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Protein

Neuronal PAS domain-containing protein 4

Gene

Npas4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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
  • protein heterodimerization activity Source: MGI
  • RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: UniProtKB
  • RNA polymerase II regulatory region DNA binding Source: MGI
  • RNA polymerase II transcription factor activity, sequence-specific DNA binding Source: UniProtKB
  • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding Source: MGI

GO - Biological processi

  • cell differentiation Source: UniProtKB-KW
  • cellular response to corticosterone stimulus Source: MGI
  • excitatory postsynaptic potential Source: UniProtKB
  • inhibitory postsynaptic potential Source: UniProtKB
  • inhibitory synapse assembly Source: UniProtKB
  • learning Source: UniProtKB
  • long-term memory Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • regulation of synaptic plasticity Source: UniProtKB
  • regulation of synaptic transmission, GABAergic Source: UniProtKB
  • short-term memory Source: UniProtKB
  • social behavior Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Differentiation, Neurogenesis, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 19

Organism-specific databases

MGIiMGI:2664186. Npas4.

Subcellular locationi

GO - Cellular componenti

  • nucleus Source: MGI
  • postsynapse Source: GOC
  • transcription factor complex Source: MGI
Complete GO annotation...

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 keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002482231 – 802Neuronal PAS domain-containing protein 4Add BLAST802

Post-translational modificationi

Ubiquitinated, leading to degradation by the proteosome.1 Publication

Keywords - PTMi

Ubl conjugation

Proteomic databases

PaxDbiQ8BGD7.
PRIDEiQ8BGD7.

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

BgeeiENSMUSG00000045903.
CleanExiMM_NPAS4.
GenevisibleiQ8BGD7. 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).3 Publications

GO - Molecular functioni

  • protein heterodimerization activity Source: MGI

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000062992.

Structurei

3D structure databases

ProteinModelPortaliQ8BGD7.
SMRiQ8BGD7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 53bHLHPROSITE-ProRule annotationAdd BLAST53
Domaini70 – 144PAS 1PROSITE-ProRule annotationAdd BLAST75
Domaini203 – 275PAS 2PROSITE-ProRule annotationAdd BLAST73
Domaini280 – 319PACAdd BLAST40

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 13Basic motif; degeneratePROSITE-ProRule annotationAdd BLAST13
Regioni14 – 53Helix-loop-helix motifPROSITE-ProRule annotationAdd BLAST40

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili5 – 38Sequence analysisAdd BLAST34
Coiled coili624 – 648Sequence analysisAdd BLAST25

Sequence similaritiesi

Contains 1 bHLH (basic helix-loop-helix) domain.PROSITE-ProRule annotation
Contains 2 PAS (PER-ARNT-SIM) domains.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil, Repeat

Phylogenomic databases

eggNOGiENOG410IISB. Eukaryota.
ENOG4110GBU. LUCA.
GeneTreeiENSGT00530000064165.
HOGENOMiHOG000113839.
HOVERGENiHBG082054.
InParanoidiQ8BGD7.
OMAiQAKPGGW.
OrthoDBiEOG091G0X71.
PhylomeDBiQ8BGD7.
TreeFamiTF319684.

Family and domain databases

Gene3Di4.10.280.10. 1 hit.
InterProiIPR011598. bHLH_dom.
IPR000014. PAS.
IPR013655. PAS_fold_3.
[Graphical view]
PfamiPF08447. PAS_3. 1 hit.
[Graphical view]
SMARTiSM00091. PAS. 2 hits.
[Graphical view]
SUPFAMiSSF55785. SSF55785. 2 hits.
PROSITEiPS50888. BHLH. 1 hit.
PS50112. PAS. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q8BGD7-1 [UniParc]FASTAAdd 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.
CCDSiCCDS29445.1.
RefSeqiNP_705781.1. NM_153553.4.
XP_006531783.1. XM_006531720.3.
XP_006531784.1. XM_006531721.3.
XP_011246921.1. XM_011248619.2.
UniGeneiMm.287867.

Genome annotation databases

EnsembliENSMUST00000056129; ENSMUSP00000062992; ENSMUSG00000045903.
GeneIDi225872.
KEGGimmu:225872.
UCSCiuc008gbu.2. mouse.

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.
CCDSiCCDS29445.1.
RefSeqiNP_705781.1. NM_153553.4.
XP_006531783.1. XM_006531720.3.
XP_006531784.1. XM_006531721.3.
XP_011246921.1. XM_011248619.2.
UniGeneiMm.287867.

3D structure databases

ProteinModelPortaliQ8BGD7.
SMRiQ8BGD7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000062992.

Proteomic databases

PaxDbiQ8BGD7.
PRIDEiQ8BGD7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000056129; ENSMUSP00000062992; ENSMUSG00000045903.
GeneIDi225872.
KEGGimmu:225872.
UCSCiuc008gbu.2. mouse.

Organism-specific databases

CTDi266743.
MGIiMGI:2664186. Npas4.

Phylogenomic databases

eggNOGiENOG410IISB. Eukaryota.
ENOG4110GBU. LUCA.
GeneTreeiENSGT00530000064165.
HOGENOMiHOG000113839.
HOVERGENiHBG082054.
InParanoidiQ8BGD7.
OMAiQAKPGGW.
OrthoDBiEOG091G0X71.
PhylomeDBiQ8BGD7.
TreeFamiTF319684.

Miscellaneous databases

PROiQ8BGD7.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000045903.
CleanExiMM_NPAS4.
GenevisibleiQ8BGD7. MM.

Family and domain databases

Gene3Di4.10.280.10. 1 hit.
InterProiIPR011598. bHLH_dom.
IPR000014. PAS.
IPR013655. PAS_fold_3.
[Graphical view]
PfamiPF08447. PAS_3. 1 hit.
[Graphical view]
SMARTiSM00091. PAS. 2 hits.
[Graphical view]
SUPFAMiSSF55785. SSF55785. 2 hits.
PROSITEiPS50888. BHLH. 1 hit.
PS50112. PAS. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNPAS4_MOUSE
AccessioniPrimary (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 30, 2016
This is version 109 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.