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O35185

- BHE40_MOUSE

UniProt

O35185 - BHE40_MOUSE

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Protein

Class E basic helix-loop-helix protein 40

Gene

Bhlhe40

Organism
Mus musculus (Mouse)
Status
Reviewed - 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 PER1/2 and in turn is repressed by PER1/2 and CRY1/2. Represses the activity of the circadian transcriptional activator: CLOCK-ARNTL/BMAL1|ARNTL2/BMAL2 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 and NR1H3/LXRA transactivation activity. May function as a transcriptional factor for neuronal differentiation.3 Publications

GO - Molecular functioni

  1. DNA binding Source: MGI
  2. E-box binding Source: UniProtKB
  3. MRF binding Source: BHF-UCL
  4. protein heterodimerization activity Source: BHF-UCL
  5. RNA polymerase II activating transcription factor binding Source: BHF-UCL
  6. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription Source: BHF-UCL
  7. RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Source: BHF-UCL
  8. RNA polymerase II transcription factor binding transcription factor activity involved in negative regulation of transcription Source: Ensembl
  9. transcription corepressor activity Source: UniProtKB

GO - Biological processi

  1. circadian regulation of gene expression Source: BHF-UCL
  2. circadian rhythm Source: UniProtKB
  3. entrainment of circadian clock by photoperiod Source: BHF-UCL
  4. negative regulation of sequence-specific DNA binding transcription factor activity Source: Ensembl
  5. negative regulation of transcription, DNA-templated Source: MGI
  6. response to light stimulus Source: BHF-UCL
  7. 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_198620. BMAL1:CLOCK,NPAS2 activates circadian gene expression.

Names & Taxonomyi

Protein namesi
Recommended name:
Class E basic helix-loop-helix protein 40
Short name:
bHLHe40
Alternative name(s):
Class B basic helix-loop-helix protein 2
Short name:
bHLHb2
E47 interaction protein 1
Short name:
EIP1
Stimulated by retinoic acid gene 13 protein
Gene namesi
Name:Bhlhe40
Synonyms:Bhlhb2, Clast5, Stra13
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 6

Organism-specific databases

MGIiMGI:1097714. Bhlhe40.

Subcellular locationi

Cytoplasm By similarity. Nucleus PROSITE-ProRule annotation. Nucleusnucleolus By similarity
Note: Predominantly localized in the nucleus.By similarity

GO - Cellular componenti

  1. Golgi apparatus Source: Ensembl
  2. nucleolus Source: Ensembl
  3. nucleoplasm Source: Reactome
  4. nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 411411Class E basic helix-loop-helix protein 40PRO_0000127145Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Cross-linki159 – 159Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1, SUMO2 and SUMO3)By similarity
Cross-linki279 – 279Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1, SUMO2 and SUMO3)By similarity

Post-translational modificationi

Ubiquitinated; which may lead to proteasomal degradation.By similarity
Sumoylation inhibits its ubiquitination and promotes its negative regulation of the CLOCK-ARNTL/BMAL1 heterodimer transcriptional activator activity.By similarity

Keywords - PTMi

Isopeptide bond, Ubl conjugation

Proteomic databases

MaxQBiO35185.
PRIDEiO35185.

PTM databases

PhosphoSiteiO35185.

Expressioni

Developmental stagei

Expressed from E9.5 day to E17.5 day in the ventricular layer of the brain and spinal cord, but also in the retinal pigment epithelium, developing eyelids, nasal epithelium, serous gland, vibrissae, epithelium of the mouth cavity and the tooth buds. Highly expressed in the heart, thymus and adrenal glands followed by lung, liver parenchyma, kidney tubules, epithelium of the esophagus and stomach. From E15.5 to E17.5 it is expressed in urinary bladder and urethra. From E17.5, it is expressed in developing muscle.

Inductioni

Stimulated by retinoic acid (RA). Expressed in a circadian manner in the liver with a peak at ZT10.1 Publication

Gene expression databases

BgeeiO35185.
CleanExiMM_STRA13.
ExpressionAtlasiO35185. baseline and differential.
GenevestigatoriO35185.

Interactioni

Subunit structurei

Homodimer. Heterodimer with BHLHE41/DEC2. Interacts with ubiquitin-conjugating enzyme UBE2I/UBC9. Interacts with HDAC1, SUMO1, RXRA and ARNTL/BMAL1 (By similarity). Interacts with TCF3/E47.By similarity1 Publication

Protein-protein interaction databases

BioGridi203554. 4 interactions.
IntActiO35185. 1 interaction.

Structurei

3D structure databases

ProteinModelPortaliO35185.
SMRiO35185. Positions 49-109.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini52 – 10756bHLHPROSITE-ProRule annotationAdd
BLAST
Domaini142 – 17534OrangePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 139139Essential for its interaction with ARNTL/BMAL1, E-box binding and repressor activity against the CLOCK-ARNTL/BMAL1 heterodimerBy similarityAdd
BLAST
Regioni75 – 795Necessary for its interaction with RXRA and repressor activity against RXRABy similarity

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiNOG281955.
HOGENOMiHOG000234381.
InParanoidiO35185.
KOiK03729.
OMAiEQPYFKS.
OrthoDBiEOG712TWC.
PhylomeDBiO35185.
TreeFamiTF330859.

Family and domain databases

Gene3Di4.10.280.10. 1 hit.
InterProiIPR011598. bHLH_dom.
IPR003650. Orange.
IPR018352. Orange_subgr.
[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.

O35185-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MERIPSAQPP PTCLPKAPGL EHGDLSGMDF AHMYQVYKSR RGIKRSEDSK
60 70 80 90 100
ETYKLPHRLI EKKRRDRINE CIAQLKDLLP EHLKLTTLGH LEKAVVLELT
110 120 130 140 150
LKHVKALTNL IDQQQQKIIA LQSGLQAGDL SGRNLEAGQE MFCSGFQTCA
160 170 180 190 200
REVLQYLAKH ENTRDLKSSQ LVTHLHRVVS ELLQGGASRK PLDSAPKAVD
210 220 230 240 250
LKEKPSFLAK GSEGPGKNCV PVIQRTFAPS GGEQSGSDTD TDSGYGGELE
260 270 280 290 300
KGDLRSEQPY FKSDHGRRFA VGERVSTIKQ ESEEPPTKKS RMQLSEEEGH
310 320 330 340 350
FAGSDLMGSP FLGPHPHQPP FCLPFYLIPP SATAYLPMLE KCWYPTSVPV
360 370 380 390 400
LYPGLNTSAA ALSSFMNPDK IPTPLLLPQR LPSPLAHSSL DSSALLQALK
410
QIPPLNLETK D
Length:411
Mass (Da):45,361
Last modified:January 1, 1998 - v1
Checksum:iB392893CD49292BC
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti288 – 2881K → T in CAA69169. (PubMed:9050988)Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF010305 mRNA. Translation: AAB64228.1.
Y07836 mRNA. Translation: CAA69169.1.
AF364051 mRNA. Translation: AAK50859.1.
BC010720 mRNA. Translation: AAH10720.1.
CCDSiCCDS20400.1.
RefSeqiNP_035628.1. NM_011498.4.
UniGeneiMm.2436.

Genome annotation databases

EnsembliENSMUST00000032194; ENSMUSP00000032194; ENSMUSG00000030103.
GeneIDi20893.
KEGGimmu:20893.
UCSCiuc009ddn.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF010305 mRNA. Translation: AAB64228.1 .
Y07836 mRNA. Translation: CAA69169.1 .
AF364051 mRNA. Translation: AAK50859.1 .
BC010720 mRNA. Translation: AAH10720.1 .
CCDSi CCDS20400.1.
RefSeqi NP_035628.1. NM_011498.4.
UniGenei Mm.2436.

3D structure databases

ProteinModelPortali O35185.
SMRi O35185. Positions 49-109.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 203554. 4 interactions.
IntActi O35185. 1 interaction.

PTM databases

PhosphoSitei O35185.

Proteomic databases

MaxQBi O35185.
PRIDEi O35185.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000032194 ; ENSMUSP00000032194 ; ENSMUSG00000030103 .
GeneIDi 20893.
KEGGi mmu:20893.
UCSCi uc009ddn.1. mouse.

Organism-specific databases

CTDi 8553.
MGIi MGI:1097714. Bhlhe40.

Phylogenomic databases

eggNOGi NOG281955.
HOGENOMi HOG000234381.
InParanoidi O35185.
KOi K03729.
OMAi EQPYFKS.
OrthoDBi EOG712TWC.
PhylomeDBi O35185.
TreeFami TF330859.

Enzyme and pathway databases

Reactomei REACT_115781. Bmal1:Clock,Npas2 activates circadian gene expression.
REACT_198620. BMAL1:CLOCK,NPAS2 activates circadian gene expression.

Miscellaneous databases

NextBioi 299753.
PROi O35185.
SOURCEi Search...

Gene expression databases

Bgeei O35185.
CleanExi MM_STRA13.
ExpressionAtlasi O35185. baseline and differential.
Genevestigatori O35185.

Family and domain databases

Gene3Di 4.10.280.10. 1 hit.
InterProi IPR011598. bHLH_dom.
IPR003650. Orange.
IPR018352. Orange_subgr.
[Graphical view ]
Pfami PF07527. Hairy_orange. 1 hit.
PF00010. HLH. 1 hit.
[Graphical view ]
SMARTi SM00353. HLH. 1 hit.
SM00511. ORANGE. 1 hit.
[Graphical view ]
SUPFAMi SSF47459. SSF47459. 1 hit.
PROSITEi PS50888. BHLH. 1 hit.
PS51054. ORANGE. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Overexpression of Stra13, a novel retinoic acid-inducible gene of the basic helix-loop-helix family, inhibits mesodermal and promotes neuronal differentiation of P19 cells."
    Boudjelal M., Taneja R., Matsubara S., Bouillet P., Dolle P., Chambon P.
    Genes Dev. 11:2052-2065(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Embryonic carcinoma.
  2. "Identification of interaction partners for the basic-helix-loop-helix protein E47."
    Dear T.N., Hainzl T., Follo M., Nehls M., Wilmore H., Matena K., Boehm T.
    Oncogene 14:891-898(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH TCF3/E47.
    Strain: BALB/c.
  3. "Isolation of a CD40-activated gene from murine splenic B cells."
    O-Wang J.
    Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: C57BL/6.
    Tissue: Spleen.
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Mammary gland.
  5. Cited for: FUNCTION.
  6. "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 BHLHE41/DEC2.
  7. Cited for: FUNCTION.
  8. "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.

Entry informationi

Entry nameiBHE40_MOUSE
AccessioniPrimary (citable) accession number: O35185
Secondary accession number(s): P97289
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 5, 2002
Last sequence update: January 1, 1998
Last modified: October 29, 2014
This is version 126 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

External Data

Dasty 3