FOXL2_MOUSE
ID FOXL2_MOUSE Reviewed; 375 AA.
AC O88470; Q8K3X9;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2005, sequence version 2.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Forkhead box protein L2;
DE AltName: Full=Pituitary forkhead factor;
DE Short=P-Frk;
GN Name=Foxl2; Synonyms=Pfrk;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=12471206; DOI=10.1136/jmg.39.12.916;
RA Cocquet J., Pailhoux E., Jaubert F., Servel N., Xia X., Pannetier M.,
RA De Baere E., Messiaen L., Cotinot C., Fellous M., Veitia R.A.;
RT "Evolution and expression of FOXL2.";
RL J. Med. Genet. 39:916-921(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 50-139.
RX PubMed=9620855; DOI=10.1101/gad.12.11.1691;
RA Treier M., Gleiberman A.S., O'Connell S.M., Szeto D.P., McMahon J.A.,
RA McMahon A.P., Rosenfeld M.G.;
RT "Multistep signaling requirements for pituitary organogenesis in vivo.";
RL Genes Dev. 12:1691-1704(1998).
RN [3]
RP FUNCTION AS TRANSCRIPTIONAL REPRESSOR OF STAR, AND TISSUE SPECIFICITY.
RX PubMed=15059956; DOI=10.1210/en.2003-1141;
RA Pisarska M.D., Bae J., Klein C., Hsueh A.J.;
RT "Forkhead l2 is expressed in the ovary and represses the promoter activity
RT of the steroidogenic acute regulatory gene.";
RL Endocrinology 145:3424-3433(2004).
RN [4]
RP INTERACTION WITH DDX20/DP103.
RX PubMed=16153597; DOI=10.1016/j.bbrc.2005.08.184;
RA Lee K., Pisarska M.D., Ko J.J., Kang Y., Yoon S., Ryou S.M., Cha K.Y.,
RA Bae J.;
RT "Transcriptional factor FOXL2 interacts with DP103 and induces apoptosis.";
RL Biochem. Biophys. Res. Commun. 336:876-881(2005).
RN [5]
RP FUNCTION IN OVARY DIFFERENTIATION.
RX PubMed=15944199; DOI=10.1093/hmg/ddi210;
RA Ottolenghi C., Omari S., Garcia-Ortiz J.E., Uda M., Crisponi L.,
RA Forabosco A., Pilia G., Schlessinger D.;
RT "Foxl2 is required for commitment to ovary differentiation.";
RL Hum. Mol. Genet. 14:2053-2062(2005).
RN [6]
RP ROLE IN OVARY MAINTENANCE, FUNCTION AS TRANSCRIPTIONAL REPRESSOR OF SOX9,
RP AND INTERACTION WITH ESR1.
RX PubMed=20005806; DOI=10.1016/j.cell.2009.11.021;
RA Uhlenhaut N.H., Jakob S., Anlag K., Eisenberger T., Sekido R., Kress J.,
RA Treier A.C., Klugmann C., Klasen C., Holter N.I., Riethmacher D.,
RA Schutz G., Cooney A.J., Lovell-Badge R., Treier M.;
RT "Somatic sex reprogramming of adult ovaries to testes by FOXL2 ablation.";
RL Cell 139:1130-1142(2009).
RN [7]
RP FUNCTION AS TRANSCRIPTIONAL REPRESSOR OF PTGS2, INTERACTION WITH ESR1, AND
RP SUBCELLULAR LOCATION.
RX PubMed=19797124; DOI=10.1210/en.2009-0313;
RA Kim S.Y., Weiss J., Tong M., Laronda M.M., Lee E.J., Jameson J.L.;
RT "Foxl2, a forkhead transcription factor, modulates nonclassical activity of
RT the estrogen receptor-alpha.";
RL Endocrinology 150:5085-5093(2009).
RN [8]
RP FUNCTION AS TRANSCRIPTIONAL REGULATOR OF FST, INTERACTION WITH SMAD3, AND
RP TISSUE SPECIFICITY.
RX PubMed=19106105; DOI=10.1074/jbc.m806676200;
RA Blount A.L., Schmidt K., Justice N.J., Vale W.W., Fischer W.H.,
RA Bilezikjian L.M.;
RT "FoxL2 and Smad3 coordinately regulate follistatin gene transcription.";
RL J. Biol. Chem. 284:7631-7645(2009).
CC -!- FUNCTION: Transcriptional regulator. Critical factor essential for
CC ovary differentiation and maintenance, and repression of the genetic
CC program for somatic testis determination. Prevents trans-
CC differentiation of ovary to testis through transcriptional repression
CC of the Sertoli cell-promoting gene SOX9. Has apoptotic activity in
CC ovarian cells. Suppresses ESR1-mediated transcription of PTGS2/COX2
CC stimulated by tamoxifen. Activates SIRT1 transcription under cellular
CC stress conditions. Activates transcription of OSR2. Is a regulator of
CC CYP19 expression. Is a transcriptional repressor of STAR. Participates
CC in SMAD3-dependent transcription of FST via the intronic SMAD-binding
CC element. {ECO:0000269|PubMed:15059956, ECO:0000269|PubMed:15944199,
CC ECO:0000269|PubMed:19106105, ECO:0000269|PubMed:19797124,
CC ECO:0000269|PubMed:20005806}.
CC -!- SUBUNIT: Interacts with ESR1. Interacts with UBE2I/UBC9 (By
CC similarity). Interacts with SMAD3. Interacts with DDX20. {ECO:0000250,
CC ECO:0000269|PubMed:16153597, ECO:0000269|PubMed:19106105,
CC ECO:0000269|PubMed:19797124, ECO:0000269|PubMed:20005806}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00089,
CC ECO:0000269|PubMed:19797124}.
CC -!- TISSUE SPECIFICITY: Expressed in the mesenchyme of developing eyelids.
CC Expressed in ovaries throughout development and adulthood, localized to
CC the undifferentiated granulosa cells in small and medium follicles as
CC well as cumulus cells of preovulatory follicles. Expressed in the
CC pituitary. {ECO:0000269|PubMed:15059956, ECO:0000269|PubMed:19106105}.
CC -!- PTM: Sumoylated with SUMO1; sumoylation is required for transcriptional
CC repression activity. {ECO:0000250}.
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DR EMBL; AF522275; AAN04088.1; -; Genomic_DNA.
DR EMBL; AF060873; AAC27508.1; -; mRNA.
DR CCDS; CCDS23430.1; -.
DR RefSeq; NP_036150.1; NM_012020.2.
DR AlphaFoldDB; O88470; -.
DR SMR; O88470; -.
DR BioGRID; 205068; 25.
DR IntAct; O88470; 2.
DR STRING; 10090.ENSMUSP00000053297; -.
DR MoonDB; O88470; Predicted.
DR PhosphoSitePlus; O88470; -.
DR PaxDb; O88470; -.
DR PRIDE; O88470; -.
DR ProteomicsDB; 271594; -.
DR Antibodypedia; 17961; 380 antibodies from 37 providers.
DR DNASU; 26927; -.
DR Ensembl; ENSMUST00000051312; ENSMUSP00000053297; ENSMUSG00000050397.
DR GeneID; 26927; -.
DR KEGG; mmu:26927; -.
DR UCSC; uc009rdr.2; mouse.
DR CTD; 668; -.
DR MGI; MGI:1349428; Foxl2.
DR VEuPathDB; HostDB:ENSMUSG00000050397; -.
DR eggNOG; KOG2294; Eukaryota.
DR GeneTree; ENSGT00940000162075; -.
DR HOGENOM; CLU_023357_1_0_1; -.
DR InParanoid; O88470; -.
DR OMA; CQMASGN; -.
DR OrthoDB; 1270467at2759; -.
DR PhylomeDB; O88470; -.
DR TreeFam; TF316127; -.
DR Reactome; R-MMU-3232118; SUMOylation of transcription factors.
DR BioGRID-ORCS; 26927; 0 hits in 74 CRISPR screens.
DR PRO; PR:O88470; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; O88470; protein.
DR Bgee; ENSMUSG00000050397; Expressed in granulosa cell layer and 53 other tissues.
DR ExpressionAtlas; O88470; baseline and differential.
DR Genevisible; O88470; MM.
DR GO; GO:0090543; C:Flemming body; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0043028; F:cysteine-type endopeptidase regulator activity involved in apoptotic process; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0030331; F:nuclear estrogen receptor binding; IPI:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0031624; F:ubiquitin conjugating enzyme binding; ISO:MGI.
DR GO; GO:0009653; P:anatomical structure morphogenesis; IBA:GO_Central.
DR GO; GO:0006309; P:apoptotic DNA fragmentation; ISS:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0048048; P:embryonic eye morphogenesis; IMP:MGI.
DR GO; GO:0002074; P:extraocular skeletal muscle development; ISS:UniProtKB.
DR GO; GO:0008585; P:female gonad development; IGI:MGI.
DR GO; GO:0019101; P:female somatic sex determination; IMP:MGI.
DR GO; GO:0060014; P:granulosa cell differentiation; IMP:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IMP:MGI.
DR GO; GO:0001541; P:ovarian follicle development; IMP:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB.
DR GO; GO:0046881; P:positive regulation of follicle-stimulating hormone secretion; IGI:MGI.
DR GO; GO:0033686; P:positive regulation of luteinizing hormone secretion; IGI:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0007338; P:single fertilization; IGI:MGI.
DR GO; GO:0060065; P:uterus development; IGI:MGI.
DR CDD; cd00059; FH; 1.
DR Gene3D; 1.10.10.10; -; 1.
DR InterPro; IPR001766; Fork_head_dom.
DR InterPro; IPR018122; TF_fork_head_CS_1.
DR InterPro; IPR030456; TF_fork_head_CS_2.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR Pfam; PF00250; Forkhead; 1.
DR PRINTS; PR00053; FORKHEAD.
DR SMART; SM00339; FH; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR PROSITE; PS00657; FORK_HEAD_1; 1.
DR PROSITE; PS00658; FORK_HEAD_2; 1.
DR PROSITE; PS50039; FORK_HEAD_3; 1.
PE 1: Evidence at protein level;
KW Differentiation; DNA-binding; Isopeptide bond; Nucleus; Phosphoprotein;
KW Reference proteome; Transcription; Transcription regulation;
KW Ubl conjugation.
FT CHAIN 1..375
FT /note="Forkhead box protein L2"
FT /id="PRO_0000091862"
FT DNA_BIND 50..144
FT /note="Fork-head"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00089"
FT REGION 1..50
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 272..341
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 275..289
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 302..338
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 33
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P58012"
FT CROSSLNK 25
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
SQ SEQUENCE 375 AA; 38887 MW; F920C8407686C4B6 CRC64;
MMASYPEPED TAGTLLAPES GRAVKEAEAS PPSPGKGGGT TPEKPDPAQK PPYSYVALIA
MAIRESAEKR LTLSGIYQYI IAKFPFYEKN KKGWQNSIRH NLSLNECFIK VPREGGGERK
GNYWTLDPAC EDMFEKGNYR RRRRMKRPFR PPPAHFQPGK GLFGSGGAAG GCGVPGAGAD
GYGYLAPPKY LQSGFLNNSW PLPQPPSPMP YASCQMAAAA AAAAAAAAAA GPGSPGAAAV
VKGLAGPAAS YGPYSRVQSM ALPPGVVNSY NGLGGPPAAP PPPPPPPHPH PHPHAHHLHA
AAAPPPAPPH HGAAAPPPGQ LSPASPATAA PPAPAPTSAP GLQFACARQP ELAMMHCSYW
DHDSKTGALH SRLDL
