InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Foxa2

Summary

InnateDB Protein

IDBP-208947.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Foxa2

Protein Name

forkhead box A2

Synonyms

Hnf-3b; HNF3-beta; Hnf3b; HNF3beta; Tcf-3b; Tcf3b;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000045918

InnateDB Gene

IDBG-208945 (Foxa2)

Protein Structure

UniProt Annotation

Function

Transcription factor that is involved in embryonic development, establishment of tissue-specific gene expression and regulation of gene expression in differentiated tissues. Is thought to act as a 'pioneer' factor opening the compacted chromatin for other proteins through interactions with nucleosomal core histones and thereby replacing linker histones at target enhancer and/or promoter sites. Binds DNA with the consensus sequence 5'-[AC]A[AT]T[AG]TT[GT][AG][CT]T[CT]-3' (By similarity). In embryonic development is required for notochord formation. Involved in the development of multiple endoderm-derived organ systems such as the liver, pancreas and lungs; Foxa1 and Foxa2 seem to have at least in part redundant roles. FOXA1 and FOXA2 are essential for hepatic specification. FOXA1 and FOXA2 are required for morphogenesis and cell differentiation during formation of the lung. FOXA1 and FOXA2 are involved in bile duct formation; they positively regulate the binding glucocorticoid receptor/NR3C1 to the IL6 promoter. FOXA1 and FOXA2 regulate multiple phases of midbrain dopaminergic neuron development; they regulate expression of NEUROG2 at the beginning of mDA neurogenesis and of NR4A2 and EN1 in immature mDA neurons. Modulates the transcriptional activity of nuclear hormone receptors; inhibits AR-mediated transcription from the LCN5 promoter. Binds to fibrinogen beta promoter and is involved in IL6-induced fibrinogen beta transcriptional activation. Originally described as a transcription activator for a number of liver genes such as AFP, albumin, tyrosine aminotransferase, PEPCK, etc. Interacts with the cis-acting regulatory regions of these genes. Involved in glucose homeostasis; regulates the expression of genes important for glucose sensing in pancreatic beta-cells and glucose homeostasis. In pancreatic beta cells activates transcription of potassium channel subunits KCNJ11 and ABCC8. Involved in regulation of fat metabolism; activates transcriptional programs of lipid metabolism and ketogenesis at low insulin state. Involved in transcriptional regulation of MUC2 in the intestine. {ECO:0000250, ECO:0000269PubMed:11445544, ECO:0000269PubMed:11875061, ECO:0000269PubMed:15616563, ECO:0000269PubMed:15668254, ECO:0000269PubMed:15959514, ECO:0000269PubMed:16740652, ECO:0000269PubMed:17596284, ECO:0000269PubMed:18336786, ECO:0000269PubMed:19141476, ECO:0000269PubMed:19436110, ECO:0000269PubMed:8069909}.

Subcellular Localization

Nucleus {ECO:0000255PROSITE- ProRule:PRU00089, ECO:0000269PubMed:15616563}. Cytoplasm {ECO:0000269PubMed:15616563}. Note=Shuttles between the nucleus and cytoplasm in a CRM1-dependent manner; in response to insulin signaling via AKT1 is exported from the nucleus.

Disease Associations

Tissue Specificity

Restricted mainly to endoderm-derived tissues (lung, liver, stomach, and small intestine). Expressed in epididymis with region-specific expression pattern: no expression is observed in initial segment, low expression in proximal caput, gradiently higher levels of expression in middle and distal caput and highest level in corpus and cauda (at protein level). {ECO:0000269PubMed:16740652}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 19 experimentally validated interaction(s) in this database.
They are also associated with 11 interaction(s) predicted by orthology.

Experimentally validated
Total	19 [view]
Protein-Protein	5 [view]
Protein-DNA	14 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	11 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000978	RNA polymerase II core promoter proximal region sequence-specific DNA binding
GO:0001205	RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription
GO:0003677	DNA binding
GO:0003690	double-stranded DNA binding
GO:0003700	sequence-specific DNA binding transcription factor activity
GO:0003705	RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity
GO:0005515	protein binding
GO:0008134	transcription factor binding
GO:0008301	DNA binding, bending
GO:0019904	protein domain specific binding
GO:0043565	sequence-specific DNA binding
GO:0044212	transcription regulatory region DNA binding

Biological Process

GO:0000432	positive regulation of transcription from RNA polymerase II promoter by glucose
GO:0000433	negative regulation of transcription from RNA polymerase II promoter by glucose
GO:0001701	in utero embryonic development
GO:0001705	ectoderm formation
GO:0001708	cell fate specification
GO:0006355	regulation of transcription, DNA-templated
GO:0006357	regulation of transcription from RNA polymerase II promoter
GO:0006366	transcription from RNA polymerase II promoter
GO:0007389	pattern specification process
GO:0008344	adult locomotory behavior
GO:0009653	anatomical structure morphogenesis
GO:0009952	anterior/posterior pattern specification
GO:0009953	dorsal/ventral pattern formation
GO:0010468	regulation of gene expression
GO:0010719	negative regulation of epithelial to mesenchymal transition
GO:0016568	chromatin modification
GO:0019216	regulation of lipid metabolic process
GO:0019218	regulation of steroid metabolic process
GO:0021533	cell differentiation in hindbrain
GO:0021904	dorsal/ventral neural tube patterning
GO:0023019	signal transduction involved in regulation of gene expression
GO:0030193	regulation of blood coagulation
GO:0030324	lung development
GO:0031018	endocrine pancreas development
GO:0032525	somite rostral/caudal axis specification
GO:0033132	negative regulation of glucokinase activity
GO:0040019	positive regulation of embryonic development
GO:0043433	negative regulation of sequence-specific DNA binding transcription factor activity
GO:0045087	innate immune response (InnateDB)
GO:0045665	negative regulation of neuron differentiation
GO:0045666	positive regulation of neuron differentiation
GO:0045880	positive regulation of smoothened signaling pathway
GO:0045893	positive regulation of transcription, DNA-templated
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0045945	positive regulation of transcription from RNA polymerase III promoter
GO:0048468	cell development
GO:0048646	anatomical structure formation involved in morphogenesis
GO:0048665	neuron fate specification
GO:0051090	regulation of sequence-specific DNA binding transcription factor activity
GO:0060441	epithelial tube branching involved in lung morphogenesis
GO:0060487	lung epithelial cell differentiation
GO:0061178	regulation of insulin secretion involved in cellular response to glucose stimulus
GO:0061448	connective tissue development
GO:0070741	response to interleukin-6
GO:0071542	dopaminergic neuron differentiation
GO:0090009	primitive streak formation
GO:2000543	positive regulation of gastrulation
GO:2000971	negative regulation of detection of glucose
GO:2000976	regulation of transcription from RNA polymerase II promoter involved in detection of glucose