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| | <StructureSection load='3v42' size='340' side='right'caption='[[3v42]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='3v42' size='340' side='right'caption='[[3v42]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3v42]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3V42 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3V42 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3v42]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3V42 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3V42 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BHD, FLCN ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3v42 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3v42 OCA], [https://pdbe.org/3v42 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3v42 RCSB], [https://www.ebi.ac.uk/pdbsum/3v42 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3v42 ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3v42 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3v42 OCA], [https://pdbe.org/3v42 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3v42 RCSB], [https://www.ebi.ac.uk/pdbsum/3v42 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3v42 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[https://www.uniprot.org/uniprot/FLCN_HUMAN FLCN_HUMAN]] Familial spontaneous pneumothorax;Birt-Hogg-Dube syndrome. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The gene represented in this entry may be involved in disease pathogenesis.
| + | [https://www.uniprot.org/uniprot/FLCN_HUMAN FLCN_HUMAN] Familial spontaneous pneumothorax;Birt-Hogg-Dube syndrome. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The gene represented in this entry may be involved in disease pathogenesis. |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/FLCN_HUMAN FLCN_HUMAN]] May play a role in the pathogenesis of an uncommon form of kidney cancer through its association with an inherited disorder of the hair follicle (fibrofolliculomas). May be a tumor suppressor. May be involved in colorectal tumorigenesis. May be involved in energy and/or nutrient sensing through the AMPK and mTOR signaling pathways. May regulate phosphorylation of RPS6KB1.<ref>PMID:12204536</ref> <ref>PMID:17028174</ref> <ref>PMID:18663353</ref>
| + | [https://www.uniprot.org/uniprot/FLCN_HUMAN FLCN_HUMAN] May play a role in the pathogenesis of an uncommon form of kidney cancer through its association with an inherited disorder of the hair follicle (fibrofolliculomas). May be a tumor suppressor. May be involved in colorectal tumorigenesis. May be involved in energy and/or nutrient sensing through the AMPK and mTOR signaling pathways. May regulate phosphorylation of RPS6KB1.<ref>PMID:12204536</ref> <ref>PMID:17028174</ref> <ref>PMID:18663353</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Mutations in the renal tumour suppressor protein, folliculin, lead to proliferative skin lesions, lung complications and renal cell carcinoma. Folliculin has been reported to interact with AMP-activated kinase, a key component of the mammalian target of rapamycin pathway. Most cancer-causing mutations lead to a carboxy-terminal truncation of folliculin, pointing to a functional importance of this domain in tumour suppression. We present here the crystal structure of folliculin carboxy-terminal domain and demonstrate that it is distantly related to differentially expressed in normal cells and neoplasia (DENN) domain proteins, a family of Rab guanine nucleotide exchange factors (GEFs). Using biochemical analysis, we show that folliculin has GEF activity, indicating that folliculin is probably a distantly related member of this class of Rab GEFs.
| + | |
| - | | + | |
| - | Crystal structure of folliculin reveals a hidDENN function in genetically inherited renal cancer.,Nookala RK, Langemeyer L, Pacitto A, Ochoa-Montano B, Donaldson JC, Blaszczyk BK, Chirgadze DY, Barr FA, Bazan JF, Blundell TL Open Biol. 2012 Aug;2(8):120071. PMID:22977732<ref>PMID:22977732</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 3v42" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Blundell, T L]] | + | [[Category: Blundell TL]] |
| - | [[Category: Chirgadze, D Y]] | + | [[Category: Chirgadze DY]] |
| - | [[Category: Nookala, R K]] | + | [[Category: Nookala RK]] |
| - | [[Category: Folliculin]]
| + | |
| - | [[Category: Protein binding]]
| + | |
| - | [[Category: Tumor suppressor]]
| + | |
| Structural highlights
Disease
FLCN_HUMAN Familial spontaneous pneumothorax;Birt-Hogg-Dube syndrome. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The gene represented in this entry may be involved in disease pathogenesis.
Function
FLCN_HUMAN May play a role in the pathogenesis of an uncommon form of kidney cancer through its association with an inherited disorder of the hair follicle (fibrofolliculomas). May be a tumor suppressor. May be involved in colorectal tumorigenesis. May be involved in energy and/or nutrient sensing through the AMPK and mTOR signaling pathways. May regulate phosphorylation of RPS6KB1.[1] [2] [3]
References
- ↑ Nickerson ML, Warren MB, Toro JR, Matrosova V, Glenn G, Turner ML, Duray P, Merino M, Choyke P, Pavlovich CP, Sharma N, Walther M, Munroe D, Hill R, Maher E, Greenberg C, Lerman MI, Linehan WM, Zbar B, Schmidt LS. Mutations in a novel gene lead to kidney tumors, lung wall defects, and benign tumors of the hair follicle in patients with the Birt-Hogg-Dube syndrome. Cancer Cell. 2002 Aug;2(2):157-64. PMID:12204536
- ↑ Baba M, Hong SB, Sharma N, Warren MB, Nickerson ML, Iwamatsu A, Esposito D, Gillette WK, Hopkins RF 3rd, Hartley JL, Furihata M, Oishi S, Zhen W, Burke TR Jr, Linehan WM, Schmidt LS, Zbar B. Folliculin encoded by the BHD gene interacts with a binding protein, FNIP1, and AMPK, and is involved in AMPK and mTOR signaling. Proc Natl Acad Sci U S A. 2006 Oct 17;103(42):15552-7. Epub 2006 Oct 6. PMID:17028174 doi:http://dx.doi.org/0603781103
- ↑ Takagi Y, Kobayashi T, Shiono M, Wang L, Piao X, Sun G, Zhang D, Abe M, Hagiwara Y, Takahashi K, Hino O. Interaction of folliculin (Birt-Hogg-Dube gene product) with a novel Fnip1-like (FnipL/Fnip2) protein. Oncogene. 2008 Sep 11;27(40):5339-47. doi: 10.1038/onc.2008.261. Epub 2008 Jul, 28. PMID:18663353 doi:http://dx.doi.org/10.1038/onc.2008.261
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