|
|
| (One intermediate revision not shown.) |
| Line 3: |
Line 3: |
| | <StructureSection load='6ako' size='340' side='right'caption='[[6ako]], [[Resolution|resolution]] 2.40Å' scene=''> | | <StructureSection load='6ako' size='340' side='right'caption='[[6ako]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6ako]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/ ] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AKO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AKO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6ako]] is a 3 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=6AKO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AKO FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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]] 2.396Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FOXC2, FKHL14, MFH1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ako FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ako OCA], [http://pdbe.org/6ako PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ako RCSB], [http://www.ebi.ac.uk/pdbsum/6ako PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ako 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=6ako FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ako OCA], [https://pdbe.org/6ako PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ako RCSB], [https://www.ebi.ac.uk/pdbsum/6ako PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ako ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/FOXC2_HUMAN FOXC2_HUMAN]] Defects in FOXC2 are the cause of lymphedema hereditary type 2 (LMPH2) [MIM:[http://omim.org/entry/153200 153200]]; also known as Meige lymphedema. Hereditary lymphedema is a chronic disabling condition which results in swelling of the extremities due to altered lymphatic flow. Patients with lymphedema suffer from recurrent local infections, and physical impairment.<ref>PMID:11078474</ref> Defects in FOXC2 are a cause of lymphedema-yellow nails (LYYN) [MIM:[http://omim.org/entry/153300 153300]]. LYYN is characterized by yellow, dystrophic, thick and slowly growing nails, associated with lymphedema and respiratory involvement. Lymphedema occurs more often in the lower limbs. It can appear at birth or later in life. Onset generally follows the onset of ungual abnormalities. Defects in FOXC2 are a cause of lymphedema-distichiasis (LYD) [MIM:[http://omim.org/entry/153400 153400]]. LYD is characterized by primary limb lymphedema usually starting at puberty (but in some cases later or at birth) and associated with distichiasis (double rows of eyelashes, with extra eyelashes growing from the Meibomian gland orifices).<ref>PMID:11499682</ref> | + | [https://www.uniprot.org/uniprot/FOXC2_HUMAN FOXC2_HUMAN] Defects in FOXC2 are the cause of lymphedema hereditary type 2 (LMPH2) [MIM:[https://omim.org/entry/153200 153200]; also known as Meige lymphedema. Hereditary lymphedema is a chronic disabling condition which results in swelling of the extremities due to altered lymphatic flow. Patients with lymphedema suffer from recurrent local infections, and physical impairment.<ref>PMID:11078474</ref> Defects in FOXC2 are a cause of lymphedema-yellow nails (LYYN) [MIM:[https://omim.org/entry/153300 153300]. LYYN is characterized by yellow, dystrophic, thick and slowly growing nails, associated with lymphedema and respiratory involvement. Lymphedema occurs more often in the lower limbs. It can appear at birth or later in life. Onset generally follows the onset of ungual abnormalities. Defects in FOXC2 are a cause of lymphedema-distichiasis (LYD) [MIM:[https://omim.org/entry/153400 153400]. LYD is characterized by primary limb lymphedema usually starting at puberty (but in some cases later or at birth) and associated with distichiasis (double rows of eyelashes, with extra eyelashes growing from the Meibomian gland orifices).<ref>PMID:11499682</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/FOXC2_HUMAN FOXC2_HUMAN]] Transcriptional activator. Might be involved in the formation of special mesenchymal tissues.<ref>PMID:9169153</ref> | + | [https://www.uniprot.org/uniprot/FOXC2_HUMAN FOXC2_HUMAN] Transcriptional activator. Might be involved in the formation of special mesenchymal tissues.<ref>PMID:9169153</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 21: |
Line 21: |
| | </div> | | </div> |
| | <div class="pdbe-citations 6ako" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6ako" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[FOX 3D structures|FOX 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Chen, X]] | + | [[Category: Chen X]] |
| - | [[Category: Chen, Y]] | + | [[Category: Chen Y]] |
| - | [[Category: Dai, S]] | + | [[Category: Dai S]] |
| - | [[Category: Guo, M]] | + | [[Category: Guo M]] |
| - | [[Category: Jiang, L]] | + | [[Category: Jiang L]] |
| - | [[Category: Li, J]] | + | [[Category: Li J]] |
| - | [[Category: Liang, X]] | + | [[Category: Liang X]] |
| - | [[Category: Wei, H]] | + | [[Category: Wei H]] |
| - | [[Category: Crystal structure]]
| + | |
| - | [[Category: Dna binding domain]]
| + | |
| - | [[Category: Dna binding protein-dna complex]]
| + | |
| - | [[Category: Dna recognition]]
| + | |
| - | [[Category: Foxc]]
| + | |
| - | [[Category: Lymphoedema distichiasis syndrome]]
| + | |
| Structural highlights
Disease
FOXC2_HUMAN Defects in FOXC2 are the cause of lymphedema hereditary type 2 (LMPH2) [MIM:153200; also known as Meige lymphedema. Hereditary lymphedema is a chronic disabling condition which results in swelling of the extremities due to altered lymphatic flow. Patients with lymphedema suffer from recurrent local infections, and physical impairment.[1] Defects in FOXC2 are a cause of lymphedema-yellow nails (LYYN) [MIM:153300. LYYN is characterized by yellow, dystrophic, thick and slowly growing nails, associated with lymphedema and respiratory involvement. Lymphedema occurs more often in the lower limbs. It can appear at birth or later in life. Onset generally follows the onset of ungual abnormalities. Defects in FOXC2 are a cause of lymphedema-distichiasis (LYD) [MIM:153400. LYD is characterized by primary limb lymphedema usually starting at puberty (but in some cases later or at birth) and associated with distichiasis (double rows of eyelashes, with extra eyelashes growing from the Meibomian gland orifices).[2]
Function
FOXC2_HUMAN Transcriptional activator. Might be involved in the formation of special mesenchymal tissues.[3]
Publication Abstract from PubMed
The FOXC family of transcription factors (FOXC1 and FOXC2) plays essential roles in the regulation of embryonic, ocular, and cardiac development. Mutations and abnormal expression of FOXC proteins are implicated in genetic diseases as well as cancer. In this study, we determined two crystal structures of the DNA-binding domain (DBD) of human FOXC2 protein, in complex with different DNA sites. The FOXC2-DBD adopts the winged-helix fold with helix H3 contributing to all the base specific contacts, while the N-terminus, wing 1, and the C-terminus of FOXC2-DBD all make additional contacts with the phosphate groups of DNA. Our structural, biochemical, and bioinformatics analyses allow us to revise the previously proposed DNA recognition mechanism and provide a model of DNA binding for the FOXC proteins. In addition, our structural analysis and accompanying biochemical assays provide a molecular basis for understanding disease-causing mutations in FOXC1 and FOXC2.
Structural basis for DNA recognition by FOXC2.,Chen X, Wei H, Li J, Liang X, Dai S, Jiang L, Guo M, Qu L, Chen Z, Chen L, Chen Y Nucleic Acids Res. 2019 Feb 5. pii: 5306577. doi: 10.1093/nar/gkz077. PMID:30722065[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Fang J, Dagenais SL, Erickson RP, Arlt MF, Glynn MW, Gorski JL, Seaver LH, Glover TW. Mutations in FOXC2 (MFH-1), a forkhead family transcription factor, are responsible for the hereditary lymphedema-distichiasis syndrome. Am J Hum Genet. 2000 Dec;67(6):1382-8. Epub 2000 Nov 8. PMID:11078474 doi:S0002-9297(07)63207-8
- ↑ Bell R, Brice G, Child AH, Murday VA, Mansour S, Sandy CJ, Collin JR, Brady AF, Callen DF, Burnand K, Mortimer P, Jeffery S. Analysis of lymphoedema-distichiasis families for FOXC2 mutations reveals small insertions and deletions throughout the gene. Hum Genet. 2001 Jun;108(6):546-51. PMID:11499682
- ↑ Miura N, Iida K, Kakinuma H, Yang XL, Sugiyama T. Isolation of the mouse (MFH-1) and human (FKHL 14) mesenchyme fork head-1 genes reveals conservation of their gene and protein structures. Genomics. 1997 May 1;41(3):489-92. PMID:9169153 doi:S0888-7543(97)94695-4
- ↑ Chen X, Wei H, Li J, Liang X, Dai S, Jiang L, Guo M, Qu L, Chen Z, Chen L, Chen Y. Structural basis for DNA recognition by FOXC2. Nucleic Acids Res. 2019 Feb 5. pii: 5306577. doi: 10.1093/nar/gkz077. PMID:30722065 doi:http://dx.doi.org/10.1093/nar/gkz077
|
