Steroidogenic factor 1

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Nuclear receptor subfamily 5, group A, member 1
Protein NR5A1 PDB 1ymt.png
PDB rendering based on 1ymt.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols NR5A1 ; AD4BP; ELP; FTZ1; FTZF1; POF7; SF-1; SF1; SPGF8; SRXY3
External IDs OMIM184757 MGI1346833 HomoloGene3638 IUPHAR: NR5A1 ChEMBL: 4666 GeneCards: NR5A1 Gene
RNA expression pattern
PBB GE NR5A1 210333 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 2516 26423
Ensembl ENSG00000136931 ENSMUSG00000026751
UniProt Q13285 P33242
RefSeq (mRNA) NM_004959 NM_139051
RefSeq (protein) NP_004950 NP_620639
Location (UCSC) Chr 9:
127.24 – 127.27 Mb
Chr 2:
38.69 – 38.71 Mb
PubMed search [1] [2]

The steroidogenic factor 1 (SF1) protein controls sexual development in the embryo and at puberty.

SF1 is a member of the nuclear receptor family of intracellular transcription factors and is encoded by the NR5A1 gene (nuclear receptor subfamily 5, group A, member 1).[1]

Function[edit]

SF-1 is a critical regulator of reproduction, regulating the transcription of key genes involved in sexual development and reproduction. It can form a transcriptional complex with TDF to up-regulate transcription of the Sox9 gene. Its targets include genes at every level of the hypothalamic-pituitary-gonadal axis, as well as many genes involved in gonadal and adrenal steroidogenesis.[2]

Clinical significance[edit]

Mutations in NR5A1 can produce intersex genitals, absence of puberty, and infertility. It is one cause of arrest of ovarian function in women <40 years of age, which occurs in 1% of all women.

Missense, in-frame and frameshift mutations of NR5A1 have been found in families with 46,XY disorders of sex development, 46,XX gonadal dysgenesis and 46,XX primary ovarian insufficiency. 46,XY individuals may have ambiguous or female genitals. Individuals of either karyotype may not enter puberty, although expression of the phenotype, penetrance, fertility, and modes of inheritance can vary. Some mutations are dominant, some are recessive.[3]

Interactions[edit]

Steroidogenic factor 1 has been shown to interact with:

References[edit]

  1. ^ Taketo M, Parker KL, Howard TA, Tsukiyama T, Wong M, Niwa O, Morton CC, Miron PM, Seldin MF (1995). "Homologs of Drosophila Fushi-Tarazu factor 1 map to mouse chromosome 2 and human chromosome 9q33.". Genomics 25 (2): 565–7. doi:10.1016/0888-7543(95)80059-U. PMID 7789992. 
  2. ^ Jameson JL (2004). "Of mice and men: The tale of steroidogenic factor-1.". J. Clin. Endocrinol. Metab. 89 (12): 5927–9. doi:10.1210/jc.2004-2047. PMID 15579738. 
  3. ^ Lourenço 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 (March 2009). "Mutations in NR5A1 associated with ovarian insufficiency". N. Engl. J. Med. 360 (12): 1200–10. doi:10.1056/NEJMoa0806228. PMC 2778147. PMID 19246354. 
  4. ^ Kennell JA, O'Leary EE, Gummow BM, Hammer GD, MacDougald OA (August 2003). "T-cell factor 4N (TCF-4N), a novel isoform of mouse TCF-4, synergizes with beta-catenin to coactivate C/EBPalpha and steroidogenic factor 1 transcription factors". Mol. Cell. Biol. 23 (15): 5366–75. doi:10.1128/MCB.23.15.5366-5375.2003. PMC 165725. PMID 12861022. 
  5. ^ Mizusaki H, Kawabe K, Mukai T, Ariyoshi E, Kasahara M, Yoshioka H, Swain A, Morohashi K (April 2003). "Dax-1 (dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome, gene 1) gene transcription is regulated by wnt4 in the female developing gonad". Mol. Endocrinol. 17 (4): 507–19. doi:10.1210/me.2002-0362. PMID 12554773. 
  6. ^ Lopez D, Shea-Eaton W, Sanchez MD, McLean MP (December 2001). "DAX-1 represses the high-density lipoprotein receptor through interaction with positive regulators sterol regulatory element-binding protein-1a and steroidogenic factor-1". Endocrinology 142 (12): 5097–106. doi:10.1210/en.142.12.5097. PMID 11713202. 
  7. ^ Sugawara T, Saito M, Fujimoto S (August 2000). "Sp1 and SF-1 interact and cooperate in the regulation of human steroidogenic acute regulatory protein gene expression". Endocrinology 141 (8): 2895–903. doi:10.1210/en.141.8.2895. PMID 10919277. 
  8. ^ Mellgren G, Børud B, Hoang T, Yri OE, Fladeby C, Lien EA, Lund J (May 2003). "Characterization of receptor-interacting protein RIP140 in the regulation of SF-1 responsive target genes". Mol. Cell. Endocrinol. 203 (1-2): 91–103. doi:10.1016/S0303-7207(03)00097-2. PMID 12782406. 
  9. ^ Sugawara T, Abe S, Sakuragi N, Fujimoto Y, Nomura E, Fujieda K, Saito M, Fujimoto S (August 2001). "RIP 140 modulates transcription of the steroidogenic acute regulatory protein gene through interactions with both SF-1 and DAX-1". Endocrinology 142 (8): 3570–7. doi:10.1210/en.142.8.3570. PMID 11459805. 
  10. ^ De Santa Barbara P, Bonneaud N, Boizet B, Desclozeaux M, Moniot B, Sudbeck P, Scherer G, Poulat F, Berta P (November 1998). "Direct interaction of SRY-related protein SOX9 and steroidogenic factor 1 regulates transcription of the human anti-Müllerian hormone gene". Mol. Cell. Biol. 18 (11): 6653–65. PMC 109250. PMID 9774680. 
  11. ^ Gizard F, Lavallee B, DeWitte F, Teissier E, Staels B, Hum DW (October 2002). "The transcriptional regulating protein of 132 kDa (TReP-132) enhances P450scc gene transcription through interaction with steroidogenic factor-1 in human adrenal cells". J. Biol. Chem. 277 (42): 39144–55. doi:10.1074/jbc.M205786200. PMID 12101186. 

Further reading[edit]

External links[edit]