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Protein

Class E basic helix-loop-helix protein 41

Gene

Bhlhe41

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

Functioni

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.5 Publications

GO - Molecular functioni

  • bHLH transcription factor binding Source: BHF-UCL
  • E-box binding Source: BHF-UCL
  • histone deacetylase binding Source: BHF-UCL
  • MRF binding Source: BHF-UCL
  • protein heterodimerization activity Source: BHF-UCL
  • protein homodimerization activity Source: BHF-UCL
  • RNA polymerase II activating transcription factor binding Source: BHF-UCL
  • RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: BHF-UCL
  • RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription Source: BHF-UCL
  • RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Source: BHF-UCL
  • RNA polymerase II transcription factor binding transcription factor activity involved in negative regulation of transcription Source: BHF-UCL
  • sequence-specific DNA binding RNA polymerase II transcription factor activity Source: BHF-UCL
  • transcription corepressor activity Source: UniProtKB

GO - Biological processi

  • circadian regulation of gene expression Source: BHF-UCL
  • circadian rhythm Source: UniProtKB
  • negative regulation of myotube differentiation Source: BHF-UCL
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • negative regulation of transcription by competitive promoter binding Source: BHF-UCL
  • negative regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • transcription from RNA polymerase II promoter Source: GOC
Complete GO annotation...

Keywords - Molecular functioni

Repressor

Keywords - Biological processi

Biological rhythms, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiREACT_115781. Bmal1:Clock,Npas2 activates circadian gene expression.
REACT_344843. BMAL1:CLOCK,NPAS2 activates circadian gene expression.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:Bhlhe41
Synonyms:Bhlhb3, Dec2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 6

Organism-specific databases

MGIiMGI:1930704. Bhlhe41.

Subcellular locationi

  • Nucleus PROSITE-ProRule annotation

GO - Cellular componenti

  • nucleoplasm Source: Reactome
  • transcriptional repressor complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 410410Class E basic helix-loop-helix protein 41PRO_0000127148Add
BLAST

Proteomic databases

PRIDEiQ99PV5.

PTM databases

PhosphoSiteiQ99PV5.

Expressioni

Tissue specificityi

Expressed in skeletal muscle, brain and lung.

Inductioni

Expressed in a circdadian manner in the liver with a peak at ZT10.1 Publication

Gene expression databases

BgeeiQ99PV5.
ExpressionAtlasiQ99PV5. baseline and differential.
GenevisibleiQ99PV5. MM.

Interactioni

Subunit structurei

Homodimer. Interacts with CIART. Interacts with ARNTL/BMAL1 and RXRA.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CebpbP280335EBI-6143801,EBI-1029979

Protein-protein interaction databases

BioGridi219755. 3 interactions.
DIPiDIP-57696N.
IntActiQ99PV5. 21 interactions.
MINTiMINT-7012655.
STRINGi10090.ENSMUSP00000032386.

Structurei

3D structure databases

ProteinModelPortaliQ99PV5.
SMRiQ99PV5. Positions 36-100.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini44 – 9956bHLHPROSITE-ProRule annotationAdd
BLAST
Domaini131 – 16636OrangePROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi321 – 37353Ala/Gly-richAdd
BLAST

Sequence similaritiesi

Contains 1 bHLH (basic helix-loop-helix) domain.PROSITE-ProRule annotation
Contains 1 Orange domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiNOG235394.
GeneTreeiENSGT00510000046898.
HOGENOMiHOG000234381.
InParanoidiQ99PV5.
KOiK03730.
OMAiAYKLPHR.
OrthoDBiEOG75XGKZ.
PhylomeDBiQ99PV5.
TreeFamiTF330859.

Family and domain databases

Gene3Di4.10.280.10. 1 hit.
InterProiIPR011598. bHLH_dom.
IPR003650. Orange.
[Graphical view]
PfamiPF07527. Hairy_orange. 1 hit.
PF00010. HLH. 1 hit.
[Graphical view]
SMARTiSM00353. HLH. 1 hit.
SM00511. ORANGE. 1 hit.
[Graphical view]
SUPFAMiSSF47459. SSF47459. 1 hit.
PROSITEiPS50888. BHLH. 1 hit.
PS51054. ORANGE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q99PV5-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDEGIPHLQE RQLLEHRDFI GLDYSSLYMC KPKRSLKRDD TKDTYKLPHR
60 70 80 90 100
LIEKKRRDRI NECIAQLKDL LPEHLKLTTL GHLEKAVVLE LTLKHLKALT
110 120 130 140 150
ALTEQQHQKI IALQNGERSL KSPVQADLDA FHSGFQTCAK EVLQYLARFE
160 170 180 190 200
SWTPREPRCA QLVSHLHAVA TQLLTPQVPS GRGSGRAPCS AGAAAASGPE
210 220 230 240 250
RVARCVPVIQ RTQPGTEPEH DTDTDSGYGG EAEQGRAAVK QEPPGDSSPA
260 270 280 290 300
PKRPKLEARG ALLGPEPALL GSLVALGGGA PFAQPAAAPF CLPFYLLSPS
310 320 330 340 350
AAAYVQPWLD KSGLDKYLYP AAAAPFPLLY PGIPAAAAAA AAAAFPCLSS
360 370 380 390 400
VLSPPPEKAG ATAGAPFLAH EVAPPGPLRP QHAHSRTHLP RAVNPESSQE
410
DATQPAKDAP
Length:410
Mass (Da):43,946
Last modified:June 1, 2001 - v1
Checksum:i40A87281B08E233D
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB044090 mRNA. Translation: BAB21503.1.
CCDSiCCDS20697.1.
PIRiJC7584.
RefSeqiNP_001258697.1. NM_001271768.1.
NP_077789.1. NM_024469.2.
UniGeneiMm.154529.

Genome annotation databases

EnsembliENSMUST00000032386; ENSMUSP00000032386; ENSMUSG00000030256.
GeneIDi79362.
KEGGimmu:79362.
UCSCiuc009ert.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB044090 mRNA. Translation: BAB21503.1.
CCDSiCCDS20697.1.
PIRiJC7584.
RefSeqiNP_001258697.1. NM_001271768.1.
NP_077789.1. NM_024469.2.
UniGeneiMm.154529.

3D structure databases

ProteinModelPortaliQ99PV5.
SMRiQ99PV5. Positions 36-100.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi219755. 3 interactions.
DIPiDIP-57696N.
IntActiQ99PV5. 21 interactions.
MINTiMINT-7012655.
STRINGi10090.ENSMUSP00000032386.

PTM databases

PhosphoSiteiQ99PV5.

Proteomic databases

PRIDEiQ99PV5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000032386; ENSMUSP00000032386; ENSMUSG00000030256.
GeneIDi79362.
KEGGimmu:79362.
UCSCiuc009ert.1. mouse.

Organism-specific databases

CTDi79365.
MGIiMGI:1930704. Bhlhe41.

Phylogenomic databases

eggNOGiNOG235394.
GeneTreeiENSGT00510000046898.
HOGENOMiHOG000234381.
InParanoidiQ99PV5.
KOiK03730.
OMAiAYKLPHR.
OrthoDBiEOG75XGKZ.
PhylomeDBiQ99PV5.
TreeFamiTF330859.

Enzyme and pathway databases

ReactomeiREACT_115781. Bmal1:Clock,Npas2 activates circadian gene expression.
REACT_344843. BMAL1:CLOCK,NPAS2 activates circadian gene expression.

Miscellaneous databases

ChiTaRSiBhlhe41. mouse.
NextBioi349911.
PROiQ99PV5.
SOURCEiSearch...

Gene expression databases

BgeeiQ99PV5.
ExpressionAtlasiQ99PV5. baseline and differential.
GenevisibleiQ99PV5. MM.

Family and domain databases

Gene3Di4.10.280.10. 1 hit.
InterProiIPR011598. bHLH_dom.
IPR003650. Orange.
[Graphical view]
PfamiPF07527. Hairy_orange. 1 hit.
PF00010. HLH. 1 hit.
[Graphical view]
SMARTiSM00353. HLH. 1 hit.
SM00511. ORANGE. 1 hit.
[Graphical view]
SUPFAMiSSF47459. SSF47459. 1 hit.
PROSITEiPS50888. BHLH. 1 hit.
PS51054. ORANGE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  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. 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. 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. Cited for: FUNCTION, INTERACTION WITH CIART.

Entry informationi

Entry nameiBHE41_MOUSE
AccessioniPrimary (citable) accession number: Q99PV5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 5, 2002
Last sequence update: June 1, 2001
Last modified: June 24, 2015
This is version 111 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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.

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

External Data

Dasty 3

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 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.