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UniProtKB - O35625 (AXIN1_MOUSE)

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Protein

Axin-1

Gene

Axin1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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 (By similarity). Controls dorsoventral patterning via two opposing effects; down-regulates CTNNB1 to inhibit the Wnt signaling pathway and ventralize embryos, but also dorsalizes embryos by activating a Wnt-independent JNK signaling pathway. In Wnt signaling, probably facilitates the phosphorylation of CTNNB1 and APC by GSK3B. Likely to function as a tumor suppressor. 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). Also component of the AXIN1-HIPK2-TP53 complex which controls cell growth, apoptosis and development.By similarity3 Publications

GO - Molecular functioni

  • armadillo repeat domain binding Source: MGI
  • beta-catenin binding Source: MGI
  • enzyme binding Source: MGI
  • GTPase activator activity Source: GO_Central
  • identical protein binding Source: MGI
  • I-SMAD binding Source: BHF-UCL
  • p53 binding Source: MGI
  • protein-containing complex scaffold activity Source: BHF-UCL
  • protein C-terminus binding Source: MGI
  • protein domain specific binding Source: MGI
  • protein homodimerization activity Source: UniProtKB
  • protein kinase binding Source: ParkinsonsUK-UCL
  • protein self-association Source: MGI
  • receptor signaling complex scaffold activity Source: InterPro
  • R-SMAD binding Source: MGI
  • signaling receptor binding Source: MGI
  • SMAD binding Source: MGI
  • ubiquitin protein ligase binding Source: BHF-UCL
View the complete GO annotation on QuickGO ...

GO - Biological processi

  • activation of JUN kinase activity Source: GO_Central
  • activation of protein kinase activity Source: MGI
  • apoptotic process Source: UniProtKB-KW
  • axial mesoderm development Source: MGI
  • axial mesoderm formation Source: MGI
  • canonical Wnt signaling pathway Source: MGI
  • canonical Wnt signaling pathway involved in neural plate anterior/posterior pattern formation Source: GO_Central
  • cellular protein-containing complex assembly Source: MGI
  • cytoplasmic microtubule organization Source: MGI
  • determination of left/right symmetry Source: GO_Central
  • dorsal/ventral axis specification Source: MGI
  • dorsal/ventral pattern formation Source: MGI
  • embryonic eye morphogenesis Source: GO_Central
  • forebrain anterior/posterior pattern specification Source: GO_Central
  • genetic imprinting Source: MGI
  • head development Source: MGI
  • in utero embryonic development Source: MGI
  • muscle cell development Source: GO_Central
  • negative regulation of canonical Wnt signaling pathway Source: MGI
  • negative regulation of fat cell differentiation Source: MGI
  • negative regulation of gene expression Source: MGI
  • negative regulation of protein metabolic process Source: MGI
  • negative regulation of transcription elongation from RNA polymerase II promoter Source: MGI
  • negative regulation of Wnt signaling pathway Source: MGI
  • nucleocytoplasmic transport Source: MGI
  • olfactory placode formation Source: GO_Central
  • optic placode formation Source: GO_Central
  • positive regulation of JNK cascade Source: UniProtKB
  • positive regulation of JUN kinase activity Source: MGI
  • positive regulation of peptidyl-serine phosphorylation Source: ParkinsonsUK-UCL
  • positive regulation of peptidyl-threonine phosphorylation Source: ParkinsonsUK-UCL
  • positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: MGI
  • positive regulation of protein catabolic process Source: MGI
  • positive regulation of protein kinase activity Source: CACAO
  • positive regulation of protein phosphorylation Source: MGI
  • positive regulation of protein ubiquitination Source: MGI
  • positive regulation of transcription, DNA-templated Source: BHF-UCL
  • positive regulation of transforming growth factor beta receptor signaling pathway Source: MGI
  • positive regulation of ubiquitin-dependent protein catabolic process Source: MGI
  • positive regulation of ubiquitin-protein transferase activity Source: BHF-UCL
  • post-anal tail morphogenesis Source: MGI
  • protein catabolic process Source: MGI
  • protein homooligomerization Source: MGI
  • protein polyubiquitination Source: MGI
  • regulation of canonical Wnt signaling pathway Source: MGI
  • regulation of protein phosphorylation Source: MGI
  • sensory perception of sound Source: MGI
  • Wnt-activated signaling pathway involved in forebrain neuron fate commitment Source: GO_Central
  • Wnt signaling pathway Source: MGI
View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionDevelopmental protein
Biological processApoptosis, Wnt signaling pathway

Names & Taxonomyi

Protein namesi
Recommended name:
Axin-1
Alternative name(s):
Axis inhibition protein 1
Protein Fused
Gene namesi
Name:Axin1
Synonyms:Axin, Fu
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1096327 Axin1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi480T → A: Greatly reduced GSK3B-mediated phosphorylation; when associated with A-485 and A-492. 1 Publication1
Mutagenesisi485S → A: Greatly reduced GSK3B-mediated phosphorylation and large effect on the inhibitory activity in Wnt-signaling; when associated with A-480 and A-492. 1 Publication1
Mutagenesisi492S → A: Greatly reduced GSK3B-mediated phosphorylation; when associated with A-480 and A-485. 1 Publication1
Mutagenesisi492S → I: Little effect on inhibitory activity on Wnt-signaling. 1 Publication1
Mutagenesisi495S → A: No effect on phosphorylation. Little effect on inhibitory activity on Wnt-signaling. 1 Publication1
Mutagenesisi858 – 863Missing : Abolishes binding of PIAS1 and PIAS2. Dramatically reduces sumoylation and abolishes AXIN1-mediated JNK activation. No effect on homodimerization nor on Wnt-signaling. 1 Publication6
Mutagenesisi858K → A: Decreased sumoylation followed by increased ubiquitination; when associated with A-861. 1 Publication1
Mutagenesisi861K → A: Decreased sumoylation followed by increased ubiquitination; when associated with A-858. 1 Publication1

Keywords - Diseasei

Tumor suppressor

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002208891 – 863Axin-1Add BLAST863

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei75PhosphoserineCombined sources1
Modified residuei77Phosphoserine; by CK1By similarity1
Modified residuei217PhosphoserineCombined sources1
Modified residuei468Phosphoserine; by CK1By similarity1
Modified residuei480Phosphothreonine; by GSK3-beta1 Publication1
Modified residuei485Phosphoserine; by GSK3-beta1 Publication1
Modified residuei492Phosphoserine1 Publication1
Modified residuei509PhosphoserineBy similarity1
Cross-linki858Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)2 Publications
Cross-linki861Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)2 Publications

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 (By similarity). Also phosphorylated by CDK2 which regulates interaction with CTNBB1.By similarity2 Publications
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. 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). Sumoylation at Lys-858 and Lys-861 prevents ubiquitination and degradation. Sumoylation is required for AXIN1-mediated JNK activation.By similarity2 Publications

Keywords - PTMi

ADP-ribosylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiO35625
PaxDbiO35625
PRIDEiO35625

PTM databases

iPTMnetiO35625
PhosphoSitePlusiO35625

Expressioni

Tissue specificityi

Expressed in embryonic stem cells.

Developmental stagei

Widely expressed at E10.5 to E16.5 day.

Gene expression databases

CleanExiMM_AXIN1

Interactioni

Subunit structurei

Homodimer (PubMed:17681137). Component of the beta-catenin destruction complex, containing at least CTNNB1, an axin and GSK3B, that regulates CTNNB1 protein levels through phosphorylation and ubiquitination (By similarity). Interacts with GSK3B; the interaction hyperphosphorylates CTNNB1 leading to its ubiquitination and destruction (By similarity). 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 (By similarity). Also interacts with APC, RNF111, SMAD6 and SMAD7 (By similarity). Interacts (via the C-terminal) with PPP1CA; the interaction dephosphorylates AXIN1 and regulates interaction with GSK3B (By similarity). Interacts with PPP2CA; the interaction dephosphorylates AXIN1 (By similarity). Interacts with MDFI; the interaction decreases AXIN1-mediated JUN N-terminal kinase (JNK) activation (By similarity). Interacts with MDFIC; the interaction inhibits beta-cateninin-mediated signaling and AXIN1-mediated JUN N-terminal kinase (JNK) activation (By similarity). Binds ANKRD6, PIAS1, PIAS2, PIAS4, SUMO1, MAP3K1 and MAP3K4 (PubMed:12183362, PubMed:12223491). Component of the AXIN1-HIPK2-TP53 complex (PubMed:15526030). Interacts directly in the complex with TP53 and HIPK2 (PubMed:15526030). Interacts with DIXDC1; the interaction prevents interaction with MAP3K1 (PubMed:15262978). Interacts with AIDA; the interaction blocks the AXIN1-mediated JNK activation through disrupting AXIN1 homodimerization and Wnt signaling (PubMed:17681137). Interacts with LRP5 (via its phosphorylated PPPSP motifs); the interaction is stimulated by WNT1 and GSK3B and activates beta-catenin signaling (PubMed:11336703). Interacts with CTNNB1 (via the armadillo repeats 2-7) (PubMed:10581160, PubMed:15063782). Interacts with MACF1 (By similarity). Found in a complex composed of MACF1, APC, AXIN1, CTNNB1 and GSK3B (By similarity). Interacts with TNKS (By similarity). Interacts with DAB2; the interaction is mutually exclusive with the AXIN1:PPP1CA interaction (PubMed:19581931). Interacts with ZBED3 (via PPPSP motif); the interaction is direct, enhanced by protein kinase GSK3B and casein kinase CSNK1E activities and decreases GSK3B-induced beta-catenin serine and threonine phosphorylations (PubMed:19141611). Interacts with WDR26 (By similarity). Interacts with GID8 (By similarity).By similarity10 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • armadillo repeat domain binding Source: MGI
  • beta-catenin binding Source: MGI
  • enzyme binding Source: MGI
  • identical protein binding Source: MGI
  • I-SMAD binding Source: BHF-UCL
  • p53 binding Source: MGI
  • protein-containing complex scaffold activity Source: BHF-UCL
  • protein C-terminus binding Source: MGI
  • protein domain specific binding Source: MGI
  • protein homodimerization activity Source: UniProtKB
  • protein kinase binding Source: ParkinsonsUK-UCL
  • protein self-association Source: MGI
  • receptor signaling complex scaffold activity Source: InterPro
  • R-SMAD binding Source: MGI
  • signaling receptor binding Source: MGI
  • SMAD binding Source: MGI
  • ubiquitin protein ligase binding Source: BHF-UCL
View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi198287, 34 interactors
ComplexPortaliCPX-103 Beta-catenin destruction core complex, variant 1
CPX-448 Beta-catenin destruction core complex, variant 2
CPX-453 Beta-catenin destruction core complex, variant 5
CPX-456 Beta-catenin destruction core complex, variant 6
CORUMiO35625
DIPiDIP-42637N
ELMiO35625
IntActiO35625, 28 interactors
MINTiO35625
STRINGi10090.ENSMUSP00000073974

Structurei

Secondary structure

1863
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi64 – 66Combined sources3

3D structure databases

ProteinModelPortaliO35625
SMRiO35625
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini88 – 211RGSPROSITE-ProRule annotationAdd BLAST124
Domaini781 – 863DIXPROSITE-ProRule annotationAdd BLAST83

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni209 – 338Interaction with TP531 PublicationAdd BLAST130
Regioni348 – 432Interaction with GSK3BBy similarityAdd BLAST85
Regioni433 – 501Interaction with beta-cateninBy similarityAdd BLAST69
Regioni505 – 758Interaction with RNF111By similarityAdd BLAST254
Regioni572 – 790Interaction with PPP2CABy similarityAdd BLAST219
Regioni678 – 753Interaction with HIPK21 PublicationAdd BLAST76

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi20 – 29Tankyrase-binding motif10

Domaini

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

Phylogenomic databases

eggNOGiKOG3589 Eukaryota
ENOG410YMJD LUCA
HOVERGENiHBG004324
InParanoidiO35625
KOiK02157

Family and domain databases

CDDicd11582 Axin_TNKS_binding, 1 hit
Gene3Di1.10.196.10, 2 hits
3.10.20.380, 1 hit
InterProiView protein in InterPro
IPR029797 AXIN1
IPR014936 Axin_b-cat-bd
IPR032101 Axin_TNKS-bd
IPR001158 DIX
IPR038207 DIX_dom_sf
IPR016137 RGS
IPR036305 RGS_sf
IPR024066 RGS_subdom1/3
IPR029071 Ubiquitin-like_domsf
PANTHERiPTHR10845:SF11 PTHR10845:SF11, 1 hit
PfamiView protein in Pfam
PF16646 AXIN1_TNKS_BD, 1 hit
PF08833 Axin_b-cat_bind, 1 hit
PF00778 DIX, 1 hit
PF00615 RGS, 1 hit
PRINTSiPR01301 RGSPROTEIN
SMARTiView protein in SMART
SM00021 DAX, 1 hit
SM00315 RGS, 1 hit
SUPFAMiSSF48097 SSF48097, 1 hit
SSF54236 SSF54236, 1 hit
PROSITEiView protein in PROSITE
PS50841 DIX, 1 hit
PS50132 RGS, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O35625-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MNVQEQGFPL DLGASFTEDA PRPPVPGEEG ELVSTDSRPV NHSFCSGKGT 
        60         70         80         90        100
SIKSETSTAT PRRSDLDLGY EPEGSASPTP PYLRWAESLH SLLDDQDGIS 
       110        120        130        140        150
LFRTFLKQEG CADLLDFWFA CSGFRKLEPC DSNEEKRLKL ARAIYRKYIL 
       160        170        180        190        200
DSNGIVSRQT KPATKSFIKD CVMKQQIDPA MFDQAQTEIQ STMEENTYPS 
       210        220        230        240        250
FLKSDIYLEY TRTGSESPKV CSDQSSGSGT GKGMSGYLPT LNEDEEWKCD 
       260        270        280        290        300
QDADEDDGRD PLPPSRLTQK LLLETAAPRA PSSRRYNEGR ELRYGSWREP 
       310        320        330        340        350
VNPYYVNSGY ALAPATSAND SEQQSLSSDA DTLSLTDSSV DGIPPYRIRK 
       360        370        380        390        400
QHRREMQESI QVNGRVPLPH IPRTYRMPKE IRVEPQKFAE ELIHRLEAVQ 
       410        420        430        440        450
RTREAEEKLE ERLKRVRMEE EGEDGEMPSG PMASHKLPSV PAWHHFPPRY 
       460        470        480        490        500
VDMGCSGLRD AHEENPESIL DEHVQRVMRT PGCQSPGPGH RSPDSGHVAK 
       510        520        530        540        550
TAVLGGTASG HGKHVPKLGL KLDTAGLHHH RHVHHHVHHN SARPKEQMEA 
       560        570        580        590        600
EVARRVQSSF SWGPETHGHA KPRSYSENAG TTLSAGDLAF GGKTSAPSKR 
       610        620        630        640        650
NTKKAESGKN ANAEVPSTTE DAEKNQKIMQ WIIEGEKEIS RHRKAGHGSS 
       660        670        680        690        700
GLRKQQAHES SRPLSIERPG AVHPWVSAQL RNSVQPSHLF IQDPTMPPNP 
       710        720        730        740        750
APNPLTQLEE ARRRLEEEEK RANKLPSKQR YVQAVMQRGR TCVRPACAPV 
       760        770        780        790        800
LSVVPAVSDL ELSETETKSQ RKAGGGSAPP CDSIVVAYYF CGEPIPYRTL 
       810        820        830        840        850
VRGRAVTLGQ FKELLTKKGS YRYYFKKVSD EFDCGVVFEE VREDEAVLPV 
       860 
FEEKIIGKVE KVD
Length:863
Mass (Da):96,276
Last modified:October 3, 2012 - v3
Checksum:i2216D66E92387B81
GO
Isoform 2 (identifier: O35625-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     731-766: Missing.

Show »
Length:827
Mass (Da):92,418
Checksum:i0D99A235EEDC597E
GO

Sequence cautioni

The sequence AAC53285 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti589A → P in AAC53285 (PubMed:9230313).Curated1
Sequence conflicti787A → G in AAC53285 (PubMed:9230313).Curated1
Sequence conflicti846A → P in AAC53285 (PubMed:9230313).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_000452731 – 766Missing in isoform 2. 1 PublicationAdd BLAST36

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF009011 mRNA Translation: AAC53285.1 Different initiation.
AC126438 Genomic DNA No translation available.
AC140047 Genomic DNA No translation available.
RefSeqiNP_033863.2, NM_009733.2
UniGeneiMm.23684

Genome annotation databases

GeneIDi12005
KEGGimmu:12005

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiAXIN1_MOUSE
AccessioniPrimary (citable) accession number: O35625
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: October 3, 2012
Last modified: July 18, 2018
This is version 182 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

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