UniProtKB - O35780 (BHE40_RAT)
Class E basic helix-loop-helix protein 40
Bhlhe40
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 be involved in the regulation of chondrocyte differentiation via the cAMP pathway (By similarity).
Represses the transcription of NR0B2 and attentuates the transactivation of NR0B2 by the CLOCK-ARNTL/BMAL1 complex (By similarity).
Drives the circadian rhythm of blood pressure through transcriptional repression of ATP1B1 in the cardiovascular system (By similarity).
By similarityGO - Molecular functioni
- bHLH transcription factor binding Source: RGD
- DNA binding Source: RGD
- DNA-binding transcription factor activity, RNA polymerase II-specific Source: RGD
- DNA-binding transcription repressor activity, RNA polymerase II-specific Source: UniProtKB
- E-box binding Source: UniProtKB
- MRF binding Source: RGD
- protein domain specific binding Source: RGD
- protein heterodimerization activity Source: RGD
- protein homodimerization activity Source: RGD
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: RGD
- RNA polymerase II-specific DNA-binding transcription factor binding Source: RGD
- sequence-specific double-stranded DNA binding Source: RGD
GO - Biological processi
- anterior/posterior pattern specification Source: GO_Central
- circadian regulation of gene expression Source: UniProtKB
- circadian rhythm Source: UniProtKB
- entrainment of circadian clock by photoperiod Source: RGD
- negative regulation of DNA-binding transcription factor activity Source: RGD
- negative regulation of transcription, DNA-templated Source: UniProtKB
- negative regulation of transcription by RNA polymerase II Source: RGD
- nervous system development Source: RGD
- regulation of circadian rhythm Source: UniProtKB
- regulation of neurogenesis Source: GO_Central
- regulation of neuronal synaptic plasticity Source: RGD
- regulation of transcription by RNA polymerase II Source: GO_Central
- response to light stimulus Source: UniProtKB
Keywordsi
Molecular function | DNA-binding, Repressor |
Biological process | Biological rhythms, Transcription, Transcription regulation |
Names & Taxonomyi
Protein namesi | Recommended name: Class E basic helix-loop-helix protein 40Short name: bHLHe40 Alternative name(s): Class B basic helix-loop-helix protein 2 Short name: bHLHb2 Enhancer-of-split and hairy-related protein 2 Short name: SHARP-2 |
Gene namesi | Name:Bhlhe40 Synonyms:Bhlhb2, Sharp2 |
Organismi | Rattus norvegicus (Rat) |
Taxonomic identifieri | 10116 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus |
Proteomesi |
|
Organism-specific databases
RGDi | 68439, Bhlhe40 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000127146 | 1 – 411 | Class E basic helix-loop-helix protein 40Add BLAST | 411 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Cross-linki | 159 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1, SUMO2 and SUMO3)By similarity | ||
Cross-linki | 167 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity | ||
Modified residuei | 235 | PhosphoserineBy similarity | 1 | |
Cross-linki | 279 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternateBy similarity | ||
Cross-linki | 279 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1, SUMO2 and SUMO3); alternateBy similarity | ||
Cross-linki | 279 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity | ||
Cross-linki | 288 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity | ||
Modified residuei | 383 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
Keywords - PTMi
Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
PaxDbi | O35780 |
PRIDEi | O35780 |
PTM databases
iPTMneti | O35780 |
PhosphoSitePlusi | O35780 |
Expressioni
Tissue specificityi
Inductioni
Interactioni
Subunit structurei
Homodimer. Heterodimer with BHLHE41/DEC2.
Interacts with TCF3/E47.
Interacts with ubiquitin-conjugating enzyme UBE2I/UBC9.
Interacts with HDAC1, SUMO1, RXRA and ARNTL/BMAL1 (By similarity).
By similarityGO - Molecular functioni
- bHLH transcription factor binding Source: RGD
- MRF binding Source: RGD
- protein domain specific binding Source: RGD
- protein heterodimerization activity Source: RGD
- protein homodimerization activity Source: RGD
- RNA polymerase II-specific DNA-binding transcription factor binding Source: RGD
Protein-protein interaction databases
STRINGi | 10116.ENSRNOP00000009564 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 52 – 107 | bHLHPROSITE-ProRule annotationAdd BLAST | 56 | |
Domaini | 142 – 175 | OrangePROSITE-ProRule annotationAdd BLAST | 34 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 139 | Essential for interaction with ARNTL/BMAL1, E-box binding and repressor activity against the CLOCK-ARNTL/BMAL1 heterodimerBy similarityAdd BLAST | 139 | |
Regioni | 1 – 21 | DisorderedSequence analysisAdd BLAST | 21 | |
Regioni | 75 – 79 | Necessary for interaction with RXRA and repressor activity against RXRABy similarity | 5 | |
Regioni | 186 – 293 | DisorderedSequence analysisAdd BLAST | 108 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 228 – 242 | Polar residuesSequence analysisAdd BLAST | 15 | |
Compositional biasi | 244 – 293 | Basic and acidic residuesSequence analysisAdd BLAST | 50 |
Phylogenomic databases
eggNOGi | KOG4304, Eukaryota |
InParanoidi | O35780 |
OrthoDBi | 629563at2759 |
PhylomeDBi | O35780 |
Family and domain databases
Gene3Di | 4.10.280.10, 1 hit |
InterProi | View protein in InterPro IPR011598, bHLH_dom IPR036638, HLH_DNA-bd_sf IPR003650, Orange_dom |
Pfami | View protein in Pfam PF07527, Hairy_orange, 1 hit PF00010, HLH, 1 hit |
SMARTi | View protein in SMART SM00353, HLH, 1 hit SM00511, ORANGE, 1 hit |
SUPFAMi | SSF47459, SSF47459, 1 hit |
PROSITEi | View protein in PROSITE PS50888, BHLH, 1 hit PS51054, ORANGE, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
10 20 30 40 50
MERIPSAQPP PTCLPKTPGL EHGDLSGMDF AHMYQVYKSR RGIKRSEDSK
60 70 80 90 100
ETYKLPHRLI EKKRRDRINE CIAQLKDLLP EHLKLTTLGH LEKAVVLELT
110 120 130 140 150
LKHVKALTNL IDQQQQKIMA LQSGLQAGDL SGKNIEAGQE MFCSGFQTCA
160 170 180 190 200
REVLQYLAKH ENTRDLKSSQ LVTHLHRVVS ELLQGSASRK PLDSAPKPVD
210 220 230 240 250
FKEKPSFLAK GSEGPGKNCV PVIQRTFAPS GGEQSGSDTD TDSGYGGELE
260 270 280 290 300
KGDLRSEQPY FKSDHGRRFT VGERVSTIKQ ESEEPPTKKS RMQLSDEEGH
310 320 330 340 350
FVGSDLMGSP FLGPHPHQPP FCLPFYLIPP SATAYLPMLE KCWYPTSVPL
360 370 380 390 400
LYPGLNTSAA ALSSFMNPDK IPTPLLLPQR LPSPLAHSSL DSSALLQALK
410
QIPPLNLETK D
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketQ76JQ4 | Q76JQ4_RAT | Basic helix-loop-helix domain conta... | Bhlhe40 Bhlhb2, SHARP-2, rCG_56541 | 411 | Annotation score: |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF009330 mRNA Translation: AAB63587.1 |
RefSeqi | NP_445780.1, NM_053328.1 |
Genome annotation databases
GeneIDi | 79431 |
KEGGi | rno:79431 |
UCSCi | RGD:68439, rat |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF009330 mRNA Translation: AAB63587.1 |
RefSeqi | NP_445780.1, NM_053328.1 |
3D structure databases
SMRi | O35780 |
ModBasei | Search... |
Protein-protein interaction databases
STRINGi | 10116.ENSRNOP00000009564 |
PTM databases
iPTMneti | O35780 |
PhosphoSitePlusi | O35780 |
Proteomic databases
PaxDbi | O35780 |
PRIDEi | O35780 |
Genome annotation databases
GeneIDi | 79431 |
KEGGi | rno:79431 |
UCSCi | RGD:68439, rat |
Organism-specific databases
CTDi | 8553 |
RGDi | 68439, Bhlhe40 |
Phylogenomic databases
eggNOGi | KOG4304, Eukaryota |
InParanoidi | O35780 |
OrthoDBi | 629563at2759 |
PhylomeDBi | O35780 |
Miscellaneous databases
PROi | PR:O35780 |
Family and domain databases
Gene3Di | 4.10.280.10, 1 hit |
InterProi | View protein in InterPro IPR011598, bHLH_dom IPR036638, HLH_DNA-bd_sf IPR003650, Orange_dom |
Pfami | View protein in Pfam PF07527, Hairy_orange, 1 hit PF00010, HLH, 1 hit |
SMARTi | View protein in SMART SM00353, HLH, 1 hit SM00511, ORANGE, 1 hit |
SUPFAMi | SSF47459, SSF47459, 1 hit |
PROSITEi | View protein in PROSITE PS50888, BHLH, 1 hit PS51054, ORANGE, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | BHE40_RAT | |
Accessioni | O35780Primary (citable) accession number: O35780 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | March 5, 2002 |
Last sequence update: | January 1, 1998 | |
Last modified: | September 29, 2021 | |
This is version 140 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |