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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

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.

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 transcription factor activity, sequence-specific DNA binding Source: BHF-UCL
  • transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding Source: BHF-UCL
  • transcriptional repressor activity, RNA polymerase II transcription factor binding Source: BHF-UCL
  • transcription corepressor activity Source: UniProtKB
  • transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding Source: BHF-UCL

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, DNA-templated Source: UniProtKB-KW

Keywordsi

Molecular functionDNA-binding, Repressor
Biological processBiological rhythms, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-MMU-1368108. BMAL1:CLOCK,NPAS2 activates circadian gene expression.
R-MMU-1368110. 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 6

Organism-specific databases

MGIiMGI:1930704. Bhlhe41.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001271481 – 410Class E basic helix-loop-helix protein 41Add BLAST410

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki31Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki121Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki240Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity

Keywords - PTMi

Isopeptide bond, Ubl conjugation

Proteomic databases

MaxQBiQ99PV5.
PaxDbiQ99PV5.
PRIDEiQ99PV5.

PTM databases

iPTMnetiQ99PV5.
PhosphoSitePlusiQ99PV5.

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

BgeeiENSMUSG00000030256.
ExpressionAtlasiQ99PV5. baseline and differential.
GenevisibleiQ99PV5. MM.

Interactioni

Subunit structurei

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

Binary interactionsi

Show more details

GO - Molecular functioni

  • bHLH transcription factor 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

Protein-protein interaction databases

BioGridi219755. 3 interactors.
DIPiDIP-57696N.
IntActiQ99PV5. 25 interactors.
MINTiMINT-7012655.
STRINGi10090.ENSMUSP00000032386.

Structurei

3D structure databases

ProteinModelPortaliQ99PV5.
SMRiQ99PV5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini44 – 99bHLHPROSITE-ProRule annotationAdd BLAST56
Domaini131 – 166OrangePROSITE-ProRule annotationAdd BLAST36

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi321 – 373Ala/Gly-richAdd BLAST53

Phylogenomic databases

eggNOGiKOG4304. Eukaryota.
ENOG4111F0X. LUCA.
GeneTreeiENSGT00510000046898.
HOGENOMiHOG000234381.
InParanoidiQ99PV5.
KOiK03730.
OMAiLYMCKSK.
OrthoDBiEOG091G0D3I.
PhylomeDBiQ99PV5.
TreeFamiTF330859.

Family and domain databases

CDDicd00083. HLH. 1 hit.
Gene3Di4.10.280.10. 1 hit.
InterProiView protein in InterPro
IPR011598. bHLH_dom.
IPR036638. HLH_DNA-bd_sf.
IPR003650. Orange_dom.
PfamiView protein in Pfam
PF07527. Hairy_orange. 1 hit.
PF00010. HLH. 1 hit.
SMARTiView protein in SMART
SM00353. HLH. 1 hit.
SM00511. ORANGE. 1 hit.
SUPFAMiSSF47459. SSF47459. 1 hit.
PROSITEiView protein in PROSITE
PS50888. BHLH. 1 hit.
PS51054. ORANGE. 1 hit.

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.2. mouse.

Similar proteinsi

Entry informationi

Entry nameiBHE41_MOUSE
AccessioniPrimary (citable) accession number: Q99PV5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 5, 2002
Last sequence update: June 1, 2001
Last modified: October 25, 2017
This is version 129 of the entry and version 1 of the sequence. See 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