P58012 (FOXL2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Forkhead box protein L2

Gene names

Name:

FOXL2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	376 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 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. Ref.4 Ref.5 Ref.6 Ref.7
Subunit structure	Interacts with ESR1 By similarity. Interacts with SMAD3 By similarity. Interacts with DDX20. Interacts with UBE2I/UBC9. Ref.4 Ref.5
Subcellular location	Nucleus Ref.5.
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.
Induction	In granulosa-like cells, up-regulated at transcript and protein levels under oxidative stress and heat-shock conditions. Down-regulated by SIRT1. Ref.6
Post-translational modification	Sumoylated with SUMO1; sumoylation is required for transcriptional repression activity. Ref.5
Involvement in disease	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. 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. Ref.1 Ref.2 Ref.9 Ref.10 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Ref.12
Sequence similarities	Contains 1 fork-head DNA-binding domain.

Ontologies

Keywords
Biological process	Differentiation Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Polymorphism Triplet repeat expansion
Disease	Disease mutation Premature ovarian failure
Ligand	DNA-binding
PTM	Isopeptide bond Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic DNA fragmentation Inferred from mutant phenotype Ref.4. Source: UniProtKB cell differentiation Non-traceable author statement PubMed 12471206. Source: UniProtKB convergent extension Inferred from Biological aspect of Ancestor. Source: RefGenome embryonic eye morphogenesis Inferred from Biological aspect of Ancestor. Source: RefGenome extraocular skeletal muscle development Inferred from mutant phenotype Ref.14. Source: UniProtKB female somatic sex determination Inferred from Biological aspect of Ancestor. Source: RefGenome granulosa cell differentiation Inferred from electronic annotation. Source: Compara induction of apoptosis Inferred from Biological aspect of Ancestor. Source: RefGenome menstruation Inferred from mutant phenotype Ref.12Ref.11. Source: UniProtKB negative regulation of transcription, DNA-dependent Inferred from direct assay Ref.5. Source: UniProtKB ovarian follicle development Inferred from mutant phenotype Ref.11. 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 mutant phenotype Ref.4. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from Biological aspect of Ancestor. Source: RefGenome 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 mutant phenotype Ref.4. Source: UniProtKB double-stranded DNA binding Inferred from Biological aspect of Ancestor. Source: RefGenome estrogen receptor 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
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 376	376	Forkhead box protein L2		PRO_0000091861
Regions
	DNA binding	54 – 148	95	Fork-head
	Compositional bias	35 – 43	9	Poly-Gly
	Compositional bias	221 – 234	14	Poly-Ala
	Compositional bias	284 – 292	9	Poly-Pro
	Compositional bias	301 – 304	4	Poly-Ala
Amino acid modifications
	Cross-link	25		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.5
Natural variations
	Natural variant	58	1	S → L in BPES; sporadic; nuclear and cytoplasmic aggregation; impaired transactivation activity. Ref.19 Ref.21		VAR_021196
	Natural variant	63	1	I → T in BPES. Ref.17		VAR_062545
	Natural variant	65	1	M → V in BPES. Ref.21		VAR_046490
	Natural variant	66	1	A → V in BPES; nuclear and cytoplasmic aggregation; impaired transactivation activity. Ref.19 Ref.21		VAR_021197
	Natural variant	69	1	E → K in BPES; sporadic; nuclear aggregation; normal transactivation activity. Ref.19 Ref.21		VAR_021198
	Natural variant	80	1	I → T in BPES; nuclear and cytoplasmic aggregation; impaired transactivation activity. Ref.19 Ref.21		VAR_046491
	Natural variant	84	1	I → N in BPES; nuclear and cytoplasmic aggregation; impaired transactivation activity. Ref.19 Ref.21		VAR_046492
	Natural variant	84	1	I → S in BPES; type I. Ref.14 Corresponds to variant rs28937884 [ dbSNP | Ensembl ].		VAR_016883
	Natural variant	85	1	Missing in BPES; sporadic. Ref.9		VAR_016884
	Natural variant	90	1	F → S in BPES; nuclear and cytoplasmic aggregation; impaired transactivation activity. Ref.19 Ref.21		VAR_046493
	Natural variant	98	1	W → G in BPES; nuclear and cytoplasmic aggregation; impaired transactivation activity. Ref.19 Ref.21		VAR_046494
	Natural variant	98	1	W → R in BPES. Ref.20		VAR_062546
	Natural variant	101	1	S → R in BPES; nuclear aggregation; impaired transactivation activity. Ref.19 Ref.21		VAR_046495
	Natural variant	102	1	I → T in BPES; nuclear and cytoplasmic aggregation; impaired transactivation activity. Ref.19 Ref.21		VAR_046496
	Natural variant	103	1	R → C in BPES; nuclear and cytoplasmic aggregation; normal transactivation activity. Ref.19 Ref.21		VAR_046497
	Natural variant	104	1	H → R in BPES; diffuse nuclear localization as wild type; normal transactivation activity. Ref.15 Ref.19		VAR_021199
	Natural variant	105	1	N → S in BPES; type II.		VAR_021200
	Natural variant	106	1	L → F in BPES; sporadic; nuclear and cytoplasmic aggregation; impaired transactivation activity. Ref.13 Ref.19		VAR_016885
	Natural variant	106	1	L → P in BPES; nuclear and cytoplasmic aggregation; impaired transactivation activity. Ref.19 Ref.21		VAR_046498
	Natural variant	108	1	L → P in BPES; nuclear aggregation and cytoplasmic mislocalization; impaired transactivation activity. Ref.20		VAR_062547
	Natural variant	109	1	N → K in BPES; type II; diffuse nuclear localization as wild type; impaired transactivation activity. Ref.13 Ref.19		VAR_016886
	Natural variant	134	1	C → W in granulosa-cell tumors of the ovary; not commonly found in other tumor types. Ref.22 Ref.23		VAR_062548
	Natural variant	179	1	A → G. Ref.12 Ref.20 Corresponds to variant rs7432551 [ dbSNP | Ensembl ].		VAR_021201
	Natural variant	187	1	G → D in POF3; does not affect nuclear localization; reduces transcriptional activation of OSR2. Ref.7 Ref.11		VAR_015181
	Natural variant	193	1	K → R in BPES; type II.		VAR_021202
	Natural variant	215	1	Y → C in BPES. Ref.16 Ref.20		VAR_021203
	Natural variant	217	1	S → C in BPES; diffuse nuclear localization; normal transcriptional activation. Ref.20		VAR_062549
	Natural variant	217	1	S → F in BPES; diffuse nuclear localization; increased transactivation activity. Ref.9 Ref.13 Ref.19		VAR_016887
	Natural variant	234	1	A → AAAAAA in BPES; significant higher cytoplasmic retention compared to the wild-type protein. Ref.1 Ref.2 Ref.10 Ref.18		VAR_037303
	Natural variant	234	1	A → AAAAAAAAAAA in BPES; type II. Ref.1 Ref.2 Ref.10 Ref.18		VAR_010782
	Natural variant	234	1	A → AAAAAAAAAAAA in BPES. Ref.1 Ref.2 Ref.10 Ref.18		VAR_025306
	Natural variant	258	1	Y → N in POF3. Ref.12 Corresponds to variant rs28937885 [ dbSNP | Ensembl ].		VAR_021204
	Natural variant	285	1	P → S. Ref.11		VAR_015182
Experimental info
	Mutagenesis	25	1	K → R: Results in reduced sumoylation. Loss of transcriptional repression activity. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	P58012 [UniParc]. Last modified April 27, 2001. Version 1. Checksum: B4952F2A0380E533	FASTA	376	38,772
	10 20 30 40 50 60 MMASYPEPED AAGALLAPET GRTVKEPEGP PPSPGKGGGG GGGTAPEKPD PAQKPPYSYV 70 80 90 100 110 120 ALIAMAIRES AEKRLTLSGI YQYIIAKFPF YEKNKKGWQN SIRHNLSLNE CFIKVPREGG 130 140 150 160 170 180 GERKGNYWTL DPACEDMFEK GNYRRRRRMK RPFRPPPAHF QPGKGLFGAG GAAGGCGVAG 190 200 210 220 230 240 AGADGYGYLA PPKYLQSGFL NNSWPLPQPP SPMPYASCQM AAAAAAAAAA AAAAGPGSPG 250 260 270 280 290 300 AAAVVKGLAG PAASYGPYTR VQSMALPPGV VNSYNGLGGP PAAPPPPPHP HPHPHAHHLH 310 320 330 340 350 360 AAAAPPPAPP HHGAAAPPPG QLSPASPATA APPAPAPTSA PGLQFACARQ PELAMMHCSY 370 WDHDSKTGAL HSRLDL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The putative forkhead transcription factor FOXL2 is mutated in blepharophimosis/ptosis/epicanthus inversus syndrome." Crisponi L., Deiana M., Loi A., Chiappe F., Uda M., Amati P., Bisceglia L., Zelante L., Nagaraja R., Porcu S., Ristaldi M.S., Marzella R., Rocchi M., Nicolino M., Lienhardt-Roussie A., Nivelon A., Verloes A., Schlessinger D. , Gasparini P., Bonneau D., Cao A., Pilia G. Nat. Genet. 27:159-166(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT BPES ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-234 INS.
[2]	"Study of mutations of FOXL2 gene in a Chinese TongHai family with blepharophimosis-ptosis-epicanthus inversus syndrome." Xu Y. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT BPES ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-234 INS.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Pancreas.
[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: FUNCTION IN APOPTOSIS, INTERACTION WITH DDX20.
[5]	"Sumoylation of forkhead L2 by Ubc9 is required for its activity as a transcriptional repressor of the Steroidogenic Acute Regulatory gene." Kuo F.T., Bentsi-Barnes I.K., Barlow G.M., Bae J., Pisarska M.D. Cell. Signal. 21:1935-1944(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS TRANSCRIPTIONAL REPRESSOR OF STAR, INTERACTION WITH UBE2I, SUMOYLATION AT LYS-25, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-25.
[6]	"Positive and negative feedback regulates the transcription factor FOXL2 in response to cell stress: evidence for a regulatory imbalance induced by disease-causing mutations." Benayoun B.A., Batista F., Auer J., Dipietromaria A., L'Hote D., De Baere E., Veitia R.A. Hum. Mol. Genet. 18:632-644(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS TRANSCRIPTIONAL ACTIVATOR OF SIRT1, INDUCTION.
[7]	"Functional evidence implicating FOXL2 in non-syndromic premature ovarian failure and in the regulation of the transcription factor OSR2." Laissue P., Lakhal B., Benayoun B.A., Dipietromaria A., Braham R., Elghezal H., Philibert P., Saad A., Sultan C., Fellous M., Veitia R.A. J. Med. Genet. 46:455-457(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS TRANSCRIPTIONAL ACTIVATOR OF OSR2, VARIANT POF3 ASP-187, CHARACTERIZATION OF VARIANT POF3 ASP-187.
[8]	"The human FOXL2 mutation database." Beysen D., Vandesompele J., Messiaen L., De Paepe A., De Baere E. Hum. Mutat. 24:189-193(2004) [PubMed] [Europe PMC] [Abstract] Cited for: DATABASE OF FOXL2 VARIANTS.
[9]	"Spectrum of FOXL2 gene mutations in blepharophimosis-ptosis-epicanthus inversus (BPES) families demonstrates a genotype --phenotype correlation." De Baere E., Dixon M.J., Small K.W., Jabs E.W., Leroy B.P., Devriendt K., Gillerot Y., Mortier G., Meire F., Van Maldergem L., Courtens W., Hjalgrim H., Huang S., Liebaers I., Van Regemorter N., Touraine P., Praphanphoj V., Verloes A. , Udar N., Yellore V., Chalukya M., Yelchits S., De Paepe A., Kuttenn F., Fellous M., Veitia R., Messiaen L. Hum. Mol. Genet. 10:1591-1600(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS BPES ILE-85 DEL AND PHE-217.
[10]	"Mutations in FOXL2 underlying BPES (types 1 and 2) in Colombian families." Ramirez-Castro J.L., Pineda-Trujillo N., Valencia A.V., Muneton C.M., Botero O., Trujillo O., Vasquez G., Mora B.E., Durango N., Bedoya G., Ruiz-Linares A. Am. J. Med. Genet. 113:47-51(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT BPES ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-234 INS.
[11]	"FOXL2 mutation screening in a large panel of POF patients and XX males." De Baere E., Lemercier B., Christin-Maitre S., Durval D., Messiaen L., Fellous M., Veitia R. J. Med. Genet. 39:E43-E43(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ASP-187 AND SER-285.
[12]	"Identification of novel mutations in FOXL2 associated with premature ovarian failure." Harris S.E., Chand A.L., Winship I.M., Gersak K., Aittomaeki K., Shelling A.N. Mol. Hum. Reprod. 8:729-733(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS POF3 221-ALA--ALA-230 DEL AND ASN-258, VARIANT GLY-179.
[13]	"FOXL2 and BPES: mutational hotspots, phenotypic variability, and revision of the genotype-phenotype correlation." De Baere E., Beysen D., Oley C., Lorenz B., Cocquet J., De Sutter P., Devriendt K., Dixon M.J., Fellous M., Fryns J.-P., Garza A., Jonsrud C., Koivisto P.A., Krause A., Leroy B.P., Meire F., Plomp A., Van Maldergem L. , De Paepe A., Veitia R., Messiaen L. Am. J. Hum. Genet. 72:478-487(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS BPES PHE-106; LYS-109 AND PHE-217.
[14]	"Sporadic and familial blepharophimosis -ptosis-epicanthus inversus syndrome: FOXL2 mutation screen and MRI study of the superior levator eyelid muscle." Dollfus H., Stoetzel C., Riehm S., Lahlou Boukoffa W., Bediard Boulaneb F., Quillet R., Abu-Eid M., Speeg-Schatz C., Francfort J.J., Flament J., Veillon F., Perrin-Schmitt F. Clin. Genet. 63:117-120(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT BPES SER-84.
[15]	"Comparative analysis of the FOXL2 gene and characterization of mutations in BPES patients." Udar N., Yellore V., Chalukya M., Yelchits S., Silva-Garcia R., Small K. Hum. Mutat. 22:222-228(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT BPES ARG-104.
[16]	"Genetic analysis of a five generation Indian family with BPES: a novel missense mutation (p.Y215C)." Kumar A., Babu M., Raghunath A., Venkatesh C.P. Mol. Vis. 10:445-449(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT BPES CYS-215.
[17]	"Three novel FOXL2 gene mutations in Chinese patients with blepharophimosis-ptosis-epicanthus inversus syndrome." Or S.F., Tong M.F., Lo F.M., Lam T.S. Chin. Med. J. 119:49-52(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT BPES THR-63.
[18]	"A novel polyalanine expansion in FOXL2: the first evidence for a recessive form of the blepharophimosis syndrome (BPES) associated with ovarian dysfunction." Nallathambi J., Moumne L., De Baere E., Beysen D., Usha K., Sundaresan P., Veitia R.A. Hum. Genet. 121:107-112(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT BPES ALA-ALA-ALA-ALA-ALA-234 INS, CHARACTERIZATION OF VARIANT BPES ALA-ALA-ALA-ALA-ALA-234 INS.
[19]	"Missense mutations in the forkhead domain of FOXL2 lead to subcellular mislocalization, protein aggregation and impaired transactivation." Beysen D., Moumne L., Veitia R., Peters H., Leroy B.P., De Paepe A., De Baere E. Hum. Mol. Genet. 17:2030-2038(2008) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS BPES LEU-58; VAL-66; LYS-69; THR-80; ASN-84; SER-90; GLY-98; ARG-101; THR-102; CYS-103; ARG-104; PHE-106; PRO-106; LYS-109 AND PHE-217.
[20]	"Differential functional effects of novel mutations of the transcription factor FOXL2 in BPES patients." Nallathambi J., Laissue P., Batista F., Benayoun B.A., Lesaffre C., Moumne L., Pandaranayaka P.E., Usha K., Krishnaswamy S., Sundaresan P., Veitia R.A. Hum. Mutat. 29:E123-E131(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS BPES ARG-98; PRO-108; CYS-215; CYS-217 AND ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-234 INS, VARIANT GLY-179, CHARACTERIZATION OF VARIANTS BPES PRO-108 AND CYS-217.
[21]	"Identification of 34 novel and 56 known FOXL2 mutations in patients with blepharophimosis syndrome." Beysen D., De Jaegere S., Amor D., Bouchard P., Christin-Maitre S., Fellous M., Touraine P., Grix A.W., Hennekam R., Meire F., Oyen N., Wilson L.C., Barel D., Clayton-Smith J., de Ravel T., Decock C., Delbeke P., Ensenauer R. , Ebinger F., Gillessen-Kaesbach G., Hendriks Y., Kimonis V., Laframboise R., Laissue P., Leppig K., Leroy B.P., Miller D.T., Mowat D., Neumann L., Plomp A., Van Regemorter N., Wieczorek D., Veitia R.A., De Paepe A., De Baere E. Hum. Mutat. 29:E205-E219(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS BPES LEU-58; VAL-65; VAL-66; LYS-69; THR-80; ASN-84; SER-90; GLY-98; ARG-101; THR-102; CYS-103 AND PRO-106.
[22]	"Mutation of FOXL2 in granulosa-cell tumors of the ovary." Shah S.P., Kobel M., Senz J., Morin R.D., Clarke B.A., Wiegand K.C., Leung G., Zayed A., Mehl E., Kalloger S.E., Sun M., Giuliany R., Yorida E., Jones S., Varhol R., Swenerton K.D., Miller D., Clement P.B. , Crane C., Madore J., Provencher D., Leung P., DeFazio A., Khattra J., Turashvili G., Zhao Y., Zeng T., Glover J.N., Vanderhyden B., Zhao C., Parkinson C.A., Jimenez-Linan M., Bowtell D.D., Mes-Masson A.M., Brenton J.D., Aparicio S.A., Boyd N., Hirst M., Gilks C.B., Marra M., Huntsman D.G. N. Engl. J. Med. 360:2719-2729(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT TRP-134.
[23]	"The specificity of the FOXL2 c.402C>G Somatic mutation: a survey of solid tumors." Schrader K.A., Gorbatcheva B., Senz J., Heravi-Moussavi A., Melnyk N., Salamanca C., Maines-Bandiera S., Cooke S.L., Leung P., Brenton J.D., Gilks C.B., Monahan J., Huntsman D.G. PLoS ONE 4:E7988-E7988(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT TRP-134.
+	Additional computationally mapped references.

Web resources

Forkhead box L2 (FOXL2)

Leiden Open Variation Database (LOVD)

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF301906 mRNA. Translation: AAK01352.1. DQ016609 Genomic DNA. Translation: AAY21823.1. BC062549 mRNA. Translation: AAH62549.1.
IPI	IPI00010550.
RefSeq	NP_075555.1. NM_023067.3.
UniGene	Hs.289292.
3D structure databases
ProteinModelPortal	P58012.
ModBase	Search...
Protein-protein interaction databases
IntAct	P58012. 2 interactions.
STRING	9606.ENSP00000333188.
PTM databases
PhosphoSite	P58012.
Polymorphism databases
DMDM	13626838.
Proteomic databases
PaxDb	P58012.
PRIDE	P58012.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000330315; ENSP00000333188; ENSG00000183770.
GeneID	668.
KEGG	hsa:668.
UCSC	uc003esw.3. human.
Organism-specific databases
CTD	668.
GeneCards	GC03M138663.
HGNC	HGNC:1092. FOXL2.
MIM	110100. phenotype. 605597. gene. 608996. phenotype.
neXtProt	NX_P58012.
Orphanet	126. Blepharophimosis - epicanthus inversus - ptosis. 261559. Blepharophimosis - epicanthus inversus - ptosis, due to 3q23 microdeletion. 619. Primary ovarian failure.
PharmGKB	PA28235.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5025.
HOVERGEN	HBG051651.
InParanoid	P58012.
KO	K09405.
OMA	QPAELSM.
Gene expression databases
ArrayExpress	P58012.
Bgee	P58012.
CleanEx	HS_FOXL2.
Genevestigator	P58012.
GermOnline	ENSG00000183770. Homo sapiens.
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
GenomeRNAi	668.
NextBio	2732.
SOURCE	Search...

Entry information

Entry name

FOXL2_HUMAN

Accession

Primary (citable) accession number: P58012
Secondary accession number(s): Q4ZGJ3

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 27, 2001
Last sequence update:	April 27, 2001
Last modified:	May 1, 2013
This is version 125 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.