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FLASH GENE

Symbol

NPAS4

contributors: shn/mct - updated : 26-06-2015

HGNC name	neuronal PAS domain protein 4
HGNC id	18983

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	an activation domain as a transcription activator
	a PAS domain

HOMOLOGY

interspecies	ortholog to Npas4, Mus musculus
	ortholog to Nxf, Rattus norvegicus
	ortholog to NPAS4, Pan troglodytes

Homologene

FAMILY

member of the basic helix-loop-helix-PER-ARNT-SIM (bHLH-PAS) class of transcriptional regulators

CATEGORY

transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus

basic FUNCTION	playing a positive regulatory role in dendritic-cytoskeleton modulator drebrin gene expression
	Npas4 is critical for activity-dependent regulation of GABAergic synapse development
	Npas4 plays a role in the development of inhibitory synapses by regulating the expression of activity-dependent genes
	Npas4 plays an important role in regulating the number of
	functional inhibitory synapses received by an excitatory neuron
	Npas4 functions as a transcriptional repressor as well as an activator, and/or that Npas4 indirectly affects gene expression by altering neuronal excitation
	master regulator of activity-regulated gene programs and is central to memory formation
	may play a major role in the regulation of cognitive and social functions in the brain with possible implications for developmental disorders such as schizophrenia and autism
	brain-specific basic helix-loop-helix transcription factor, regulating the development of the GABAergic inhibitory synapses and transcription program for contextual memory formation in the hippocampus
	may play an important role in the structural and functional plasticity of neurons
	activity-dependent transcription factor, necessary for the changes in the input synapses of new neurons in the adult dentate gyrus, but not involved in changes to their axonal synapses
	key activity-dependent regulator that improves beta-cell efficiency in the face of stress

CELLULAR PROCESS

nucleotide, transcription, regulation

PHYSIOLOGICAL PROCESS

nervous system

PATHWAY

metabolism

signaling

signal transduction

a component

Npas4 could heterodimerize with Arnt-type bHLH-PAS subfamily members ould heterodimerize; ARNT, ARNT2 and BMAL1

INTERACTION

DNA	BDNF promoters I and IV

RNA

small molecule

protein	DBN1
	NPAS4 could heterodimerize with Arnt-type bHLH-PAS subfamily members ould heterodimerize; ARNT, ARNT2 and BMAL1
	MAGED1 binds and positively regulates the transcriptional activity of family members SIM1, SIM2, NPAS4 and ARNT2, but does not interact with AHR, HIF1A and ARNT

cell & other

REGULATION

activated by

GABAA-receptor antagonist bicuculline

induced by

classical endoplasmic reticulum (ER) stressors

repressed by

stress via the binding of agonist-bound glucocorticoid receptor to its promoter

Other

regulated in response to cerebral ischemia

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   highly in ischemic tissues following both focal and global cerebral ischemic insults

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed diabete type 2   could be a novel therapeutic target in type 2 diabetes that could both reduce ER stress and cell death and maintain basal cell function

ANIMAL & CELL MODELS

	Npas4 knockout mice appear anxious and hyperactive, are prone to seizures and have a shortened lifespan compared with their wild-type littermates, phenotypically resembling other knockout mice lacking genes that control the formation
	or function of inhibitory circuits (Lin et al, 2008)