77 – 771Phosphoserine; by CK1 By similarity
Modified residuei217 – 2171Phosphoserine; by CK1 By similarity
Modified residuei468 – 4681Phosphoserine; by CK1 By similarity
Modified residuei480 – 4801Phosphothreonine; by GSK3-beta Inferred
Modified residuei485 – 4851Phosphoserine; by GSK3-beta By similarity
Modified residuei492 – 4921Phosphoserine By 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.1 Publication
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.

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.2 Publications

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.

Miscellaneous databases

EvolutionaryTraceiO70239.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini88 – 211124RGSAdd
BLAST
Domaini745 – 82783DIXAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni209 – 338130Interaction with TP53 By 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.
Contains 1 RGS domain.

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

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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: September 3, 2014
This is version 124 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

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