4kng

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m (Protected "4kng" [edit=sysop:move=sysop])
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'''Unreleased structure'''
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{{STRUCTURE_4kng| PDB=4kng | SCENE= }}
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===Crystal structure of human LGR5-RSPO1-RNF43===
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{{ABSTRACT_PUBMED_23756651}}
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The entry 4kng is ON HOLD
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==Disease==
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[[http://www.uniprot.org/uniprot/RSPO1_HUMAN RSPO1_HUMAN]] Palmoplantar keratoderma - XX sex reversal - predisposition to squamous cell carcinoma. Keratoderma, palmoplantar, with squamous cell carcinoma of skin and sex reversal (PKKSCC) [MIM:[http://omim.org/entry/610644 610644]]: A recessive syndrome characterized by XX (female to male) SRY-independent sex reversal, palmoplantar hyperkeratosis and predisposition to squamous cell carcinoma of the skin. Note=The disease is caused by mutations affecting the gene represented in this entry.
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Authors: Chen, PH, He, X
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==Function==
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[[http://www.uniprot.org/uniprot/LGR5_HUMAN LGR5_HUMAN]] Orphan receptor. Stem cell marker of the intestinal epithelium and the hair follicle. Target gene of Wnt signaling. [[http://www.uniprot.org/uniprot/RNF43_HUMAN RNF43_HUMAN]] E3 ubiquitin-protein ligase that acts as a negative regulator of the Wnt signaling pathway by mediating the ubiquitination, endocytosis and subsequent degradation of Wnt receptor complex components Frizzled. Acts on both canonical and non-canonical Wnt signaling pathway. Acts as a tumor suppressor in the intestinal stem cell zone by inhibiting the Wnt signaling pathway, thereby resticting the size of the intestinal stem cell zone.<ref>PMID:18313049</ref> <ref>PMID:22575959</ref> <ref>PMID:22895187</ref> [[http://www.uniprot.org/uniprot/RSPO1_HUMAN RSPO1_HUMAN]] Activator of the beta-catenin signaling cascade, leading to TCF-dependent gene activation. Acts both in the canonical Wnt/beta-catenin-dependent pathway and in non-canonical Wnt signaling pathway, probably by acting as an inhibitor of ZNRF3, an important regulator of the Wnt signaling pathway. Acts as a ligand for frizzled FZD8 and LRP6. May negatively regulate the TGF-beta pathway. Has a essential roles in ovary determination.<ref>PMID:16109882</ref> <ref>PMID:22575959</ref>
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Description: Crystal structure of human LGR5-RSPO1-RNF43
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==About this Structure==
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[[4kng]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KNG OCA].
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==Reference==
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<ref group="xtra">PMID:023756651</ref><references group="xtra"/><references/>
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[[Category: Homo sapiens]]
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[[Category: Chen, P H.]]
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[[Category: He, X.]]
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[[Category: Cysteine-rich domain]]
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[[Category: Furin-repeat]]
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[[Category: Leucine-rich repeat]]
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[[Category: Ligand recognition]]
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[[Category: Membrane protein]]
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[[Category: N-linked glycosylation]]
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[[Category: Protease-associated domain]]
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[[Category: Protein-protein interaction]]
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[[Category: Signaling protein]]

Revision as of 13:27, 19 June 2013

Template:STRUCTURE 4kng

Contents

Crystal structure of human LGR5-RSPO1-RNF43

Template:ABSTRACT PUBMED 23756651

Disease

[RSPO1_HUMAN] Palmoplantar keratoderma - XX sex reversal - predisposition to squamous cell carcinoma. Keratoderma, palmoplantar, with squamous cell carcinoma of skin and sex reversal (PKKSCC) [MIM:610644]: A recessive syndrome characterized by XX (female to male) SRY-independent sex reversal, palmoplantar hyperkeratosis and predisposition to squamous cell carcinoma of the skin. Note=The disease is caused by mutations affecting the gene represented in this entry.

Function

[LGR5_HUMAN] Orphan receptor. Stem cell marker of the intestinal epithelium and the hair follicle. Target gene of Wnt signaling. [RNF43_HUMAN] E3 ubiquitin-protein ligase that acts as a negative regulator of the Wnt signaling pathway by mediating the ubiquitination, endocytosis and subsequent degradation of Wnt receptor complex components Frizzled. Acts on both canonical and non-canonical Wnt signaling pathway. Acts as a tumor suppressor in the intestinal stem cell zone by inhibiting the Wnt signaling pathway, thereby resticting the size of the intestinal stem cell zone.[1] [2] [3] [RSPO1_HUMAN] Activator of the beta-catenin signaling cascade, leading to TCF-dependent gene activation. Acts both in the canonical Wnt/beta-catenin-dependent pathway and in non-canonical Wnt signaling pathway, probably by acting as an inhibitor of ZNRF3, an important regulator of the Wnt signaling pathway. Acts as a ligand for frizzled FZD8 and LRP6. May negatively regulate the TGF-beta pathway. Has a essential roles in ovary determination.[4] [5]

About this Structure

4kng is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

  • Chen PH, Chen X, Lin Z, Fang D, He X. The structural basis of R-spondin recognition by LGR5 and RNF43. Genes Dev. 2013 Jun 11. PMID:23756651 doi:10.1101/gad.219915.113
  1. ↑ Sugiura T, Yamaguchi A, Miyamoto K. A cancer-associated RING finger protein, RNF43, is a ubiquitin ligase that interacts with a nuclear protein, HAP95. Exp Cell Res. 2008 Apr 15;314(7):1519-28. doi: 10.1016/j.yexcr.2008.01.013. Epub , 2008 Jan 26. PMID:18313049 doi:10.1016/j.yexcr.2008.01.013
  2. ↑ Hao HX, Xie Y, Zhang Y, Charlat O, Oster E, Avello M, Lei H, Mickanin C, Liu D, Ruffner H, Mao X, Ma Q, Zamponi R, Bouwmeester T, Finan PM, Kirschner MW, Porter JA, Serluca FC, Cong F. ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner. Nature. 2012 Apr 29;485(7397):195-200. doi: 10.1038/nature11019. PMID:22575959 doi:10.1038/nature11019
  3. ↑ Koo BK, Spit M, Jordens I, Low TY, Stange DE, van de Wetering M, van Es JH, Mohammed S, Heck AJ, Maurice MM, Clevers H. Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis of Wnt receptors. Nature. 2012 Aug 30;488(7413):665-9. doi: 10.1038/nature11308. PMID:22895187 doi:10.1038/nature11308
  4. ↑ Kim KA, Kakitani M, Zhao J, Oshima T, Tang T, Binnerts M, Liu Y, Boyle B, Park E, Emtage P, Funk WD, Tomizuka K. Mitogenic influence of human R-spondin1 on the intestinal epithelium. Science. 2005 Aug 19;309(5738):1256-9. PMID:16109882 doi:309/5738/1256
  5. ↑ Hao HX, Xie Y, Zhang Y, Charlat O, Oster E, Avello M, Lei H, Mickanin C, Liu D, Ruffner H, Mao X, Ma Q, Zamponi R, Bouwmeester T, Finan PM, Kirschner MW, Porter JA, Serluca FC, Cong F. ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner. Nature. 2012 Apr 29;485(7397):195-200. doi: 10.1038/nature11019. PMID:22575959 doi:10.1038/nature11019

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