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==CRYSTAL STRUCTURE OF THE RGS-HOMOLOGOUS DOMAIN OF AXIN==
==CRYSTAL STRUCTURE OF THE RGS-HOMOLOGOUS DOMAIN OF AXIN==
<StructureSection load='1dk8' size='340' side='right' caption='[[1dk8]], [[Resolution|resolution]] 1.57&Aring;' scene=''>
<StructureSection load='1dk8' size='340' side='right'caption='[[1dk8]], [[Resolution|resolution]] 1.57&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1dk8]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DK8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1DK8 FirstGlance]. <br>
<table><tr><td colspan='2'>[[1dk8]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DK8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1DK8 FirstGlance]. <br>
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==See Also==
==See Also==
*[[Axin|Axin]]
*[[Axin 3D structures|Axin 3D structures]]
== References ==
== References ==
<references/>
<references/>
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</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Polakis, P]]
[[Category: Polakis, P]]
[[Category: Spink, K E]]
[[Category: Spink, K E]]

Revision as of 17:25, 16 October 2019

CRYSTAL STRUCTURE OF THE RGS-HOMOLOGOUS DOMAIN OF AXINCRYSTAL STRUCTURE OF THE RGS-HOMOLOGOUS DOMAIN OF AXIN

Structural highlights

1dk8 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[AXIN1_HUMAN] Defects in AXIN1 are involved in hepatocellular carcinoma (HCC) [MIM:114550].[1] [2] Defects in AXIN1 are a cause of caudal duplication anomaly (CADUA) [MIM:607864]. Caudal duplication anomaly is characterized by the occurrence of duplications of different organs in the caudal region. Note=Caudal duplication anomaly is associated with hypermethylation of the AXIN1 promoter.[3]

Function

[AXIN1_HUMAN] 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.[4] [5] [6]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Axin and the adenomatous polyposis coli (APC) tumor suppressor protein are components of the Wnt/Wingless growth factor signaling pathway. In the absence of Wnt signal, Axin and APC regulate cytoplasmic levels of the proto-oncogene beta-catenin through the formation of a large complex containing these three proteins, glycogen synthase kinase 3beta (GSK3beta) and several other proteins. Both Axin and APC are known to be critical for beta-catenin regulation, and truncations in APC that eliminate the Axin-binding site result in human cancers. A protease-resistant domain of Axin that contains the APC-binding site is a member of the regulators of G-protein signaling (RGS) superfamily. The crystal structures of this domain alone and in complex with an Axin-binding sequence from APC reveal that the Axin-APC interaction occurs at a conserved groove on a face of the protein that is distinct from the G-protein interface of classical RGS proteins. The molecular interactions observed in the Axin-APC complex provide a rationale for the evolutionary conservation seen in both proteins.

Structural basis of the Axin-adenomatous polyposis coli interaction.,Spink KE, Polakis P, Weis WI EMBO J. 2000 May 15;19(10):2270-9. PMID:10811618[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ 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. PMID:10700176 doi:10.1038/73448
  2. ↑ 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. PMID:12101426 doi:10.1038/sj.onc.1205591
  3. ↑ 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. PMID:10700176 doi:10.1038/73448
  4. ↑ 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. PMID:12192039
  5. ↑ 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. PMID:16601693 doi:7601057
  6. ↑ 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. PMID:17210684 doi:10.1158/0008-5472.CAN-06-1671
  7. ↑ Spink KE, Polakis P, Weis WI. Structural basis of the Axin-adenomatous polyposis coli interaction. EMBO J. 2000 May 15;19(10):2270-9. PMID:10811618 doi:http://dx.doi.org/10.1093/emboj/19.10.2270

1dk8, resolution 1.57Å

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