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O35185

- BHE40_MOUSE

UniProt

O35185 - BHE40_MOUSE

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
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    • History
      Entry version 125 (01 Oct 2014)
      Sequence version 1 (01 Jan 1998)
      Previous versions | rss
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    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 binding Source: MGI
    5. protein heterodimerization activity Source: BHF-UCL
    6. RNA polymerase II activating transcription factor binding Source: BHF-UCL
    7. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription Source: BHF-UCL
    8. RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Source: BHF-UCL
    9. RNA polymerase II transcription factor binding transcription factor activity involved in negative regulation of transcription Source: Ensembl
    10. 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

    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: UniProtKB-SubCell
    3. nucleoplasm Source: Reactome
    4. nucleus Source: MGI

    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

    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

    ArrayExpressiO35185.
    BgeeiO35185.
    CleanExiMM_STRA13.
    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

    MERIPSAQPP PTCLPKAPGL EHGDLSGMDF AHMYQVYKSR RGIKRSEDSK    50
    ETYKLPHRLI EKKRRDRINE CIAQLKDLLP EHLKLTTLGH LEKAVVLELT 100
    LKHVKALTNL IDQQQQKIIA LQSGLQAGDL SGRNLEAGQE MFCSGFQTCA 150
    REVLQYLAKH ENTRDLKSSQ LVTHLHRVVS ELLQGGASRK PLDSAPKAVD 200
    LKEKPSFLAK GSEGPGKNCV PVIQRTFAPS GGEQSGSDTD TDSGYGGELE 250
    KGDLRSEQPY FKSDHGRRFA VGERVSTIKQ ESEEPPTKKS RMQLSEEEGH 300
    FAGSDLMGSP FLGPHPHQPP FCLPFYLIPP SATAYLPMLE KCWYPTSVPV 350
    LYPGLNTSAA ALSSFMNPDK IPTPLLLPQR LPSPLAHSSL DSSALLQALK 400
    QIPPLNLETK D 411
    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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

    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

    ArrayExpressi O35185.
    Bgeei O35185.
    CleanExi MM_STRA13.
    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

    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 1, 2014
    This is version 125 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