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Protein

Axin-2

Gene

AXIN2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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

GO - Molecular functioni

  • beta-catenin binding Source: BHF-UCL
  • enzyme binding Source: UniProtKB
  • GTPase activator activity Source: GO_Central
  • I-SMAD binding Source: Ensembl
  • ubiquitin protein ligase binding Source: UniProtKB

GO - Biological processi

  • beta-catenin-TCF complex assembly Source: Reactome
  • bone mineralization Source: Ensembl
  • cell proliferation Source: Ensembl
  • cellular protein localization Source: BHF-UCL
  • chondrocyte differentiation involved in endochondral bone morphogenesis Source: Ensembl
  • intramembranous ossification Source: GO_Central
  • maintenance of DNA repeat elements Source: BHF-UCL
  • mRNA stabilization Source: BHF-UCL
  • negative regulation of canonical Wnt signaling pathway Source: BHF-UCL
  • negative regulation of cell proliferation Source: BHF-UCL
  • negative regulation of osteoblast differentiation Source: GO_Central
  • odontogenesis Source: BHF-UCL
  • positive regulation of canonical Wnt signaling pathway Source: Reactome
  • positive regulation of cell death Source: BHF-UCL
  • positive regulation of epithelial to mesenchymal transition Source: BHF-UCL
  • positive regulation of protein phosphorylation Source: BHF-UCL
  • regulation of centromeric sister chromatid cohesion Source: BHF-UCL
  • regulation of chondrocyte development Source: Ensembl
  • regulation of mismatch repair Source: BHF-UCL
  • secondary heart field specification Source: Ensembl
  • somitogenesis Source: Ensembl
  • Wnt signaling pathway Source: UniProtKB-KW

Keywordsi

Molecular functionDevelopmental protein
Biological processWnt signaling pathway

Enzyme and pathway databases

ReactomeiR-HSA-201681 TCF dependent signaling in response to WNT
R-HSA-4411364 Binding of TCF/LEF:CTNNB1 to target gene promoters
R-HSA-4641257 Degradation of AXIN
R-HSA-5689880 Ub-specific processing proteases
SignaLinkiQ9Y2T1
SIGNORiQ9Y2T1

Names & Taxonomyi

Protein namesi
Recommended name:
Axin-2
Alternative name(s):
Axin-like protein
Short name:
Axil
Axis inhibition protein 2
Conductin
Gene namesi
Name:AXIN2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000168646.12
HGNCiHGNC:904 AXIN2
MIMi604025 gene
neXtProtiNX_Q9Y2T1

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

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Colorectal cancer (CRC)1 Publication
The gene represented in this entry is involved in disease pathogenesis.
Disease descriptionA 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.
See also OMIM:114500
Oligodontia-colorectal cancer syndrome (ODCRCS)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAffected individuals manifest severe tooth agenesis and colorectal cancer or precancerous lesions of variable types.
See also OMIM:608615

Organism-specific databases

DisGeNETi8313
MalaCardsiAXIN2
MIMi114500 phenotype
608615 phenotype
Orphaneti401911 AXIN2-related attenuated familial adenomatous polyposis
2227 Hypodontia
99798 Oligodontia
300576 Oligodontia - cancer predisposition syndrome
PharmGKBiPA25196

Chemistry databases

ChEMBLiCHEMBL1255167

Polymorphism and mutation databases

BioMutaiAXIN2
DMDMi12643949

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002208951 – 843Axin-2Add BLAST843

Post-translational modificationi

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.1 Publication
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.1 Publication

Keywords - PTMi

ADP-ribosylation, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ9Y2T1
PaxDbiQ9Y2T1
PeptideAtlasiQ9Y2T1
PRIDEiQ9Y2T1

PTM databases

iPTMnetiQ9Y2T1
PhosphoSitePlusiQ9Y2T1

Expressioni

Tissue specificityi

Expressed in brain and lymphoblast.

Gene expression databases

BgeeiENSG00000168646
CleanExiHS_AXIN2
ExpressionAtlasiQ9Y2T1 baseline and differential
GenevisibleiQ9Y2T1 HS

Organism-specific databases

HPAiCAB012283
CAB017783

Interactioni

Subunit structurei

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.By similarity3 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • beta-catenin binding Source: BHF-UCL
  • enzyme binding Source: UniProtKB
  • I-SMAD binding Source: Ensembl
  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi113910, 16 interactors
DIPiDIP-59293N
IntActiQ9Y2T1, 61 interactors
MINTiQ9Y2T1
STRINGi9606.ENSP00000302625

Chemistry databases

BindingDBiQ9Y2T1

Structurei

3D structure databases

ProteinModelPortaliQ9Y2T1
SMRiQ9Y2T1
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini81 – 200RGSPROSITE-ProRule annotationAdd BLAST120
Domaini761 – 843DIXPROSITE-ProRule annotationAdd BLAST83

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni327 – 413Interaction with GSK3BBy similarityAdd BLAST87
Regioni413 – 476Interaction with beta-cateninBy similarityAdd BLAST64

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi21 – 30Tankyrase-binding motif10

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi469 – 474Poly-His6

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
InParanoidiQ9Y2T1
KOiK04385
OrthoDBiEOG091G0ABG
PhylomeDBiQ9Y2T1
TreeFamiTF315454

Family and domain databases

CDDicd11582 Axin_TNKS_binding, 1 hit
Gene3Di1.10.196.10, 1 hit
3.10.20.380, 1 hit
InterProiView protein in InterPro
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
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

Sequencei

Sequence statusi: Complete.

Q9Y2T1-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSSAMLVTCL PDPSSSFRED APRPPVPGEE GETPPCQPGV GKGQVTKPMS
60 70 80 90 100
VSSNTRRNED GLGEPEGRAS PDSPLTRWTK SLHSLLGDQD GAYLFRTFLE
110 120 130 140 150
REKCVDTLDF WFACNGFRQM NLKDTKTLRV AKAIYKRYIE NNSIVSKQLK
160 170 180 190 200
PATKTYIRDG IKKQQIDSIM FDQAQTEIQS VMEENAYQMF LTSDIYLEYV
210 220 230 240 250
RSGGENTAYM SNGGLGSLKV VCGYLPTLNE EEEWTCADFK CKLSPTVVGL
260 270 280 290 300
SSKTLRATAS VRSTETVDSG YRSFKRSDPV NPYHIGSGYV FAPATSANDS
310 320 330 340 350
EISSDALTDD SMSMTDSSVD GIPPYRVGSK KQLQREMHRS VKANGQVSLP
360 370 380 390 400
HFPRTHRLPK EMTPVEPATF AAELISRLEK LKLELESRHS LEERLQQIRE
410 420 430 440 450
DEEREGSELT LNSREGAPTQ HPLSLLPSGS YEEDPQTILD DHLSRVLKTP
460 470 480 490 500
GCQSPGVGRY SPRSRSPDHH HHHHSQYHSL LPPGGKLPPA AASPGACPLL
510 520 530 540 550
GGKGFVTKQT TKHVHHHYIH HHAVPKTKEE IEAEATQRVH CFCPGGSEYY
560 570 580 590 600
CYSKCKSHSK APETMPSEQF GGSRGSTLPK RNGKGTEPGL ALPAREGGAP
610 620 630 640 650
GGAGALQLPR EEGDRSQDVW QWMLESERQS KPKPHSAQST KKAYPLESAR
660 670 680 690 700
SSPGERASRH HLWGGNSGHP RTTPRAHLFT QDPAMPPLTP PNTLAQLEEA
710 720 730 740 750
CRRLAEVSKP PKQRCCVASQ QRDRNHSATV QTGATPFSNP SLAPEDHKEP
760 770 780 790 800
KKLAGVHALQ ASELVVTYFF CGEEIPYRRM LKAQSLTLGH FKEQLSKKGN
810 820 830 840
YRYYFKKASD EFACGAVFEE IWEDETVLPM YEGRILGKVE RID
Length:843
Mass (Da):93,558
Last modified:November 1, 1999 - v1
Checksum:iF7B62BED6AB4664D
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti37 – 62QPGVG…NEDGL → HHGGQGPGHQTHVCLFQHQA ERRWV in AAF22799 (Ref. 2) CuratedAdd BLAST26
Sequence conflicti346Q → R in AAF22799 (Ref. 2) Curated1
Sequence conflicti572 – 636Missing in AAF22799 (Ref. 2) CuratedAdd BLAST65
Sequence conflicti687P → S in AAF22799 (Ref. 2) Curated1
Sequence conflicti696Q → H in AAF22799 (Ref. 2) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05486050S → P in polymorphism associated with increased risk of lung cancer. 1 PublicationCorresponds to variant dbSNP:rs2240308Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS11662.1
RefSeqiNP_004646.3, NM_004655.3
UniGeneiHs.156527

Genome annotation databases

EnsembliENST00000307078; ENSP00000302625; ENSG00000168646
GeneIDi8313
KEGGihsa:8313
UCSCiuc002jfi.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiAXIN2_HUMAN
AccessioniPrimary (citable) accession number: Q9Y2T1
Secondary accession number(s): Q3MJ88, Q9H3M6, Q9UH84
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: November 1, 1999
Last modified: May 23, 2018
This is version 175 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

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