Steroidogenic factor 1

Details

Name

Steroidogenic factor 1

Synonyms

• AD4BP
• Adrenal 4-binding protein
• FTZF1
• Fushi tarazu factor homolog 1
• Nuclear receptor subfamily 5 group A member 1
• SF-1
• SF1
• Steroid hormone receptor Ad4BP

Gene Name

NR5A1

Organism

Humans

Amino acid sequence

>lcl|BSEQ0019413|Steroidogenic factor 1
MDYSYDEDLDELCPVCGDKVSGYHYGLLTCESCKGFFKRTVQNNKHYTCTESQSCKIDKT
QRKRCPFCRFQKCLTVGMRLEAVRADRMRGGRNKFGPMYKRDRALKQQKKAQIRANGFKL
ETGPPMGVPPPPPPAPDYVLPPSLHGPEPKGLAAGPPAGPLGDFGAPALPMAVPGAHGPL
AGYLYPAFPGRAIKSEYPEPYASPPQPGLPYGYPEPFSGGPNVPELILQLLQLEPDEDQV
RARILGCLQEPTKSRPDQPAAFGLLCRMADQTFISIVDWARRCMVFKELEVADQMTLLQN
CWSELLVFDHIYRQVQHGKEGSILLVTGQEVELTTVATQAGSLLHSLVLRAQELVLQLLA
LQLDRQEFVCLKFIILFSLDLKFLNNHILVKDAQEKANAALLDYTLCHYPHCGDKFQQLL
LCLVEVRALSMQAKEYLYHKHLGNEMPRNNLLIEMLQAKQT

Number of residues

461

Molecular Weight

51635.47

Theoretical pI

7.73

GO Classification

Functions

chromatin binding / DNA binding / enzyme binding / phospholipid binding / RNA polymerase II distal enhancer sequence-specific DNA binding / RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding / steroid hormone receptor activity / transcription coactivator activity / transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding / transcription regulatory region sequence-specific DNA binding / zinc ion binding

Processes

adrenal gland development / cell differentiation / cell-cell signaling / gene expression / hormone metabolic process / hormone-mediated signaling pathway / intracellular receptor signaling pathway / luteinization / maintenance of protein location in nucleus / male gonad development / multicellular organismal aging / negative regulation of female gonad development / positive regulation of male gonad development / positive regulation of transcription from RNA polymerase II promoter / primary sex determination / regulation of steroid biosynthetic process / tissue development / transcription initiation from RNA polymerase II promoter

Components

nucleoplasm / nucleus / RNA polymerase II transcription factor complex

General Function

Zinc ion binding

Specific Function

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.

Pfam Domain Function

• Hormone_recep (PF00104)
• zf-C4 (PF00105)

Transmembrane Regions

Not Available

Cellular Location

Nucleus

Gene sequence

>lcl|BSEQ0019414|Steroidogenic factor 1 (NR5A1)
ATGGACTATTCGTACGACGAGGACCTGGACGAGCTGTGCCCCGTGTGCGGGGACAAGGTG
TCCGGCTACCACTACGGACTGCTCACGTGTGAGAGCTGCAAGGGCTTCTTCAAGCGCACG
GTGCAGAACAACAAGCACTACACGTGCACCGAGAGCCAGAGCTGCAAGATCGACAAGACG
CAGCGCAAGCGCTGTCCCTTCTGCCGCTTCCAGAAATGCCTGACGGTGGGGATGCGCCTG
GAAGCCGTGCGCGCTGACCGTATGAGGGGTGGCCGGAACAAGTTTGGGCCGATGTACAAG
CGGGACCGGGCCCTGAAACAGCAGAAGAAGGCACAGATTCGGGCCAATGGCTTCAAGCTG
GAGACAGGGCCCCCGATGGGGGTGCCCCCGCCGCCCCCTCCCGCACCGGACTACGTGCTG
CCTCCCAGCCTGCATGGGCCTGAGCCCAAGGGCCTGGCCGCCGGTCCACCTGCTGGGCCA
CTGGGCGACTTTGGGGCCCCAGCACTGCCCATGGCCGTGCCCGGTGCCCACGGGCCACTG
GCTGGCTACCTCTACCCTGCCTTTCCTGGCCGTGCCATCAAGTCTGAGTACCCGGAGCCT
TATGCCAGCCCCCCACAGCCTGGGCTGCCGTACGGCTACCCAGAGCCCTTCTCTGGAGGG
CCCAACGTGCCTGAGCTCATCCTGCAGCTGCTGCAGCTGGAGCCGGATGAGGACCAGGTG
CGGGCCCGCATCTTGGGCTGCCTGCAGGAGCCCACCAAAAGCCGCCCCGACCAGCCGGCG
GCCTTCGGCCTCCTGTGCAGAATGGCCGACCAGACCTTCATCTCCATCGTGGACTGGGCA
CGCAGGTGCATGGTCTTCAAGGAGCTGGAGGTGGCCGACCAGATGACGCTGCTGCAGAAC
TGCTGGAGCGAGCTGCTGGTGTTCGACCACATCTACCGCCAGGTCCAGCACGGCAAGGAG
GGCAGCATCCTGCTGGTCACCGGGCAGGAGGTGGAGCTGACCACAGTGGCCACCCAGGCG
GGCTCGCTGCTGCACAGCCTGGTGTTGCGGGCGCAGGAGCTGGTGCTGCAGCTGCTTGCG
CTGCAGCTGGACCGGCAGGAGTTTGTCTGCCTCAAGTTCATCATCCTCTTCAGCCTGGAT
TTGAAGTTCCTGAATAACCACATCCTGGTGAAAGACGCTCAGGAGAAGGCCAACGCCGCC
CTGCTTGACTACACCCTGTGCCACTACCCGCACTGCGGGGACAAATTCCAGCAGCTGCTG
CTGTGCCTGGTGGAGGTGCGGGCCCTGAGCATGCAGGCCAAGGAGTACCTGTACCACAAG
CACCTGGGCAACGAGATGCCCCGCAACAACCTGCTCATCGAAATGCTGCAAGCCAAGCAG
ACTTGA

Chromosome Location

9

Locus

9q33

External Identifiers

Resource	Link
UniProtKB ID	Q13285
UniProtKB Entry Name	STF1_HUMAN
GenBank Gene ID	U76388
GenAtlas ID	NR5A1
HGNC ID	HGNC:7983

General References

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4. Hammer GD, Krylova I, Zhang Y, Darimont BD, Simpson K, Weigel NL, Ingraham HA: Phosphorylation of the nuclear receptor SF-1 modulates cofactor recruitment: integration of hormone signaling in reproduction and stress. Mol Cell. 1999 Apr;3(4):521-6. [Article]
5. Jacob AL, Lund J, Martinez P, Hedin L: Acetylation of steroidogenic factor 1 protein regulates its transcriptional activity and recruits the coactivator GCN5. J Biol Chem. 2001 Oct 5;276(40):37659-64. Epub 2001 Jul 30. [Article]
6. Sewer MB, Nguyen VQ, Huang CJ, Tucker PW, Kagawa N, Waterman MR: Transcriptional activation of human CYP17 in H295R adrenocortical cells depends on complex formation among p54(nrb)/NonO, protein-associated splicing factor, and SF-1, a complex that also participates in repression of transcription. Endocrinology. 2002 Apr;143(4):1280-90. [Article]
7. Komatsu T, Mizusaki H, Mukai T, Ogawa H, Baba D, Shirakawa M, Hatakeyama S, Nakayama KI, Yamamoto H, Kikuchi A, Morohashi K: Small ubiquitin-like modifier 1 (SUMO-1) modification of the synergy control motif of Ad4 binding protein/steroidogenic factor 1 (Ad4BP/SF-1) regulates synergistic transcription between Ad4BP/SF-1 and Sox9. Mol Endocrinol. 2004 Oct;18(10):2451-62. Epub 2004 Jun 10. [Article]
8. 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. [Article]
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15. 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. [Article]
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18. 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. [Article]
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Drug Relations

Drug Relations

DrugBank ID	Name	Drug group	Pharmacological action?	Actions	Details
DB04683	(2R)-3-{[{[(2S)-2,3-DIHYDROXYPROPYL]OXY}(HYDROXY)PHOSPHORYL]OXY}-2-[(9E)-HEXADEC-9-ENOYLOXY]PROPYL (9E)-OCTADEC-9-ENOATE	experimental	unknown		Details
DB04752	Phosphatidyl ethanol	experimental	unknown		Details