FOXA1

FOXA1
Identifiers
Aliases	FOXA1, HNF3A, TCF3A, forkhead box A1
External IDs	OMIM: 602294; MGI: 1347472; HomoloGene: 3307; GeneCards: FOXA1; OMA:FOXA1 - orthologs
Gene location (Human) Chr. Chromosome 14 (human)[1] Band 14q21.1 Start 37,589,552 bp[1] End 37,596,059 bp[1]
Gene location (Mouse) Chr. Chromosome 12 (mouse)[2] Band 12 C1|12 24.7 cM Start 57,587,414 bp[2] End 57,593,702 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in bronchial epithelial cell right lobe of liver prostate rectum body of stomach pancreatic ductal cell minor salivary glands palpebral conjunctiva urinary bladder right lung Top expressed in mucosa of urinary bladder epithelium of stomach mucous cell of stomach lacrimal gland pyloric antrum Paneth cell right lung lobe left colon substantia nigra left lung lobe More reference expression data BioGPS n/a
Gene ontology Molecular function sequence-specific DNA binding protein domain specific binding DNA-binding transcription activator activity, RNA polymerase II-specific transcription factor binding DNA-binding transcription factor activity DNA binding protein binding DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component microvillus nucleus fibrillar center nucleoplasm Biological process Notch signaling pathway prostate gland stromal morphogenesis dopaminergic neuron differentiation positive regulation of intracellular estrogen receptor signaling pathway response to estradiol regulation of transcription, DNA-templated lung morphogenesis glucose homeostasis positive regulation of smoothened signaling pathway lung development regulation of transcription by RNA polymerase II neuron fate specification anatomical structure formation involved in morphogenesis positive regulation of mitotic cell cycle positive regulation of DNA-binding transcription factor activity negative regulation of transcription by RNA polymerase II transcription by RNA polymerase II tube morphogenesis secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development transcription, DNA-templated regulation of cell cycle multicellular organism development prostate gland epithelium morphogenesis connective tissue development positive regulation of neuron differentiation epithelial cell maturation involved in prostate gland development regulation of gene expression lung epithelial cell differentiation dorsal/ventral neural tube patterning epithelial-mesenchymal signaling involved in prostate gland development epithelial tube branching involved in lung morphogenesis respiratory basal cell differentiation hormone metabolic process alveolar secondary septum development negative regulation of epithelial to mesenchymal transition positive regulation of cell-cell adhesion mediated by cadherin positive regulation of transcription by RNA polymerase II chromatin remodeling anatomical structure morphogenesis positive regulation of apoptotic process chromatin organization cell differentiation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3169 15375 Ensembl ENSG00000129514 ENSMUSG00000035451 UniProt P55317 P35582 RefSeq (mRNA) NM_004496 NM_008259 RefSeq (protein) NP_004487 NP_032285 Location (UCSC) Chr 14: 37.59 – 37.6 Mb Chr 12: 57.59 – 57.59 Mb PubMed search [3] [4]
Wikidata
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Forkhead box protein A1 (FOXA1), also known as hepatocyte nuclear factor 3-alpha (HNF-3A), is a protein that in humans is encoded by the FOXA1 gene.^[5][6][7]

Function

FOXA1 is a pioneer factor, a transcription factor that directly binds condensed chromatin, facilitating the binding of other transcription factors.^[8] In prostate cells, FOXA1 interacts with the androgen receptor (AR) to drive transcription of prostate-specific genes.^[8]

FOXA1 is a member of the forkhead class of DNA-binding proteins. Similar family members in mice have roles in the regulation of metabolism and in the differentiation of the pancreas and liver.^[5]

Structure

FOXA1 is a member of the forkhead domain transcription factor family. The forkhead domain is essential for its DNA-binding function, and consists of three alpha helices, three beta strands, and two loops (called "wings"). The domain binds along the DNA major groove and the wings directly contact the DNA.^[9]

Marker in breast cancer

FOXA1 in breast cancer is highly correlated with ERα⁺, GATA3⁺, and PR⁺ protein expression as well as endocrine signaling. FOXA1 acts as a pioneer factor for ERa in ERα⁺ breast cancer, and its expression might identify ERα⁺ cancers that undergo rapid reprogramming of ERa signaling that is associated with poor outcomes and treatment resistance.^[10] Conversely, in ERα⁻ breast cancer FOXA1 is highly correlated with low-grade morphology and improved disease free survival. FOXA1 is a downstream target of GATA3 in the mammary gland.^[11] Expression in ERα⁻ cancers may identify a subset of tumors that is responsive to other endocrine therapies such as androgen receptor antagonist treatment.^[12][13]

Role in cancer

FOXA1 is one of the most frequently altered genes in prostate cancer, with mutations in the coding sequence of up to 9% of localized prostate cancer cases, and 13% of metastatic treatment-resistant prostate cancers.^[8] Most cancer-associated FOXA1 mutations are missense mutations, changing the amino acid sequence of the fork head domain's DNA-binding sites.^[8]

Expression of FOXA1 correlates with two EMT markers, namely Twist1 and E-cadherin in breast cancer.^[14]

References

External links

• FactorBook FOXA1

This article incorporates text from the United States National Library of Medicine, which is in the public domain.