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O88470 (FOXL2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 114. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Forkhead box protein L2
Alternative name(s):
Pituitary forkhead factor
Short name=P-Frk
Gene names
Name:Foxl2
Synonyms:Pfrk
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length375 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Has apoptotic activity in ovarian cells. Suppresses ESR1-mediated transcription of PTGS2/COX2 stimulated by tamoxifen. Activates SIRT1 transcription under cellular stress conditions. Activates transcription of OSR2. Is a regulator of CYP19 expression. Is a transcriptional repressor of STAR. Participates in SMAD3-dependent transcription of FST via the intronic SMAD-binding element. Ref.3 Ref.5 Ref.6 Ref.7 Ref.8

Subunit structure

Interacts with ESR1. Interacts with UBE2I/UBC9 By similarity. Interacts with SMAD3. Interacts with DDX20. Ref.4 Ref.6 Ref.7 Ref.8

Subcellular location

Nucleus Ref.7.

Tissue specificity

Expressed in the mesenchyme of developing eyelids. Expressed in ovaries throughout development and adulthood, localized to the undifferentiated granulosa cells in small and medium follicles as well as cumulus cells of preovulatory follicles. Expressed in the pituitary. Ref.3 Ref.8

Post-translational modification

Sumoylated with SUMO1; sumoylation is required for transcriptional repression activity By similarity.

Sequence similarities

Contains 1 fork-head DNA-binding domain.

Ontologies

Keywords
   Biological processDifferentiation
Transcription
Transcription regulation
   Cellular componentNucleus
   LigandDNA-binding
   PTMIsopeptide bond
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic DNA fragmentation

Inferred from sequence or structural similarity. Source: UniProtKB

embryonic eye morphogenesis

Inferred from mutant phenotype PubMed 15056605. Source: MGI

extraocular skeletal muscle development

Inferred from sequence or structural similarity. Source: UniProtKB

female somatic sex determination

Inferred from mutant phenotype Ref.5. Source: MGI

granulosa cell differentiation

Inferred from mutant phenotype PubMed 14736745. Source: MGI

menstruation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype PubMed 21757499. Source: MGI

negative regulation of transcription, DNA-templated

Inferred from mutant phenotype PubMed 21757499. Source: MGI

ovarian follicle development

Inferred from sequence or structural similarity. Source: UniProtKB

pattern specification process

Inferred from Biological aspect of Ancestor. Source: RefGenome

positive regulation of apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 12943993. Source: MGI

regulation of sequence-specific DNA binding transcription factor activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

transcription from RNA polymerase II promoter

Inferred from Biological aspect of Ancestor. Source: GOC

   Cellular_componentnucleus

Inferred from direct assay Ref.7. Source: UniProtKB

transcription factor complex

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Molecular_functionDNA binding

Inferred from sequence or structural similarity. Source: UniProtKB

DNA binding, bending

Inferred from Biological aspect of Ancestor. Source: RefGenome

RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

cysteine-type endopeptidase regulator activity involved in apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

double-stranded DNA binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

estrogen receptor binding

Inferred from physical interaction Ref.7Ref.6. Source: UniProtKB

sequence-specific DNA binding

Inferred from electronic annotation. Source: InterPro

sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 12943993. Source: MGI

transcription factor binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

ubiquitin conjugating enzyme binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 375375Forkhead box protein L2
PRO_0000091862

Regions

DNA binding50 – 14495Fork-head
Compositional bias217 – 23014Poly-Ala
Compositional bias280 – 2878Poly-Pro
Compositional bias300 – 3034Poly-Ala

Amino acid modifications

Cross-link25Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Sequences

Sequence LengthMass (Da)Tools
O88470 [UniParc].

Last modified March 15, 2005. Version 2.
Checksum: F920C8407686C4B6

FASTA37538,887
        10         20         30         40         50         60 
MMASYPEPED TAGTLLAPES GRAVKEAEAS PPSPGKGGGT TPEKPDPAQK PPYSYVALIA 

        70         80         90        100        110        120 
MAIRESAEKR LTLSGIYQYI IAKFPFYEKN KKGWQNSIRH NLSLNECFIK VPREGGGERK 

       130        140        150        160        170        180 
GNYWTLDPAC EDMFEKGNYR RRRRMKRPFR PPPAHFQPGK GLFGSGGAAG GCGVPGAGAD 

       190        200        210        220        230        240 
GYGYLAPPKY LQSGFLNNSW PLPQPPSPMP YASCQMAAAA AAAAAAAAAA GPGSPGAAAV 

       250        260        270        280        290        300 
VKGLAGPAAS YGPYSRVQSM ALPPGVVNSY NGLGGPPAAP PPPPPPPHPH PHPHAHHLHA 

       310        320        330        340        350        360 
AAAPPPAPPH HGAAAPPPGQ LSPASPATAA PPAPAPTSAP GLQFACARQP ELAMMHCSYW 

       370 
DHDSKTGALH SRLDL 

« Hide

References

[1]"Evolution and expression of FOXL2."
Cocquet J., Pailhoux E., Jaubert F., Servel N., Xia X., Pannetier M., De Baere E., Messiaen L., Cotinot C., Fellous M., Veitia R.A.
J. Med. Genet. 39:916-921(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"Multistep signaling requirements for pituitary organogenesis in vivo."
Treier M., Gleiberman A.S., O'Connell S.M., Szeto D.P., McMahon J.A., McMahon A.P., Rosenfeld M.G.
Genes Dev. 12:1691-1704(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 50-139.
[3]"Forkhead l2 is expressed in the ovary and represses the promoter activity of the steroidogenic acute regulatory gene."
Pisarska M.D., Bae J., Klein C., Hsueh A.J.
Endocrinology 145:3424-3433(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS TRANSCRIPTIONAL REPRESSOR OF STAR, TISSUE SPECIFICITY.
[4]"Transcriptional factor FOXL2 interacts with DP103 and induces apoptosis."
Lee K., Pisarska M.D., Ko J.J., Kang Y., Yoon S., Ryou S.M., Cha K.Y., Bae J.
Biochem. Biophys. Res. Commun. 336:876-881(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DDX20/DP103.
[5]"Foxl2 is required for commitment to ovary differentiation."
Ottolenghi C., Omari S., Garcia-Ortiz J.E., Uda M., Crisponi L., Forabosco A., Pilia G., Schlessinger D.
Hum. Mol. Genet. 14:2053-2062(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN OVARY DIFFERENTIATION.
[6]"Somatic sex reprogramming of adult ovaries to testes by FOXL2 ablation."
Uhlenhaut N.H., Jakob S., Anlag K., Eisenberger T., Sekido R., Kress J., Treier A.C., Klugmann C., Klasen C., Holter N.I., Riethmacher D., Schutz G., Cooney A.J., Lovell-Badge R., Treier M.
Cell 139:1130-1142(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ROLE IN OVARY MAINTENANCE, FUNCTION AS TRANSCRIPTIONAL REPRESSOR OF SOX9, INTERACTION WITH ESR1.
[7]"Foxl2, a forkhead transcription factor, modulates nonclassical activity of the estrogen receptor-alpha."
Kim S.Y., Weiss J., Tong M., Laronda M.M., Lee E.J., Jameson J.L.
Endocrinology 150:5085-5093(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS TRANSCRIPTIONAL REPRESSOR OF PTGS2, INTERACTION WITH ESR1, SUBCELLULAR LOCATION.
[8]"FoxL2 and Smad3 coordinately regulate follistatin gene transcription."
Blount A.L., Schmidt K., Justice N.J., Vale W.W., Fischer W.H., Bilezikjian L.M.
J. Biol. Chem. 284:7631-7645(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS TRANSCRIPTIONAL REGULATOR OF FST, INTERACTION WITH SMAD3, TISSUE SPECIFICITY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF522275 Genomic DNA. Translation: AAN04088.1.
AF060873 mRNA. Translation: AAC27508.1.
RefSeqNP_036150.1. NM_012020.2.
UniGeneMm.151239.

3D structure databases

ProteinModelPortalO88470.
SMRO88470. Positions 50-139.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActO88470. 2 interactions.

PTM databases

PhosphoSiteO88470.

Proteomic databases

PRIDEO88470.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000051312; ENSMUSP00000053297; ENSMUSG00000050397.
GeneID26927.
KEGGmmu:26927.
UCSCuc009rdr.2. mouse.

Organism-specific databases

CTD668.
MGIMGI:1349428. Foxl2.

Phylogenomic databases

eggNOGCOG5025.
HOGENOMHOG000218632.
HOVERGENHBG051651.
InParanoidO88470.
KOK09405.
OMAAELSMMH.
OrthoDBEOG7C8GHD.
PhylomeDBO88470.
TreeFamTF316127.

Gene expression databases

BgeeO88470.
CleanExMM_FOXL2.
GenevestigatorO88470.

Family and domain databases

Gene3D1.10.10.10. 1 hit.
InterProIPR001766. TF_fork_head.
IPR018122. TF_fork_head_CS.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamPF00250. Fork_head. 1 hit.
[Graphical view]
PRINTSPR00053. FORKHEAD.
SMARTSM00339. FH. 1 hit.
[Graphical view]
PROSITEPS00657. FORK_HEAD_1. 1 hit.
PS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio304821.
PROO88470.
SOURCESearch...

Entry information

Entry nameFOXL2_MOUSE
AccessionPrimary (citable) accession number: O88470
Secondary accession number(s): Q8K3X9
Entry history
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: March 15, 2005
Last modified: April 16, 2014
This is version 114 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot