AXIN1

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Axin 1
Protein AXIN1 PDB 1dk8.png
PDB rendering based on 1dk8.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols AXIN1 ; AXIN; PPP1R49
External IDs OMIM603816 MGI1096327 HomoloGene2614 ChEMBL: 1255127 GeneCards: AXIN1 Gene
RNA expression pattern
PBB GE AXIN1 212849 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 8312 12005
Ensembl ENSG00000103126 ENSMUSG00000024182
UniProt O15169 O35625
RefSeq (mRNA) NM_003502 NM_001159598
RefSeq (protein) NP_003493 NP_001153070
Location (UCSC) Chr 16:
0.34 – 0.4 Mb
Chr 17:
26.14 – 26.2 Mb
PubMed search [1] [2]

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

Function[edit]

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 phosphate 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 medullablastomas. Two transcript variants encoding distinct isoforms have been identified for this gene.[2]

Structure[edit]

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. [3]

Interactions[edit]

AXIN1 has been shown to interact with:

References[edit]

  1. ^ Zeng L, Fagotto F, Zhang T, Hsu W, Vasicek TJ, Perry WL 3rd, 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. doi:10.1016/S0092-8674(00)80324-4. PMID 9230313. 
  2. ^ "Entrez Gene: AXIN1 axin 1". 
  3. ^ 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". J Mol Biol. 405 (3): 773–86. doi:10.1016/j.jmb.2010.11.013. PMID 21087614. 
  4. ^ a b c 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. 
  5. ^ 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. doi:10.1093/emboj/cdg286. PMC 162138. PMID 12805222. 
  6. ^ a b c 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. doi:10.1074/jbc.M111982200. PMID 11884395. 
  7. ^ a b 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. doi:10.1096/fj.08-113910. PMC 2574027. PMID 18632848. 
  8. ^ 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. doi:10.1093/emboj/18.15.4233. PMC 1171499. PMID 10428961. 
  9. ^ a b 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. doi:10.1074/jbc.C200473200. PMID 12511557. 
  10. ^ 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. 
  11. ^ 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. doi:10.1074/jbc.M002491200. PMID 10829020. 
  12. ^ 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. doi:10.1074/jbc.M100443200. PMID 11297546. 

Further reading[edit]