Q9Y2T1 (AXIN2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Axin-2

Alternative name(s):
Axin-like protein
Short name=Axil
Axis inhibition protein 2
Conductin

Gene names

Name:

AXIN2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	843 AA.
Sequence status	Complete.
Protein existence	Evidence 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.10 Ref.12
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. Ref.9 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.10 Ref.11 Ref.12
Involvement in disease	Defects in AXIN2 are involved in colorectal cancer (CRC) [MIM:114500]. They appear to be specifically associated with defective mismatch repair. Defects in AXIN2 are the cause of oligodontia-colorectal cancer syndrome (ODCRCS) [MIM:608615]. Affected individuals manifest severe tooth agenesis and colorectal cancer or precancerous lesions of variable types. Ref.7
Sequence similarities	Contains 1 DIX domain. Contains 1 RGS domain.

Ontologies

Keywords
Biological process	Wnt signaling pathway
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Molecular function	Developmental protein
PTM	ADP-ribosylation Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	Wnt receptor signaling pathway involved in somitogenesis Inferred from Biological aspect of Ancestor. Source: RefGenome cellular protein localization Inferred from direct assay. Source: BHF-UCL cellular response to organic cyclic compound Inferred from Biological aspect of Ancestor. Source: RefGenome 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. Source: BHF-UCL maintenance of DNA repeat elements Inferred from mutant phenotype. Source: BHF-UCL negative regulation of canonical Wnt receptor signaling pathway Inferred from direct assay. 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. Source: BHF-UCL negative regulation of osteoblast differentiation Inferred from Biological aspect of Ancestor. Source: RefGenome odontogenesis Inferred from mutant phenotype Ref.7. Source: BHF-UCL positive regulation of cell death Inferred from mutant phenotype. Source: BHF-UCL positive regulation of epithelial to mesenchymal transition Inferred from mutant phenotype. Source: BHF-UCL positive regulation of protein phosphorylation Inferred from mutant phenotype. Source: BHF-UCL regulation of centromeric sister chromatid cohesion Inferred from mutant phenotype. Source: BHF-UCL regulation of mismatch repair Inferred from mutant phenotype Ref.6. Source: BHF-UCL
Cellular component	Axin-APC-beta-catenin-GSK3B 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. Source: BHF-UCL 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.11. Source: UniProtKB plasma membrane Inferred from Biological aspect of Ancestor. Source: RefGenome postsynaptic density Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular function	GTPase 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 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.12. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 843	843	Axin-2		PRO_0000220895
Regions
	Domain	81 – 200	120	RGS
	Domain	761 – 843	83	DIX
	Region	327 – 413	87	Interaction with GSK3B By similarity
	Region	413 – 476	64	Interaction with beta-catenin By similarity
	Motif	21 – 30	10	Tankyrase-binding motif
	Compositional bias	469 – 474	6	Poly-His
Amino acid modifications
	Modified residue	460	1	Phosphotyrosine By similarity
	Modified residue	464	1	Phosphoserine By similarity
	Modified residue	630	1	Phosphoserine Ref.9
	Modified residue	639	1	Phosphoserine Ref.9
	Modified residue	640	1	Phosphothreonine Ref.9
Natural variations
	Natural variant	50	1	S → P in polymorphism associated with increased risk of lung cancer. Ref.13 Corresponds to variant rs2240308 [ dbSNP | Ensembl ].		VAR_054860
Experimental info
	Sequence conflict	37 – 62	26	QPGVG…NEDGL → HHGGQGPGHQTHVCLFQHQA ERRWV in AAF22799. Ref.2
	Sequence conflict	346	1	Q → R in AAF22799. Ref.2
	Sequence conflict	572 – 636	65	Missing in AAF22799. Ref.2
	Sequence conflict	687	1	P → S in AAF22799. Ref.2
	Sequence conflict	696	1	Q → H in AAF22799. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q9Y2T1 [UniParc]. Last modified November 1, 1999. Version 1. Checksum: F7B62BED6AB4664D	FASTA	843	93,558
	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

References

	« Hide 'large scale' referencesShow '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: 10049590] [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. , 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: 16625196] [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: 15489334] [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: 11017067] [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: 15042511] [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: 16601693] [Abstract] Cited for: INTERACTION WITH SMAD7 AND RNF111.
[9]	"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra." Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D. J. Proteome Res. 6:4150-4162(2007) [PubMed: 17924679] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-630; SER-639 AND THR-640, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"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. , 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: 19759537] [Abstract] Cited for: ADP-RIBOSYLATION, UBIQUITINATION, INTERACTION WITH TNKS AND TNKS2.
[11]	"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: 21383061] [Abstract] Cited for: UBIQUITINATION, DEUBIQUITINATION BY USP34.
[12]	"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: 21478859] [Abstract] Cited for: ADP-RIBOSYLATION, UBIQUITINATION, INTERACTION WITH RNF146; TNKS AND TNKS2.
[13]	"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: 16820935] [Abstract] Cited for: VARIANT PRO-50.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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.
IPI	IPI00294274.
RefSeq	NP_004646.3. NM_004655.3.
UniGene	Hs.156527.
3D structure databases
ProteinModelPortal	Q9Y2T1.
SMR	Q9Y2T1. Positions 74-199, 764-843.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9Y2T1. 2 interactions.
STRING	Q9Y2T1.
PTM databases
PhosphoSite	Q9Y2T1.
Polymorphism databases
DMDM	12643949.
Proteomic databases
PRIDE	Q9Y2T1.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000307078; ENSP00000302625; ENSG00000168646.
GeneID	8313.
KEGG	hsa:8313.
UCSC	uc002jfh.1. human.
Organism-specific databases
CTD	8313.
GeneCards	GC17M063524.
HGNC	HGNC:904. AXIN2.
HPA	CAB012283. CAB017783.
MIM	114500. phenotype. 604025. gene. 608615. phenotype.
neXtProt	NX_Q9Y2T1.
Orphanet	2227. Hypodontia.
PharmGKB	PA25196.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG07843.
GeneTree	ENSGT00390000010011.
HOGENOM	HBG714290.
HOVERGEN	HBG004324.
InParanoid	Q9Y2T1.
OrthoDB	EOG4X3H11.
Enzyme and pathway databases
Pathway_Interaction_DB	wnt_canonical_pathway. Canonical Wnt signaling pathway.
Gene expression databases
ArrayExpress	Q9Y2T1.
Bgee	Q9Y2T1.
CleanEx	HS_AXIN2.
Genevestigator	Q9Y2T1.
GermOnline	ENSG00000168646. Homo sapiens.
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	K04385.
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
SOURCE	Search...

Entry information

Entry name

AXIN2_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 112 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.