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P58012 (FOXL2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 137. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Forkhead box protein L2
Gene names
Name:FOXL2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length376 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 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 processDifferentiation
Transcription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityPolymorphism
Triplet repeat expansion
   DiseaseDisease mutation
Premature ovarian failure
   LigandDNA-binding
   PTMIsopeptide bond
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic DNA fragmentation

Inferred from mutant phenotype Ref.4. Source: UniProtKB

cell differentiation

Non-traceable author statement PubMed 12471206. Source: UniProtKB

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: Ensembl

menstruation

Inferred from mutant phenotype Ref.12Ref.11. Source: UniProtKB

negative regulation of transcription from RNA polymerase II promoter

Inferred from Biological aspect of Ancestor. Source: RefGenome

negative regulation of transcription, DNA-templated

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 apoptotic process

Inferred from mutant phenotype Ref.4. Source: UniProtKB

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

positive regulation of transcription, DNA-templated

Inferred from sequence or structural similarity. Source: UniProtKB

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 PubMed 12471206. Source: UniProtKB

transcription factor complex

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Molecular_functionDNA binding

Inferred from direct assay PubMed 16720712. 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 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

protein binding

Inferred from physical interaction Ref.4. Source: UniProtKB

sequence-specific DNA binding

Inferred from electronic annotation. Source: InterPro

sequence-specific DNA binding transcription factor activity

Inferred from sequence or structural similarity. Source: UniProtKB

transcription factor binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

ubiquitin conjugating enzyme binding

Inferred from physical interaction Ref.5. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 376376Forkhead box protein L2
PRO_0000091861

Regions

DNA binding54 – 14895Fork-head
Compositional bias35 – 439Poly-Gly
Compositional bias221 – 23414Poly-Ala
Compositional bias284 – 2929Poly-Pro
Compositional bias301 – 3044Poly-Ala

Amino acid modifications

Cross-link25Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.5

Natural variations

Natural variant581S → L in BPES; sporadic; nuclear and cytoplasmic aggregation; impaired transactivation activity. Ref.19 Ref.21
VAR_021196
Natural variant631I → T in BPES. Ref.17
VAR_062545
Natural variant651M → V in BPES. Ref.21
VAR_046490
Natural variant661A → V in BPES; nuclear and cytoplasmic aggregation; impaired transactivation activity. Ref.19 Ref.21
VAR_021197
Natural variant691E → K in BPES; sporadic; nuclear aggregation; normal transactivation activity. Ref.19 Ref.21
VAR_021198
Natural variant801I → T in BPES; nuclear and cytoplasmic aggregation; impaired transactivation activity. Ref.19 Ref.21
VAR_046491
Natural variant841I → N in BPES; nuclear and cytoplasmic aggregation; impaired transactivation activity. Ref.19 Ref.21
VAR_046492
Natural variant841I → S in BPES; type I. Ref.14
Corresponds to variant rs28937884 [ dbSNP | Ensembl ].
VAR_016883
Natural variant851Missing in BPES; sporadic. Ref.9
VAR_016884
Natural variant901F → S in BPES; nuclear and cytoplasmic aggregation; impaired transactivation activity. Ref.19 Ref.21
VAR_046493
Natural variant981W → G in BPES; nuclear and cytoplasmic aggregation; impaired transactivation activity. Ref.19 Ref.21
VAR_046494
Natural variant981W → R in BPES. Ref.20
VAR_062546
Natural variant1011S → R in BPES; nuclear aggregation; impaired transactivation activity. Ref.19 Ref.21
VAR_046495
Natural variant1021I → T in BPES; nuclear and cytoplasmic aggregation; impaired transactivation activity. Ref.19 Ref.21
VAR_046496
Natural variant1031R → C in BPES; nuclear and cytoplasmic aggregation; normal transactivation activity. Ref.19 Ref.21
VAR_046497
Natural variant1041H → R in BPES; diffuse nuclear localization as wild type; normal transactivation activity. Ref.15 Ref.19
VAR_021199
Natural variant1051N → S in BPES; type II.
VAR_021200
Natural variant1061L → F in BPES; sporadic; nuclear and cytoplasmic aggregation; impaired transactivation activity. Ref.13 Ref.19
VAR_016885
Natural variant1061L → P in BPES; nuclear and cytoplasmic aggregation; impaired transactivation activity. Ref.19 Ref.21
VAR_046498
Natural variant1081L → P in BPES; nuclear aggregation and cytoplasmic mislocalization; impaired transactivation activity. Ref.20
VAR_062547
Natural variant1091N → K in BPES; type II; diffuse nuclear localization as wild type; impaired transactivation activity. Ref.13 Ref.19
VAR_016886
Natural variant1341C → W in granulosa-cell tumors of the ovary; not commonly found in other tumor types. Ref.22 Ref.23
VAR_062548
Natural variant1791A → G. Ref.12 Ref.20
Corresponds to variant rs7432551 [ dbSNP | Ensembl ].
VAR_021201
Natural variant1871G → D in POF3; does not affect nuclear localization; reduces transcriptional activation of OSR2. Ref.7 Ref.11
VAR_015181
Natural variant1931K → R in BPES; type II.
VAR_021202
Natural variant2151Y → C in BPES. Ref.16 Ref.20
VAR_021203
Natural variant2171S → C in BPES; diffuse nuclear localization; normal transcriptional activation. Ref.20
VAR_062549
Natural variant2171S → F in BPES; diffuse nuclear localization; increased transactivation activity. Ref.9 Ref.13 Ref.19
VAR_016887
Natural variant2341A → AAAAAA in BPES; significant higher cytoplasmic retention compared to the wild-type protein. Ref.1 Ref.2 Ref.10 Ref.18
VAR_037303
Natural variant2341A → AAAAAAAAAAA in BPES; type II. Ref.1 Ref.2 Ref.10 Ref.18
VAR_010782
Natural variant2341A → AAAAAAAAAAAA in BPES. Ref.1 Ref.2 Ref.10 Ref.18
VAR_025306
Natural variant2581Y → N in POF3. Ref.12
Corresponds to variant rs28937885 [ dbSNP | Ensembl ].
VAR_021204
Natural variant2851P → S. Ref.11
VAR_015182

Experimental info

Mutagenesis251K → R: Results in reduced sumoylation. Loss of transcriptional repression activity. Ref.5

Sequences

Sequence LengthMass (Da)Tools
P58012 [UniParc].

Last modified April 27, 2001. Version 1.
Checksum: B4952F2A0380E533

FASTA37638,772
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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)

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF301906 mRNA. Translation: AAK01352.1.
DQ016609 Genomic DNA. Translation: AAY21823.1.
BC062549 mRNA. Translation: AAH62549.1.
CCDSCCDS3105.1.
RefSeqNP_075555.1. NM_023067.3.
UniGeneHs.289292.

3D structure databases

ProteinModelPortalP58012.
SMRP58012. Positions 54-143.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107136. 5 interactions.
IntActP58012. 2 interactions.
STRING9606.ENSP00000333188.

PTM databases

PhosphoSiteP58012.

Polymorphism databases

DMDM13626838.

Proteomic databases

MaxQBP58012.
PaxDbP58012.
PRIDEP58012.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000330315; ENSP00000333188; ENSG00000183770.
GeneID668.
KEGGhsa:668.
UCSCuc003esw.3. human.

Organism-specific databases

CTD668.
GeneCardsGC03M138663.
GeneReviewsFOXL2.
HGNCHGNC:1092. FOXL2.
MIM110100. phenotype.
605597. gene.
608996. phenotype.
neXtProtNX_P58012.
Orphanet261559. Blepharophimosis - epicanthus inversus - ptosis due to 3q23 microdeletion.
261572. Blepharophimosis - epicanthus inversus - ptosis due to a point mutation.
619. Primary ovarian failure.
PharmGKBPA28235.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5025.
HOVERGENHBG051651.
InParanoidP58012.
KOK09405.
OMAELSMMHC.
OrthoDBEOG7C8GHD.
PhylomeDBP58012.
TreeFamTF316127.

Gene expression databases

ArrayExpressP58012.
BgeeP58012.
CleanExHS_FOXL2.
GenevestigatorP58012.

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.
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Other

GeneWikiForkhead_box_L2.
GenomeRNAi668.
NextBio2732.
PROP58012.
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Entry information

Entry nameFOXL2_HUMAN
AccessionPrimary (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: July 9, 2014
This is version 137 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM