FOXA2

This gene encodes a member of the forkhead class of DNA-binding proteins. These hepatocyte nuclear factors are transcriptional activators for liver-specific genes such as albumin and transthyretin, and they also interact with chromatin. Similar family members in mice have roles in the regulation of metabolism and in the differentiation of the pancreas and liver. This gene has been linked to sporadic cases of maturity-onset diabetes of the young. Transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Oct 2008]

Full Name

Forkhead Box A2

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. 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. Involved in regulation of fat metabolism. Binds to fibrinogen beta promoter and is involved in IL6-induced fibrinogen beta transcriptional activation.

Biological Process

Adult locomotory behavior Source: ParkinsonsUK-UCL
Anatomical structure morphogenesis Source: GO_Central
Cell differentiation Source: GO_Central
Cell fate specification Source: ParkinsonsUK-UCL
Chromatin organization Source: UniProtKB-KW
Dopaminergic neuron differentiation Source: ParkinsonsUK-UCL
Endocrine pancreas development Source: BHF-UCL
Negative regulation of detection of glucose Source: BHF-UCL
Negative regulation of DNA-binding transcription factor activity Source: BHF-UCL
Negative regulation of epithelial to mesenchymal transition Source: BHF-UCL
Negative regulation of glucokinase activity Source: BHF-UCL
Negative regulation of transcription from RNA polymerase II promoter by glucose Source: BHF-UCL
Positive regulation of cell-cell adhesion mediated by cadherin Source: BHF-UCL
Positive regulation of embryonic development Source: UniProtKB
Positive regulation of gastrulation Source: UniProtKB
Positive regulation of transcription, DNA-templated Source: UniProtKB
Positive regulation of transcription by RNA polymerase II Source: BHF-UCL
Positive regulation of transcription from RNA polymerase II promoter by glucose Source: BHF-UCL
Primitive streak formation Source: UniProtKB
Regulation of blood coagulation Source: UniProtKB
Regulation of insulin secretion involved in cellular response to glucose stimulus Source: BHF-UCL
Regulation of transcription by RNA polymerase II Source: BHF-UCL
Response to interleukin-6 Source: UniProtKB

Cellular Location

Cytoplasm; Nucleus. Shuttles between the nucleus and cytoplasm in a CRM1-dependent manner; in response to insulin signaling via AKT1 is exported from the nucleus.

PTM

Phosphorylation on Thr-156 abolishes binding to target promoters and subsequent transcription activation upon insulin stimulation.