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FLASH GENE

Symbol

FOXJ1

contributors: mct - updated : 19-10-2018

HGNC name	forkhead box J1
HGNC id	3816

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive mouth tongue       Nervous plexus choroid       highly Homo sapiens   spinal cord         Homo sapiens Reproductive female system oviduct         male system testis       Skeleton axial skeleton skull face mandible     axial skeleton skull face maxilla

cells

System Cell Pubmed Species Stage Rna symbol Nervous ependymal cell Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a forkhead (FH, winged helix) domain
	two loops-wings on the C-terminal side of helix-turn-helix homeo domain

HOMOLOGY

interspecies	ortholog to murine hepatocyte nuclear factor 4 HFH4
	ortholog to Drosophila homeo forkhead DNA binding domain

Homologene

FAMILY	HNF-3 FKH family of transcriptional activators
	Forkhead box family of transcription factors

CATEGORY

transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus,chromatin/chromosome

basic FUNCTION	embryonic transcriptional regulator
	modulating inflammatory reactions and preventing autoimmunity by antagonizing proinflammatory transcriptional activities
	transcription factor that can suppress T cell activity, at least partially, through the repression of NFkappaB activity
	playing a role in oro-facial morphogenesis (Shankar 2008)
	implicated in motile cilia formation, and controling cilia formation by regulating aspects of cell polarity, in particular, by modulating the localization and/or activity of proteins such as Ezrin and Rho that are important for actin cytoskeleton organization (Yu 2008)
	involved in ciliogenesis in multiciliated cells but also for expression of axonemal proteins related to ciliary motility
	time- and cell-specific expression of FOXJ1 in the brain acts on an array of target genes to regulate the differentiation of ependymal cells and a small subset of astrocytes in the adult stem cell niche
	regulates floor plate cilia architecture and modifies the response of cells to sonic hedgehog signalling
	is essential for ciliogenesis upstream of RFX3 in the node
	function of FOXJ1 in vertebrate organs of asymmetry is conserved, and NOTO regulates node morphogenesis and the posterior localization of cilia on node cells independently of FOXJ1
	FOXJ1 functions as the master regulator of motile cilia biogenesis
	plays likly an important role on neuronal production and neurogenesis in the adult brain after cerebral ischemia
	FOXJ1 is an important regulator of cilia gene expression during ciliated cell differentiation
	transcription factor that controls centriole docking and ciliary motility
	key regulators of motile ciliogenesis are the transcription factors FOXJ1 and NOTO, which are conserved throughout vertebrate
	essential for ependymal cell maturation, which might contribute to the development of hydrocephalus in FOXJ1-mutant individuals
	FOXJ1 might also affect ciliogenesis in the female reproductive tract
	is an essential component in signaling pathways for the generation of motile cilia
	is an essential component in signaling pathways for the generation of motile cilia
	mlticiliated cells (MCC) differentiation program is initiated by GMNC and MCIDAS, that activate key transcription factors, including p73 and FOXJ1, to control the multiciliogenesis program

CELLULAR PROCESS

nucleotide, transcription

PHYSIOLOGICAL PROCESS

development

text	in left-right axis determination

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA	binding, regulating expression of members of the dynein family of genes

RNA

small molecule

protein	NFKB repressor
	physically interacts with the PITX2 homeodomain to synergistically regulate FOXJJ1, providing a positive feedback mechanism for FOXJ1 expression (Shankar 2008)
	NOTO transcriptionally activates FOXJ1 expression and thus also regulates ciliogenesis
	ANK3 expression is controlled by FOXJ1, a transcriptional regulator of multicilia formation
	RER1 depletion reduced ciliary length and function by increasing gamma-secretase complex assembly and activity and, consequently, enhancing NOTCH1 signaling as well as reducing FOXJ1 expression
	RFX3 is a transcriptional co-activator to FOXJ1, helping to induce the expression of cilia genes in the process of ciliated cell differentiation of basal/progenitor cells
	BBOF1 is induced during the early phases of Multiciliate cells (MCCs) differentiation by the master regulator FOXJ1
	conditional inactivation of MYB in the developing airways blocks or delays centriole amplification and expression of FOXJ1
	MCIDAS is a key regulator of CCNO/FOXJ1 for human multiciliated cell differentiation
	GMNC directly transactivates the MCIDAS and FOXJ1 upstream regulatory sequences, and its activity is enhanced by E2F5 and inhibited by Geminin
	TP73 directly activates the key regulators FOXJ1, RFX2, RFX3
	ULK4 modulates expression of the master regulator of ciliogenesis, FOXJ1, and other ciliogenesis molecules
	NOTO-dependent activation of FOXJ1 at the left/right organizer is crucial for proper determination of the left/right asymmetry, probably explaining situs anomalies in some FOXJ1 mutant individuals
	TP73 acts upstream of FOXJ1 and downstream of MCIDAS

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

ICS44

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   in aggressive ependymoma and choroid plexus tumours

Susceptibility

to allergic rhinitis

Variant & Polymorphism SNP	associated with susceptibility to allergic rhinitis

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

	randomization of left/right (L/R) asymetry in mutant mice deficient in HFH4
	zebrafish Foxj1 homolog, foxj1a, is a target of Hedgehog signaling in the floor plate (Yu 2008)
	Foxj1-deficient mice develop hydrocephalus