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Q99PV5 (BHE41_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 104. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Class E basic helix-loop-helix protein 41

Short name=bHLHe41
Alternative name(s):
Class B basic helix-loop-helix protein 3
Short name=bHLHb3
Differentially expressed in chondrocytes protein 2
Short name=mDEC2
Gene names
Name:Bhlhe41
Synonyms:Bhlhb3, Dec2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length410 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Transcriptional repressor involved in the regulation of the circadian rhythm by negatively regulating the activity of the clock genes and clock-controlled genes. Acts as the negative limb of a novel autoregulatory feedback loop (DEC loop) which differs from the one formed by the PER and CRY transcriptional repressors (PER/CRY loop). Both these loops are interlocked as it represses the expression of PER1 and in turn is repressed by PER1/2 and CRY1/2. Represses the activity of the circadian transcriptional activator: CLOCK-ARNTL/BMAL1 heterodimer by competing for the binding to E-box elements (5'-CACGTG-3') found within the promoters of its target genes. Negatively regulates its own expression and the expression of DBP and BHLHE41/DEC2. Acts as a corepressor of RXR and the RXR-LXR heterodimers and represses the ligand-induced RXRA/B/G, NR1H3/LXRA, NR1H4 and VDR transactivation activity. Ref.2 Ref.3 Ref.5 Ref.6 Ref.8

Subunit structure

Homodimer. Interacts with CIART. Interacts with ARNTL/BMAL1 and RXRA. Ref.2 Ref.4 Ref.8

Subcellular location

Nucleus By similarity.

Tissue specificity

Expressed in skeletal muscle, brain and lung.

Induction

Expressed in a circdadian manner in the liver with a peak at ZT10. Ref.6

Miscellaneous

Activity profiles and sleep recordings of transgenic mice carrying the mutation Arg-325 show increased vigilance time and less sleep time than control mice in a zeitgeber time- and sleep deprivation-dependent manner.

Sequence similarities

Contains 1 bHLH (basic helix-loop-helix) domain.

Contains 1 Orange domain.

Ontologies

Keywords
   Biological processBiological rhythms
Transcription
Transcription regulation
   Cellular componentNucleus
   LigandDNA-binding
   Molecular functionRepressor
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcircadian regulation of gene expression

Inferred from mutant phenotype Ref.5. Source: BHF-UCL

circadian rhythm

Inferred from expression pattern. Source: BHF-UCL

negative regulation of myotube differentiation

Inferred from direct assay PubMed 12657651. Source: BHF-UCL

negative regulation of transcription by competitive promoter binding

Inferred from direct assay PubMed 12657651. Source: BHF-UCL

negative regulation of transcription from RNA polymerase II promoter

Inferred from direct assay Ref.2. Source: BHF-UCL

negative regulation of transcription, DNA-templated

Inferred from direct assay Ref.2Ref.8. Source: UniProtKB

transcription from RNA polymerase II promoter

Inferred from direct assay Ref.2PubMed 15147242. Source: GOC

   Cellular_componentnucleoplasm

Traceable author statement. Source: Reactome

transcriptional repressor complex

Traceable author statement PubMed 12175508. Source: MGI

   Molecular_functionE-box binding

Inferred from direct assay Ref.2PubMed 12657651PubMed 15147242PubMed 17487425. Source: BHF-UCL

MRF binding

Inferred from direct assay PubMed 12657651PubMed 17487425. Source: BHF-UCL

RNA polymerase II activating transcription factor binding

Inferred from direct assay PubMed 17487425. Source: BHF-UCL

RNA polymerase II core promoter proximal region sequence-specific DNA binding

Inferred from direct assay PubMed 12657651. Source: BHF-UCL

RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription

Inferred from direct assay PubMed 12657651PubMed 15147242PubMed 17487425. Source: BHF-UCL

RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 15147242. Source: BHF-UCL

RNA polymerase II transcription factor binding transcription factor activity involved in negative regulation of transcription

Inferred from direct assay Ref.2PubMed 12657651. Source: BHF-UCL

bHLH transcription factor binding

Inferred from direct assay PubMed 12657651. Source: BHF-UCL

histone deacetylase binding

Inferred from direct assay PubMed 17487425. Source: BHF-UCL

protein binding

Inferred from physical interaction Ref.2Ref.8. Source: UniProtKB

protein heterodimerization activity

Inferred from direct assay PubMed 17487425. Source: BHF-UCL

protein homodimerization activity

Inferred from physical interaction PubMed 17487425. Source: BHF-UCL

sequence-specific DNA binding RNA polymerase II transcription factor activity

Inferred from direct assay Ref.2. Source: BHF-UCL

transcription corepressor activity

Traceable author statement. Source: MGI

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CebpbP280335EBI-6143801,EBI-1029979

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 410410Class E basic helix-loop-helix protein 41
PRO_0000127148

Regions

Domain44 – 9956bHLH
Domain131 – 16636Orange
Compositional bias321 – 37353Ala/Gly-rich

Sequences

Sequence LengthMass (Da)Tools
Q99PV5 [UniParc].

Last modified June 1, 2001. Version 1.
Checksum: 40A87281B08E233D

FASTA41043,946
        10         20         30         40         50         60 
MDEGIPHLQE RQLLEHRDFI GLDYSSLYMC KPKRSLKRDD TKDTYKLPHR LIEKKRRDRI 

        70         80         90        100        110        120 
NECIAQLKDL LPEHLKLTTL GHLEKAVVLE LTLKHLKALT ALTEQQHQKI IALQNGERSL 

       130        140        150        160        170        180 
KSPVQADLDA FHSGFQTCAK EVLQYLARFE SWTPREPRCA QLVSHLHAVA TQLLTPQVPS 

       190        200        210        220        230        240 
GRGSGRAPCS AGAAAASGPE RVARCVPVIQ RTQPGTEPEH DTDTDSGYGG EAEQGRAAVK 

       250        260        270        280        290        300 
QEPPGDSSPA PKRPKLEARG ALLGPEPALL GSLVALGGGA PFAQPAAAPF CLPFYLLSPS 

       310        320        330        340        350        360 
AAAYVQPWLD KSGLDKYLYP AAAAPFPLLY PGIPAAAAAA AAAAFPCLSS VLSPPPEKAG 

       370        380        390        400        410 
ATAGAPFLAH EVAPPGPLRP QHAHSRTHLP RAVNPESSQE DATQPAKDAP 

« Hide

References

[1]"Molecular cloning and characterization of DEC2, a new member of basic helix-loop-helix proteins."
Fujimoto K., Shen M., Noshiro M., Matsubara K., Shingu S., Honda K., Yoshida E., Suardita K., Matsuda Y., Kato Y.
Biochem. Biophys. Res. Commun. 280:164-171(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Dec1 and Dec2 are regulators of the mammalian molecular clock."
Honma S., Kawamoto T., Takagi Y., Fujimoto K., Sato F., Noshiro M., Kato Y., Honma K.I.
Nature 419:841-844(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ARNTL.
[3]"A novel autofeedback loop of Dec1 transcription involved in circadian rhythm regulation."
Kawamoto T., Noshiro M., Sato F., Maemura K., Takeda N., Nagai R., Iwata T., Fujimoto K., Furukawa M., Miyazaki K., Honma S., Honma K.I., Kato Y.
Biochem. Biophys. Res. Commun. 313:117-124(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[4]"Functional analysis of the basic helix-loop-helix transcription factor DEC1 in circadian regulation. Interaction with BMAL1."
Sato F., Kawamoto T., Fujimoto K., Noshiro M., Honda K.K., Honma S., Honma K., Kato Y.
Eur. J. Biochem. 271:4409-4419(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: HETERODIMERIZATION WITH BHLHE40.
[5]"DEC1 modulates the circadian phase of clock gene expression."
Nakashima A., Kawamoto T., Honda K.K., Ueshima T., Noshiro M., Iwata T., Fujimoto K., Kubo H., Honma S., Yorioka N., Kohno N., Kato Y.
Mol. Cell. Biol. 28:4080-4092(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[6]"The basic helix-loop-helix proteins differentiated embryo chondrocyte (DEC) 1 and DEC2 function as corepressors of retinoid X receptors."
Cho Y., Noshiro M., Choi M., Morita K., Kawamoto T., Fujimoto K., Kato Y., Makishima M.
Mol. Pharmacol. 76:1360-1369(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INDUCTION.
[7]"The transcriptional repressor DEC2 regulates sleep length in mammals."
He Y., Jones C.R., Fujiki N., Xu Y., Guo B., Holder J.L. Jr., Rossner M.J., Nishino S., Fu Y.H.
Science 325:866-870(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: TRANSGENIC MICE.
[8]"A novel protein, CHRONO, functions as a core component of the mammalian circadian clock."
Goriki A., Hatanaka F., Myung J., Kim J.K., Yoritaka T., Tanoue S., Abe T., Kiyonari H., Fujimoto K., Kato Y., Todo T., Matsubara A., Forger D., Takumi T.
PLoS Biol. 12:E1001839-E1001839(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CIART.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB044090 mRNA. Translation: BAB21503.1.
CCDSCCDS20697.1.
PIRJC7584.
RefSeqNP_001258697.1. NM_001271768.1.
NP_077789.1. NM_024469.2.
UniGeneMm.154529.

3D structure databases

ProteinModelPortalQ99PV5.
SMRQ99PV5. Positions 36-100.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid219755. 3 interactions.
DIPDIP-57696N.
IntActQ99PV5. 21 interactions.
MINTMINT-7012655.
STRING10090.ENSMUSP00000032386.

PTM databases

PhosphoSiteQ99PV5.

Proteomic databases

PRIDEQ99PV5.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000032386; ENSMUSP00000032386; ENSMUSG00000030256.
GeneID79362.
KEGGmmu:79362.
UCSCuc009ert.1. mouse.

Organism-specific databases

CTD79365.
MGIMGI:1930704. Bhlhe41.

Phylogenomic databases

eggNOGNOG235394.
GeneTreeENSGT00510000046898.
HOGENOMHOG000234381.
InParanoidQ99PV5.
KOK03730.
OMAAYKLPHR.
OrthoDBEOG75XGKZ.
PhylomeDBQ99PV5.
TreeFamTF330859.

Enzyme and pathway databases

ReactomeREACT_200794. Mus musculus biological processes.

Gene expression databases

ArrayExpressQ99PV5.
BgeeQ99PV5.
GenevestigatorQ99PV5.

Family and domain databases

Gene3D4.10.280.10. 1 hit.
InterProIPR011598. bHLH_dom.
IPR003650. Orange.
IPR018352. Orange_subgr.
[Graphical view]
PfamPF07527. Hairy_orange. 1 hit.
PF00010. HLH. 1 hit.
[Graphical view]
SMARTSM00353. HLH. 1 hit.
SM00511. ORANGE. 1 hit.
[Graphical view]
SUPFAMSSF47459. SSF47459. 1 hit.
PROSITEPS50888. BHLH. 1 hit.
PS51054. ORANGE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSBHLHE41. mouse.
NextBio349911.
PROQ99PV5.
SOURCESearch...

Entry information

Entry nameBHE41_MOUSE
AccessionPrimary (citable) accession number: Q99PV5
Entry history
Integrated into UniProtKB/Swiss-Prot: March 5, 2002
Last sequence update: June 1, 2001
Last modified: July 9, 2014
This is version 104 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

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