Npas4

Functionⁱ

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 hyppocampus (PubMed:18815592, PubMed:22194569, PubMed:23029555, PubMed:24201284, PubMed:24855953). Plays a key role in the structural and functional plasticity of neurons (PubMed:23172225). 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 (PubMed:24201284, PubMed:24855953). 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 (PubMed:18815592, PubMed:22194569, PubMed:24201284). 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 (PubMed:24855953). 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 (PubMed:18815592, PubMed:22194569, PubMed:23029555, PubMed:24201284, PubMed:27238022). Acts as a regulator of dendritic spine development in olfactory bulb granule cells in a sensory-experience-dependent manner by regulating expression of MDM2 (PubMed:25088421). Efficient DNA binding requires dimerization with another bHLH protein, such as ARNT, ARNT2 or BMAL1 (PubMed:14701734, PubMed:15363889, PubMed:19284974). Can activate the CME (CNS midline enhancer) element (PubMed:14701734, PubMed:15363889).10 Publications

GO - Molecular functionⁱ

DNA binding
Source: MGI
Inferred from direct assayⁱ
- 14701734
DNA-binding transcription factor activity, RNA polymerase II-specific
Source: UniProtKB
Inferred from mutant phenotypeⁱ
protein heterodimerization activity
Source: UniProtKB
Inferred from direct assayⁱ
- 27782878
proximal promoter DNA-binding transcription activator activity, RNA polymerase II-specific Source: MGI
RNA polymerase II proximal promoter sequence-specific DNA binding
Source: UniProtKB
Inferred from direct assayⁱ
- 22194569
RNA polymerase II regulatory region DNA binding
Source: MGI
Inferred from direct assayⁱ
- 24201284

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

cell differentiation Source: UniProtKB-KW
cellular response to corticosterone stimulus
Source: MGI
Inferred from direct assayⁱ
- 20626564
excitatory postsynaptic potential
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 24855953
inhibitory postsynaptic potential
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 18815592
- 24855953
inhibitory synapse assembly
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 18815592
learning
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 22194569
long-term memory
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 22194569
- 23029555
positive regulation of transcription, DNA-templated
Source: MGI
Inferred from direct assayⁱ
- 15363889
positive regulation of transcription by RNA polymerase II
Source: MGI
Inferred from direct assayⁱ
- 14701734
regulation of synaptic plasticity
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 18815592
regulation of synaptic transmission, GABAergic
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 18815592
regulation of transcription by RNA polymerase II
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
short-term memory
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 22194569
social behavior
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 23029555

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Activator, DNA-binding
Biological process	Differentiation, Neurogenesis, Transcription, Transcription regulation

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Neuronal PAS domain-containing protein 4Curated Short name: Neuronal PAS4Curated Alternative name(s): HLH-PAS transcription factor NXF1 Publication Limbic-enhanced PAS protein1 Publication Short name: LE-PAS1 Publication
Gene namesⁱ	Name:Npas4Imported Synonyms:Nxf1 Publication
Organismⁱ	Mus musculus (Mouse)
Taxonomic identifierⁱ	10090 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus
Proteomesⁱ	UP000000589 Componentⁱ: Chromosome 19

Organism-specific databases

MGIⁱ	MGI:2664186 Npas4

Keywords - Cellular componentⁱ

Nucleus

Pathology & Biotechⁱ

Disruption phenotypeⁱ

Mice appear anxious and hyperactive, are prone to seizures and have a shortened lifespan compared with their wild-type littermates (PubMed:18815592, PubMed:19001414, PubMed:23029555, PubMed:25549857). Mice show learning and memory deficits: while having intact memories 5 minutes after training, memory is significantly reduced one hour or 24 hours following training, suggesting that both short-term memory and long-term memory are impaired (PubMed:22194569). Mice show social and cognitive defects: they are hyperactive in a novel environment, spend less time exploring, show higher social dominance than their wild-type littermates and display pre-pulse inhibition, working memory, long-term memory and cognitive flexibility deficits (PubMed:23029555). When exposed to an enriched environment, a significantly less frequent and slightly smaller amplitude inhibitory postsynaptic current is observed (PubMed:24201284). Mice show a reduction in the dendritic spine density in olfactory bulb granule cells, leading to impaired odor discrimination learning (PubMed:25088421). Mice also show increased vulnerability to juvenile stress: mice exposed to chronic mild stress during adolescence, but not during adulthood, develop prefrontal cortex-dependent cognitive deficits in adulthood (PubMed:25911220).8 Publications

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000248223	1 – 802	Neuronal PAS domain-containing protein 4Add BLAST		802

Post-translational modificationⁱ

Ubiquitinated, leading to degradation by the proteosome.1 Publication

Keywords - PTMⁱ

Ubl conjugation

Proteomic databases

PaxDbⁱ	Q8BGD7
PRIDEⁱ	Q8BGD7

Expressionⁱ

Tissue specificityⁱ

Mainly expressed in brain (PubMed:14701734, PubMed:15363889). Expressed in the limbic system and olfactory bulb (PubMed:15363889, PubMed:25088421). Specifically expressed in CA1 and CA3 region of the hippocampus after contextual learning (at protein level) (PubMed:22194569, PubMed:23029555). Also expressed in pancreatic beta cells (PubMed:26663079).6 Publications

Inductionⁱ

Induced upon calcium influx (PubMed:26663079). Expression is regulated by neuronal activity (at protein level) (PubMed:18815592, PubMed:22194569, PubMed:24201284, PubMed:24855953). Induced in CA3 region of the hippocampus after contextual learning (PubMed:22194569). Induced following sensory input in newborn olfactory bulb interneurons (PubMed:25088421). Induced in the medial prefrontal cortex cells of the brain following experiences with positive valence (PubMed:27238022). Induced in pancreatic beta cells in response to calcium influx (PubMed:26663079). Down-regulated by REST (PubMed:24291638). Transcripts are regulated by a subset of miRNAs, such as miR-203, miR-224 and miR-744, that bind to its 3'-UTR region and down-regulate its expression (PubMed:24291638, PubMed:27189618).9 Publications

Gene expression databases

Bgeeⁱ	ENSMUSG00000045903 Expressed in 50 organ(s), highest expression level in islet of Langerhans
CleanExⁱ	MM_NPAS4
Genevisibleⁱ	Q8BGD7 MM

Interactionⁱ

Subunit structureⁱ

Efficient DNA binding requires dimerization with another bHLH protein (PubMed:14701734, PubMed:15363889, PubMed:19284974). Heterodimer; forms a heterodimer with ARNT, ARNT2 or BMAL1 (PubMed:14701734, PubMed:15363889, PubMed:19284974).4 Publications

GO - Molecular functionⁱ

protein heterodimerization activity
Source: UniProtKB
Inferred from direct assayⁱ
- 27782878

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

STRINGⁱ	10090.ENSMUSP00000062992

STRINGⁱ

10090.ENSMUSP00000062992

Structureⁱ

3D structure databases

ProteinModelPortalⁱ	Q8BGD7
SMRⁱ	Q8BGD7
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Length
Domainⁱ	1 – 53	bHLHPROSITE-ProRule annotationAdd BLAST	53
Domainⁱ	70 – 144	PAS 1PROSITE-ProRule annotationAdd BLAST	75
Domainⁱ	203 – 275	PAS 2PROSITE-ProRule annotationAdd BLAST	73
Domainⁱ	280 – 319	PACAdd BLAST	40

Region

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Regionⁱ	1 – 13	Basic motif; degeneratePROSITE-ProRule annotationAdd BLAST		13
Regionⁱ	14 – 53	Helix-loop-helix motifPROSITE-ProRule annotationAdd BLAST		40

Coiled coil

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Coiled coilⁱ	5 – 38	Sequence analysisAdd BLAST		34
Coiled coilⁱ	624 – 648	Sequence analysisAdd BLAST		25

Keywords - Domainⁱ

Coiled coil, Repeat

Phylogenomic databases

eggNOGⁱ	ENOG410IISB Eukaryota ENOG4110GBU LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00530000064165
HOGENOMⁱ	HOG000113839
HOVERGENⁱ	HBG082054
InParanoidⁱ	Q8BGD7
OMAⁱ	PDPNGEW
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G0X71
PhylomeDBⁱ	Q8BGD7
TreeFamⁱ	TF319684

Family and domain databases

Conserved Domains Database More...CDDⁱ	cd00130 PAS, 2 hits
InterProⁱ	View protein in InterPro IPR011598 bHLH_dom IPR000014 PAS IPR035965 PAS-like_dom_sf IPR013655 PAS_fold_3
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF08447 PAS_3, 1 hit
SMARTⁱ	View protein in SMART SM00091 PAS, 2 hits
SUPFAMⁱ	SSF55785 SSF55785, 2 hits
PROSITEⁱ	View protein in PROSITE PS50888 BHLH, 1 hit PS50112 PAS, 2 hits

Sequenceⁱ

Sequence statusⁱ: Complete.

Q8BGD7-1 [UniParc]FASTA Add to basket

« Hide

        10         20         30         40         50
MYRSTKGASK ARRDQINAEI RNLKELLPLA EADKVRLSYL HIMSLACIYT 
        60         70         80         90        100
RKGVFFAGGT PLAGPTGLLS AQELEDIVAA LPGFLLVFTA EGKLLYLSES 
       110        120        130        140        150
VSEHLGHSMV DLVAQGDSIY DIIDPADHLT VRQQLTMPSA LDADRLFRCR 
       160        170        180        190        200
FNTSKSLRRQ SSGNKLVLIR GRFHAHPPGA YWAGNPVFTA FCAPLEPRPR 
       210        220        230        240        250
PGPGPGPGPG PASLFLAMFQ SRHAKDLALL DVSESVLIYL GFERSELLCK 
       260        270        280        290        300
SWYGLLHPED LAQASSQHYR LLAESGDIQA EMVVRLQAKH GGWTWIYCML 
       310        320        330        340        350
YSEGPEGPFT ANNYPISDTE AWSLRQQLNS EDTQAAYVLG TPAVLPSFSE 
       360        370        380        390        400
NVFSQEQCSN PLFTPSLGTP RSASFPRAPE LGVISTPEEL PQPSKELDFS 
       410        420        430        440        450
YLPFPARPEP SLQADLSKDL VCTPPYTPHQ PGGCAFLFSL HEPFQTHLPP 
       460        470        480        490        500
PSSSLQEQLT PSTVTFSEQL TPSSATFPDP LTSSLQGQLT ESSARSFEDQ 
       510        520        530        540        550
LTPCTSSFPD QLLPSTATFP EPLGSPAHEQ LTPPSTAFQA HLNSPSQTFP 
       560        570        580        590        600
EQLSPNPTKT YFAQEGCSFL YEKLPPSPSS PGNGDCTLLA LAQLRGPLSV 
       610        620        630        640        650
DVPLVPEGLL TPEASPVKQS FFHYTEKEQN EIDRLIQQIS QLAQGVDRPF 
       660        670        680        690        700
SAEAGTGGLE PLGGLEPLNP NLSLSGAGPP VLSLDLKPWK CQELDFLVDP 
       710        720        730        740        750
DNLFLEETPV EDIFMDLSTP DPNGEWGSGD PEAEVPGGTL SPCNNLSPED 
       760        770        780        790        800
HSFLEDLATY ETAFETGVST FPYEGFADEL HQLQSQVQDS FHEDGSGGEP 

TF

Length:802

Mass (Da):87,286

Last modified:March 1, 2003 - v1

Checksum:ⁱA38663C689FBEAB5

GO

Sequence cautionⁱ

The sequence BAE20480 differs from that shown. Reason: Frameshift at position 307.Curated

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	AB049835 mRNA Translation: BAC19831.1 AB054577 Genomic DNA Translation: BAC53755.1 AY730724 mRNA Translation: AAV28629.1 AK032607 mRNA Translation: BAE20480.1 Frameshift.
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS29445.1
NCBI Reference Sequences More...RefSeqⁱ	NP_705781.1, NM_153553.5 XP_006531783.1, XM_006531720.3 XP_006531784.1, XM_006531721.3 XP_011246921.1, XM_011248619.2
UniGeneⁱ	Mm.287867

Genome annotation databases

Ensemblⁱ	ENSMUST00000056129; ENSMUSP00000062992; ENSMUSG00000045903
GeneIDⁱ	225872
KEGGⁱ	mmu:225872
UCSC genome browser More...UCSCⁱ	uc008gbu.2 mouse

Similar proteinsⁱ

90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
Q8BGD7	Neuronal PAS domain-containing protein 4		HUMAN		802	UniRef90_Q8BGD7
Neuronal PAS domain-containing protein 4		RAT		802
Neuronal PAS domain-containing protein 4		FUKDA		972
Uncharacterized protein		PAPAN		816
Neuronal PAS domain-containing protein 4 (Fragment)		ESCRO		805
+122

Protein	Similar proteins		Species	Score	Length	Source
Q8BGD7	Neuronal PAS domain-containing protein 4		RAT		802	UniRef50_Q8BGD7
Neuronal PAS domain-containing protein 4		HUMAN		802
Neuronal PAS domain-containing protein 4		FUKDA		972
Uncharacterized protein		PAPAN		816
Neuronal PAS domain-containing protein 4 (Fragment)		ESCRO		805
+126

Cross-referencesⁱ

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	AB049835 mRNA Translation: BAC19831.1 AB054577 Genomic DNA Translation: BAC53755.1 AY730724 mRNA Translation: AAV28629.1 AK032607 mRNA Translation: BAE20480.1 Frameshift.
CCDSⁱ	CCDS29445.1
RefSeqⁱ	NP_705781.1, NM_153553.5 XP_006531783.1, XM_006531720.3 XP_006531784.1, XM_006531721.3 XP_011246921.1, XM_011248619.2
UniGeneⁱ	Mm.287867

3D structure databases

ProteinModelPortalⁱ	Q8BGD7
SMRⁱ	Q8BGD7
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

STRINGⁱ	10090.ENSMUSP00000062992

STRINGⁱ

10090.ENSMUSP00000062992

Proteomic databases

PaxDbⁱ	Q8BGD7
PRIDEⁱ	Q8BGD7

Protocols and materials databases

Structural Biology Knowledgebase	Search...

Structural Biology Knowledgebase

Search...

Genome annotation databases

Ensemblⁱ	ENSMUST00000056129; ENSMUSP00000062992; ENSMUSG00000045903
GeneIDⁱ	225872
KEGGⁱ	mmu:225872
UCSCⁱ	uc008gbu.2 mouse

Organism-specific databases

CTDⁱ	266743
MGIⁱ	MGI:2664186 Npas4

Phylogenomic databases

eggNOGⁱ	ENOG410IISB Eukaryota ENOG4110GBU LUCA
GeneTreeⁱ	ENSGT00530000064165
HOGENOMⁱ	HOG000113839
HOVERGENⁱ	HBG082054
InParanoidⁱ	Q8BGD7
OMAⁱ	PDPNGEW
OrthoDBⁱ	EOG091G0X71
PhylomeDBⁱ	Q8BGD7
TreeFamⁱ	TF319684

Miscellaneous databases

Protein Ontology More...PROⁱ	PR:Q8BGD7
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSMUSG00000045903 Expressed in 50 organ(s), highest expression level in islet of Langerhans
CleanExⁱ	MM_NPAS4
Genevisibleⁱ	Q8BGD7 MM

Family and domain databases

CDDⁱ	cd00130 PAS, 2 hits
InterProⁱ	View protein in InterPro IPR011598 bHLH_dom IPR000014 PAS IPR035965 PAS-like_dom_sf IPR013655 PAS_fold_3
Pfamⁱ	View protein in Pfam PF08447 PAS_3, 1 hit
SMARTⁱ	View protein in SMART SM00091 PAS, 2 hits
SUPFAMⁱ	SSF55785 SSF55785, 2 hits
PROSITEⁱ	View protein in PROSITE PS50888 BHLH, 1 hit PS50112 PAS, 2 hits
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	NPAS4_MOUSE
Accessionⁱ	Q8BGD7Primary (citable) accession number: Q8BGD7 Secondary accession number(s): Q3V3U3
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	September 5, 2006
	Last sequence update:	March 1, 2003
	Last modified:	November 7, 2018
	This is version 121 of the entry and version 1 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program

Miscellaneousⁱ

Keywords - Technical termⁱ

Complete proteome, Reference proteome

Documents

MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

UniProtKB

UniParc

Help

UniRef

Proteomes

Annotation systems

Supporting data

UniProtKB - Q8BGD7 (NPAS4_MOUSE)

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Neuronal PAS domain-containing protein 4

Select a section on the left to see content.

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Nucleus

Nucleus

Other locations

Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Keywords - PTMi

Proteomic databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

GO - Molecular functioni

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Region

Coiled coil

Keywords - Domaini

Phylogenomic databases

Family and domain databases

<p>This subsection of the ‘Sequence’ section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

Sequence databases

Genome annotation databases

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

3D structure databases

Protein-protein interaction databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

Documents

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Keywords - Domainⁱ

Sequence cautionⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ