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Identification
HMDB Protein ID HMDBP14519
Secondary Accession Numbers None
Name Axin-1
Synonyms
  1. Axis inhibition protein 1
  2. hAxin
Gene Name AXIN1
Protein Type Unknown
Biological Properties
General Function Not Available
Specific 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). 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 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).
Pathways
  • Alzheimer disease
  • Basal cell carcinoma
  • Breast cancer
  • Colorectal cancer
  • Cushing syndrome
  • Endometrial cancer
  • Gastric cancer
  • Hepatocellular carcinoma
  • Hippo signaling pathway
  • Human papillomavirus infection
  • Pathways of neurodegeneration - multiple diseases
  • Signaling pathways regulating pluripotency of stem cells
  • Wnt signaling pathway
Reactions Not Available
GO Classification
Biological Process
multicellular organismal development
positive regulation of canonical Wnt receptor signaling pathway
positive regulation of protein catabolic process
apoptotic process
positive regulation of protein ubiquitination
positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process
positive regulation of protein phosphorylation
Wnt receptor signaling pathway
positive regulation of peptidyl-threonine phosphorylation
positive regulation of ubiquitin-protein ligase activity
regulation of Wnt receptor signaling pathway
positive regulation of transcription, DNA-dependent
negative regulation of canonical Wnt receptor signaling pathway
beta-catenin destruction complex assembly
beta-catenin destruction complex disassembly
positive regulation of JNK cascade
activation of protein kinase activity
regulation of intracellular estrogen receptor signaling pathway
positive regulation of peptidyl-serine phosphorylation
cellular protein-containing complex assembly
Cellular Component
cytosol
cytoplasm
perinuclear region of cytoplasm
nucleus
cell periphery
lateral plasma membrane
beta-catenin destruction complex
cytoplasmic vesicle
Molecular Function
protein kinase binding
ubiquitin protein ligase binding
molecular adaptor activity
protein homodimerization activity
enzyme binding
I-SMAD binding
armadillo repeat domain binding
signaling receptor complex adaptor activity
signaling adaptor activity
beta-catenin binding
identical protein binding
SMAD binding
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 862
Molecular Weight 95634.205
Theoretical pI 6.959
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID O15169
UniProtKB/Swiss-Prot Entry Name AXIN1_HUMAN
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
  1. 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. [PubMed:15489334 ]
  2. 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. [PubMed:18669648 ]
  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. [PubMed:15616553 ]
  4. 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. [PubMed:11157797 ]
  5. 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. [PubMed:15262978 ]
  6. 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. [PubMed:9920888 ]
  7. 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. [PubMed:17318175 ]
  8. 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. [PubMed:12554650 ]
  9. 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. [PubMed:16601693 ]
  10. 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. [PubMed:11336703 ]
  11. Zhou H, Di Palma S, Preisinger C, Peng M, Polat AN, Heck AJ, Mohammed S: Toward a comprehensive characterization of a human cancer cell phosphoproteome. J Proteome Res. 2013 Jan 4;12(1):260-71. doi: 10.1021/pr300630k. Epub 2012 Dec 18. [PubMed:23186163 ]
  12. 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. [PubMed:24275569 ]
  13. 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. doi: 10.1016/s0092-8674(00)80324-4. [PubMed:9230313 ]
  14. 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. doi: 10.1038/73448. [PubMed:10700176 ]
  15. 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. doi: 10.1128/MCB.22.18.6393-6405.2002. [PubMed:12192039 ]
  16. 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. doi: 10.1093/emboj/cdg286. [PubMed:12805222 ]
  17. 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. doi: 10.1086/505031. Epub 2006 May 22. [PubMed:16773576 ]
  18. 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. [PubMed:18632848 ]
  19. 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. [PubMed:19759537 ]
  20. 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. [PubMed:21383061 ]
  21. 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. [PubMed:21478859 ]
  22. 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. [PubMed:21799911 ]
  23. Goto T, Matsuzawa J, Iemura S, Natsume T, Shibuya H: WDR26 is a new partner of Axin1 in the canonical Wnt signaling pathway. FEBS Lett. 2016 May;590(9):1291-303. doi: 10.1002/1873-3468.12180. Epub 2016 May 3. [PubMed:27098453 ]
  24. Lu Y, Xie S, Zhang W, Zhang C, Gao C, Sun Q, Cai Y, Xu Z, Xiao M, Xu Y, Huang X, Wu X, Liu W, Wang F, Kang Y, Zhou T: Twa1/Gid8 is a beta-catenin nuclear retention factor in Wnt signaling and colorectal tumorigenesis. Cell Res. 2017 Dec;27(12):1422-1440. doi: 10.1038/cr.2017.107. Epub 2017 Aug 22. [PubMed:28829046 ]
  25. Spink KE, Polakis P, Weis WI: Structural basis of the Axin-adenomatous polyposis coli interaction. EMBO J. 2000 May 15;19(10):2270-9. doi: 10.1093/emboj/19.10.2270. [PubMed:10811618 ]
  26. 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. doi: 10.1038/sj.onc.1205591. [PubMed:12101426 ]