P58012 · FOXL2_HUMAN
- ProteinForkhead box protein L2
- GeneFOXL2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids376 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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
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
Features
Showing features for dna binding.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
DNA binding | 54-148 | Fork-head | ||||
Sequence: KPPYSYVALIAMAIRESAEKRLTLSGIYQYIIAKFPFYEKNKKGWQNSIRHNLSLNECFIKVPREGGGERKGNYWTLDPACEDMFEKGNYRRRRR |
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameForkhead box protein L2
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP58012
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
Blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES)
- Note
- DescriptionA 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.
- See alsoMIM:110100
Natural variants in BPES
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_021196 | 58 | S>L | in BPES; sporadic; nuclear and cytoplasmic aggregation; impaired transactivation activity | |
VAR_062545 | 63 | I>T | in BPES; dbSNP:rs1315073489 | |
VAR_046490 | 65 | M>V | in BPES; dbSNP:rs1559922621 | |
VAR_021197 | 66 | A>V | in BPES; nuclear and cytoplasmic aggregation; impaired transactivation activity | |
VAR_021198 | 69 | E>K | in BPES; sporadic; nuclear aggregation; normal transactivation activity; dbSNP:rs387906920 | |
VAR_046491 | 80 | I>T | in BPES; nuclear and cytoplasmic aggregation; impaired transactivation activity | |
VAR_046492 | 84 | I>N | in BPES; nuclear and cytoplasmic aggregation; impaired transactivation activity | |
VAR_016883 | 84 | I>S | in BPES; type I; dbSNP:rs28937884 | |
VAR_016884 | 85 | missing | in BPES; sporadic | |
VAR_046493 | 90 | F>S | in BPES; nuclear and cytoplasmic aggregation; impaired transactivation activity | |
VAR_046494 | 98 | W>G | in BPES; nuclear and cytoplasmic aggregation; impaired transactivation activity | |
VAR_062546 | 98 | W>R | in BPES; dbSNP:rs1057516149 | |
VAR_046495 | 101 | S>R | in BPES; nuclear aggregation; impaired transactivation activity; dbSNP:rs1057516151 | |
VAR_046496 | 102 | I>T | in BPES; nuclear and cytoplasmic aggregation; impaired transactivation activity; dbSNP:rs2107744725 | |
VAR_046497 | 103 | R>C | in BPES; nuclear and cytoplasmic aggregation; normal transactivation activity | |
VAR_021199 | 104 | H>R | in BPES; diffuse nuclear localization as wild type; normal transactivation activity; dbSNP:rs1057516153 | |
VAR_021200 | 105 | N>S | in BPES; type II | |
VAR_016885 | 106 | L>F | in BPES; sporadic; nuclear and cytoplasmic aggregation; impaired transactivation activity; dbSNP:rs1057516156 | |
VAR_046498 | 106 | L>P | in BPES; nuclear and cytoplasmic aggregation; impaired transactivation activity; dbSNP:rs2107744697 | |
VAR_062547 | 108 | L>P | in BPES; nuclear aggregation and cytoplasmic mislocalization; impaired transactivation activity; dbSNP:rs2107744687 | |
VAR_016886 | 109 | N>K | in BPES; type II; diffuse nuclear localization as wild type; impaired transactivation activity; dbSNP:rs2107744671 | |
VAR_021202 | 193 | K>R | in BPES; type II; dbSNP:rs1057516162 | |
VAR_021203 | 215 | Y>C | in BPES; dbSNP:rs1057516168 | |
VAR_062549 | 217 | S>C | in BPES; diffuse nuclear localization; normal transcriptional activation | |
VAR_016887 | 217 | S>F | in BPES; diffuse nuclear localization; increased transactivation activity; dbSNP:rs797044527 | |
VAR_037303 | 234 | A>AAAAAA | in BPES; significant higher cytoplasmic retention compared to the wild-type protein | |
VAR_010782 | 234 | A>AAAAAAAAAAA | in BPES; type II | |
VAR_025306 | 234 | A>AAAAAAAAAAAA | in BPES |
Premature ovarian failure 3 (POF3)
- Note
- DescriptionAn 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.
- See alsoMIM:608996
Natural variants in POF3
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_015181 | 187 | G>D | in POF3; does not affect nuclear localization; reduces transcriptional activation of OSR2; dbSNP:rs121908359 | |
VAR_021204 | 258 | Y>N | in POF3; dbSNP:rs28937885 |
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 25 | Results in reduced sumoylation. Loss of transcriptional repression activity. | ||||
Sequence: K → R | ||||||
Natural variant | VAR_021196 | 58 | in BPES; sporadic; nuclear and cytoplasmic aggregation; impaired transactivation activity | |||
Sequence: S → L | ||||||
Natural variant | VAR_062545 | 63 | in BPES; dbSNP:rs1315073489 | |||
Sequence: I → T | ||||||
Natural variant | VAR_046490 | 65 | in BPES; dbSNP:rs1559922621 | |||
Sequence: M → V | ||||||
Natural variant | VAR_021197 | 66 | in BPES; nuclear and cytoplasmic aggregation; impaired transactivation activity | |||
Sequence: A → V | ||||||
Natural variant | VAR_021198 | 69 | in BPES; sporadic; nuclear aggregation; normal transactivation activity; dbSNP:rs387906920 | |||
Sequence: E → K | ||||||
Natural variant | VAR_046491 | 80 | in BPES; nuclear and cytoplasmic aggregation; impaired transactivation activity | |||
Sequence: I → T | ||||||
Natural variant | VAR_046492 | 84 | in BPES; nuclear and cytoplasmic aggregation; impaired transactivation activity | |||
Sequence: I → N | ||||||
Natural variant | VAR_016883 | 84 | in BPES; type I; dbSNP:rs28937884 | |||
Sequence: I → S | ||||||
Natural variant | VAR_016884 | 85 | in BPES; sporadic | |||
Sequence: Missing | ||||||
Natural variant | VAR_046493 | 90 | in BPES; nuclear and cytoplasmic aggregation; impaired transactivation activity | |||
Sequence: F → S | ||||||
Natural variant | VAR_046494 | 98 | in BPES; nuclear and cytoplasmic aggregation; impaired transactivation activity | |||
Sequence: W → G | ||||||
Natural variant | VAR_062546 | 98 | in BPES; dbSNP:rs1057516149 | |||
Sequence: W → R | ||||||
Natural variant | VAR_046495 | 101 | in BPES; nuclear aggregation; impaired transactivation activity; dbSNP:rs1057516151 | |||
Sequence: S → R | ||||||
Natural variant | VAR_046496 | 102 | in BPES; nuclear and cytoplasmic aggregation; impaired transactivation activity; dbSNP:rs2107744725 | |||
Sequence: I → T | ||||||
Natural variant | VAR_046497 | 103 | in BPES; nuclear and cytoplasmic aggregation; normal transactivation activity | |||
Sequence: R → C | ||||||
Natural variant | VAR_021199 | 104 | in BPES; diffuse nuclear localization as wild type; normal transactivation activity; dbSNP:rs1057516153 | |||
Sequence: H → R | ||||||
Natural variant | VAR_021200 | 105 | in BPES; type II | |||
Sequence: N → S | ||||||
Natural variant | VAR_016885 | 106 | in BPES; sporadic; nuclear and cytoplasmic aggregation; impaired transactivation activity; dbSNP:rs1057516156 | |||
Sequence: L → F | ||||||
Natural variant | VAR_046498 | 106 | in BPES; nuclear and cytoplasmic aggregation; impaired transactivation activity; dbSNP:rs2107744697 | |||
Sequence: L → P | ||||||
Natural variant | VAR_062547 | 108 | in BPES; nuclear aggregation and cytoplasmic mislocalization; impaired transactivation activity; dbSNP:rs2107744687 | |||
Sequence: L → P | ||||||
Natural variant | VAR_016886 | 109 | in BPES; type II; diffuse nuclear localization as wild type; impaired transactivation activity; dbSNP:rs2107744671 | |||
Sequence: N → K | ||||||
Natural variant | VAR_062548 | 134 | in granulosa-cell tumors of the ovary; not commonly found in other tumor types; dbSNP:rs1057519865 | |||
Sequence: C → W | ||||||
Natural variant | VAR_021201 | 179 | in dbSNP:rs7432551 | |||
Sequence: A → G | ||||||
Natural variant | VAR_015181 | 187 | in POF3; does not affect nuclear localization; reduces transcriptional activation of OSR2; dbSNP:rs121908359 | |||
Sequence: G → D | ||||||
Natural variant | VAR_021202 | 193 | in BPES; type II; dbSNP:rs1057516162 | |||
Sequence: K → R | ||||||
Natural variant | VAR_021203 | 215 | in BPES; dbSNP:rs1057516168 | |||
Sequence: Y → C | ||||||
Natural variant | VAR_062549 | 217 | in BPES; diffuse nuclear localization; normal transcriptional activation | |||
Sequence: S → C | ||||||
Natural variant | VAR_016887 | 217 | in BPES; diffuse nuclear localization; increased transactivation activity; dbSNP:rs797044527 | |||
Sequence: S → F | ||||||
Natural variant | VAR_037303 | 234 | in BPES; significant higher cytoplasmic retention compared to the wild-type protein | |||
Sequence: A → AAAAAA | ||||||
Natural variant | VAR_010782 | 234 | in BPES; type II | |||
Sequence: A → AAAAAAAAAAA | ||||||
Natural variant | VAR_025306 | 234 | in BPES | |||
Sequence: A → AAAAAAAAAAAA | ||||||
Natural variant | VAR_021204 | 258 | in POF3; dbSNP:rs28937885 | |||
Sequence: Y → N | ||||||
Natural variant | VAR_015182 | 285 | ||||
Sequence: P → S | ||||||
Natural variant | VAR_078138 | 349 | in dbSNP:rs201840174 | |||
Sequence: R → G |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 1,095 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, cross-link, modified residue, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000091861 | 1-376 | UniProt | Forkhead box protein L2 | |||
Sequence: MMASYPEPEDAAGALLAPETGRTVKEPEGPPPSPGKGGGGGGGTAPEKPDPAQKPPYSYVALIAMAIRESAEKRLTLSGIYQYIIAKFPFYEKNKKGWQNSIRHNLSLNECFIKVPREGGGERKGNYWTLDPACEDMFEKGNYRRRRRMKRPFRPPPAHFQPGKGLFGAGGAAGGCGVAGAGADGYGYLAPPKYLQSGFLNNSWPLPQPPSPMPYASCQMAAAAAAAAAAAAAAGPGSPGAAAVVKGLAGPAASYGPYTRVQSMALPPGVVNSYNGLGGPPAAPPPPPHPHPHPHAHHLHAAAAPPPAPPHHGAAAPPPGQLSPASPATAAPPAPAPTSAPGLQFACARQPELAMMHCSYWDHDSKTGALHSRLDL | |||||||
Cross-link | 25 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) | ||||
Sequence: K | |||||||
Modified residue | 33 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 33 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 101 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Sumoylated with SUMO1; sumoylation is required for transcriptional repression activity.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
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.
Gene expression databases
Organism-specific databases
Structure
Family & Domains
Features
Showing features for region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-53 | Disordered | ||||
Sequence: MMASYPEPEDAAGALLAPETGRTVKEPEGPPPSPGKGGGGGGGTAPEKPDPAQ | ||||||
Region | 276-342 | Disordered | ||||
Sequence: GLGGPPAAPPPPPHPHPHPHAHHLHAAAAPPPAPPHHGAAAPPPGQLSPASPATAAPPAPAPTSAPG | ||||||
Compositional bias | 303-339 | Pro residues | ||||
Sequence: AAPPPAPPHHGAAAPPPGQLSPASPATAAPPAPAPTS |
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length376
- Mass (Da)38,772
- Last updated2001-04-27 v1
- ChecksumB4952F2A0380E533
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 303-339 | Pro residues | ||||
Sequence: AAPPPAPPHHGAAAPPPGQLSPASPATAAPPAPAPTS |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF301906 EMBL· GenBank· DDBJ | AAK01352.1 EMBL· GenBank· DDBJ | mRNA | ||
DQ016609 EMBL· GenBank· DDBJ | AAY21823.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC062549 EMBL· GenBank· DDBJ | AAH62549.1 EMBL· GenBank· DDBJ | mRNA |