Axin-1

Details

Name

Axin-1

Kind

protein

Synonyms

• AXIN
• Axis inhibition protein 1
• hAxin

Gene Name

AXIN1

UniProtKB Entry

O15169Swiss-Prot

Organism

Humans

NCBI Taxonomy ID

9606

Amino acid sequence

>lcl|BSEQ0006469|Axin-1
MNIQEQGFPLDLGASFTEDAPRPPVPGEEGELVSTDPRPASYSFCSGKGVGIKGETSTAT
PRRSDLDLGYEPEGSASPTPPYLKWAESLHSLLDDQDGISLFRTFLKQEGCADLLDFWFA
CTGFRKLEPCDSNEEKRLKLARAIYRKYILDNNGIVSRQTKPATKSFIKGCIMKQLIDPA
MFDQAQTEIQATMEENTYPSFLKSDIYLEYTRTGSESPKVCSDQSSGSGTGKGISGYLPT
LNEDEEWKCDQDMDEDDGRDAAPPGRLPQKLLLETAAPRVSSSRRYSEGREFRYGSWREP
VNPYYVNAGYALAPATSANDSEQQSLSSDADTLSLTDSSVDGIPPYRIRKQHRREMQESV
QVNGRVPLPHIPRTYRVPKEVRVEPQKFAEELIHRLEAVQRTREAEEKLEERLKRVRMEE
EGEDGDPSSGPPGPCHKLPPAPAWHHFPPRCVDMGCAGLRDAHEENPESILDEHVQRVLR
TPGRQSPGPGHRSPDSGHVAKMPVALGGAASGHGKHVPKSGAKLDAAGLHHHRHVHHHVH
HSTARPKEQVEAEATRRAQSSFAWGLEPHSHGARSRGYSESVGAAPNASDGLAHSGKVGV
ACKRNAKKAESGKSASTEVPGASEDAEKNQKIMQWIIEGEKEISRHRRTGHGSSGTRKPQ
PHENSRPLSLEHPWAGPQLRTSVQPSHLFIQDPTMPPHPAPNPLTQLEEARRRLEEEEKR
ASRAPSKQRYVQEVMRRGRACVRPACAPVLHVVPAVSDMELSETETRSQRKVGGGSAQPC
DSIVVAYYFCGEPIPYRTLVRGRAVTLGQFKELLTKKGSYRYYFKKVSDEFDCGVVFEEV
REDEAVLPVFEEKIIGKVEKVD

Number of residues

862

Molecular Weight

95634.205

Theoretical pI

6.95

GO Classification

Functions

molecular adaptor activity / p53 binding / R-SMAD binding / signaling adaptor activity / ubiquitin-like ligase-substrate adaptor activity

Processes

cell development / epigenetic programming in the zygotic pronuclei / head development / negative regulation of gene expression / negative regulation of transcription elongation by RNA polymerase II / positive regulation of ubiquitin-dependent protein catabolic process / proteasome-mediated ubiquitin-dependent protein catabolic process / protein-containing complex assembly

Components

microtubule cytoskeleton / nucleolus / plasma membrane / Wnt signalosome

General Function

Component of the beta-catenin destruction complex required for regulating CTNNB1 levels through phosphorylation and ubiquitination, and modulating Wnt-signaling (PubMed:12192039, PubMed:27098453, PubMed:28829046). 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 (PubMed:12192039). In Wnt signaling, probably facilitates the phosphorylation of CTNNB1 and APC by GSK3B (PubMed:12192039). Likely to function as a tumor suppressor. Enhances TGF-beta signaling by recruiting the RNF111 E3 ubiquitin ligase and promoting the degradation of inhibitory SMAD7 (PubMed:16601693). Also a component of the AXIN1-HIPK2-TP53 complex which controls cell growth, apoptosis and development (PubMed:17210684). Facilitates the phosphorylation of TP53 by HIPK2 upon ultraviolet irradiation (PubMed:17210684)

Specific Function

armadillo repeat domain binding

Pfam Domain Function

• RGS (PF00615)
• Axin_b-cat_bind (PF08833)
• DIX (PF00778)
• AXIN1_TNKS_BD (PF16646)

Signal Regions

Not Available

Transmembrane Regions

Not Available

Cellular Location

Cytoplasm

Gene sequence

>lcl|BSEQ0021962|Axin-1 (AXIN1)
ATGAATATCCAAGAGCAGGGTTTCCCCTTGGACCTCGGAGCAAGTTTCACCGAAGATGCT
CCCCGACCCCCAGTGCCTGGTGAGGAGGGAGAACTGGTGTCCACAGACCCGAGGCCCGCC
AGCTACAGTTTCTGCTCCGGGAAAGGTGTTGGCATTAAAGGTGAGACTTCGACGGCCACT
CCGAGGCGCTCGGATCTGGACCTGGGGTATGAGCCTGAGGGCAGTGCCTCCCCCACCCCA
CCATACTTGAAGTGGGCTGAGTCACTGCATTCCCTGCTGGATGACCAAGATGGGATAAGC
CTGTTCAGGACTTTCCTGAAGCAGGAGGGCTGTGCCGACTTGCTGGACTTCTGGTTTGCC
TGCACTGGCTTCAGGAAGCTGGAGCCCTGTGACTCGAACGAGGAGAAGAGGCTGAAGCTG
GCGAGAGCCATCTACCGAAAGTACATTCTTGATAACAATGGCATCGTGTCCCGGCAGACC
AAGCCAGCCACCAAGAGCTTCATAAAGGGCTGCATCATGAAGCAGCTGATCGATCCTGCC
ATGTTTGACCAGGCCCAGACCGAAATCCAGGCCACTATGGAGGAAAACACCTATCCCTCC
TTCCTTAAGTCTGATATTTATTTGGAATATACGAGGACAGGCTCGGAGAGCCCCAAAGTC
TGTAGTGACCAGAGCTCTGGGTCAGGGACAGGGAAGGGCATATCTGGATACCTGCCGACC
TTAAATGAAGATGAGGAATGGAAGTGTGACCAGGACATGGATGAGGACGATGGCAGAGAC
GCTGCTCCCCCCGGAAGACTCCCTCAGAAGCTGCTCCTGGAGACAGCTGCCCCGAGGGTC
TCCTCCAGTAGACGGTACAGCGAAGGCAGAGAGTTCAGGTATGGATCCTGGCGGGAGCCA
GTCAACCCCTATTATGTCAATGCCGGCTATGCCCTGGCCCCAGCCACCAGTGCCAACGAC
AGCGAGCAGCAGAGCCTGTCCAGCGATGCAGACACCCTGTCCCTCACGGACAGCAGCGTG
GATGGGATCCCCCCATACAGGATCCGTAAGCAGCACCGCAGGGAGATGCAGGAGAGCGTG
CAGGTCAATGGGCGGGTGCCCCTACCTCACATTCCCCGCACGTACCGGGTGCCGAAGGAG
GTCCGCGTGGAGCCTCAGAAGTTCGCGGAGGAGCTCATCCACCGCCTGGAGGCTGTGCAG
CGCACGCGGGAGGCCGAGGAGAAGCTGGAGGAGCGGCTGAAGCGCGTGCGCATGGAGGAG
GAAGGTGAGGACGGCGATCCATCGTCAGGGCCCCCAGGGCCGTGTCACAAGCTGCCTCCC
GCCCCCGCTTGGCACCACTTCCCGCCCCGCTGTGTGGACATGGGCTGTGCCGGGCTCCGG
GATGCACACGAGGAGAACCCTGAGAGCATCCTGGACGAGCACGTACAGCGTGTGCTGAGG
ACACCTGGCCGCCAGTCGCCTGGGCCTGGCCATCGCTCCCCGGACAGTGGGCACGTGGCC
AAGATGCCAGTGGCACTGGGGGGTGCCGCCTCGGGGCACGGGAAGCACGTACCCAAGTCA
GGGGCGAAGCTGGACGCGGCCGGCCTGCACCACCACCGACACGTCCACCACCACGTCCAC
CACAGCACAGCCCGGCCCAAGGAGCAGGTGGAGGCCGAGGCCACCCGCAGGGCCCAGAGC
AGCTTCGCCTGGGGCCTGGAACCACACAGCCATGGGGCAAGGTCCCGAGGCTACTCAGAG
AGTGTTGGCGCTGCCCCCAACGCCAGTGATGGCCTCGCCCACAGTGGGAAGGTGGGCGTG
GCGTGCAAAAGAAATGCCAAGAAGGCTGAGTCGGGGAAGAGCGCCAGCACCGAGGTGCCA
GGTGCCTCGGAGGATGCGGAGAAGAACCAGAAAATCATGCAGTGGATCATTGAGGGGGAA
AAGGAGATCAGCAGGCACCGCAGGACCGGCCACGGGTCTTCGGGGACGAGGAAGCCACAG
CCCCATGAGAACTCCAGACCCTTGTCCCTTGAGCACCCCTGGGCCGGCCCTCAGCTCCGG
ACCTCCGTGCAGCCCTCCCACCTCTTCATCCAAGACCCCACCATGCCACCCCACCCAGCT
CCCAACCCCCTAACCCAGCTGGAGGAGGCGCGCCGACGTCTGGAGGAGGAAGAAAAGAGA
GCCAGCCGAGCACCCTCCAAGCAGAGGTATGTGCAGGAGGTTATGCGGCGGGGACGCGCC
TGCGTCAGGCCAGCGTGCGCGCCGGTGCTGCACGTGGTACCAGCCGTGTCGGACATGGAG
CTCTCCGAGACAGAGACAAGATCGCAGAGGAAGGTGGGCGGCGGGAGTGCCCAGCCGTGT
GACAGCATCGTTGTGGCGTACTACTTCTGCGGGGAACCCATCCCCTACCGCACCCTGGTG
AGGGGCCGCGCTGTCACCCTGGGCCAGTTCAAGGAGCTGCTGACCAAAAAGGGCAGCTAC
AGATACTACTTCAAGAAAGTGAGCGACGAGTTTGACTGTGGGGTGGTGTTTGAGGAGGTT
CGAGAGGACGAGGCCGTCCTGCCCGTCTTTGAGGAGAAGATCATCGGCAAAGTGGAGAAG
GTGGACTGA

Chromosome Location

16

Locus

16p13.3

External Identifiers

Resource	Link
UniProtKB ID	O15169
UniProtKB Entry Name	AXIN1_HUMAN
GenBank Gene ID	AE006463
GeneCard ID	AXIN1
GenAtlas ID	AXIN1
HGNC ID	HGNC:903
PDB ID(s)	1DK8, 1EMU, 1O9U, 3ZDI, 4B7T, 4NM0, 4NM3, 4NM5, 4NM7, 4NU1, 5WZZ, 6JCK, 7SXF, 7SXG, 7SXH, 7SXJ, 7Y1P
KEGG ID	hsa:8312
NCBI Gene ID	8312

General References

1. Zeng L, Fagotto F, Zhang T, Hsu W, Vasicek TJ, Perry WL 3rd, Lee JJ, Tilghman SM, Gumbiner BM, Costantini F: The mouse Fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation. Cell. 1997 Jul 11;90(1):181-92. [Article]
2. Daniels RJ, Peden JF, Lloyd C, Horsley SW, Clark K, Tufarelli C, Kearney L, Buckle VJ, Doggett NA, Flint J, Higgs DR: Sequence, structure and pathology of the fully annotated terminal 2 Mb of the short arm of human chromosome 16. Hum Mol Genet. 2001 Feb 15;10(4):339-52. [Article]
3. Martin J, Han C, Gordon LA, Terry A, Prabhakar S, She X, Xie G, Hellsten U, Chan YM, Altherr M, Couronne O, Aerts A, Bajorek E, Black S, Blumer H, Branscomb E, Brown NC, Bruno WJ, Buckingham JM, Callen DF, Campbell CS, Campbell ML, Campbell EW, Caoile C, Challacombe JF, Chasteen LA, Chertkov O, Chi HC, Christensen M, Clark LM, Cohn JD, Denys M, Detter JC, Dickson M, Dimitrijevic-Bussod M, Escobar J, Fawcett JJ, Flowers D, Fotopulos D, Glavina T, Gomez M, Gonzales E, Goodstein D, Goodwin LA, Grady DL, Grigoriev I, Groza M, Hammon N, Hawkins T, Haydu L, Hildebrand CE, Huang W, Israni S, Jett J, Jewett PB, Kadner K, Kimball H, Kobayashi A, Krawczyk MC, Leyba T, Longmire JL, Lopez F, Lou Y, Lowry S, Ludeman T, Manohar CF, Mark GA, McMurray KL, Meincke LJ, Morgan J, Moyzis RK, Mundt MO, Munk AC, Nandkeshwar RD, Pitluck S, Pollard M, Predki P, Parson-Quintana B, Ramirez L, Rash S, Retterer J, Ricke DO, Robinson DL, Rodriguez A, Salamov A, Saunders EH, Scott D, Shough T, Stallings RL, Stalvey M, Sutherland RD, Tapia R, Tesmer JG, Thayer N, Thompson LS, Tice H, Torney DC, Tran-Gyamfi M, Tsai M, Ulanovsky LE, Ustaszewska A, Vo N, White PS, Williams AL, Wills PL, Wu JR, Wu K, Yang J, Dejong P, Bruce D, Doggett NA, Deaven L, Schmutz J, Grimwood J, Richardson P, Rokhsar DS, Eichler EE, Gilna P, Lucas SM, Myers RM, Rubin EM, Pennacchio LA: The sequence and analysis of duplication-rich human chromosome 16. Nature. 2004 Dec 23;432(7020):988-94. [Article]
4. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
5. Hsu W, Zeng L, Costantini F: Identification of a domain of Axin that binds to the serine/threonine protein phosphatase 2A and a self-binding domain. J Biol Chem. 1999 Feb 5;274(6):3439-45. [Article]
6. 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: AXIN1 mutations in hepatocellular carcinomas, and growth suppression in cancer cells by virus-mediated transfer of AXIN1. Nat Genet. 2000 Mar;24(3):245-50. [Article]
7. Mao J, Wang J, Liu B, Pan W, Farr GH 3rd, Flynn C, Yuan H, Takada S, Kimelman D, Li L, Wu D: Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signaling pathway. Mol Cell. 2001 Apr;7(4):801-9. [Article]
8. Kusano S, Raab-Traub N: I-mfa domain proteins interact with Axin and affect its regulation of the Wnt and c-Jun N-terminal kinase signaling pathways. Mol Cell Biol. 2002 Sep;22(18):6393-405. [Article]
9. Hocevar BA, Mou F, Rennolds JL, Morris SM, Cooper JA, Howe PH: Regulation of the Wnt signaling pathway by disabled-2 (Dab2). EMBO J. 2003 Jun 16;22(12):3084-94. [Article]
10. Wong CK, Luo W, Deng Y, Zou H, Ye Z, Lin SC: The DIX domain protein coiled-coil-DIX1 inhibits c-Jun N-terminal kinase activation by Axin and dishevelled through distinct mechanisms. J Biol Chem. 2004 Sep 17;279(38):39366-73. Epub 2004 Jul 15. [Article]
11. Oates NA, van Vliet J, Duffy DL, Kroes HY, Martin NG, Boomsma DI, Campbell M, Coulthard MG, Whitelaw E, Chong S: Increased DNA methylation at the AXIN1 gene in a monozygotic twin from a pair discordant for a caudal duplication anomaly. Am J Hum Genet. 2006 Jul;79(1):155-62. Epub 2006 May 22. [Article]
12. Liu W, Rui H, Wang J, Lin S, He Y, Chen M, Li Q, Ye Z, Zhang S, Chan SC, Chen YG, Han J, Lin SC: Axin is a scaffold protein in TGF-beta signaling that promotes degradation of Smad7 by Arkadia. EMBO J. 2006 Apr 19;25(8):1646-58. Epub 2006 Apr 6. [Article]
13. Li Q, Wang X, Wu X, Rui Y, Liu W, Wang J, Wang X, Liou YC, Ye Z, Lin SC: Daxx cooperates with the Axin/HIPK2/p53 complex to induce cell death. Cancer Res. 2007 Jan 1;67(1):66-74. [Article]
14. Luo W, Peterson A, Garcia BA, Coombs G, Kofahl B, Heinrich R, Shabanowitz J, Hunt DF, Yost HJ, Virshup DM: Protein phosphatase 1 regulates assembly and function of the beta-catenin degradation complex. EMBO J. 2007 Mar 21;26(6):1511-21. Epub 2007 Feb 22. [Article]
15. Kim MJ, Chia IV, Costantini F: SUMOylation target sites at the C terminus protect Axin from ubiquitination and confer protein stability. FASEB J. 2008 Nov;22(11):3785-94. doi: 10.1096/fj.08-113910. Epub 2008 Jul 16. [Article]
16. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [Article]
17. Huang SM, Mishina YM, Liu S, Cheung A, Stegmeier F, Michaud GA, Charlat O, Wiellette E, Zhang Y, Wiessner S, Hild M, Shi X, Wilson CJ, 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 MW, Lengauer C, Finan PM, Tallarico JA, Bouwmeester T, Porter JA, Bauer A, Cong F: Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. Nature. 2009 Oct 1;461(7264):614-20. doi: 10.1038/nature08356. Epub 2009 Sep 16. [Article]
18. Lui TT, Lacroix C, Ahmed SM, Goldenberg SJ, Leach CA, Daulat AM, Angers S: The ubiquitin-specific protease USP34 regulates axin stability and Wnt/beta-catenin signaling. Mol Cell Biol. 2011 May;31(10):2053-65. doi: 10.1128/MCB.01094-10. Epub 2011 Mar 7. [Article]
19. Zhang Y, Liu S, Mickanin C, Feng Y, Charlat O, Michaud GA, Schirle M, Shi X, Hild M, Bauer A, Myer VE, Finan PM, Porter JA, Huang SM, Cong F: RNF146 is a poly(ADP-ribose)-directed E3 ligase that regulates axin degradation and Wnt signalling. Nat Cell Biol. 2011 May;13(5):623-9. doi: 10.1038/ncb2222. Epub 2011 Apr 10. [Article]
20. Callow MG, Tran H, Phu L, Lau T, Lee J, Sandoval WN, Liu PS, Bheddah S, Tao J, Lill JR, Hongo JA, Davis D, Kirkpatrick DS, Polakis P, Costa M: Ubiquitin ligase RNF146 regulates tankyrase and Axin to promote Wnt signaling. PLoS One. 2011;6(7):e22595. doi: 10.1371/journal.pone.0022595. Epub 2011 Jul 25. [Article]
21. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
22. Spink KE, Polakis P, Weis WI: Structural basis of the Axin-adenomatous polyposis coli interaction. EMBO J. 2000 May 15;19(10):2270-9. [Article]
23. Dajani R, Fraser E, Roe SM, Yeo M, Good VM, Thompson V, Dale TC, Pearl LH: Structural basis for recruitment of glycogen synthase kinase 3beta to the axin-APC scaffold complex. EMBO J. 2003 Feb 3;22(3):494-501. [Article]
24. Taniguchi K, Roberts LR, Aderca IN, Dong X, Qian C, Murphy LM, Nagorney DM, Burgart LJ, Roche PC, Smith DI, Ross JA, Liu W: Mutational spectrum of beta-catenin, AXIN1, and AXIN2 in hepatocellular carcinomas and hepatoblastomas. Oncogene. 2002 Jul 18;21(31):4863-71. [Article]

Associated Data

Drug Relations

Drug	Drug group	Pharmacological action?	Type	Actions	Details
1,4-Dithiothreitol	experimental	unknown	target		Details