AXIN1

AXIN1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesAXIN1, AXIN, PPP1R49, axin 1
External IDsMGI: 1096327 HomoloGene: 2614 GeneCards: AXIN1
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

8312

12005

Ensembl

ENSG00000103126

ENSMUSG00000024182

UniProt

O15169

O35625

RefSeq (mRNA)

NM_003502
NM_181050

NM_001159598
NM_009733

RefSeq (protein)

NP_003493
NP_851393

NP_001153070
NP_033863

Location (UCSC)Chr 16: 0.29 – 0.35 MbChr 17: 26.14 – 26.2 Mb
PubMed search[1][2]
Wikidata
View/Edit HumanView/Edit Mouse

Axin-1 is a protein that in humans is encoded by the AXIN1 gene.[3]

Function

This gene encodes a cytoplasmic protein which contains a regulation of G-protein signaling (RGS) domain and a dishevelled and axin (DIX) domain. The encoded protein interacts with adenomatosis polyposis coli, catenin (cadherin-associated protein) beta 1, glycogen synthase kinase 3 beta, protein phosphatase 2, and itself. This protein functions as a negative regulator of the wingless-type MMTV integration site family, member 1 (WNT) signaling pathway and can induce apoptosis. The crystal structure of a portion of this protein, alone and in a complex with other proteins, has been resolved. Mutations in this gene have been associated with hepatocellular carcinoma, hepatoblastomas, ovarian endometriod adenocarcinomas, and medulloblastomas. Two transcript variants encoding distinct isoforms have been identified for this gene.[4]

Structure

The full-length human protein comprises 862 amino acids with a (predicted) molecular mass of 96 kDa. The N-terminal RGS domain, a GSK3 kinase interacting peptide of Axin1 and homologs of the C-terminal DIX domains have been solved at atomic resolution. Large WNT-downregulating central regions have been characterized as intrinsically disordered by biophysical experiments and bioinformatic analysis.[5] Biophysical destabilization of the folded RGS domain induces formation of nanoaggregates that expose and locally concentrate intrinsically disordered regions, which in turn misregulate Wnt signalling. Many other large IDPs are affected by missense mutations, such as BRCA1, Adenomatous polyposis coli(APC), CREB-binding protein/(CBP) and might be affected in similar ways by missense mutations of their folded domains.[6]

Interactions

AXIN1 has been shown to interact with:

References

  1. ↑ "Human PubMed Reference:".
  2. ↑ "Mouse PubMed Reference:".
  3. ↑ Zeng L, Fagotto F, Zhang T, Hsu W, Vasicek TJ, Perry WL, Lee JJ, Tilghman SM, Gumbiner BM, Costantini F (August 1997). "The mouse Fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation". Cell. 90 (1): 181–92. PMID 9230313. doi:10.1016/S0092-8674(00)80324-4.
  4. ↑ "Entrez Gene: AXIN1 axin 1".
  5. ↑ Noutsou M, Duarte AM, Anvarian Z, Didenko T, Minde DP, Kuper I, de Ridder I, Oikonomou C, Friedler A, Boelens R, Rüdiger SG, Maurice MM (2011). "Critical scaffolding regions of the tumor suppressor Axin1 are natively unfolded" (PDF). J Mol Biol. 405 (3): 773–86. PMID 21087614. doi:10.1016/j.jmb.2010.11.013.
  6. ↑ Anvarian Z, Nojima H, van Kappel EC, Madl T, Spit M, Viertler M, Jordens I, Low TY, van Scherpenzeel RC, Kuper I, Richter K, Heck AJ, Boelens R, Vincent JP, Rüdiger SG, Maurice MM (2016). "Axin cancer mutants form nanoaggregates to rewire the Wnt signaling network". Nat Struct Mol Biol. 23: 324–32. PMID 26974125. doi:10.1038/nsmb.3191.
  7. 1 2 3 Nakamura T, Hamada F, Ishidate T, Anai K, Kawahara K, Toyoshima K, Akiyama T (June 1998). "Axin, an inhibitor of the Wnt signalling pathway, interacts with beta-catenin, GSK-3beta and APC and reduces the beta-catenin level". Genes Cells. 3 (6): 395–403. PMID 9734785. doi:10.1046/j.1365-2443.1998.00198.x.
  8. ↑ Hocevar BA, Mou F, Rennolds JL, Morris SM, Cooper JA, Howe PH (June 2003). "Regulation of the Wnt signaling pathway by disabled-2 (Dab2)". EMBO J. 22 (12): 3084–94. PMC 162138 Freely accessible. PMID 12805222. doi:10.1093/emboj/cdg286.
  9. 1 2 3 Zhang Y, Qiu WJ, Chan SC, Han J, He X, Lin SC (May 2002). "Casein kinase I and casein kinase II differentially regulate axin function in Wnt and JNK pathways". J. Biol. Chem. 277 (20): 17706–12. PMID 11884395. doi:10.1074/jbc.M111982200.
  10. 1 2 Kim MJ, Chia IV, Costantini F (November 2008). "SUMOylation target sites at the C terminus protect Axin from ubiquitination and confer protein stability". FASEB J. 22 (11): 3785–94. PMC 2574027 Freely accessible. PMID 18632848. doi:10.1096/fj.08-113910.
  11. ↑ Li L, Yuan H, Weaver CD, Mao J, Farr GH, Sussman DJ, Jonkers J, Kimelman D, Wu D (August 1999). "Axin and Frat1 interact with dvl and GSK, bridging Dvl to GSK in Wnt-mediated regulation of LEF-1". EMBO J. 18 (15): 4233–40. PMC 1171499 Freely accessible. PMID 10428961. doi:10.1093/emboj/18.15.4233.
  12. 1 2 Mak BC, Takemaru K, Kenerson HL, Moon RT, Yeung RS (February 2003). "The tuberin-hamartin complex negatively regulates beta-catenin signaling activity". J. Biol. Chem. 278 (8): 5947–51. PMID 12511557. doi:10.1074/jbc.C200473200.
  13. ↑ Mao J, Wang J, Liu B, Pan W, Farr GH, Flynn C, Yuan H, Takada S, Kimelman D, Li L, Wu D (April 2001). "Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signaling pathway". Mol. Cell. 7 (4): 801–9. PMID 11336703. doi:10.1016/S1097-2765(01)00224-6.
  14. ↑ Zhang Y, Neo SY, Han J, Lin SC (August 2000). "Dimerization choices control the ability of axin and dishevelled to activate c-Jun N-terminal kinase/stress-activated protein kinase". J. Biol. Chem. 275 (32): 25008–14. PMID 10829020. doi:10.1074/jbc.M002491200.
  15. ↑ Yamamoto H, Hinoi T, Michiue T, Fukui A, Usui H, Janssens V, Van Hoof C, Goris J, Asashima M, Kikuchi A (July 2001). "Inhibition of the Wnt signaling pathway by the PR61 subunit of protein phosphatase 2A". J. Biol. Chem. 276 (29): 26875–82. PMID 11297546. doi:10.1074/jbc.M100443200.

Further reading

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