O70239 (AXIN1_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Axin-1

Alternative name(s):
Axis inhibition protein 1
Short name=rAxin

Gene names

Name:	Axin1
Synonyms:	Axin

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	827 AA.
Sequence status	Complete.
Protein existence	Evidence 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. 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. Ref.1 Ref.2
Subcellular location	Cytoplasm By similarity. Nucleus By similarity. Cell membrane. 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 process	Apoptosis Wnt signaling pathway
Cellular component	Cell membrane Cytoplasm Membrane Nucleus
Molecular function	Developmental protein
PTM	ADP-ribosylation Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	Wnt receptor signaling pathway involved in forebrain neuron fate commitment Inferred from Biological aspect of Ancestor. Source: RefGenome Wnt receptor signaling pathway involved in somitogenesis 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 receptor signaling pathway involved in neural plate anterior/posterior pattern formation Inferred from Biological aspect of Ancestor. Source: RefGenome 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 muscle cell development Inferred from Biological aspect of Ancestor. Source: RefGenome negative regulation of canonical Wnt receptor signaling pathway Inferred from Biological aspect of Ancestor. Source: RefGenome negative regulation of fat cell differentiation Inferred from Biological aspect of Ancestor. Source: RefGenome 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 JNK cascade Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process Inferred from direct assay. Source: BHF-UCL protein homooligomerization Inferred from direct assay. Source: RGD regulation of catenin import into nucleus Inferred from Biological aspect of Ancestor. Source: RefGenome tail morphogenesis Inferred from Biological aspect of Ancestor. Source: RefGenome
Cellular component	Axin-APC-beta-catenin-GSK3B complex Inferred from direct assay. Source: BHF-UCL beta-catenin destruction complex Inferred from direct assay. 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 nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from direct assay Ref.2. Source: UniProtKB postsynaptic density Inferred from direct assay. Source: RGD
Molecular function	GTPase 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 protein homodimerization activity Inferred from sequence or structural similarity. Source: UniProtKB protein kinase binding Inferred from physical interaction. Source: BHF-UCL signal transducer activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 827

827

Axin-1

PRO_0000220890

Regions

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

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

827

Helix Strand Turn

Details...

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

Sequences

	Sequence		Length	Mass (Da)
	O70239 [UniParc]. Last modified May 10, 2002. Version 3. Checksum: BB1EE9CCECF6D487	FASTA	827	92,285
	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

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: 9482734] [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: 16815997] [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.

IPI

IPI00231576.

PIR

T08422.

RefSeq

NP_077381.1. NM_024405.1.

UniGene

Rn.31781.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]

ProteinModelPortal

O70239.

SMR

O70239. Positions 74-220, 744-827.

ModBase

Search...

Protein-protein interaction databases

STRING

O70239.

PTM databases

PhosphoSite

O70239.

Proteomic databases

PRIDE

O70239.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSRNOT00000027705; ENSRNOP00000027705; ENSRNOG00000020414.

GeneID

79257.

KEGG

rno:79257.

UCSC

AF017756. rat.

Organism-specific databases

CTD

8312.

RGD

620859. Axin1.

Phylogenomic databases

eggNOG

roNOG11401.

GeneTree

ENSGT00390000010011.

HOVERGEN

HBG004324.

Gene expression databases

ArrayExpress

O70239.

Genevestigator

O70239.

GermOnline

ENSRNOG00000020414. Rattus norvegicus.

Family and domain databases

InterPro

IPR014936. Axin_b-cat-bd.
IPR001158. DIX.
IPR000342. Regulat_G_prot_signal.
IPR024066. Regulat_G_prot_signal_dom1.
IPR016137. Regulat_G_prot_signal_superfam.
[Graphical view]

Gene3D

G3DSA:1.10.196.10. G3DSA:1.10.196.10. 2 hits.

KO

K02157.

Pfam

PF08833. Axin_b-cat_bind. 1 hit.
PF00778. DIX. 1 hit.
PF00615. RGS. 1 hit.
[Graphical view]

PRINTS

PR01301. RGSPROTEIN.

SMART

SM00021. DAX. 1 hit.
SM00315. RGS. 1 hit.
[Graphical view]

SUPFAM

SSF48097. Regulat_G_prot_signal_superfam. 1 hit.

PROSITE

PS50841. DIX. 1 hit.
PS50132. RGS. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

614758.

Entry information

Entry name

AXIN1_RAT

Accession

Primary (citable) accession number: O70239

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	May 10, 2002
Last modified:	November 16, 2011
This is version 104 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program