Alternative titles; symbols
HGNC Approved Gene Symbol: FOXF2
Cytogenetic location: 6p25.3 Genomic coordinates (GRCh38) : 6:1,389,576-1,395,603 (from NCBI)
The forkhead domain is a 100-amino acid monomeric DNA binding motif originally identified as a region of homology between the Drosophila forkhead protein and rat HNF3. Pierrou et al. (1994) identified 7 human genes containing forkhead domains and designated them forkhead related activators (FREAC) 1 through 7. Northern blot analysis revealed that the FREAC2, or FKHL6, gene is expressed as a 2.4-kb mRNA primarily in placenta and adult and fetal lung. Pierrou et al. (1994) determined the DNA binding specificity of FKHL6 through selection of high-affinity binding sites from random sequence oligonucleotides.
Hellqvist et al. (1996) reported the sequence of a partial FREAC2 cDNA. The predicted 408-amino acid protein is missing the N-terminal region. Sequence analysis revealed that the FREAC1 (FKHL5; 601089) and FREAC2 proteins are nearly identical within a 112-residue region containing the forkhead domain and adjacent sequences, and within the C-terminal region. Using a reporter gene construct containing in the promoter the FREAC2 binding sequences identified by Pierrou et al. (1994), Hellqvist et al. (1996) demonstrated that both FREAC1 and FREAC2 have C-terminal transcriptional activation domains. FREAC1/FREAC2 binding sequences are present in the promoters of several lung-specific genes, including CC10 (192020) and SPB (SFTPB; 178640). Both FREAC1 and FREAC2 transactivated an SPB promoter construct. Blixt et al. (1998) reported that the full-length FREAC2 protein contains 444 amino acids.
Hellqvist et al. (1998) identified the regions of the FREAC2 protein responsible for transcriptional activation. They also demonstrated that FREAC2 binds to the general transcription factors TFIIB (189963) and TBP (600075) in vitro. Overexpression of TFIIB potentiates transcriptional activation by FREAC2, suggesting that FREAC2 regulates transcription, in part, through recruitment of TFIIB. By expressing clones consisting of portions of FREAC2 fused to green fluorescent protein (GFP), Hellqvist et al. (1998) showed that FREAC2 contains a bipartite nuclear localization signal within the forkhead domain.
The FREAC2 gene contains 2 exons (Blixt et al., 1998).
By fluorescence in situ hybridization, Blixt et al. (1998) mapped the FREAC2 gene to chromosome 6p25-p24. They refined the localization to 6p25.3 by radiation hybrid mapping.
Blixt, A., Mahlapuu, M., Bjursell, C., Darnfors, C., Johannesson, T., Enerback, S., Carlsson, P. The two-exon gene of the human forkhead transcription factor FREAC-2 (FKHL6) is located at 6p25.3. Genomics 53: 387-390, 1998. [PubMed: 9799607] [Full Text: https://doi.org/10.1006/geno.1998.5451]
Hellqvist, M., Mahlapuu, M., Blixt, A., Enerback, S., Carlsson, P. The human forkhead protein FREAC-2 contains two functionally redundant activation domains and interacts with TBP and TFIIB. J. Biol. Chem. 273: 23335-23343, 1998. [PubMed: 9722567] [Full Text: https://doi.org/10.1074/jbc.273.36.23335]
Hellqvist, M., Mahlapuu, M., Samuelsson, L., Enerback, S., Carlsson, P. Differential activation of lung-specific genes by two forkhead proteins, FREAC-1 and FREAC-2. J. Biol. Chem. 271: 4482-4490, 1996. [PubMed: 8626802] [Full Text: https://doi.org/10.1074/jbc.271.8.4482]
Pierrou, S., Hellqvist, M., Samuelsson, L., Enerback, S., Carlsson, P. Cloning and characterization of seven human forkhead proteins: binding site specificity and DNA bending. EMBO J. 13: 5002-5012, 1994. [PubMed: 7957066] [Full Text: https://doi.org/10.1002/j.1460-2075.1994.tb06827.x]