Forkhead box protein J1 is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

that in humans is encoded by the ''FOXJ1''

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

. It is a member of the Forkhead/winged helix (

FOX Foxes are small to medium-sized, omnivorous mammals belonging to several genera of the family Canidae. They have a flattened skull, upright, triangular ears, a pointed, slightly upturned snout, and a long bushy tail (or ''brush''). Twelve sp ...

) family of

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The f ...

s that is involved in

ciliogenesis Ciliogenesis is defined as the building of the cell's antenna ( primary cilia) or extracellular fluid mediation mechanism ( motile cilium). It includes the assembly and disassembly of the cilia during the cell cycle. Cilia are important organell ...

. FOXJ1 is expressed in ciliated cells of the lung,

choroid plexus The choroid plexus, or plica choroidea, is a plexus of cells that arises from the tela choroidea in each of the ventricles of the brain. Regions of the choroid plexus produce and secrete most of the cerebrospinal fluid (CSF) of the central nerv ...

reproductive tract The reproductive system of an organism, also known as the genital system, is the biological system made up of all the anatomical organs involved in sexual reproduction. Many non-living substances such as fluids, hormones, and pheromones are al ...

, embryonic kidney and pre-somite embryo stage.

Gene Location

The human ''FOXJ1'' gene is located on the long arm of chromosome 17, region 2, band 5, sub-band 1.

Structure

FOXJ1 has a conserved 100 amino acid long DNA binding domain.

Function

This gene encodes a member of the

forkhead FOX (forkhead box) proteins are a family of transcription factors that play important roles in regulating the expression of genes involved in cell growth, proliferation, differentiation, and longevity. Many FOX proteins are important to embryon ...

family of transcription factors. Similar genes in zebrafish and mouse have been shown to regulate the transcription of genes that control the production of motile cilia. The mouse ortholog also functions in the determination of

left-right asymmetry Left-right asymmetry, (LR asymmetry) is the process in early embryonic development that breaks the normal symmetry in the bilateral embryo. In vertebrates, left-right asymmetry is established early in development at a structure called the left-ri ...

Ciliogenesis

Primary

is FOXJ1 dependent and this transcription factor is required for motile

ciliated The cilium, plural cilia (), is a membrane-bound organelle found on most types of eukaryotic cell, and certain microorganisms known as ciliates. Cilia are absent in bacteria and archaea. The cilium has the shape of a slender threadlike project ...

cell differentiation. The onset of FOXJ1 expression is indicative of cells fated to become motile cilliated cells. Cells commit towards ciliogenesis prior to FOXJ1 activation. Activation promotes

basal body A basal body (synonymous with basal granule, kinetosome, and in older cytological literature with blepharoplast) is a protein structure found at the base of a eukaryotic undulipodium (cilium or flagellum). The basal body was named by Theodor Wi ...

trafficking, docking at the apical membrane and subsequent

axoneme An axoneme, also called an axial filament is the microtubule-based cytoskeletal structure that forms the core of a cilium or flagellum. Cilia and flagella are found on many cells, organisms, and microorganisms, to provide motility. The axo ...

growth. The protein p73 a member of the p53 protein family directly regulates ''FOXJ1'' and is a requirement for ciliated cell formation. The 10,000bp long transcription start site of ''FOXJ1'' features three sequence specific binding sites for p73.

Immune system

In mammalian cells, FOXJ1 has been shown to suppress NFκB, a key regulator in the immune response and also inhibits the humoral response in B-cells. This occurs via regulation of an inhibitory component of NFκB called IκBβ and IL-6.

Development

FOXJ1 is expressed at various points during embryonic development in relation to teeth germination, enamel, oral and tongue epithelium formation, and formation of sub-mandibular salivary glands and hair follicles. Absence of FOXJ1 expression decreases

calpastatin Calpastatin is a protein that in humans is encoded by the ''CAST'' gene. The protein encoded by this gene is an endogenous calpain (calcium-dependent cysteine protease) inhibitor. It consists of an N-terminal domain L and four repetitive calpain- ...

, an inhibitor of the protease

calpain A calpain (; , ) is a protein belonging to the family of calcium-dependent, non-lysosomal cysteine proteases ( proteolytic enzymes) expressed ubiquitously in mammals and many other organisms. Calpains constitute the C2 family of protease clan C ...

. Calpain dysregulation affects basal body anchoring to the apical cytoskeleton affecting axeonemal formation. Expression of FOXJ1 is inhibited by IL-13.

Clinical significance

Polymorphisms in this gene are associated with systemic lupus erythematosus and

allergic rhinitis Allergic rhinitis, of which the seasonal type is called hay fever, is a type of inflammation in the nose that occurs when the immune system overreacts to allergens in the air. Signs and symptoms include a runny or stuffy nose, sneezing, red, i ...

. Viral infections of the respiratory system have been found to lower the expression of FOXJ1. This affects ciliogenesis and impacts mucocillary action.

Breast cancer

Studies into human breast tissue lines and primary breast tumors have observed that the gene ''FOXJ1'' are aberrantly hypermethylated in primary tumors. This hypermethylation serves to silence production of the FOXJ1 protein and has been proposed as a potentially important event in tumor formation.

Clear renal cell carcinoma

FOXJ1 expression has been shown to be elevated in clear cell renal carcinoma patients and indicative of tumor stage,

histological Histology, also known as microscopic anatomy or microanatomy, is the branch of biology which studies the microscopic anatomy of biological tissues. Histology is the microscopic counterpart to gross anatomy, which looks at larger structures vis ...

grade and tumor size. High expression of FOXJ1 in CRCC patients was associated with poor prognosis. There is potential for FOXJ1 to act as an

oncogene An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.

marker for CRCC patients and has value as a therapeutic target.

Axenfeld–Rieger syndrome

Axenfeld–Rieger syndrome patients have a point mutation in

PITX2 Paired-like homeodomain transcription factor 2 also known as pituitary homeobox 2 is a protein that in humans is encoded by the ''PITX2'' gene. Function This gene encodes a member of the RIEG/PITX homeobox family, which is in the bicoid clas ...

a regulatory protein of the ''FOXJ1'' gene. PITX2 alongside LEF-1 and

β-Catenin Catenin beta-1, also known as beta-catenin (β-catenin), is a protein that in humans is encoded by the ''CTNNB1'' gene. Beta-catenin is a dual function protein, involved in regulation and coordination of cell–cell adhesion and gene transcripti ...

regulate ''FOXJ1''. FOXJ1 in turn interacts with PITX2 to form a positive feedback mechanism. In the PITX2 point mutant whilst able to bind with FOXJ1 lacks the ability to activate the ''FOXJ1'' promoter, this results in improper oro-facial morphogenesis a factor in ARS.

Hydrocephalus

Mutations in this gene have been associated with an autosomal dominant syndrome that includes

hydrocephalus Hydrocephalus is a condition in which an accumulation of cerebrospinal fluid (CSF) occurs within the brain. This typically causes increased pressure inside the skull. Older people may have headaches, double vision, poor balance, urinary inc ...

and randomization of left/right body asymmetry.