InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: FOXL2

Summary

InnateDB Protein

IDBP-58708.5

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

FOXL2

Protein Name

forkhead box L2

Synonyms

BPES; BPES1; PFRK; PINTO; POF3;

Species

Homo sapiens

Ensembl Protein

ENSP00000333188

InnateDB Gene

IDBG-58706 (FOXL2)

Protein Structure

UniProt Annotation

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. {ECO:0000250, ECO:0000269PubMed:16153597, ECO:0000269PubMed:19010791, ECO:0000269PubMed:19429596, ECO:0000269PubMed:19744555}.

Subcellular Localization

Nucleus {ECO:0000255PROSITE- ProRule:PRU00089, ECO:0000269PubMed:19744555}.

Disease Associations

Blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES) [MIM:110100]: 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. {ECO:0000269PubMed:11175783, ECO:0000269PubMed:11468277, ECO:0000269PubMed:12400065, ECO:0000269PubMed:12529855, ECO:0000269PubMed:12630957, ECO:0000269PubMed:12938087, ECO:0000269PubMed:15257268, ECO:0000269PubMed:16454982, ECO:0000269PubMed:17089161, ECO:0000269PubMed:18484667, ECO:0000269PubMed:18642388, ECO:0000269Ref.2}. Note=The disease is caused by mutations 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) [MIM:608996]: 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. {ECO:0000269PubMed:12149404, ECO:0000269PubMed:19429596}. Note=The disease is caused by mutations 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.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 7 experimentally validated interaction(s) in this database.
They are also associated with 3 interaction(s) predicted by orthology.

Experimentally validated
Total	7 [view]
Protein-Protein	7 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	3 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003677	DNA binding
GO:0003700	sequence-specific DNA binding transcription factor activity
GO:0005515	protein binding
GO:0030331	estrogen receptor binding
GO:0031624	ubiquitin conjugating enzyme binding
GO:0043028	cysteine-type endopeptidase regulator activity involved in apoptotic process
GO:0043565	sequence-specific DNA binding

Biological Process

GO:0000122	negative regulation of transcription from RNA polymerase II promoter
GO:0001541	ovarian follicle development
GO:0002074	extraocular skeletal muscle development
GO:0006309	apoptotic DNA fragmentation
GO:0006355	regulation of transcription, DNA-templated
GO:0006366	transcription from RNA polymerase II promoter
GO:0019101	female somatic sex determination
GO:0030154	cell differentiation
GO:0042703	menstruation
GO:0043065	positive regulation of apoptotic process
GO:0043280	positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0045892	negative regulation of transcription, DNA-templated
GO:0045893	positive regulation of transcription, DNA-templated
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0048048	embryonic eye morphogenesis
GO:0060014	granulosa cell differentiation