1yow

From Proteopedia

(Difference between revisions)

Revision as of 09:29, 8 January 2015

human Steroidogenic Factor 1 LBD with bound Co-factor Peptide

Structural highlights

1yow is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	NR5A1, AD4BP, FTZF1, SF1 (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Disease

[STF1_HUMAN] Defects in NR5A1 are a cause of 46,XY sex reversal type 3 (SRXY3) [MIM:612965]. A condition characterized by male-to-female sex reversal in the presence of a normal 46,XY karyotype.^[1] ^[2] ^[3] ^[4] Defects in NR5A1 are a cause of adrenocortical insufficiency without ovarian defect (ACIWOD) [MIM:184757]. ACIWOD is characterized by severe 'slackness' muscular hypotonia. There is decreased sodium, increased potassium and elevated ACTH.^[5] Defects in NR5A1 are the cause of premature ovarian failure type 7 (POF7) [MIM: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.^[6] Defects in NR5A1 are the cause of spermatogenic failure type 8 (SPGF8) [MIM:613957]. SPGF8 is an infertility disorder characterized by spermatogenesis failure and severe oligozoospermia.^[7]

Function

[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.^[8]

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

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.

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^[9]

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

References

↑ Achermann JC, Ito M, Ito M, Hindmarsh PC, Jameson JL. A mutation in the gene encoding steroidogenic factor-1 causes XY sex reversal and adrenal failure in humans. Nat Genet. 1999 Jun;22(2):125-6. PMID:10369247 doi:10.1038/9629
↑ Achermann JC, Ozisik G, Ito M, Orun UA, Harmanci K, Gurakan B, Jameson JL. Gonadal determination and adrenal development are regulated by the orphan nuclear receptor steroidogenic factor-1, in a dose-dependent manner. J Clin Endocrinol Metab. 2002 Apr;87(4):1829-33. PMID:11932325
↑ Lin L, Philibert P, Ferraz-de-Souza B, Kelberman D, Homfray T, Albanese A, Molini V, Sebire NJ, Einaudi S, Conway GS, Hughes IA, Jameson JL, Sultan C, Dattani MT, Achermann JC. Heterozygous missense mutations in steroidogenic factor 1 (SF1/Ad4BP, NR5A1) are associated with 46,XY disorders of sex development with normal adrenal function. J Clin Endocrinol Metab. 2007 Mar;92(3):991-9. Epub 2007 Jan 2. PMID:17200175 doi:10.1210/jc.2006-1672
↑ Kohler B, Lin L, Ferraz-de-Souza B, Wieacker P, Heidemann P, Schroder V, Biebermann H, Schnabel D, Gruters A, Achermann JC. Five novel mutations in steroidogenic factor 1 (SF1, NR5A1) in 46,XY patients with severe underandrogenization but without adrenal insufficiency. Hum Mutat. 2008 Jan;29(1):59-64. PMID:17694559 doi:10.1002/humu.20588
↑ Biason-Lauber A, Schoenle EJ. Apparently normal ovarian differentiation in a prepubertal girl with transcriptionally inactive steroidogenic factor 1 (NR5A1/SF-1) and adrenocortical insufficiency. Am J Hum Genet. 2000 Dec;67(6):1563-8. Epub 2000 Oct 18. PMID:11038323 doi:S0002-9297(07)63224-8
↑ Lourenco D, Brauner R, Lin L, De Perdigo A, Weryha G, Muresan M, Boudjenah R, Guerra-Junior G, Maciel-Guerra AT, Achermann JC, McElreavey K, Bashamboo A. Mutations in NR5A1 associated with ovarian insufficiency. N Engl J Med. 2009 Mar 19;360(12):1200-10. doi: 10.1056/NEJMoa0806228. Epub 2009 , Feb 25. PMID:19246354 doi:10.1056/NEJMoa0806228
↑ Bashamboo A, Ferraz-de-Souza B, Lourenco D, Lin L, Sebire NJ, Montjean D, Bignon-Topalovic J, Mandelbaum J, Siffroi JP, Christin-Maitre S, Radhakrishna U, Rouba H, Ravel C, Seeler J, Achermann JC, McElreavey K. Human male infertility associated with mutations in NR5A1 encoding steroidogenic factor 1. Am J Hum Genet. 2010 Oct 8;87(4):505-12. doi: 10.1016/j.ajhg.2010.09.009. PMID:20887963 doi:10.1016/j.ajhg.2010.09.009
↑ Lan HC, Li HJ, Lin G, Lai PY, Chung BC. Cyclic AMP stimulates SF-1-dependent CYP11A1 expression through homeodomain-interacting protein kinase 3-mediated Jun N-terminal kinase and c-Jun phosphorylation. Mol Cell Biol. 2007 Mar;27(6):2027-36. Epub 2007 Jan 8. PMID:17210646 doi:10.1128/MCB.02253-06
↑ 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. Structural analyses reveal phosphatidyl inositols as ligands for the NR5 orphan receptors SF-1 and LRH-1. Cell. 2005 Feb 11;120(3):343-55. PMID:15707893 doi:10.1016/j.cell.2005.01.024

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1yow"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <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>
-</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=P0E:PHOSPHATIDYL+ETHANOL'>P0E</scene><br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=P0E:PHOSPHATIDYL+ETHANOL'>P0E</scene></td></tr>
-<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>
+<tr id='gene'><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>
-<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>
+<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=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>
-<table>
+</table>
 == Disease ==
 [[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>
@@ Line 34: / Line 34: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Bynum, J M.]]
+[[Category: Bynum, J M]]
-[[Category: Guy, R K.]]
+[[Category: Guy, R K]]
-[[Category: Ingraham, H A.]]
+[[Category: Ingraham, H A]]
-[[Category: Juzumiene, D.]]
+[[Category: Juzumiene, D]]
-[[Category: Krylova, I N.]]
+[[Category: Krylova, I N]]
-[[Category: Lebedeva, L.]]
+[[Category: Lebedeva, L]]
-[[Category: MacKay, J A.]]
+[[Category: MacKay, J A]]
-[[Category: Madauss, K P.]]
+[[Category: Madauss, K P]]
-[[Category: Montana, V.]]
+[[Category: Montana, V]]
-[[Category: Moore, J.]]
+[[Category: Moore, J]]
-[[Category: Sablin, E P.]]
+[[Category: Sablin, E P]]
-[[Category: Suzawa, M.]]
+[[Category: Suzawa, M]]
-[[Category: Thornton, J W.]]
+[[Category: Thornton, J W]]
-[[Category: Waitt, G M.]]
+[[Category: Waitt, G M]]
-[[Category: Williams, J D.]]
+[[Category: Williams, J D]]
-[[Category: Williams, S P.]]
+[[Category: Williams, S P]]
-[[Category: Willson, T M.]]
+[[Category: Willson, T M]]
-[[Category: Xu, R X.]]
+[[Category: Xu, R X]]
 [[Category: Phosphatidyl ethanolamine]]
 [[Category: Phosphatidyl glycerol]]

1yow

From Proteopedia

Revision as of 09:29, 8 January 2015

human Steroidogenic Factor 1 LBD with bound Co-factor Peptide

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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