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]
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
Steroidogenic factor 1 (SF1) is a member of the NR5A subfamily of nuclear hormone receptors and is considered a master regulator of reproduction because it regulates a number of genes encoding reproductive hormones and enzymes involved in steroid hormone biosynthesis. Like other NR5A members, SF1 harbors a highly conserved approximately 30-residue segment called the FTZ-F1 box C-terminal to the core DNA binding domain (DBD) common to all nuclear receptors and binds to 9-bp DNA sequences as a monomer. Here we describe the solution structure of the SF1 DBD in complex with an atypical sequence in the proximal promoter region of the inhibin-alpha gene that encodes a subunit of a reproductive hormone. SF1 forms a specific complex with the DNA through a bipartite motif binding to the major and minor grooves through the core DBD and the N-terminal segment of the FTZ-F1 box, respectively, in a manner previously described for two other monomeric receptors, nerve growth factor-induced-B and estrogen-related receptor 2. However, unlike these receptors, SF1 harbors a helix in the C-terminal segment of the FTZ-F1 box that interacts with both the core DBD and DNA and serves as an important determinant of stability of the complex. We propose that the FTZ-F1 helix along with the core DBD serves as a platform for interactions with coactivators and other DNA-bound factors in the vicinity.
Sequence-specific deoxyribonucleic acid (DNA) recognition by steroidogenic factor 1: a helix at the carboxy terminus of the DNA binding domain is necessary for complex stability.,Little TH, Zhang Y, Matulis CK, Weck J, Zhang Z, Ramachandran A, Mayo KE, Radhakrishnan I Mol Endocrinol. 2006 Apr;20(4):831-43. Epub 2005 Dec 8. PMID:16339274[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
- ↑ Little TH, Zhang Y, Matulis CK, Weck J, Zhang Z, Ramachandran A, Mayo KE, Radhakrishnan I. Sequence-specific deoxyribonucleic acid (DNA) recognition by steroidogenic factor 1: a helix at the carboxy terminus of the DNA binding domain is necessary for complex stability. Mol Endocrinol. 2006 Apr;20(4):831-43. Epub 2005 Dec 8. PMID:16339274 doi:10.1210/me.2005-0384
