Recombinant Human Forkhead box protein L2 (FOXL2)

Function

Transcriptional regulator. Critical factor essential for ovary differentiation and maintenance, and repression of the genetic program for somatic testis determination. Prevents trans-differentiation of ovary to testis through transcriptional repression of the Sertoli cell-promoting gene SOX9 (By similarity). Has apoptotic activity in ovarian cells. Suppresses ESR1-mediated transcription of PTGS2/COX2 stimulated by tamoxifen (By similarity). Is a regulator of CYP19 expression (By similarity). Participates in SMAD3-dependent transcription of FST via the intronic SMAD-binding element (By similarity). Is a transcriptional repressor of STAR. Activates SIRT1 transcription under cellular stress conditions. Activates transcription of OSR2

Subcellular Location

Nucleus

Disease Association

Blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES) : A disorder characterized by eyelid dysplasia, small palpebral fissures, drooping eyelids and a skin fold curving in the mediolateral direction, inferior to the inner canthus. In type I BPSE (BPES1) eyelid abnormalities are associated with female infertility. Affected females show an ovarian deficit due to primary amenorrhea or to premature ovarian failure (POF). In type II BPSE (BPES2) affected individuals show only the eyelid defects. [The disease is caused by variants affecting the gene represented in this entry. There is a mutational hotspot in the region coding for the poly-Ala domain, since 30% of all mutations in the ORF lead to poly-Ala expansions, resulting mainly in BPES type II] | Premature ovarian failure 3 (POF3) : An ovarian disorder defined as the cessation of ovarian function under the age of 40 years. It is characterized by oligomenorrhea or amenorrhea, in the presence of elevated levels of serum gonadotropins and low estradiol. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

In addition to its expression in the developing eyelid, it is transcribed very early in somatic cells of the developing gonad (before sex determination) and its expression persists in the follicular cells of the adult ovary

Subunit

Interacts with ESR1 (By similarity). Interacts with SMAD3 (By similarity). Interacts with DDX20. Interacts with UBE2I/UBC9

• Crisponi L. et al. The putative forkhead transcription factor FOXL2 is mutated in blepharophimosis/ptosis/epicanthus inversus syndrome. — Nat. Genet. (2001)
• Xu Y. et al. Study of mutations of FOXL2 gene in a Chinese TongHai family with blepharophimosis-ptosis-epicanthus inversus syndrome. (MAR-)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Lee K. et al. Transcriptional factor FOXL2 interacts with DP103 and induces apoptosis. — Biochem. Biophys. Res. Commun. (2005)
• Kuo F.T. et al. Sumoylation of forkhead L2 by Ubc9 is required for its activity as a transcriptional repressor of the steroidogenic acute regulatory gene. — Cell. Signal. (2009)
• Benayoun B.A. et al. Positive and negative feedback regulates the transcription factor FOXL2 in response to cell stress: evidence for a regulatory imbalance induced by disease-causing mutations. — Hum. Mol. Genet. (2009)
• Laissue P. et al. Functional evidence implicating FOXL2 in non-syndromic premature ovarian failure and in the regulation of the transcription factor OSR2. — J. Med. Genet. (2009)
• Zhou H. et al. Toward a comprehensive characterization of a human cancer cell phosphoproteome. — J. Proteome Res. (2013)