O88470 (FOXL2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Forkhead box protein L2

Alternative name(s):
Pituitary forkhead factor
Short name=P-Frk

Gene names

Name:	Foxl2
Synonyms:	Pfrk

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	375 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Differentiation Transcription Transcription regulation
Cellular component	Nucleus
Ligand	DNA-binding
PTM	Isopeptide bond Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic DNA fragmentation Inferred from sequence or structural similarity. Source: UniProtKB convergent extension Inferred from Biological aspect of Ancestor. Source: RefGenome 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 induction of apoptosis Inferred from direct assay Ref.4. Source: MGI menstruation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of transcription from RNA polymerase II promoter Inferred from Biological aspect of Ancestor. Source: RefGenome 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 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
Cellular_component	transcription factor complex Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular_function	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 sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 375	375	Forkhead box protein L2		PRO_0000091862
Regions
	DNA binding	50 – 144	95	Fork-head
	Compositional bias	217 – 230	14	Poly-Ala
	Compositional bias	280 – 287	8	Poly-Pro
	Compositional bias	300 – 303	4	Poly-Ala
Amino acid modifications
	Cross-link	25		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Sequences

	Sequence		Length	Mass (Da)
	O88470 [UniParc]. Last modified March 15, 2005. Version 2. Checksum: F920C8407686C4B6	FASTA	375	38,887
	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

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.
IPI	IPI00230400.
RefSeq	NP_036150.1. NM_012020.2.
UniGene	Mm.151239.
3D structure databases
ProteinModelPortal	O88470.
SMR	O88470. Positions 50-139.
ModBase	Search...
Protein-protein interaction databases
IntAct	O88470. 2 interactions.
PTM databases
PhosphoSite	O88470.
Proteomic databases
PRIDE	O88470.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000051312; ENSMUSP00000053297; ENSMUSG00000050397.
GeneID	26927.
KEGG	mmu:26927.
Organism-specific databases
CTD	668.
MGI	MGI:1349428. Foxl2.
Phylogenomic databases
eggNOG	COG5025.
HOGENOM	HOG000218632.
HOVERGEN	HBG051651.
InParanoid	O88470.
KO	K09405.
OMA	QPAELSM.
OrthoDB	EOG4B5P7G.
Gene expression databases
ArrayExpress	O88470.
Bgee	O88470.
CleanEx	MM_FOXL2.
Genevestigator	O88470.
GermOnline	ENSMUSG00000050397. Mus musculus.
Family and domain databases
Gene3D	1.10.10.10. 1 hit.
InterPro	IPR001766. TF_fork_head. IPR018122. TF_fork_head_CS. IPR011991. WHTH_DNA-bd_dom. [Graphical view]
Pfam	PF00250. Fork_head. 1 hit. [Graphical view]
PRINTS	PR00053. FORKHEAD.
SMART	SM00339. FH. 1 hit. [Graphical view]
PROSITE	PS00657. FORK_HEAD_1. 1 hit. PS00658. FORK_HEAD_2. 1 hit. PS50039. FORK_HEAD_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	304821.
SOURCE	Search...

Entry information

Entry name

FOXL2_MOUSE

Accession

Primary (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:	May 1, 2013
This is version 106 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program