Structural highlights
Function
[STF1_MOUSE] 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 (By similarity). Transcription repressor of the Moloney leukemia virus long terminal repeat in undifferentiated murine embryonal carcinoma cells. Binds phosphatidylcholine and phospholipids with a phosphatidylinositol (PI) headgroup, in particular phosphatidyl(3,4)bisphosphate, phosphatidyl(3,5)bisphosphate and phosphatidyl(3,4,5)triphosphate. Activated by the phosphorylation of NR5A1 by HIPK3 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation.[1] [2] [NR0B2_RAT] Acts as a transcriptional regulator. Acts as a negative regulator of receptor-dependent signaling pathways. Specifically inhibits transactivation of the nuclear receptor with whom it interacts. Inhibits transcriptional activity of NEUROD1 on E-box-containing promoter by interfering with the coactivation function of the p300/CBP-mediated trancription complex for NEUROD1.
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
The orphan nuclear receptor steroidogenic factor 1 (SF-1) regulates the differentiation and function of endocrine glands. Although SF-1 is constitutively active in cell-based assays, it is not known whether this transcriptional activity is modulated by ligands. Here, we describe the 1.5 angstroms crystal structure of the SF-1 ligand binding domain in complex with an LXXLL motif from a coregulator protein. The structure reveals the presence of a phospholipid ligand in a surprisingly large pocket (approximately 1600 angstroms3), with the receptor adopting the canonical active conformation. The bound phospholipid is readily exchanged and modulates SF-1 interactions with coactivators. Mutations designed to reduce the size of the SF-1 pocket or to disrupt hydrogen bonds with the phospholipid abolish SF-1/coactivator interactions and significantly reduce SF-1 transcriptional activity. These findings provide evidence that SF-1 is regulated by endogenous ligands and suggest an unexpected relationship between phospholipids and endocrine development and function.
Crystallographic identification and functional characterization of phospholipids as ligands for the orphan nuclear receptor steroidogenic factor-1.,Li Y, Choi M, Cavey G, Daugherty J, Suino K, Kovach A, Bingham NC, Kliewer SA, Xu HE Mol Cell. 2005 Feb 18;17(4):491-502. PMID:15721253[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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
- ↑ Sablin EP, Blind RD, Krylova IN, Ingraham JG, Cai F, Williams JD, Fletterick RJ, Ingraham HA. Structure of SF-1 bound by different phospholipids: evidence for regulatory ligands. Mol Endocrinol. 2009 Jan;23(1):25-34. Epub 2008 Nov 6. PMID:18988706 doi:10.1210/me.2007-0508
- ↑ Li Y, Choi M, Cavey G, Daugherty J, Suino K, Kovach A, Bingham NC, Kliewer SA, Xu HE. Crystallographic identification and functional characterization of phospholipids as ligands for the orphan nuclear receptor steroidogenic factor-1. Mol Cell. 2005 Feb 18;17(4):491-502. PMID:15721253 doi:http://dx.doi.org/10.1016/j.molcel.2005.02.002
