FOXJ1

FOXJ1
Identifiers
Aliases	FOXJ1, FKHL13, HFH-4, HFH4, forkhead box J1, CILD43
External IDs	OMIM: 602291; MGI: 1347474; HomoloGene: 1117; GeneCards: FOXJ1; OMA:FOXJ1 - orthologs
Gene location (Human) Chr. Chromosome 17 (human) Band 17q25.1 Start 76,136,333 bp End 76,141,245 bp
Gene location (Mouse) Chr. Chromosome 11 (mouse) Band 11 E2|11 81.16 cM Start 116,221,530 bp End 116,226,225 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right uterine tube olfactory zone of nasal mucosa epithelium of bronchus bronchial epithelial cell nasal epithelium mucosa of paranasal sinus testicle ventricular zone epithelium of nasopharynx trachea Top expressed in choroid plexus of fourth ventricle spermatid Epithelium of choroid plexus embryonic organizer seminiferous tubule respiratory epithelium nasal epithelium olfactory epithelium choroid plexus of lateral ventricle right lung lobe More reference expression data BioGPS n/a
Gene ontology Molecular function transcription cis-regulatory region binding RNA polymerase II cis-regulatory region sequence-specific DNA binding sequence-specific DNA binding DNA binding DNA-binding transcription factor activity protein binding DNA-binding transcription activator activity, RNA polymerase II-specific DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component nucleus Biological process determination of left/right symmetry positive regulation of lung ciliated cell differentiation cell projection organization regulation of transcription, DNA-templated metanephric part of ureteric bud development pattern specification process transcription, DNA-templated glomerular parietal epithelial cell development regulation of epithelial cell differentiation transcription by RNA polymerase II negative regulation of T cell proliferation left/right pattern formation spermatogenesis heart development negative regulation of T cell differentiation in thymus cilium assembly establishment of apical/basal cell polarity activation of GTPase activity negative regulation of B cell activation positive regulation of central B cell tolerance induction negative regulation of transcription by RNA polymerase II epithelium development negative regulation of humoral immune response mediated by circulating immunoglobulin brain development humoral immune response negative regulation of germinal center formation central tolerance induction negative regulation of NF-kappaB transcription factor activity lung epithelium development actin cytoskeleton organization leukocyte migration positive regulation of transcription by RNA polymerase II motile cilium assembly positive regulation of transcription, DNA-templated Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 2302 15223 Ensembl ENSG00000129654 ENSMUSG00000034227 UniProt Q92949 Q61660 RefSeq (mRNA) NM_001454 NM_008240 RefSeq (protein) NP_001445 NP_032266 Location (UCSC) Chr 17: 76.14 – 76.14 Mb Chr 11: 116.22 – 116.23 Mb PubMed search
Wikidata
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Forkhead box protein J1 is a protein that in humans is encoded by the FOXJ1 gene. It is a member of the Forkhead/winged helix (FOX) family of transcription factors that is involved in ciliogenesis. FOXJ1 is expressed in ciliated cells of the lung, choroid plexus, reproductive tract, 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 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.

Ciliogenesis

Primary ciliogenesis is FOXJ1 dependent and this transcription factor is required for motile ciliated cell differentiation. The onset of FOXJ1 expression is indicative of cells fated to become motile ciliated cells. Cells commit towards ciliogenesis prior to FOXJ1 activation. Activation promotes basal body trafficking, docking at the apical membrane and subsequent axoneme 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, an inhibitor of the protease calpain. 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.

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

Axenfeld–Rieger syndrome

Axenfeld–Rieger syndrome patients have a point mutation in PITX2 a regulatory protein of the FOXJ1 gene. PITX2 alongside LEF-1 and β-Catenin 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 and randomization of left/right body asymmetry.

Further reading

• Li CS, Zhang Q, Lim MK, Sheen DH, Shim SC, Kim JY, et al. (December 2007). "Association of FOXJ1 polymorphisms with systemic lupus erythematosus and rheumatoid arthritis in Korean population". Experimental & Molecular Medicine. 39 (6): 805–11. doi:10.1038/emm.2007.87. PMID 18160851.
• Li CS, Chae SC, Lee JH, Zhang Q, Chung HT (2006). "Identification of single nucleotide polymorphisms in FOXJ1 and their association with allergic rhinitis". Journal of Human Genetics. 51 (4): 292–7. doi:10.1007/s10038-006-0359-8. PMID 16518568.
• Turner J, Roger J, Fitau J, Combe D, Giddings J, Heeke GV, et al. (March 2011). "Goblet cells are derived from a FOXJ1-expressing progenitor in a human airway epithelium". American Journal of Respiratory Cell and Molecular Biology. 44 (3): 276–84. doi:10.1165/rcmb.2009-0304OC. PMID 20539013.
• Murphy DB, Seemann S, Wiese S, Kirschner R, Grzeschik KH, Thies U (March 1997). "The human hepatocyte nuclear factor 3/fork head gene FKHL13: genomic structure and pattern of expression". Genomics. 40 (3): 462–9. doi:10.1006/geno.1996.4587. PMID 9073514.
• Maiti AK, Bartoloni L, Mitchison HM, Meeks M, Chung E, Spiden S, et al. (2000). "No deleterious mutations in the FOXJ1 (alias HFH-4) gene in patients with primary ciliary dyskinesia (PCD)". Cytogenetics and Cell Genetics. 90 (1–2): 119–22. doi:10.1159/000015645. PMID 11060460. S2CID 21880343.
• LeSimple P, van Seuningen I, Buisine MP, Copin MC, Hinz M, Hoffmann W, et al. (March 2007). "Trefoil factor family 3 peptide promotes human airway epithelial ciliated cell differentiation". American Journal of Respiratory Cell and Molecular Biology. 36 (3): 296–303. doi:10.1165/rcmb.2006-0270OC. PMID 17008636.
• Lim L, Zhou H, Costa RH (April 1997). "The winged helix transcription factor HFH-4 is expressed during choroid plexus epithelial development in the mouse embryo". Proceedings of the National Academy of Sciences of the United States of America. 94 (7): 3094–9. Bibcode:1997PNAS...94.3094L. doi:10.1073/pnas.94.7.3094. PMC 20327. PMID 9096351.
• Pelletier GJ, Brody SL, Liapis H, White RA, Hackett BP (March 1998). "A human forkhead/winged-helix transcription factor expressed in developing pulmonary and renal epithelium". The American Journal of Physiology. 274 (3 Pt 1): L351–9. doi:10.1152/ajplung.1998.274.3.L351. PMID 9530170.
• Wu C, Ma MH, Brown KR, Geisler M, Li L, Tzeng E, et al. (June 2007). "Systematic identification of SH3 domain-mediated human protein-protein interactions by peptide array target screening". Proteomics. 7 (11): 1775–85. doi:10.1002/pmic.200601006. PMID 17474147. S2CID 22474278.

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