1yow

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{{STRUCTURE_1yow| PDB=1yow | SCENE= }}
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==human Steroidogenic Factor 1 LBD with bound Co-factor Peptide==
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===human Steroidogenic Factor 1 LBD with bound Co-factor Peptide===
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<StructureSection load='1yow' size='340' side='right' caption='[[1yow]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
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{{ABSTRACT_PUBMED_15707893}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1yow]] is a 2 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=1YOW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1YOW FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=P0E:PHOSPHATIDYL+ETHANOL'>P0E</scene><br>
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<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NR5A1, AD4BP, FTZF1, SF1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1yow FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yow OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1yow RCSB], [http://www.ebi.ac.uk/pdbsum/1yow PDBsum]</span></td></tr>
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<table>
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== Disease ==
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[[http://www.uniprot.org/uniprot/STF1_HUMAN STF1_HUMAN]] Defects in NR5A1 are a cause of 46,XY sex reversal type 3 (SRXY3) [MIM:[http://omim.org/entry/612965 612965]]. A condition characterized by male-to-female sex reversal in the presence of a normal 46,XY karyotype.<ref>PMID:10369247</ref> <ref>PMID:11932325</ref> <ref>PMID:17200175</ref> <ref>PMID:17694559</ref> Defects in NR5A1 are a cause of adrenocortical insufficiency without ovarian defect (ACIWOD) [MIM:[http://omim.org/entry/184757 184757]]. ACIWOD is characterized by severe 'slackness' muscular hypotonia. There is decreased sodium, increased potassium and elevated ACTH.<ref>PMID:11038323</ref> Defects in NR5A1 are the cause of premature ovarian failure type 7 (POF7) [MIM:[http://omim.org/entry/612964 612964]]. An ovarian disorder defined as the cessation of ovarian function under the age of 40 years. It is characterized by oligomenorrhea or amenorrhea, in the presence of elevated levels of serum gonadotropins and low estradiol.<ref>PMID:19246354</ref> Defects in NR5A1 are the cause of spermatogenic failure type 8 (SPGF8) [MIM:[http://omim.org/entry/613957 613957]]. SPGF8 is an infertility disorder characterized by spermatogenesis failure and severe oligozoospermia.<ref>PMID:20887963</ref>
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== Function ==
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[[http://www.uniprot.org/uniprot/STF1_HUMAN STF1_HUMAN]] Transcriptional activator. Seems to be essential for sexual differentiation and formation of the primary steroidogenic tissues. Binds to the Ad4 site found in the promoter region of steroidogenic P450 genes such as CYP11A, CYP11B and CYP21B. Also regulates the AMH/Muellerian inhibiting substance gene as well as the AHCH and STAR genes. 5'-YCAAGGYC-3' and 5'-RRAGGTCA-3' are the consensus sequences for the recognition by NR5A1. The SFPQ-NONO-NR5A1 complex binds to the CYP17 promoter and regulates basal and cAMP-dependent transcriptional avtivity. Binds phosphatidylcholine (By similarity). Binds phospholipids with a phosphatidylinositol (PI) headgroup, in particular PI(3,4)P2 and PI(3,4,5)P3. Activated by the phosphorylation of NR5A1 by HIPK3 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation.<ref>PMID:17210646</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/yo/1yow_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Vertebrate members of the nuclear receptor NR5A subfamily, which includes steroidogenic factor 1 (SF-1) and liver receptor homolog 1 (LRH-1), regulate crucial aspects of development, endocrine homeostasis, and metabolism. Mouse LRH-1 is believed to be a ligand-independent transcription factor with a large and empty hydrophobic pocket. Here we present structural and biochemical data for three other NR5A members-mouse and human SF-1 and human LRH-1-which reveal that these receptors bind phosphatidyl inositol second messengers and that ligand binding is required for maximal activity. Evolutionary analysis of structure-function relationships across the SF-1/LRH-1 subfamily indicates that ligand binding is the ancestral state of NR5A receptors and was uniquely diminished or altered in the rodent LRH-1 lineage. We propose that phospholipids regulate gene expression by directly binding to NR5A nuclear receptors.
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==Disease==
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Structural analyses reveal phosphatidyl inositols as ligands for the NR5 orphan receptors SF-1 and LRH-1.,Krylova IN, Sablin EP, Moore J, Xu RX, Waitt GM, MacKay JA, Juzumiene D, Bynum JM, Madauss K, Montana V, Lebedeva L, Suzawa M, Williams JD, Williams SP, Guy RK, Thornton JW, Fletterick RJ, Willson TM, Ingraham HA Cell. 2005 Feb 11;120(3):343-55. PMID:15707893<ref>PMID:15707893</ref>
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[[http://www.uniprot.org/uniprot/STF1_HUMAN STF1_HUMAN]] Defects in NR5A1 are a cause of 46,XY sex reversal type 3 (SRXY3) [MIM:[http://omim.org/entry/612965 612965]]. A condition characterized by male-to-female sex reversal in the presence of a normal 46,XY karyotype.<ref>PMID:10369247</ref><ref>PMID:11932325</ref><ref>PMID:17200175</ref><ref>PMID:17694559</ref> Defects in NR5A1 are a cause of adrenocortical insufficiency without ovarian defect (ACIWOD) [MIM:[http://omim.org/entry/184757 184757]]. ACIWOD is characterized by severe 'slackness' muscular hypotonia. There is decreased sodium, increased potassium and elevated ACTH.<ref>PMID:11038323</ref> Defects in NR5A1 are the cause of premature ovarian failure type 7 (POF7) [MIM:[http://omim.org/entry/612964 612964]]. An ovarian disorder defined as the cessation of ovarian function under the age of 40 years. It is characterized by oligomenorrhea or amenorrhea, in the presence of elevated levels of serum gonadotropins and low estradiol.<ref>PMID:19246354</ref> Defects in NR5A1 are the cause of spermatogenic failure type 8 (SPGF8) [MIM:[http://omim.org/entry/613957 613957]]. SPGF8 is an infertility disorder characterized by spermatogenesis failure and severe oligozoospermia.<ref>PMID:20887963</ref>
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==Function==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[http://www.uniprot.org/uniprot/STF1_HUMAN STF1_HUMAN]] Transcriptional activator. Seems to be essential for sexual differentiation and formation of the primary steroidogenic tissues. Binds to the Ad4 site found in the promoter region of steroidogenic P450 genes such as CYP11A, CYP11B and CYP21B. Also regulates the AMH/Muellerian inhibiting substance gene as well as the AHCH and STAR genes. 5'-YCAAGGYC-3' and 5'-RRAGGTCA-3' are the consensus sequences for the recognition by NR5A1. The SFPQ-NONO-NR5A1 complex binds to the CYP17 promoter and regulates basal and cAMP-dependent transcriptional avtivity. Binds phosphatidylcholine (By similarity). Binds phospholipids with a phosphatidylinositol (PI) headgroup, in particular PI(3,4)P2 and PI(3,4,5)P3. Activated by the phosphorylation of NR5A1 by HIPK3 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation.<ref>PMID:17210646</ref>
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</div>
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== References ==
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==About this Structure==
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<references/>
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[[1yow]] is a 2 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=1YOW OCA].
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__TOC__
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</StructureSection>
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==Reference==
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<ref group="xtra">PMID:015707893</ref><references group="xtra"/><references/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Bynum, J M.]]
[[Category: Bynum, J M.]]

Revision as of 21:30, 29 September 2014

human Steroidogenic Factor 1 LBD with bound Co-factor Peptide

1yow, resolution 3.00Å

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