D3Z120 · FOXI3_MOUSE
- ProteinForkhead box protein I3
- GeneFoxi3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids399 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Transcription factor required for pharyngeal arch development, which is involved in hair, ear, jaw and dental development (PubMed:24650709, PubMed:26550799, PubMed:26992132, PubMed:30467319).
May act as a pioneer transcription factor during pharyngeal arch development (PubMed:26550799, PubMed:26992132).
Required for epithelial cell differentiation within the epidermis (PubMed:26450968).
Acts at multiple stages of otic placode induction: necessary for preplacodal ectoderm to execute an inner ear program (PubMed:26550799).
Required for hair follicle stem cell specification (PubMed:26992132).
Acts downstream of TBX1 for the formation of the thymus and parathyroid glands from the third pharyngeal pouch (PubMed:31412026).
May act as a pioneer transcription factor during pharyngeal arch development (PubMed:26550799, PubMed:26992132).
Required for epithelial cell differentiation within the epidermis (PubMed:26450968).
Acts at multiple stages of otic placode induction: necessary for preplacodal ectoderm to execute an inner ear program (PubMed:26550799).
Required for hair follicle stem cell specification (PubMed:26992132).
Acts downstream of TBX1 for the formation of the thymus and parathyroid glands from the third pharyngeal pouch (PubMed:31412026).
Features
Showing features for dna binding.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
DNA binding | 129-223 | Fork-head | ||||
Sequence: RPPYSYSALIAMAIQSAPERKLTLSHIYQFVADNFPFYQRSKAGWQNSIRHNLSLNDCFKKVPRDEDDPGKGNYWTLDPNCEKMFDNGNFRRKRR |
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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Aspect | Term | |
---|---|---|
Cellular Component | nucleus | |
Molecular Function | DNA-binding transcription factor activity, RNA polymerase II-specific | |
Molecular Function | RNA polymerase II cis-regulatory region sequence-specific DNA binding | |
Biological Process | anatomical structure morphogenesis | |
Biological Process | cell differentiation | |
Biological Process | epidermal cell fate specification | |
Biological Process | hair follicle development | |
Biological Process | odontogenesis of dentin-containing tooth | |
Biological Process | otic placode development | |
Biological Process | parathyroid gland development | |
Biological Process | pharyngeal system development | |
Biological Process | regulation of transcription by RNA polymerase II | |
Biological Process | thymus development |
Keywords
- Molecular function
- Biological process
Names & Taxonomy
Protein names
- Recommended nameForkhead box protein I3
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionD3Z120
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Phenotypes & Variants
Disruption phenotype
Embryonic lethality due to impaired pharyngeal arches segmentation (PubMed:24650709).
Embryos fail to form endodermal pouches and this results in failed pharyngeal arches segmentation leading to severe defects in the skull, jaw, and ears (PubMed:24650709, PubMed:26550799).
Craniofacial neural crest cells undergo apoptosis in the mutant embryos at 10.0 day post coitum (dpc) (PubMed:24650709).
Conditional deletion in epithelium leads to fusion of molars with abnormally patterned shallow cusps (PubMed:26450968).
Conditional deletion impairs postnatal hair growth and hair cycling, resulting in poor hair regeneration upon hair plucking; defects are caused by progressive depletion of hair follicle stem cells (PubMed:26992132).
Conditional deletion also results in defects in the distal pharyngeal apparatus (PubMed:31412026).
Embryos fail to form endodermal pouches and this results in failed pharyngeal arches segmentation leading to severe defects in the skull, jaw, and ears (PubMed:24650709, PubMed:26550799).
Craniofacial neural crest cells undergo apoptosis in the mutant embryos at 10.0 day post coitum (dpc) (PubMed:24650709).
Conditional deletion in epithelium leads to fusion of molars with abnormally patterned shallow cusps (PubMed:26450968).
Conditional deletion impairs postnatal hair growth and hair cycling, resulting in poor hair regeneration upon hair plucking; defects are caused by progressive depletion of hair follicle stem cells (PubMed:26992132).
Conditional deletion also results in defects in the distal pharyngeal apparatus (PubMed:31412026).
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 99-103 | Reduced transcription factor activity. | ||||
Sequence: SAPAS → AAPAA | ||||||
Mutagenesis | 200-224 | Knockin mice are significantly smaller and die immediately after birth. They show a partially truncated mandible and fusion of the upper and lower jaws (syngnathia) and anomalies of various bones of the ear. | ||||
Sequence: GNYWTLDPNCEKMFDNGNFRRKRRR → WRQH | ||||||
Mutagenesis | 218 | Knockin mice hemizygous for L-218 mutant and a deletion of the wild-type Foxi3 allele fail to thrive after birth, are underweight, display respiratory abnormalities and die between birth and day 5. | ||||
Sequence: F → L | ||||||
Mutagenesis | 219-225 | Abolished localization to the nucleus. | ||||
Sequence: RRKRRRR → AAAAAAA | ||||||
Mutagenesis | 224 | Does not affect nuclear localization. | ||||
Sequence: R → L | ||||||
Mutagenesis | 258 | Does not affect transcription factor activity. | ||||
Sequence: S → A | ||||||
Mutagenesis | 266-268 | Does not affect transcription factor activity. | ||||
Sequence: SQS → AQA | ||||||
Mutagenesis | 385-393 | In Mut2; strongly reduced transcription factor activity. | ||||
Sequence: SMVNSLIYP → AAAAAAAAA | ||||||
Mutagenesis | 386-391 | In Mut1; reduced transcription factor activity. | ||||
Sequence: MVNSLI → AANSAA |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 11 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000458754 | 1-399 | Forkhead box protein I3 | |||
Sequence: MALYCGDNFVYSQPAAAPGAPPTSRAPYGLSDYAAPPAAAANPYLWLNGPGVGGPASAASYLGAPPPPPGAAPGPFLQPPAAPGTFAGAQRGFAQPSASAPASPAGSAAPGELGWLSMASREDLMKMVRPPYSYSALIAMAIQSAPERKLTLSHIYQFVADNFPFYQRSKAGWQNSIRHNLSLNDCFKKVPRDEDDPGKGNYWTLDPNCEKMFDNGNFRRKRRRRAEASSNLTVPSGTSKSEGQSSRLRVSGKLEGDSPSSILRPSQSPEPPEGTKSTASSPGASTLTSTPCLNTFLSTFNTLNVNSSSSMGNQRTLPGSRRHLGGTQLPSSTFPNTSVPDSSPDSMQLSTVGGSNQLSSYYNPFSGGSSGDQSSPFSSPFYNFSMVNSLIYPRDGSDI | ||||||
Modified residue | 99 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 103 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 258 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 266 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 268 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Phosphorylation promotes the transcription factor activity (PubMed:30467319).
Dephosphorylation by protein phosphatase 2A (PP2A) reduces its activity (PubMed:30467319).
Dephosphorylation by protein phosphatase 2A (PP2A) reduces its activity (PubMed:30467319).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Specifically expressed in the epithelium in developing ectodermal appendages (PubMed:23441037).
Expressed in pharyngeal endoderm and ectoderm (PubMed:24650709).
Expressed in pre-placodal ectoderm (PubMed:26550799).
Down-regulated as the otic placode is induced (PubMed:26550799).
Expressed in teeth and hair follicles throughout embryogenesis (PubMed:23441037).
Expressed in mammary glands only during the earliest stages of development (PubMed:23441037).
Expressed in pharyngeal endoderm and ectoderm (PubMed:24650709).
Expressed in pre-placodal ectoderm (PubMed:26550799).
Down-regulated as the otic placode is induced (PubMed:26550799).
Expressed in teeth and hair follicles throughout embryogenesis (PubMed:23441037).
Expressed in mammary glands only during the earliest stages of development (PubMed:23441037).
Induction
Regulated by ectodysplasin (EDA) in skin appendage placodes.
Gene expression databases
Interaction
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for region, motif, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 87-109 | Disordered | ||||
Sequence: AGAQRGFAQPSASAPASPAGSAA | ||||||
Motif | 219-225 | Nuclear localization signal | ||||
Sequence: RRKRRRR | ||||||
Region | 221-287 | Disordered | ||||
Sequence: KRRRRAEASSNLTVPSGTSKSEGQSSRLRVSGKLEGDSPSSILRPSQSPEPPEGTKSTASSPGASTL | ||||||
Compositional bias | 229-248 | Polar residues | ||||
Sequence: SSNLTVPSGTSKSEGQSSRL | ||||||
Compositional bias | 260-287 | Polar residues | ||||
Sequence: SSILRPSQSPEPPEGTKSTASSPGASTL | ||||||
Region | 307-353 | Disordered | ||||
Sequence: SSSSMGNQRTLPGSRRHLGGTQLPSSTFPNTSVPDSSPDSMQLSTVG | ||||||
Motif | 385-393 | 9aaTAD | ||||
Sequence: SMVNSLIYP |
Domain
The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length399
- Mass (Da)42,015
- Last updated2011-04-05 v2
- ChecksumB6AF74DCAD855C58
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A9S4I865 | A0A9S4I865_MOUSE | Foxi3 | 425 |
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 229-248 | Polar residues | ||||
Sequence: SSNLTVPSGTSKSEGQSSRL | ||||||
Compositional bias | 260-287 | Polar residues | ||||
Sequence: SSILRPSQSPEPPEGTKSTASSPGASTL |
Keywords
- Technical term