Steroidogenic factor 1

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NR5A1
Protein NR5A1 PDB 1ymt.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases NR5A1, AD4BP, ELP, FTZ1, FTZF1, POF7, SF-1, SF1, SPGF8, SRXY3, hSF-1, nuclear receptor subfamily 5 group A member 1
External IDs OMIM: 184757 MGI: 1346833 HomoloGene: 3638 GeneCards: 2516
RNA expression pattern
PBB GE NR5A1 210333 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_004959

NM_139051
NM_001316687

RefSeq (protein)

NP_004950.2
NP_004950.2

NP_620639.1
NP_001303616.1

Location (UCSC) Chr 9: 124.48 – 124.51 Mb Chr 2: 38.69 – 38.71 Mb
PubMed search [1] [2]
Wikidata
View/Edit Human View/Edit Mouse

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).[3]

Function[edit]

SF-1 is a critical regulator of reproduction, regulating the transcription of key genes involved in sexual development and reproduction, most notably StAR and P450SCC. 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.[4]

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.[5]

Interactions[edit]

Steroidogenic factor 1 has been shown to interact with:

References[edit]

  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ Taketo M, Parker KL, Howard TA, Tsukiyama T, Wong M, Niwa O, Morton CC, Miron PM, Seldin MF (Jan 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. 
  4. ^ Jameson JL (Dec 2004). "Of mice and men: The tale of steroidogenic factor-1". The Journal of Clinical Endocrinology and Metabolism. 89 (12): 5927–9. doi:10.1210/jc.2004-2047. PMID 15579738. 
  5. ^ 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 (Mar 2009). "Mutations in NR5A1 associated with ovarian insufficiency". The New England Journal of Medicine. 360 (12): 1200–10. doi:10.1056/NEJMoa0806228. PMC 2778147free to read. PMID 19246354. 
  6. ^ Kennell JA, O'Leary EE, Gummow BM, Hammer GD, MacDougald OA (Aug 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". Molecular and Cellular Biology. 23 (15): 5366–75. doi:10.1128/MCB.23.15.5366-5375.2003. PMC 165725free to read. PMID 12861022. 
  7. ^ Mizusaki H, Kawabe K, Mukai T, Ariyoshi E, Kasahara M, Yoshioka H, Swain A, Morohashi K (Apr 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". Molecular Endocrinology. 17 (4): 507–19. doi:10.1210/me.2002-0362. PMID 12554773. 
  8. ^ Lopez D, Shea-Eaton W, Sanchez MD, McLean MP (Dec 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/endo.142.12.8523. PMID 11713202. 
  9. ^ Sugawara T, Saito M, Fujimoto S (Aug 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. 
  10. ^ 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". Molecular and Cellular Endocrinology. 203 (1-2): 91–103. doi:10.1016/S0303-7207(03)00097-2. PMID 12782406. 
  11. ^ Sugawara T, Abe S, Sakuragi N, Fujimoto Y, Nomura E, Fujieda K, Saito M, Fujimoto S (Aug 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. 
  12. ^ De Santa Barbara P, Bonneaud N, Boizet B, Desclozeaux M, Moniot B, Sudbeck P, Scherer G, Poulat F, Berta P (Nov 1998). "Direct interaction of SRY-related protein SOX9 and steroidogenic factor 1 regulates transcription of the human anti-Müllerian hormone gene". Molecular and Cellular Biology. 18 (11): 6653–65. doi:10.1128/mcb.18.11.6653. PMC 109250free to read. PMID 9774680. 
  13. ^ Gizard F, Lavallee B, DeWitte F, Teissier E, Staels B, Hum DW (Oct 2002). "The transcriptional regulating protein of 132 kDa (TReP-132) enhances P450scc gene transcription through interaction with steroidogenic factor-1 in human adrenal cells". The Journal of Biological Chemistry. 277 (42): 39144–55. doi:10.1074/jbc.M205786200. PMID 12101186. 

Further reading[edit]

External links[edit]