Steroidogenic factor 1

NR5A1

Available structures

Ortholog search: PDBe RCSB

List of PDB id codes
1YOW, 1ZDT, 4QJR, 4QK4

Identifiers

Aliases

NR5A1, AD4BP, ELP, FTZ1, FTZF1, POF7, SF-1, SF1, SPGF8, SRXY3, hSF-1, nuclear receptor subfamily 5 group A member 1, SRXX4

External IDs

OMIM: 184757 MGI: 1346833 HomoloGene: 3638 GeneCards: NR5A1

Gene location (Human)

Chr.	Chromosome 9 (human)^[1]

Band	No data available	Start	124,481,236 bp^[1]
Band	No data available	End	124,507,430 bp^[1]

Gene location (Mouse)

Chr.	Chromosome 2 (mouse)^[2]

Band	No data available	Start	38,692,656 bp^[2]
Band	No data available	End	38,714,542 bp^[2]

RNA expression pattern

More reference expression data

Gene ontology
Molecular function	• protein binding • zinc ion binding • lipid binding • double-stranded DNA binding • enzyme binding • transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding • steroid hormone receptor activity • transcription coactivator activity • phospholipid binding • metal ion binding • transcription factor activity, sequence-specific DNA binding • RNA polymerase II distal enhancer sequence-specific DNA binding • DNA binding • chromatin binding • RNA polymerase II regulatory region sequence-specific DNA binding • RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding • sequence-specific DNA binding
Cellular component	• nucleoplasm • RNA polymerase II transcription factor complex • nucleus
Biological process	• regulation of transcription from RNA polymerase II promoter • positive regulation of transcription, DNA-templated • regulation of steroid biosynthetic process • hormone metabolic process • luteinization • reproductive process • primary sex determination • tissue development • multicellular organism aging • cell differentiation • maintenance of protein location in nucleus • regulation of transcription, DNA-templated • adrenal gland development • transcription, DNA-templated • steroid hormone mediated signaling pathway • cell-cell signaling • transcription from RNA polymerase II promoter • negative regulation of female gonad development • transcription initiation from RNA polymerase II promoter • positive regulation of male gonad development • intracellular receptor signaling pathway • positive regulation of transcription from RNA polymerase II promoter • sex determination • male gonad development • female gonad development • positive regulation of gene expression • hormone-mediated signaling pathway • calcineurin-mediated signaling • response to gonadotropin-releasing hormone
Sources:Amigo / QuickGO

Orthologs

Species

Human

Mouse

Entrez


2516


26423

Ensembl


ENSG00000136931


ENSMUSG00000026751

UniProt


Q13285


P33242

RefSeq (mRNA)


NM_004959


NM_139051 NM_001316687

RefSeq (protein)


NP_004950 NP_004950.2


NP_001303616 NP_620639

Location (UCSC)

Chr 9: 124.48 – 124.51 Mb

Chr 9: 38.69 – 38.71 Mb

PubMed search

^[3]

^[4]

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).^[5]

Function

SF-1 is a critical regulator of reproduction, regulating the transcription of key genes involved in sexual development and reproduction, most notably StAR and P450_SCC. 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.^[6]

Clinical significance

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.^[7]

Interactions

Steroidogenic factor 1 has been shown to interact with:

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000136931 - Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000026751 - Ensembl, May 2017
↑ "Human PubMed Reference:".
↑ "Mouse PubMed Reference:".
↑ 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. PMID 7789992. doi:10.1016/0888-7543(95)80059-U.
↑ 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. PMID 15579738. doi:10.1210/jc.2004-2047.
↑ 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. PMC 2778147 . PMID 19246354. doi:10.1056/NEJMoa0806228.
↑ 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. PMC 165725 . PMID 12861022. doi:10.1128/MCB.23.15.5366-5375.2003.
↑ 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. PMID 12554773. doi:10.1210/me.2002-0362.
↑ 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. PMID 11713202. doi:10.1210/endo.142.12.8523.
↑ 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. PMID 10919277. doi:10.1210/en.141.8.2895.
↑ 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. PMID 12782406. doi:10.1016/S0303-7207(03)00097-2.
↑ 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. PMID 11459805. doi:10.1210/en.142.8.3570.
↑ 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. PMC 109250 . PMID 9774680. doi:10.1128/mcb.18.11.6653.
↑ 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. PMID 12101186. doi:10.1074/jbc.M205786200.

External links

GeneReviews/NCBI/NIH/UW entry on 46,XY Disorder of Sex Development and 46,XY Complete Gonadal Dysgenesis
OMIM entries on 46,XY Disorder of Sex Development and 46,XY Complete Gonadal Dysgenesis
steroidogenic factor 1 at the US National Library of Medicine Medical Subject Headings (MeSH)

PDB gallery

1ymt: Mouse SF-1 LBD

1yow: human Steroidogenic Factor 1 LBD with bound Co-factor Peptide

1yp0: Structure of the steroidogenic factor-1 ligand binding domain bound to phospholipid and a SHP peptide motif

1zdt: The Crystal Structure of Human Steroidogenic Factor-1

2a66: Human Liver Receptor Homologue DNA-Binding Domain (hLRH-1 DBD) in Complex with dsDNA from the hCYP7A1 Promoter

2ff0: Solution Structure of Steroidogenic Factor 1 DNA Binding Domain Bound to its Target Sequence in the Inhibin alpha-subunit Promoter

Transcription factors and intracellular receptors

(1) Basic domains

(1.1) Basic leucine zipper (bZIP)	Activating transcription factor AATF 1 2 3 4 5 6 7 AP-1 c-Fos FOSB FOSL1 FOSL2 JDP2 c-Jun JUNB JunD BACH 1 2 BATF BLZF1 C/EBP α β γ δ ε ζ CREB 1 3 L1 CREM DBP DDIT3 GABPA GCN4 HLF MAF B F G K NFE 2 L1 L2 L3 NFIL3 NRL NRF 1 2 3 XBP1
(1.2) Basic helix-loop-helix (bHLH)	ATOH1 AhR AHRR ARNT ASCL1 BHLH 2 3 9 ARNTL ARNTL ARNTL2 CLOCK EPAS1 FIGLA HAND 1 2 HES 5 6 HEY 1 2 L HES1 HIF 1A 3A ID 1 2 3 4 LYL1 MESP2 MXD4 MYCL1 MYCN Myogenic regulatory factors MyoD Myogenin MYF5 MYF6 Neurogenins 1 2 3 NeuroD 1 2 NPAS 1 2 3 OLIG 1 2 Pho4 Scleraxis SIM 1 2 TAL 1 2 Twist USF1
(1.3) bHLH-ZIP	AP-4 MAX MXD3 MITF MNT MLX MXI1 Myc SREBP 1 2
(1.4) NF-1	NFI A B C X SMAD R-SMAD 1 2 3 5 9 I-SMAD 6 7 4)
(1.5) RF-X	RFX 1 2 3 4 5 6 ANK
(1.6) Basic helix-span-helix (bHSH)	AP-2 α β γ δ ε

(2) Zinc finger DNA-binding domains

(2.1) Nuclear receptor (Cys₄)

subfamily 1	Thyroid hormone α β CAR FXR LXR α β PPAR α β/δ γ PXR RAR α β γ ROR α β γ Rev-ErbA α β VDR
subfamily 2	COUP-TF (I II Ear-2 HNF4 α γ PNR RXR α β γ Testicular receptor 2 4 TLX
subfamily 3	Steroid hormone Androgen Estrogen α β Glucocorticoid Mineralocorticoid Progesterone Estrogen related α β γ
subfamily 4	NUR NGFIB NOR1 NURR1
subfamily 5	LRH-1 SF1
subfamily 6	GCNF
subfamily 0	DAX1 SHP

(2.2) Other Cys₄

GATA
- 1
- 2
- 3
- 4
- 5
- 6
MTA
- 1
- 2
- 3
TRPS1

(2.3) Cys₂His₂

General transcription factors
- TFIIA
- TFIIB
- TFIID
- TFIIE
  - 1
  - 2
- TFIIF
- 1
- 2
  - TFIIH
  - 1
  - 2
  - 4
  - 2I
  - 3A
  - 3C1
  - 3C2

ATBF1
BCL
- 6
- 11A
- 11B
CTCF
E4F1
EGR
- 1
- 2
- 3
- 4
ERV3
GFI1
GLI-Krüppel family
- 1
- 2
- 3
- REST
- S1
- S2
- YY1
HIC
- 1
- 2
HIVEP
- 1
- 2
- 3
IKZF
- 1
- 2
- 3
ILF
- 2
- 3
KLF
- 1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 9
- 10
- 11
- 12
- 13
- 14
- 15
- 17
MTF1
MYT1
OSR1
PRDM9
SALL
- 1
- 2
- 3
- 4
SP
- 1
- 2
- 4
- 7
- 8
TSHZ3
WT1
Zbtb7
- 7A
- 7B
ZBTB
- 11
- 16
- 17
- 20
- 32
- 33
- 40
zinc finger
- 3
- 7
- 9
- 10
- 19
- 22
- 24
- 33B
- 34
- 35
- 41
- 43
- 44
- 51
- 74
- 143
- 146
- 148
- 165
- 202
- 217
- 219
- 238
- 239
- 259
- 267
- 268
- 281
- 295
- 300
- 318
- 330
- 346
- 350
- 365
- 366
- 384
- 423
- 451
- 452
- 471
- 593
- 638
- 644
- 649
- 655

(2.4) Cys₆

HIVEP1

(2.5) Alternating composition

AIRE
DIDO1
GRLF1
ING
- 1
- 2
- 4
JARID
- 1A
- 1B
- 1C
- 1D
- 2
JMJD1B

(2.6) WRKY

WRKY

(3) Helix-turn-helix domains

(3.1) Homeodomain	ARX CDX 1 2 CRX CUTL1 DBX 1 2 DLX 3 4 5 EMX 1 2 EN 1 2 FHL 1 2 3 HESX1 HHEX HLX Homeobox A1 A2 A3 A4 A5 A7 A9 A10 A11 A13 B1 B2 B3 B4 B5 B6 B7 B8 B9 B13 C4 C5 C6 C8 C9 C10 C11 C12 C13 D1 D3 D4 D8 D9 D10 D11 D12 D13 HOPX IRX 1 2 3 4 5 6 MKX LMX 1A 1B MEIS 1 2 MEOX2 MNX1 MSX 1 2 NANOG NKX 2-1 2-2 2-3 2-5 3-1 3-2 6-1 6-2 NOBOX PBX 1 2 3 PHF 1 3 6 8 10 16 17 20 21A PHOX 2A 2B PITX 1 2 3 POU domain PIT-1 BRN-3: A B C Octamer transcription factor: 1 2 3/4 6 7 11 OTX 1 2 PDX1 SATB2 SHOX2 SIX 1 2 3 4 5 VAX1 ZEB 1 2
(3.2) Paired box	PAX 1 2 3 4 5 6 7 8 9 PRRX 1 2 RAX
(3.3) Fork head / winged helix	E2F 1 2 3 4 5 FOX proteins A1 A2 A3 C1 C2 D3 D4 E1 E3 F1 G1 H1 I1 J1 J2 K1 K2 L2 M1 N1 N3 O1 O3 O4 P1 P2 P3 P4
(3.4) Heat shock factors	HSF 1 2 4
(3.5) Tryptophan clusters	ELF 2 4 5 EGF ELK 1 3 4 ERF ETS 1 2 ERG SPIB ETV 1 4 5 6 FLI1 Interferon regulatory factors 1 2 3 4 5 6 7 8 MYB MYBL2
(3.6) TEA domain	transcriptional enhancer factor 1 2 3 4

(4) β-Scaffold factors with minor groove contacts

(4.1) Rel homology region	NF-κB NFKB1 NFKB2 REL RELA RELB NFAT C1 C2 C3 C4 5
(4.2) STAT	STAT 1 2 3 4 5 6
(4.3) p53	p53 TBX 1 2 3 5 19 21 22 TBR1 TBR2 TFT MYRF TP63
(4.4) MADS box	Mef2 A B C D SRF
(4.6) TATA-binding proteins	TBP TBPL1
(4.7) High-mobility group	BBX HMGB 1 2 3 4 HMGN 1 2 3 4 HNF 1A 1B LEF1 SOX 1 2 3 4 5 6 8 9 10 11 12 13 14 15 18 21 SRY SSRP1 TCF 3 4 TOX 1 2 3 4
(4.9) Grainyhead	TFCP2
(4.10) Cold-shock domain	CSDA YBX1
(4.11) Runt	CBF CBFA2T2 CBFA2T3 RUNX1 RUNX2 RUNX3 RUNX1T1

(0) Other transcription factors

(0.2) HMGI(Y)	HMGA 1 2 HBP1
(0.3) Pocket domain	Rb RBL1 RBL2
(0.5) AP-2/EREBP-related factors	Apetala 2 EREBP B3
(0.6) Miscellaneous	ARID 1A 1B 2 3A 3B 4A CAP IFI 16 35 MLL 2 3 T1 MNDA NFY A B C Rho/Sigma

see also transcription factor/coregulator deficiencies

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