Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Neuronal PAS domain-containing protein 4

Gene

NPAS4

Organism
Homo sapiens (Human)
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 (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).By similarity1 Publication

GO - Molecular functioni

GO - Biological processi

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):
Class E basic helix-loop-helix protein 79Curated
Short name:
bHLHe79Curated
HLH-PAS transcription factor NXF1 Publication
PAS domain-containing protein 10Curated
Gene namesi
Name:NPAS4Imported
Synonyms:BHLHE79Imported, NXF1 Publication, PASD10Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:18983. NPAS4.

Subcellular locationi

  • Nucleus PROSITE-ProRule annotationBy similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi266743.
OpenTargetsiENSG00000174576.
PharmGKBiPA142671254.

Polymorphism and mutation databases

BioMutaiNPAS4.
DMDMi74714317.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002482221 – 802Neuronal PAS domain-containing protein 4Add BLAST802

Post-translational modificationi

Ubiquitinated, leading to degradation by the proteosome.By similarity

Keywords - PTMi

Ubl conjugation

Proteomic databases

PaxDbiQ8IUM7.
PeptideAtlasiQ8IUM7.
PRIDEiQ8IUM7.

PTM databases

iPTMnetiQ8IUM7.

Expressioni

Tissue specificityi

Brain.1 Publication

Gene expression databases

BgeeiENSG00000174576.
CleanExiHS_NPAS4.
GenevisibleiQ8IUM7. HS.

Organism-specific databases

HPAiHPA039255.

Interactioni

Subunit structurei

Efficient DNA binding requires dimerization with another bHLH protein (PubMed:14701734, PubMed:24465693). Heterodimer; forms a heterodimer with ARNT, ARNT2 or BMAL1 (PubMed:14701734, PubMed:24465693).2 Publications

GO - Molecular functioni

  • protein heterodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi129335. 3 interactors.
STRINGi9606.ENSP00000311196.

Structurei

3D structure databases

ProteinModelPortaliQ8IUM7.
SMRiQ8IUM7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 53bHLHPROSITE-ProRule annotationAdd BLAST53
Domaini70 – 144PAS 1PROSITE-ProRule annotationAdd BLAST75
Domaini203 – 273PAS 2PROSITE-ProRule annotationAdd BLAST71
Domaini278 – 317PACAdd 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.
InParanoidiQ8IUM7.
OMAiQAKPGGW.
OrthoDBiEOG091G0X71.
PhylomeDBiQ8IUM7.
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]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8IUM7-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« 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 VRQQLTLPSA LDTDRLFRCR
160 170 180 190 200
FNTSKSLRRQ SAGNKLVLIR GRFHAHPPGA YWAGNPVFTA FCAPLEPRPR
210 220 230 240 250
PGPGPGPGPA SLFLAMFQSR HAKDLALLDI SESVLIYLGF ERSELLCKSW
260 270 280 290 300
YGLLHPEDLA HASAQHYRLL AESGDIQAEM VVRLQAKTGG WAWIYCLLYS
310 320 330 340 350
EGPEGPITAN NYPISDMEAW SLRQQLNSED TQAAYVLGTP TMLPSFPENI
360 370 380 390 400
LSQEECSSTN PLFTAALGAP RSTSFPSAPE LSVVSASEEL PRPSKELDFS
410 420 430 440 450
YLTFPSGPEP SLQAELSKDL VCTPPYTPHQ PGGCAFLFSL HEPFQTHLPT
460 470 480 490 500
PSSTLQEQLT PSTATFSDQL TPSSATFPDP LTSPLQGQLT ETSVRSYEDQ
510 520 530 540 550
LTPCTSTFPD QLLPSTATFP EPLGSPAHEQ LTPPSTAFQA HLDSPSQTFP
560 570 580 590 600
EQLSPNPTKT YFAQEGCSFL YEKLPPSPSS PGNGDCTLLA LAQLRGPLSV
610 620 630 640 650
DVPLVPEGLL TPEASPVKQS FFHYSEKEQN EIDRLIQQIS QLAQGMDRPF
660 670 680 690 700
SAEAGTGGLE PLGGLEPLDS NLSLSGAGPP VLSLDLKPWK CQELDFLADP
710 720 730 740 750
DNMFLEETPV EDIFMDLSTP DPSEEWGSGD PEAEGPGGAP SPCNNLSPED
760 770 780 790 800
HSFLEDLATY ETAFETGVSA FPYDGFTDEL HQLQSQVQDS FHEDGSGGEP

TF
Length:802
Mass (Da):87,117
Last modified:March 1, 2003 - v1
Checksum:i0F5CB6486D0813F0
GO
Isoform 2 (identifier: Q8IUM7-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     234-234: V → G
     235-802: Missing.

Note: No experimental confirmation available.
Show »
Length:234
Mass (Da):25,492
Checksum:i8B9AD615FF7D9E0F
GO

Sequence cautioni

The sequence BAC04271 differs from that shown. Reason: Frameshift at position 681.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti72Q → R in BAC04738 (PubMed:14702039).Curated1
Sequence conflicti99E → K in BAC04738 (PubMed:14702039).Curated1
Sequence conflicti390L → H in BAC04738 (PubMed:14702039).Curated1
Sequence conflicti479D → G in BAC04271 (PubMed:14702039).Curated1
Sequence conflicti663G → E in BAC04271 (PubMed:14702039).Curated1
Sequence conflicti707E → K in BAC04271 (PubMed:14702039).Curated1
Sequence conflicti777T → A in BAC04271 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_076845147F → S Polymorphism; decreased transcription factor activity due to impaired interaction with ARNT2. 1 Publication1
Natural variantiVAR_076846208G → C Polymorphism; does not affect the transcription factor activity. 1 Publication1
Natural variantiVAR_076847257E → K Polymorphism; decreased transcription factor activity. 1 Publication1
Natural variantiVAR_076848293W → R Polymorphism; does not affect the transcription factor activity. 1 Publication1
Natural variantiVAR_076849296C → R Polymorphism; does not affect the transcription factor activity. 1 Publication1
Natural variantiVAR_076850317M → L Polymorphism; does not affect the transcription factor activity. 1 Publication1
Natural variantiVAR_076851344P → A Polymorphism; does not affect the transcription factor activity. 1 Publication1
Natural variantiVAR_076852359T → I Polymorphism; does not affect the transcription factor activity. 1 Publication1
Natural variantiVAR_076853472P → S Polymorphism; does not affect the transcription factor activity. 1 Publication1
Natural variantiVAR_076854500Q → K Polymorphism; does not affect the transcription factor activity. 1 Publication1
Natural variantiVAR_076855587T → M Polymorphism; does not affect the transcription factor activity. 1 Publication1
Natural variantiVAR_076856702N → D Polymorphism; does not affect the transcription factor activity. 1 Publication1
Natural variantiVAR_076857750D → Y Polymorphism; does not affect the transcription factor activity. 1 Publication1
Natural variantiVAR_076858777T → I Polymorphism; does not affect the transcription factor activity. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_056596234V → G in isoform 2. 1 Publication1
Alternative sequenceiVSP_056597235 – 802Missing in isoform 2. 1 PublicationAdd BLAST568

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB049469 mRNA. Translation: BAC19830.1.
AK094025 mRNA. Translation: BAC04271.1. Frameshift.
AK096253 mRNA. Translation: BAC04738.1.
AP001107 Genomic DNA. No translation available.
BC105001 mRNA. Translation: AAI05002.1.
BC105003 mRNA. Translation: AAI05004.1.
BC143630 mRNA. Translation: AAI43631.1.
CCDSiCCDS8138.1. [Q8IUM7-1]
RefSeqiNP_001305733.1. NM_001318804.1.
NP_849195.2. NM_178864.3. [Q8IUM7-1]
XP_016873028.1. XM_017017539.1. [Q8IUM7-3]
UniGeneiHs.256036.

Genome annotation databases

EnsembliENST00000311034; ENSP00000311196; ENSG00000174576. [Q8IUM7-1]
ENST00000525148; ENSP00000433135; ENSG00000174576. [Q8IUM7-3]
GeneIDi266743.
KEGGihsa:266743.
UCSCiuc001ohx.2. human. [Q8IUM7-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB049469 mRNA. Translation: BAC19830.1.
AK094025 mRNA. Translation: BAC04271.1. Frameshift.
AK096253 mRNA. Translation: BAC04738.1.
AP001107 Genomic DNA. No translation available.
BC105001 mRNA. Translation: AAI05002.1.
BC105003 mRNA. Translation: AAI05004.1.
BC143630 mRNA. Translation: AAI43631.1.
CCDSiCCDS8138.1. [Q8IUM7-1]
RefSeqiNP_001305733.1. NM_001318804.1.
NP_849195.2. NM_178864.3. [Q8IUM7-1]
XP_016873028.1. XM_017017539.1. [Q8IUM7-3]
UniGeneiHs.256036.

3D structure databases

ProteinModelPortaliQ8IUM7.
SMRiQ8IUM7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi129335. 3 interactors.
STRINGi9606.ENSP00000311196.

PTM databases

iPTMnetiQ8IUM7.

Polymorphism and mutation databases

BioMutaiNPAS4.
DMDMi74714317.

Proteomic databases

PaxDbiQ8IUM7.
PeptideAtlasiQ8IUM7.
PRIDEiQ8IUM7.

Protocols and materials databases

DNASUi266743.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000311034; ENSP00000311196; ENSG00000174576. [Q8IUM7-1]
ENST00000525148; ENSP00000433135; ENSG00000174576. [Q8IUM7-3]
GeneIDi266743.
KEGGihsa:266743.
UCSCiuc001ohx.2. human. [Q8IUM7-1]

Organism-specific databases

CTDi266743.
DisGeNETi266743.
GeneCardsiNPAS4.
HGNCiHGNC:18983. NPAS4.
HPAiHPA039255.
MIMi608554. gene.
neXtProtiNX_Q8IUM7.
OpenTargetsiENSG00000174576.
PharmGKBiPA142671254.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IISB. Eukaryota.
ENOG4110GBU. LUCA.
GeneTreeiENSGT00530000064165.
HOGENOMiHOG000113839.
HOVERGENiHBG082054.
InParanoidiQ8IUM7.
OMAiQAKPGGW.
OrthoDBiEOG091G0X71.
PhylomeDBiQ8IUM7.
TreeFamiTF319684.

Miscellaneous databases

GenomeRNAii266743.
PROiQ8IUM7.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000174576.
CleanExiHS_NPAS4.
GenevisibleiQ8IUM7. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: Q8IUM7
Secondary accession number(s): B7ZL81, Q8N8S5, Q8N9Q9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 5, 2006
Last sequence update: March 1, 2003
Last modified: November 30, 2016
This is version 115 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. 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.