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O88470

- FOXL2_MOUSE

UniProt

O88470 - FOXL2_MOUSE

Protein

Forkhead box protein L2

Gene

Foxl2

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 118 (01 Oct 2014)
      Sequence version 2 (15 Mar 2005)
      Previous versions | rss
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    Functioni

    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.5 Publications

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    DNA bindingi50 – 14495Fork-headPROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. cysteine-type endopeptidase regulator activity involved in apoptotic process Source: UniProtKB
    2. DNA binding Source: UniProtKB
    3. estrogen receptor binding Source: UniProtKB
    4. protein binding Source: MGI
    5. sequence-specific DNA binding Source: InterPro
    6. sequence-specific DNA binding transcription factor activity Source: MGI

    GO - Biological processi

    1. apoptotic DNA fragmentation Source: UniProtKB
    2. embryonic eye morphogenesis Source: MGI
    3. extraocular skeletal muscle development Source: UniProtKB
    4. female somatic sex determination Source: MGI
    5. granulosa cell differentiation Source: MGI
    6. menstruation Source: UniProtKB
    7. negative regulation of transcription, DNA-templated Source: MGI
    8. negative regulation of transcription from RNA polymerase II promoter Source: MGI
    9. ovarian follicle development Source: UniProtKB
    10. positive regulation of apoptotic process Source: UniProtKB
    11. positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
    12. positive regulation of transcription from RNA polymerase II promoter Source: MGI
    13. transcription, DNA-templated Source: UniProtKB-KW

    Keywords - Biological processi

    Differentiation, Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Forkhead box protein L2
    Alternative name(s):
    Pituitary forkhead factor
    Short name:
    P-Frk
    Gene namesi
    Name:Foxl2
    Synonyms:Pfrk
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 9

    Organism-specific databases

    MGIiMGI:1349428. Foxl2.

    Subcellular locationi

    Nucleus 1 PublicationPROSITE-ProRule annotation

    GO - Cellular componenti

    1. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 375375Forkhead box protein L2PRO_0000091862Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Cross-linki25 – 25Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity

    Post-translational modificationi

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

    Keywords - PTMi

    Isopeptide bond, Ubl conjugation

    Proteomic databases

    PRIDEiO88470.

    PTM databases

    PhosphoSiteiO88470.

    Expressioni

    Tissue specificityi

    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.2 Publications

    Gene expression databases

    BgeeiO88470.
    CleanExiMM_FOXL2.
    GenevestigatoriO88470.

    Interactioni

    Subunit structurei

    Interacts with ESR1. Interacts with UBE2I/UBC9 By similarity. Interacts with SMAD3. Interacts with DDX20.By similarity4 Publications

    Protein-protein interaction databases

    IntActiO88470. 2 interactions.

    Structurei

    3D structure databases

    ProteinModelPortaliO88470.
    SMRiO88470. Positions 50-139.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi217 – 23014Poly-AlaAdd
    BLAST
    Compositional biasi280 – 2878Poly-Pro
    Compositional biasi300 – 3034Poly-Ala

    Sequence similaritiesi

    Contains 1 fork-head DNA-binding domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG5025.
    HOGENOMiHOG000218632.
    HOVERGENiHBG051651.
    InParanoidiO88470.
    KOiK09405.
    OMAiELSMMHC.
    OrthoDBiEOG7C8GHD.
    PhylomeDBiO88470.
    TreeFamiTF316127.

    Family and domain databases

    Gene3Di1.10.10.10. 1 hit.
    InterProiIPR001766. TF_fork_head.
    IPR018122. TF_fork_head_CS.
    IPR011991. WHTH_DNA-bd_dom.
    [Graphical view]
    PfamiPF00250. Fork_head. 1 hit.
    [Graphical view]
    PRINTSiPR00053. FORKHEAD.
    SMARTiSM00339. FH. 1 hit.
    [Graphical view]
    PROSITEiPS00657. FORK_HEAD_1. 1 hit.
    PS00658. FORK_HEAD_2. 1 hit.
    PS50039. FORK_HEAD_3. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    O88470-1 [UniParc]FASTAAdd to Basket

    « Hide

    MMASYPEPED TAGTLLAPES GRAVKEAEAS PPSPGKGGGT TPEKPDPAQK    50
    PPYSYVALIA MAIRESAEKR LTLSGIYQYI IAKFPFYEKN KKGWQNSIRH 100
    NLSLNECFIK VPREGGGERK GNYWTLDPAC EDMFEKGNYR RRRRMKRPFR 150
    PPPAHFQPGK GLFGSGGAAG GCGVPGAGAD GYGYLAPPKY LQSGFLNNSW 200
    PLPQPPSPMP YASCQMAAAA AAAAAAAAAA GPGSPGAAAV VKGLAGPAAS 250
    YGPYSRVQSM ALPPGVVNSY NGLGGPPAAP PPPPPPPHPH PHPHAHHLHA 300
    AAAPPPAPPH HGAAAPPPGQ LSPASPATAA PPAPAPTSAP GLQFACARQP 350
    ELAMMHCSYW DHDSKTGALH SRLDL 375
    Length:375
    Mass (Da):38,887
    Last modified:March 15, 2005 - v2
    Checksum:iF920C8407686C4B6
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF522275 Genomic DNA. Translation: AAN04088.1.
    AF060873 mRNA. Translation: AAC27508.1.
    CCDSiCCDS23430.1.
    RefSeqiNP_036150.1. NM_012020.2.
    UniGeneiMm.151239.

    Genome annotation databases

    EnsembliENSMUST00000051312; ENSMUSP00000053297; ENSMUSG00000050397.
    GeneIDi26927.
    KEGGimmu:26927.
    UCSCiuc009rdr.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF522275 Genomic DNA. Translation: AAN04088.1 .
    AF060873 mRNA. Translation: AAC27508.1 .
    CCDSi CCDS23430.1.
    RefSeqi NP_036150.1. NM_012020.2.
    UniGenei Mm.151239.

    3D structure databases

    ProteinModelPortali O88470.
    SMRi O88470. Positions 50-139.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi O88470. 2 interactions.

    PTM databases

    PhosphoSitei O88470.

    Proteomic databases

    PRIDEi O88470.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000051312 ; ENSMUSP00000053297 ; ENSMUSG00000050397 .
    GeneIDi 26927.
    KEGGi mmu:26927.
    UCSCi uc009rdr.2. mouse.

    Organism-specific databases

    CTDi 668.
    MGIi MGI:1349428. Foxl2.

    Phylogenomic databases

    eggNOGi COG5025.
    HOGENOMi HOG000218632.
    HOVERGENi HBG051651.
    InParanoidi O88470.
    KOi K09405.
    OMAi ELSMMHC.
    OrthoDBi EOG7C8GHD.
    PhylomeDBi O88470.
    TreeFami TF316127.

    Miscellaneous databases

    NextBioi 304821.
    PROi O88470.
    SOURCEi Search...

    Gene expression databases

    Bgeei O88470.
    CleanExi MM_FOXL2.
    Genevestigatori O88470.

    Family and domain databases

    Gene3Di 1.10.10.10. 1 hit.
    InterProi IPR001766. TF_fork_head.
    IPR018122. TF_fork_head_CS.
    IPR011991. WHTH_DNA-bd_dom.
    [Graphical view ]
    Pfami PF00250. Fork_head. 1 hit.
    [Graphical view ]
    PRINTSi PR00053. FORKHEAD.
    SMARTi SM00339. FH. 1 hit.
    [Graphical view ]
    PROSITEi PS00657. FORK_HEAD_1. 1 hit.
    PS00658. FORK_HEAD_2. 1 hit.
    PS50039. FORK_HEAD_3. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    2. 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. Cited for: FUNCTION IN OVARY DIFFERENTIATION.
    6. 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.

    Entry informationi

    Entry nameiFOXL2_MOUSE
    AccessioniPrimary (citable) accession number: O88470
    Secondary accession number(s): Q8K3X9
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 27, 2001
    Last sequence update: March 15, 2005
    Last modified: October 1, 2014
    This is version 118 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3