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Reviewed, UniProtKB/Swiss-Prot O15169 (AXN1_HUMAN)

Last modified January 19, 2010. Version 114. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Axin-1
Alternative name(s):
    Axis inhibition protein 1
      Short name=hAxin
Gene names
Name: AXIN1
Synonyms: AXIN
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length862 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Function

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. In Wnt signaling, probably facilitates the phosphorylation of beta-catenin and APC by GSK3B. Likely to function as a tumor suppressor. Facilitates the phosphorylation of TP53 by HIPK2 upon ultraviolet irradiation. Wild-type axin 1 can induce apoptosis in hepatocellular and colorectal cancer cells. Enhances TGF-beta signaling by recruiting the RNF111 E3 ubiquitin ligase and promoting the degradation of inhibitory SMAD7. Ref.7

Subunit structure

Homodimer By similarity. Interacts with TP53 and HIPK2. Probably part of a complex consisting of TP53, HIPK2 and AXIN1. 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. Ternary complex. Also binds to plakoglobin (gamma-catenin), APC, DVL and PP2A. Interacts with SMAD6, SMAD7 and RNF111. Interacts with DIXDC1; prevents interaction with MAP3K1. Interacts with MAP3K4, MDFI and MDFIC. Interacts with ANKRD6. Interacts with AIDA. Ref.7 Ref.5 Ref.6

Subcellular location

Cytoplasm Ref.7.

Tissue specificity

Ubiquitously expressed.

Post-translational modification

Probably phosphorylated by GSK3B and dephosphorylated by PP2A.

Involvement in disease

Defects in AXIN1 are involved in hepatocellular carcinoma (HCC) [MIM:114550]. Ref.9 Ref.11

Hypermethylation of the AXIN1 promoter may be associated with caudal duplication anomaly [MIM:607864]. Caudal duplication anomaly is characterized by the occurrence of duplications of different organs in the caudal region. Ref.9

Sequence similarities

Contains 1 DIX domain.

Contains 1 RGS domain.

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Ontologies

Keywords
   Biological processApoptosis
Wnt signaling pathway
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
Tumor suppressor
   Molecular functionDevelopmental protein
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Gene Ontology (GO)
   Biological processWnt receptor signaling pathway through beta-catenin

Inferred by curator. Source: UniProtKB

apoptosis

Inferred from electronic annotation. Source: UniProtKB-KW

negative regulation of Wnt receptor signaling pathway

Inferred from direct assay. Source: UniProtKB

oocyte axis specification Ref.1

Traceable author statement. Source: UniProtKB

positive regulation of JNK cascade

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of peptidyl-serine phosphorylation

Inferred from direct assay. Source: UniProtKB

positive regulation of peptidyl-threonine phosphorylation

Inferred from direct assay. Source: UniProtKB

positive regulation of protein ubiquitination

Inferred from direct assay. Source: UniProtKB

   Cellular componentbeta-catenin destruction complex

Inferred from direct assay. Source: UniProtKB

cytosol

Inferred from Experiment. Source: Reactome

lateral plasma membrane

Inferred from direct assay. Source: MGI

nucleus

Inferred from direct assay. Source: MGI

   Molecular functionI-SMAD binding

Inferred from physical interaction. Source: UniProtKB

armadillo repeat domain binding

Inferred from sequence or structural similarity. Source: UniProtKB

beta-catenin binding

Inferred from direct assay. Source: UniProtKB

protein homodimerization activity

Inferred from sequence or structural similarity. Source: UniProtKB

signal transducer activity Ref.1

Non-traceable author statement. Source: UniProtKB

Complete GO annotation...

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Binary interactions

With

Entry

#Exp.

IntAct

Notes

ANP32AP396871EBI-710484,EBI-359234
CRMP1Q141941EBI-710484,EBI-473101
Ctnnb1Q022482EBI-710484,EBI-397872From a different organism.
GSK3BP498411EBI-710484,EBI-373586
SMYD2Q9NRG41EBI-710484,EBI-1055671

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Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O15169-1)

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.
Isoform 2 (identifier: O15169-2)

The sequence of this isoform differs from the canonical sequence as follows:
     730-765: Missing.

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 862862Axin-1
PRO_0000220888

Regions

Domain88 – 211124RGS
Domain780 – 86283DIX
Region209 – 338130Interaction with TP53 By similarity
Region348 – 43386Interaction with GSK3B By similarity
Region434 – 50269Interaction with beta-catenin By similarity
Region507 – 757251Interaction with RNF111
Region677 – 75276Interaction with HIPK2 By similarity

Amino acid modifications

Modified residue4931Phosphoserine By similarity

Natural variations

Alternative sequence730 – 76536Missing in isoform 2.
VSP_019398
Natural variant1061L → R in HCC. Ref.11
VAR_015589
Natural variant3451P → L in HCC. Ref.11
VAR_015590
Natural variant4251G → S in HCC. Ref.11
VAR_015591
Natural variant6501G → S in HCC and in hepatoblastoma. Ref.11
VAR_015592
Natural variant8411R → Q in hepatoblastoma. dbSNP rs34015754. Ref.11
VAR_015593

Experimental info

Sequence conflict3601V → A in AAC51624. Ref.1
Sequence conflict451 – 4555CVDMG → LCWTWA in AAC51624. Ref.1
Sequence conflict4821P → T in AAC51624. Ref.1

Secondary structure

1 ........................ 862
Helix Strand Turn

Details...

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Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 10, 2002. Version 2.
Checksum: 10779173F5092F3F

FASTA86295,635
        10         20         30         40         50         60 
MNIQEQGFPL DLGASFTEDA PRPPVPGEEG ELVSTDPRPA SYSFCSGKGV GIKGETSTAT 

        70         80         90        100        110        120 
PRRSDLDLGY EPEGSASPTP PYLKWAESLH SLLDDQDGIS LFRTFLKQEG CADLLDFWFA 

       130        140        150        160        170        180 
CTGFRKLEPC DSNEEKRLKL ARAIYRKYIL DNNGIVSRQT KPATKSFIKG CIMKQLIDPA 

       190        200        210        220        230        240 
MFDQAQTEIQ ATMEENTYPS FLKSDIYLEY TRTGSESPKV CSDQSSGSGT GKGISGYLPT 

       250        260        270        280        290        300 
LNEDEEWKCD QDMDEDDGRD AAPPGRLPQK LLLETAAPRV SSSRRYSEGR EFRYGSWREP 

       310        320        330        340        350        360 
VNPYYVNAGY ALAPATSAND SEQQSLSSDA DTLSLTDSSV DGIPPYRIRK QHRREMQESV 

       370        380        390        400        410        420 
QVNGRVPLPH IPRTYRVPKE VRVEPQKFAE ELIHRLEAVQ RTREAEEKLE ERLKRVRMEE 

       430        440        450        460        470        480 
EGEDGDPSSG PPGPCHKLPP APAWHHFPPR CVDMGCAGLR DAHEENPESI LDEHVQRVLR 

       490        500        510        520        530        540 
TPGRQSPGPG HRSPDSGHVA KMPVALGGAA SGHGKHVPKS GAKLDAAGLH HHRHVHHHVH 

       550        560        570        580        590        600 
HSTARPKEQV EAEATRRAQS SFAWGLEPHS HGARSRGYSE SVGAAPNASD GLAHSGKVGV 

       610        620        630        640        650        660 
ACKRNAKKAE SGKSASTEVP GASEDAEKNQ KIMQWIIEGE KEISRHRRTG HGSSGTRKPQ 

       670        680        690        700        710        720 
PHENSRPLSL EHPWAGPQLR TSVQPSHLFI QDPTMPPHPA PNPLTQLEEA RRRLEEEEKR 

       730        740        750        760        770        780 
ASRAPSKQRY VQEVMRRGRA CVRPACAPVL HVVPAVSDME LSETETRSQR KVGGGSAQPC 

       790        800        810        820        830        840 
DSIVVAYYFC GEPIPYRTLV RGRAVTLGQF KELLTKKGSY RYYFKKVSDE FDCGVVFEEV 

       850        860 
REDEAVLPVF EEKIIGKVEK VD

« Hide

Isoform 2.

Checksum: 4AA4187D70A5863D
Show »

FASTA82691,653

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References

« Hide 'large scale' references
[1]"The mouse Fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation."
Zeng L., Fagotto F., Zhang T., Hsu W., Vasicek T.J., Perry W.L. III, Lee J.J., Tilghman S.M., Gumbiner B.M., Costantini F.
Cell 90:181-192(1997) [PubMed: 9230313] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Sequence, structure and pathology of the fully annotated terminal 2 Mb of the short arm of human chromosome 16."
Daniels R.J., Peden J.F., Lloyd C., Horsley S.W., Clark K., Tufarelli C., Kearney L., Buckle V.J., Doggett N.A., Flint J., Higgs D.R.
Hum. Mol. Genet. 10:339-352(2001) [PubMed: 11157797] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"The sequence and analysis of duplication-rich human chromosome 16."
Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. expand/collapse author list , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A.
Nature 432:988-994(2004) [PubMed: 15616553] [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] (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 471-862 (ISOFORM 1).
Tissue: Lymphoma and Renal cell carcinoma.
[5]"I-mfa domain proteins interact with Axin and affect its regulation of the Wnt and c-Jun N-terminal kinase signaling pathways."
Kusano S., Raab-Traub N.
Mol. Cell. Biol. 22:6393-6405(2002) [PubMed: 12192039] [Abstract]
Cited for: INTERACTION WITH MDFI AND MDFIC.
[6]"The DIX domain protein coiled-coil-DIX1 inhibits c-Jun N-terminal kinase activation by Axin and dishevelled through distinct mechanisms."
Wong C.K., Luo W., Deng Y., Zou H., Ye Z., Lin S.-C.
J. Biol. Chem. 279:39366-39373(2004) [PubMed: 15262978] [Abstract]
Cited for: INTERACTION WITH DIXDC1; MAP3K1 AND MAP3K4.
[7]"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 SMAD6; SMAD7 AND RNF111, FUNCTION, SUBCELLULAR LOCATION.
[8]"Structural basis of the axin-adenomatous polyposis coli interaction."
Spink K.E., Polakis P., Weis W.I.
EMBO J. 19:2270-2279(2000) [PubMed: 10811618] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.57 ANGSTROMS) OF 74-220 IN COMPLEX WITH APC.
[9]"AXIN1 mutations in hepatocellular carcinomas, and growth suppression in cancer cells by virus-mediated transfer of AXIN1."
Satoh S., Daigo Y., Furukawa Y., Kato T., Miwa N., Nishiwaki T., Kawasoe T., Ishiguro H., Fujita M., Tokino T., Sasaki Y., Imaoka S., Murata M., Shimano T., Yamaoka Y., Nakamura Y.
Nat. Genet. 24:245-250(2000) [PubMed: 10700176] [Abstract]
Cited for: DISEASE.
[10]"Structural basis for recruitment of glycogen synthase kinase 3beta to the axin-APC scaffold complex."
Dajani R., Fraser E., Roe S.M., Yeo M., Good V.M., Thompson V., Dale T.C., Pearl L.H.
EMBO J. 22:494-501(2003) [PubMed: 12554650] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 383-400 IN COMPLEX WITH GSK3B.
[11]"Mutational spectrum of beta-catenin, AXIN1, and AXIN2 in hepatocellular carcinomas and hepatoblastomas."
Taniguchi K., Roberts L.R., Aderca I.N., Dong X., Qian C., Murphy L.M., Nagorney D.M., Burgart L.J., Roche P.C., Smith D.I., Ross J.A., Liu W.
Oncogene 21:4863-4871(2002) [PubMed: 12101426] [Abstract]
Cited for: VARIANTS HCC ARG-106; LEU-345; SER-425 AND SER-650, VARIANT HEPATOBLASTOMA GLN-841.
[12]"Increased DNA methylation at the AXIN1 gene in a monozygotic twin from a pair discordant for a caudal duplication anomaly."
Oates N.A., van Vliet J., Duffy D.L., Kroes H.Y., Martin N.G., Boomsma D.I., Campbell M., Coulthard M.G., Whitelaw E., Chong S.
Am. J. Hum. Genet. 79:155-162(2006) [PubMed: 16773576] [Abstract]
Cited for: INVOLVEMENT IN CAUDAL DUPLICATION ANOMALY.
+Additional computationally mapped references.

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Cross-references

Sequence databases

EMBL
GenBank
DDBJ		AF009674 mRNA. Translation: AAC51624.1. Different initiation.
AE006463 Genomic DNA. Translation: AAK61224.1.
Z69667, AC005202, Z99754 Genomic DNA. Translation: CAI95589.2.
Z69667, AC005202, Z99754 Genomic DNA. Translation: CAI95590.2.
Z99754, AC005202, Z69667 Genomic DNA. Translation: CAI95600.2.
Z99754, AC005202, Z69667 Genomic DNA. Translation: CAI95601.2.
BC017447 mRNA. Translation: AAH17447.1.
BC044648 mRNA. Translation: AAH44648.1.
IPIIPI00747002.
IPI00748214.
RefSeqNP_003493.1.
NP_851393.1.
UniGeneHs.592082

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1DK8X-ray1.57A74-220[»]
1EMUX-ray1.90A80-211[»]
1O9UX-ray2.40B383-400[»]
SMRO15169. Positions 779-862.
ModBaseSearch...

Protein-protein interaction databases

IntActO15169. 11 interactions.
STRINGO15169.

PTM databases

PhosphoSiteO15169.

Proteomic databases

PRIDEO15169.

Genome annotation databases

EnsemblENST00000262320; ENSP00000262320; ENSG00000103126; Homo sapiens. [Genome view]
GeneID8312.
KEGGhsa:8312.
UCSCuc002cgp.1. human.
uc002cgq.1. human.

Organism-specific databases

CTD8312.
GeneCardsGC16M000277.
HGNCHGNC:903. AXIN1.
HPACAB012987.
MIM114550. phenotype.
603816. gene.
607864. phenotype.
PharmGKBPA25195.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG16254.
HOGENOMHBG714290.
HOVERGENO15169.
InParanoidO15169.
OMAPGHRSPD.
OrthoDBEOG95TG6Z.
PhylomeDBO15169.

Enzyme and pathway databases

Pathway_Interaction_DBwnt_canonical_pathway. Canonical Wnt signaling pathway.
ps1pathway. Presenilin action in Notch and Wnt signaling.
tgfbrpathway. TGF-beta receptor signaling.
ReactomeREACT_11045. Signaling by Wnt.

Gene expression databases

ArrayExpressO15169.
BgeeO15169.
CleanExHS_AXIN1.
GenevestigatorO15169.
GermOnlineENSG00000103126. Homo sapiens.

Family and domain databases

InterProIPR014936. Axin_b-cat_bd.
IPR001158. DIX.
IPR000342. Regulat_G_prot_signal.
IPR016137. Regulat_G_prot_signal_superfam.
[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]
PROSITEPS50841. DIX. 1 hit.
PS50132. RGS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio31127.
SOURCESearch...

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Entry information

Entry nameAXN1_HUMAN
AccessionPrimary (citable) accession number: O15169
Secondary accession number(s): Q4TT26 expand/collapse secondary AC list , Q4TT27, Q86YA7, Q8WVW6, Q96S28
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: May 10, 2002
Last modified: January 19, 2010
This is version 114 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
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.

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Human chromosome 16: entries, gene names and cross-references to MIM

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List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents