NPAS4

NXF is a member of the basic helix-loop-helix-PER (MIM 602260)-ARNT (MIM 126110)-SIM (see SIM2; MIM 600892) (bHLH-PAS) class of transcriptional regulators, which are involved in a wide range of physiologic and developmental events (Ooe et al., 2004 [PubMed 14701734]).[supplied by OMIM, Mar 2008]

Full Name

Neuronal PAS Domain Protein 4

Function

Transcription factor expressed in neurons of the brain that regulates the excitatory-inhibitory balance within neural circuits and is required for contextual memory in the hippocampus (By similarity).
Plays a key role in the structural and functional plasticity of neurons (By similarity).
Acts as an early-response transcription factor in both excitatory and inhibitory neurons, where it induces distinct but overlapping sets of late-response genes in these two types of neurons, allowing the synapses that form on inhibitory and excitatory neurons to be modified by neuronal activity in a manner specific to their function within a circuit, thereby facilitating appropriate circuit responses to sensory experience (By similarity).
In excitatory neurons, activates transcription of BDNF, which in turn controls the number of GABA-releasing synapses that form on excitatory neurons, thereby promoting an increased number of inhibitory synapses on excitatory neurons (By similarity).
In inhibitory neurons, regulates a distinct set of target genes that serve to increase excitatory input onto somatostatin neurons, probably resulting in enhanced feedback inhibition within cortical circuits (By similarity).
The excitatory and inhibitory balance in neurons affects a number of processes, such as short-term and long-term memory, acquisition of experience, fear memory, response to stress and social behavior (By similarity).
Acts as a regulator of dendritic spine development in olfactory bulb granule cells in a sensory-experience-dependent manner by regulating expression of MDM2 (By similarity).
Efficient DNA binding requires dimerization with another bHLH protein, such as ARNT, ARNT2 or BMAL1 (PubMed:14701734).
Can activate the CME (CNS midline enhancer) element (PubMed:14701734).

Biological Process

Cell differentiationIEA:UniProtKB-KW
Cellular response to corticosterone stimulusIEA:Ensembl
Excitatory postsynaptic potentialISS:UniProtKB
Inhibitory postsynaptic potentialISS:UniProtKB
Inhibitory synapse assemblyISS:UniProtKB
LearningISS:UniProtKB
Long-term memoryISS:UniProtKB
Positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of synaptic plasticityISS:UniProtKB
Regulation of synaptic transmission, GABAergicISS:UniProtKB
Regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIBA:GO_Central
Short-term memoryISS:UniProtKB
Social behaviorISS:UniProtKB

Cellular Location

Nucleus

PTM

Ubiquitinated, leading to degradation by the proteosome.