O15169 (AXIN1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Axin-1

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

Gene names

Name:	AXIN1
Synonyms:	AXIN

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	862 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 CTNNB1 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 CTNNB1 and APC by GSK3B. Likely to function as a tumor suppressor. 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. Also component of the AXIN1-HIPK2-TP53 complex which controls cell growth, apoptosis and development. Ref.8 Ref.12 Ref.13
Subunit structure	Homodimer. Interacts with ZBED3; the interaction is direct, enhanced by protein kinase GSK3B and casein kinase CSNK1E activities and decreases GSK3B-induced beta-catenin serine and threonine phosphorylations 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. Component of the AXIN1-HIPK2-TP53 complex. 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 APC, SMAD6, SMAD7 and RNF111. Interacts with DIXDC1; prevents interaction with MAP3K1. Interacts with MAP3K4. Interacts with ANKRD6 and AIDA By similarity. 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. Interacts with MACF1 By similarity. Found in a complex composed of MACF1, APC, AXIN1, CTNNB1 and GSK3B By similarity. Interacts with TNKS. Interacts with DAB2; the interaction is mutually exclusive with the AXIN1:PPP1CA interaction. Ref.5 Ref.7 Ref.8 Ref.9 Ref.10 Ref.12 Ref.13 Ref.14 Ref.17 Ref.19 Ref.20
Subcellular location	Cytoplasm. Nucleus. Membrane By similarity. Cell membrane By similarity. Note: MACF1 is required for its translocation to cell membrane By similarity. On UV irradiation, translocates to the nucleus and colocalizes with DAAX. Ref.12 Ref.13 Ref.18
Tissue specificity	Ubiquitously expressed.
Domain	The tankyrase-binding motif (also named TBD) is required for interaction with tankyrase TNKS and TNKS2. Ref.17
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. Ref.5 Ref.14 ADP-ribosylated by tankyrase TNKS and TNKS2. Poly-ADP-ribosylated protein is recognized by RNF146, followed by ubiquitination at 'Lys-48' 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. Sumoylation at Lys-857 and Lys-860 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. Ref.17 Ref.18 Ref.19 Ref.20
Involvement in disease	Hepatocellular carcinoma (HCC) [MIM:114550]: A primary malignant neoplasm of epithelial liver cells. The major risk factors for HCC are chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, prolonged dietary aflatoxin exposure, alcoholic cirrhosis, and cirrhosis due to other causes. Note: The gene represented in this entry is involved in disease pathogenesis. Ref.6 Ref.23 Caudal duplication anomaly (CADUA) [MIM:607864]: A condition characterized by the occurrence of duplications of different organs in the caudal region. Note: The disease is caused by mutations affecting the gene represented in this entry. Caudal duplication anomaly is associated with hypermethylation of the AXIN1 promoter. Ref.6
Sequence similarities	Contains 1 DIX domain. Contains 1 RGS domain.
Sequence caution	The sequence AAC51624.1 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
Coding sequence diversity	Alternative splicing
Disease	Disease mutation Tumor suppressor
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 cell death Inferred from Biological aspect of Ancestor. Source: RefGenome cellular protein complex assembly Inferred from direct assay Ref.12. Source: BHF-UCL 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 genetic imprinting Inferred from electronic annotation. Source: Compara in utero embryonic development Inferred from electronic annotation. Source: Compara 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 negative regulation of protein metabolic process Inferred from electronic annotation. Source: Compara negative regulation of transcription elongation from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara nucleocytoplasmic transport Inferred from electronic annotation. Source: Compara 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 peptidyl-serine phosphorylation Inferred from direct assay PubMed 18593713. Source: BHF-UCL positive regulation of peptidyl-threonine phosphorylation Inferred from direct assay PubMed 18593713. Source: BHF-UCL positive regulation of proteasomal ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: Compara positive regulation of protein catabolic process Inferred from direct assay PubMed 9601641. Source: BHF-UCL positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of transcription, DNA-dependent Inferred from mutant phenotype Ref.12. Source: BHF-UCL positive regulation of transforming growth factor beta receptor signaling pathway Inferred from electronic annotation. Source: Compara positive regulation of ubiquitin-protein ligase activity Inferred from mutant phenotype Ref.12. Source: BHF-UCL post-anal tail morphogenesis Inferred from electronic annotation. Source: Compara protein catabolic process Inferred from electronic annotation. Source: Compara protein homooligomerization Inferred from electronic annotation. Source: Compara protein polyubiquitination Inferred from electronic annotation. Source: Compara regulation of catenin import into nucleus Inferred from Biological aspect of Ancestor. Source: RefGenome sensory perception of sound Inferred from electronic annotation. Source: Compara termination of G-protein coupled receptor signaling pathway Inferred from electronic annotation. Source: InterPro
Cellular_component	beta-catenin destruction complex Inferred from direct assay PubMed 16188939PubMed 9601641. Source: UniProtKB 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 cytosol Traceable author statement. Source: Reactome lateral plasma membrane Inferred from direct assay PubMed 12072559. Source: MGI nucleus Inferred from direct assay Ref.18. Source: UniProtKB perinuclear region of cytoplasm Inferred from direct assay PubMed 19038973. Source: BHF-UCL 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 sequence or structural similarity. Source: BHF-UCL beta-catenin binding Inferred from direct assay PubMed 10644691. Source: BHF-UCL p53 binding Inferred from direct assay PubMed 15526030. Source: MGI protein complex scaffold Inferred from direct assay PubMed 9601641. Source: BHF-UCL protein homodimerization activity Inferred from sequence or structural similarity. Source: UniProtKB protein kinase binding Inferred from sequence or structural similarity. Source: BHF-UCL signal transducer activity Inferred from direct assay PubMed 9601641. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ANP32A	P39687	2	EBI-710484,EBI-359234
CRMP1	Q14194	2	EBI-710484,EBI-473101
CSNK1E	P49674	4	EBI-710484,EBI-749343
CTNNB1	P35222	20	EBI-710484,EBI-491549
Ctnnb1	Q02248	5	EBI-710484,EBI-397872	From a different organism.
FBXW11	Q9UKB1	4	EBI-710484,EBI-355189
GSK3B	P49841	27	EBI-710484,EBI-373586
TNKS2	Q9H2K2	2	EBI-710484,EBI-4398527
TP53	P04637	4	EBI-710484,EBI-366083
TRIM29	Q14134	2	EBI-710484,EBI-702370

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.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 862

862

Axin-1

PRO_0000220888

Regions

Domain

88 – 211

124

RGS

Domain

780 – 862

83

DIX

Region

209 – 338

130

Interaction with TP53 By similarity

Region

348 – 433

86

Interaction with GSK3B By similarity

Region

434 – 502

69

Interaction with CTNNB1 By similarity

Region

507 – 757

251

Interaction with RNF111

Region

575 – 789

215

Interaction with PPP2CA

Region

677 – 752

76

Interaction with HIPK2 By similarity

Motif

20 – 29

10

Tankyrase-binding motif

Amino acid modifications

Modified residue

75

1

Phosphoserine; by CK1 Ref.14

Modified residue

77

1

Phosphoserine; by CK1 Ref.14

Modified residue

217

1

Phosphoserine; by CK1 Ref.14

Modified residue

469

1

Phosphoserine; by CK1 Ref.14

Modified residue

481

1

Phosphothreonine; by GSK3-beta Probable

Modified residue

486

1

Phosphoserine; by GSK3-beta By similarity

Modified residue

493

1

Phosphoserine By similarity

Cross-link

857

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Cross-link

860

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Natural variations

Alternative sequence

730 – 765

36

Missing in isoform 2.

VSP_019398

Natural variant

106

1

L → R in HCC. Ref.23

VAR_015589

Natural variant

345

1

P → L in HCC. Ref.23

VAR_015590

Natural variant

425

1

G → S in HCC. Ref.23

VAR_015591

Natural variant

650

1

G → S in HCC and in hepatoblastoma. Ref.23

VAR_015592

Natural variant

841

1

R → Q in hepatoblastoma. Ref.23
Corresponds to variant rs34015754 [ dbSNP | Ensembl ].

VAR_015593

Experimental info

Sequence conflict

360

1

V → A in AAC51624. Ref.1

Sequence conflict

451 – 455

5

CVDMG → LCWTWA in AAC51624. Ref.1

Sequence conflict

482

1

P → T in AAC51624. Ref.1

Secondary structure

1

.

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862

Helix Strand Turn

Details...

Helix

81 – 87

7

Helix

89 – 92

4

Helix

96 – 107

12

Turn

108 – 110

3

Helix

112 – 126

15

Helix

131 – 133

3

Helix

134 – 148

15

Helix

155 – 159

5

Helix

162 – 174

13

Turn

179 – 182

4

Helix

183 – 195

13

Helix

197 – 201

5

Helix

205 – 208

4

Turn

209 – 212

4

Helix

384 – 399

16

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 10, 2002. Version 2. Checksum: 10779173F5092F3F	FASTA	862	95,635
	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
	Isoform 2 [UniParc]. Checksum: 4AA4187D70A5863D	FASTA	826	91,653
	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 ASRAPSKQRT RSQRKVGGGS AQPCDSIVVA YYFCGEPIPY RTLVRGRAVT LGQFKELLTK 790 800 810 820 KGSYRYYFKK VSDEFDCGVV FEEVREDEAV LPVFEEKIIG KVEKVD

References

	« Hide 'large scale' referencesShow '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] [Europe PMC] [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] [Europe PMC] [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. , 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] [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] (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 471-862 (ISOFORM 1). Tissue: Lymphoma and Renal cell carcinoma.
[5]	"Identification of a domain of Axin that binds to the serine/threonine protein phosphatase 2A and a self-binding domain." Hsu W., Zeng L., Costantini F. J. Biol. Chem. 274:3439-3445(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GSK3B AND PPP2CA, PHOSPHORYLATION, DEPHOSPHORYLATION.
[6]	"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] [Europe PMC] [Abstract] Cited for: DISEASE.
[7]	"Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signaling pathway." Mao J., Wang J., Liu B., Pan W., Farr G.H. III, Flynn C., Yuan H., Takada S., Kimelman D., Li L., Wu D. Mol. Cell 7:801-809(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH LRP5.
[8]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MDFI AND MDFIC, FUNCTION.
[9]	"Regulation of the Wnt signaling pathway by disabled-2 (Dab2)." Howe P.H. EMBO J. 22:3084-3094(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DAB2.
[10]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DIXDC1; MAP3K1 AND MAP3K4.
[11]	"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] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN CAUDAL DUPLICATION ANOMALY.
[12]	"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 SMAD6; SMAD7 AND RNF111, FUNCTION, SUBCELLULAR LOCATION.
[13]	"Daxx cooperates with the Axin/HIPK2/p53 complex to induce cell death." Li Q., Wang X., Wu X., Rui Y., Liu W., Wang J., Wang X., Liou Y.C., Ye Z., Lin S.C. Cancer Res. 67:66-74(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DAXX, IDENTIFICATION AS A COMPONENT OF THE AXIN1-HIPK2-TP53 COMPLEX, SUBCELLULAR LOCATION, FUNCTION.
[14]	"Protein phosphatase 1 regulates assembly and function of the beta-catenin degradation complex." Luo W., Peterson A., Garcia B.A., Coombs G., Kofahl B., Heinrich R., Shabanowitz J., Hunt D.F., Yost H.J., Virshup D.M. EMBO J. 26:1511-1521(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-75; SER-77; SER-217 AND SER-469, MASS SPECTROMETRY, INTERACTION WITH GSK3B AND PPP1CA.
[15]	"SUMOylation target sites at the C terminus protect Axin from ubiquitination and confer protein stability." Kim M.J., Chia I.V., Costantini F. FASEB J. 22:3785-3794(2008) [PubMed] [Europe PMC] [Abstract] Cited for: SUMOYLATION.
[16]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[17]	"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] [Europe PMC] [Abstract] Cited for: ADP-RIBOSYLATION, UBIQUITINATION, DOMAIN TANKYRASE-BINDING MOTIF, INTERACTION WITH TNKS AND TNKS2.
[18]	"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, SUBCELLULAR LOCATION.
[19]	"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.
[20]	"Ubiquitin ligase RNF146 regulates tankyrase and Axin to promote Wnt signaling." Callow M.G., Tran H., Phu L., Lau T., Lee J., Sandoval W.N., Liu P.S., Bheddah S., Tao J., Lill J.R., Hongo J.A., Davis D., Kirkpatrick D.S., Polakis P., Costa M. PLoS ONE 6:E22595-E22595(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TNKS, UBIQUITINATION.
[21]	"Structural basis of the axin-adenomatous polyposis coli interaction." Spink K.E., Polakis P., Weis W.I. EMBO J. 19:2270-2279(2000) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.57 ANGSTROMS) OF 74-220 IN COMPLEX WITH APC.
[22]	"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] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 383-400 IN COMPLEX WITH GSK3B.
[23]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS HCC ARG-106; LEU-345; SER-425 AND SER-650, VARIANT HEPATOBLASTOMA GLN-841.
+	Additional computationally mapped references.

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.

IPI

IPI00747002.
IPI00748214.

RefSeq

NP_003493.1. NM_003502.3.
NP_851393.1. NM_181050.2.

UniGene

Hs.592082.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1DK8	X-ray	1.57	A	74-220	[»]
1EMU	X-ray	1.90	A	80-211	[»]
1O9U	X-ray	2.40	B	383-400	[»]
3ZDI	X-ray	2.64	B	383-400	[»]
4B7T	X-ray	2.77	B	383-400	[»]

ProteinModelPortal

O15169.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-34630N.

IntAct

O15169. 43 interactions.

MINT

MINT-100969.

STRING

9606.ENSP00000262320.

PTM databases

PhosphoSite

O15169.

Proteomic databases

PaxDb

O15169.

PRIDE

O15169.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000262320; ENSP00000262320; ENSG00000103126.
ENST00000354866; ENSP00000346935; ENSG00000103126.

GeneID

8312.

KEGG

hsa:8312.

UCSC

uc002cgp.2. human.
uc002cgq.2. human.

Organism-specific databases

CTD

8312.

GeneCards

GC16M000338.

HGNC

HGNC:903. AXIN1.

HPA

CAB012987.

MIM

114550. phenotype.
603816. gene.
607864. phenotype.

neXtProt

NX_O15169.

PharmGKB

PA25195.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG238205.

HOVERGEN

HBG004324.

InParanoid

O15169.

KO

K02157.

OMA

IMQWIIE.

OrthoDB

EOG47SSDB.

PhylomeDB

O15169.

Enzyme and pathway databases

Pathway_Interaction_DB

wnt_canonical_pathway. Canonical Wnt signaling pathway.
ps1pathway. Presenilin action in Notch and Wnt signaling.
tgfbrpathway. TGF-beta receptor signaling.

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

O15169.

Bgee

O15169.

CleanEx

HS_AXIN1.

Genevestigator

O15169.

GermOnline

ENSG00000103126. Homo sapiens.

Family and domain databases

Gene3D

1.10.196.10. 2 hits.

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]

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

ChEMBL

CHEMBL1255127.

EvolutionaryTrace

O15169.

GenomeRNAi

8312.

NextBio

31127.

SOURCE

Search...

Entry information

Entry name

AXIN1_HUMAN

Accession

Primary (citable) accession number: O15169
Secondary accession number(s): Q4TT26 , Q4TT27, Q86YA7, Q8WVW6, Q96S28

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	May 10, 2002
Last modified:	May 1, 2013
This is version 148 of the entry and version 2 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.