Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q9Y2T1 (AXIN2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 138. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Axin-2
Alternative name(s):
Axin-like protein
Short name=Axil
Axis inhibition protein 2
Conductin
Gene names
Name:AXIN2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length843 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Inhibitor of the Wnt signaling pathway. Down-regulates beta-catenin. Probably facilitate the phosphorylation of beta-catenin and APC by GSK3B By similarity.

Subunit structure

Interacts with glycogen synthase kinase-3 beta (GSK3B) and beta-catenin. The interaction between axin and beta-catenin occurs via the armadillo repeats contained in beta-catenin By similarity. Interacts with SMAD7 and RNF111. Interacts with ANKRD6. Ref.8 Ref.9 Ref.11

Subcellular location

Cytoplasm.

Tissue specificity

Expressed in brain and lymphoblast.

Domain

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

Post-translational modification

Probably phosphorylated by GSK3B and dephosphorylated by PP2A 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.

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 Wnt signaling to positively regulate beta-catenin (CTNBB1)-mediated transcription. Ref.9 Ref.10 Ref.11

Involvement in disease

Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history.
Note: The gene represented in this entry is involved in disease pathogenesis.

Oligodontia-colorectal cancer syndrome (ODCRCS) [MIM:608615]: Affected individuals manifest severe tooth agenesis and colorectal cancer or precancerous lesions of variable types.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7

Sequence similarities

Contains 1 DIX domain.

Contains 1 RGS domain.

Ontologies

Keywords
   Biological processWnt signaling pathway
   Cellular componentCytoplasm
   Coding sequence diversityPolymorphism
   Molecular functionDevelopmental protein
   PTMADP-ribosylation
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processWnt signaling pathway involved in somitogenesis

Inferred from Biological aspect of Ancestor. Source: RefGenome

bone mineralization

Inferred from electronic annotation. Source: Ensembl

cell proliferation

Inferred from electronic annotation. Source: Ensembl

cellular protein localization

Inferred from direct assay PubMed 17072303. Source: BHF-UCL

cellular response to organic cyclic compound

Inferred from Biological aspect of Ancestor. Source: RefGenome

chondrocyte differentiation involved in endochondral bone morphogenesis

Inferred from electronic annotation. Source: Ensembl

dorsal/ventral axis specification

Inferred from Biological aspect of Ancestor. Source: RefGenome

intramembranous ossification

Inferred from Biological aspect of Ancestor. Source: RefGenome

mRNA stabilization

Inferred from mutant phenotype PubMed 17072303. Source: BHF-UCL

maintenance of DNA repeat elements

Inferred from mutant phenotype PubMed 18755497. Source: BHF-UCL

negative regulation of canonical Wnt signaling pathway

Inferred from direct assay PubMed 11940574. Source: BHF-UCL

negative regulation of catenin import into nucleus

Inferred from mutant phenotype Ref.6. Source: BHF-UCL

negative regulation of cell proliferation

Inferred from mutant phenotype PubMed 16247484. Source: BHF-UCL

negative regulation of osteoblast differentiation

Inferred from Biological aspect of Ancestor. Source: RefGenome

odontogenesis

Inferred from mutant phenotype Ref.7PubMed 16432638. Source: BHF-UCL

positive regulation of GTPase activity

Inferred from Biological aspect of Ancestor. Source: GOC

positive regulation of cell death

Inferred from mutant phenotype PubMed 16247484. Source: BHF-UCL

positive regulation of epithelial to mesenchymal transition

Inferred from mutant phenotype PubMed 17072303. Source: BHF-UCL

positive regulation of protein phosphorylation

Inferred from mutant phenotype PubMed 20300119. Source: BHF-UCL

regulation of centromeric sister chromatid cohesion

Inferred from mutant phenotype PubMed 20300119. Source: BHF-UCL

regulation of chondrocyte development

Inferred from electronic annotation. Source: Ensembl

regulation of mismatch repair

Inferred from mutant phenotype Ref.6. Source: BHF-UCL

termination of G-protein coupled receptor signaling pathway

Inferred from electronic annotation. Source: InterPro

   Cellular_componentbeta-catenin destruction complex

Non-traceable author statement Ref.6. Source: BHF-UCL

cell cortex

Inferred from Biological aspect of Ancestor. Source: RefGenome

centrosome

Inferred from direct assay PubMed 20300119. Source: BHF-UCL

cytoplasm

Inferred from direct assay Ref.10. Source: UniProtKB

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 direct assay Ref.10. Source: UniProtKB

plasma membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

postsynaptic density

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Molecular_functionGTPase activator activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

armadillo repeat domain binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

beta-catenin binding

Non-traceable author statement Ref.6. Source: BHF-UCL

enzyme binding

Inferred from physical interaction Ref.9Ref.10Ref.11. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 10698523PubMed 24251807. Source: IntAct

protein kinase binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

signal transducer activity

Inferred from electronic annotation. Source: InterPro

ubiquitin protein ligase binding

Inferred from physical interaction Ref.11. Source: UniProtKB

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 843843Axin-2
PRO_0000220895

Regions

Domain81 – 200120RGS
Domain761 – 84383DIX
Region327 – 41387Interaction with GSK3B By similarity
Region413 – 47664Interaction with beta-catenin By similarity
Motif21 – 3010Tankyrase-binding motif
Compositional bias469 – 4746Poly-His

Natural variations

Natural variant501S → P in polymorphism associated with increased risk of lung cancer. Ref.12
Corresponds to variant rs2240308 [ dbSNP | Ensembl ].
VAR_054860

Experimental info

Sequence conflict37 – 6226QPGVG…NEDGL → HHGGQGPGHQTHVCLFQHQA ERRWV in AAF22799. Ref.2
Sequence conflict3461Q → R in AAF22799. Ref.2
Sequence conflict572 – 63665Missing in AAF22799. Ref.2
Sequence conflict6871P → S in AAF22799. Ref.2
Sequence conflict6961Q → H in AAF22799. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q9Y2T1 [UniParc].

Last modified November 1, 1999. Version 1.
Checksum: F7B62BED6AB4664D

FASTA84393,558
        10         20         30         40         50         60 
MSSAMLVTCL PDPSSSFRED APRPPVPGEE GETPPCQPGV GKGQVTKPMS VSSNTRRNED 

        70         80         90        100        110        120 
GLGEPEGRAS PDSPLTRWTK SLHSLLGDQD GAYLFRTFLE REKCVDTLDF WFACNGFRQM 

       130        140        150        160        170        180 
NLKDTKTLRV AKAIYKRYIE NNSIVSKQLK PATKTYIRDG IKKQQIDSIM FDQAQTEIQS 

       190        200        210        220        230        240 
VMEENAYQMF LTSDIYLEYV RSGGENTAYM SNGGLGSLKV VCGYLPTLNE EEEWTCADFK 

       250        260        270        280        290        300 
CKLSPTVVGL SSKTLRATAS VRSTETVDSG YRSFKRSDPV NPYHIGSGYV FAPATSANDS 

       310        320        330        340        350        360 
EISSDALTDD SMSMTDSSVD GIPPYRVGSK KQLQREMHRS VKANGQVSLP HFPRTHRLPK 

       370        380        390        400        410        420 
EMTPVEPATF AAELISRLEK LKLELESRHS LEERLQQIRE DEEREGSELT LNSREGAPTQ 

       430        440        450        460        470        480 
HPLSLLPSGS YEEDPQTILD DHLSRVLKTP GCQSPGVGRY SPRSRSPDHH HHHHSQYHSL 

       490        500        510        520        530        540 
LPPGGKLPPA AASPGACPLL GGKGFVTKQT TKHVHHHYIH HHAVPKTKEE IEAEATQRVH 

       550        560        570        580        590        600 
CFCPGGSEYY CYSKCKSHSK APETMPSEQF GGSRGSTLPK RNGKGTEPGL ALPAREGGAP 

       610        620        630        640        650        660 
GGAGALQLPR EEGDRSQDVW QWMLESERQS KPKPHSAQST KKAYPLESAR SSPGERASRH 

       670        680        690        700        710        720 
HLWGGNSGHP RTTPRAHLFT QDPAMPPLTP PNTLAQLEEA CRRLAEVSKP PKQRCCVASQ 

       730        740        750        760        770        780 
QRDRNHSATV QTGATPFSNP SLAPEDHKEP KKLAGVHALQ ASELVVTYFF CGEEIPYRRM 

       790        800        810        820        830        840 
LKAQSLTLGH FKEQLSKKGN YRYYFKKASD EFACGAVFEE IWEDETVLPM YEGRILGKVE 


RID 

« Hide

References

« Hide 'large scale' references
[1]"Cloning of the human homolog of conductin (AXIN2), a gene mapping to chromosome 17q23-q24."
Mai M., Qian C., Yokomizo A., Smith D.I., Liu W.
Genomics 55:341-344(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Properties of mouse Axin2 and human AXIN2: chromosomal location, expression pattern, interaction with Axin and effects on embryonic axis formation."
Zhang T., Fagotto F., Hsu W., Zeng L., Gilbert D., Copeland N.G., Jenkins N.A., Warburton D., Costantini F.
Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Brain and Lymphoblast.
[3]"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. expand/collapse author list , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[5]"Identification of 3' UTR of Axin2."
Takahashi M., Furukawa Y.
Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 697-843.
[6]"Mutations in AXIN2 cause colorectal cancer with defective mismatch repair by activating beta-catenin/TCF signalling."
Liu W., Dong X., Mai M., Seelan R.S., Taniguchi K., Krishnadath K.K., Halling K.C., Cunningham J.M., Qian C., Christensen E., Roches P.C., Smith D.I., Thibodeau S.N.
Nat. Genet. 26:146-147(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN COLORECTAL CANCER.
[7]"Mutations in AXIN2 cause familial tooth agenesis and predispose to colorectal cancer."
Lammi L., Arte S., Somer M., Jarvinen H., Lahermo P., Thesleff I., Pirinen S., Nieminen P.
Am. J. Hum. Genet. 74:1043-1050(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN ODCRCS.
[8]"Axin is a scaffold protein in TGF-beta signaling that promotes degradation of Smad7 by Arkadia."
Liu W., Rui H., Wang J., Lin S., He Y., Chen M., Li Q., Ye Z., Zhang S., Chan S.C., Chen Y.-G., Han J., Lin S.-C.
EMBO J. 25:1646-1658(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SMAD7 AND RNF111.
[9]"Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling."
Huang S.M., Mishina Y.M., Liu S., Cheung A., Stegmeier F., Michaud G.A., Charlat O., Wiellette E., Zhang Y., Wiessner S., Hild M., Shi X., Wilson C.J., Mickanin C., Myer V., Fazal A., Tomlinson R., Serluca F. expand/collapse author list , Shao W., Cheng H., Shultz M., Rau C., Schirle M., Schlegl J., Ghidelli S., Fawell S., Lu C., Curtis D., Kirschner M.W., Lengauer C., Finan P.M., Tallarico J.A., Bouwmeester T., Porter J.A., Bauer A., Cong F.
Nature 461:614-620(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ADP-RIBOSYLATION, UBIQUITINATION, INTERACTION WITH TNKS AND TNKS2.
[10]"The Ubiquitin specific protease USP34 regulates Axin stability and Wnt/beta-catenin signaling."
Lui T.T., Lacroix C., Ahmed S.M., Goldenberg S.J., Leach C.A., Daulat A.M., Angers S.
Mol. Cell. Biol. 31:2053-2065(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION, DEUBIQUITINATION BY USP34.
[11]"RNF146 is a poly(ADP-ribose)-directed E3 ligase that regulates axin degradation and Wnt signalling."
Zhang Y., Liu S., Mickanin C., Feng Y., Charlat O., Michaud G.A., Schirle M., Shi X., Hild M., Bauer A., Myer V.E., Finan P.M., Porter J.A., Huang S.M., Cong F.
Nat. Cell Biol. 13:623-629(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: ADP-RIBOSYLATION, UBIQUITINATION, INTERACTION WITH RNF146; TNKS AND TNKS2.
[12]"Single nucleotide polymorphism of the AXIN2 gene is preferentially associated with human lung cancer risk in a Japanese population."
Kanzaki H., Ouchida M., Hanafusa H., Yano M., Suzuki H., Aoe M., Imai K., Shimizu N., Nakachi K., Shimizu K.
Int. J. Mol. Med. 18:279-284(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PRO-50.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF078165 mRNA. Translation: AAD20976.1.
AF205888 mRNA. Translation: AAF22799.1.
AC115994 Genomic DNA. No translation available.
BC101533 mRNA. Translation: AAI01534.1.
AB052751 mRNA. Translation: BAB19762.1.
CCDSCCDS11662.1.
RefSeqNP_004646.3. NM_004655.3.
UniGeneHs.156527.

3D structure databases

ProteinModelPortalQ9Y2T1.
SMRQ9Y2T1. Positions 74-199, 764-843.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113910. 10 interactions.
DIPDIP-59293N.
IntActQ9Y2T1. 10 interactions.
MINTMINT-3085018.
STRING9606.ENSP00000302625.

Chemistry

ChEMBLCHEMBL1255167.

PTM databases

PhosphoSiteQ9Y2T1.

Polymorphism databases

DMDM12643949.

Proteomic databases

MaxQBQ9Y2T1.
PaxDbQ9Y2T1.
PRIDEQ9Y2T1.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000307078; ENSP00000302625; ENSG00000168646.
GeneID8313.
KEGGhsa:8313.
UCSCuc002jfi.3. human.

Organism-specific databases

CTD8313.
GeneCardsGC17M063524.
HGNCHGNC:904. AXIN2.
HPACAB012283.
CAB017783.
HPA042344.
MIM114500. phenotype.
604025. gene.
608615. phenotype.
neXtProtNX_Q9Y2T1.
Orphanet2227. Hypodontia.
99798. Oligodontia.
300576. Oligodontia - cancer predisposition syndrome.
PharmGKBPA25196.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG238205.
HOVERGENHBG004324.
InParanoidQ9Y2T1.
KOK04385.
OrthoDBEOG79PJQ0.
PhylomeDBQ9Y2T1.
TreeFamTF315454.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
SignaLinkQ9Y2T1.

Gene expression databases

ArrayExpressQ9Y2T1.
BgeeQ9Y2T1.
CleanExHS_AXIN2.
GenevestigatorQ9Y2T1.

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

ChiTaRSAXIN2. human.
GeneWikiAXIN2.
GenomeRNAi8313.
NextBio31133.
PROQ9Y2T1.
SOURCESearch...

Entry information

Entry nameAXIN2_HUMAN
AccessionPrimary (citable) accession number: Q9Y2T1
Secondary accession number(s): Q3MJ88, Q9H3M6, Q9UH84
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: November 1, 1999
Last modified: July 9, 2014
This is version 138 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM