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Protein

Class E basic helix-loop-helix protein 40

Gene

Bhlhe40

Organism
Rattus norvegicus (Rat)
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 PER1/2 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 (By similarity).By similarity

GO - Molecular functioni

GO - Biological processi

  • circadian rhythm Source: UniProtKB
  • entrainment of circadian clock Source: RGD
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: RGD
  • nervous system development Source: RGD
  • regulation of neuronal synaptic plasticity Source: RGD
  • response to light stimulus Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW

Keywordsi

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

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
Enhancer-of-split and hairy-related protein 2
Short name:
SHARP-2
Gene namesi
Name:Bhlhe40
Synonyms:Bhlhb2, Sharp2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi68439. Bhlhe40.

Subcellular locationi

  • Cytoplasm By similarity
  • Nucleus By similarity

  • Note: Predominantly localized in the nucleus (By similarity).By similarity

GO - Cellular componenti

  • cytoplasm Source: UniProtKB-SubCell
  • nucleus Source: RGD

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001271461 – 411Class E basic helix-loop-helix protein 40Add BLAST411

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki159Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1, SUMO2 and SUMO3)By similarity
Modified residuei235PhosphoserineBy similarity1
Cross-linki279Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternateBy similarity
Cross-linki279Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1, SUMO2 and SUMO3); alternateBy similarity
Cross-linki279Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Modified residuei383PhosphoserineCombined sources1

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, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiO35780.
PRIDEiO35780.

PTM databases

iPTMnetiO35780.
PhosphoSitePlusiO35780.

Expressioni

Tissue specificityi

Expressed in heart, spleen, lung, liver, muscle, kidney, uterus and gut. Highly expressed in the cerebral cortex, especially in the fifth layer, thalamus, superior colliculus, olfactory bulb, piriform cortex, hippocampus and hypothalamic nuclei.1 Publication

Inductioni

Expressed in a circadian manner in the suprachiasmatic nucleus (SCN) of the brain.1 Publication

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 similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000009564.

Structurei

3D structure databases

ProteinModelPortaliO35780.
SMRiO35780.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini52 – 107bHLHPROSITE-ProRule annotationAdd BLAST56
Domaini142 – 175OrangePROSITE-ProRule annotationAdd BLAST34

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 139Essential for interaction with ARNTL/BMAL1, E-box binding and repressor activity against the CLOCK-ARNTL/BMAL1 heterodimerBy similarityAdd BLAST139
Regioni75 – 79Necessary for interaction with RXRA and repressor activity against RXRABy similarity5

Phylogenomic databases

eggNOGiKOG4304. Eukaryota.
ENOG4111F0X. LUCA.
HOGENOMiHOG000234381.
InParanoidiO35780.
KOiK03729.
PhylomeDBiO35780.

Family and domain databases

CDDicd00083. HLH. 1 hit.
Gene3Di4.10.280.10. 1 hit.
InterProiView protein in InterPro
IPR011598. bHLH_dom.
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.

O35780-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:411
Mass (Da):45,529
Last modified:January 1, 1998 - v1
Checksum:iE56BD468D08824AD
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF009330 mRNA. Translation: AAB63587.1.
RefSeqiNP_445780.1. NM_053328.1.
UniGeneiRn.81055.

Genome annotation databases

GeneIDi79431.
KEGGirno:79431.
UCSCiRGD:68439. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF009330 mRNA. Translation: AAB63587.1.
RefSeqiNP_445780.1. NM_053328.1.
UniGeneiRn.81055.

3D structure databases

ProteinModelPortaliO35780.
SMRiO35780.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000009564.

PTM databases

iPTMnetiO35780.
PhosphoSitePlusiO35780.

Proteomic databases

PaxDbiO35780.
PRIDEiO35780.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi79431.
KEGGirno:79431.
UCSCiRGD:68439. rat.

Organism-specific databases

CTDi8553.
RGDi68439. Bhlhe40.

Phylogenomic databases

eggNOGiKOG4304. Eukaryota.
ENOG4111F0X. LUCA.
HOGENOMiHOG000234381.
InParanoidiO35780.
KOiK03729.
PhylomeDBiO35780.

Miscellaneous databases

PROiPR:O35780.

Family and domain databases

CDDicd00083. HLH. 1 hit.
Gene3Di4.10.280.10. 1 hit.
InterProiView protein in InterPro
IPR011598. bHLH_dom.
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.
ProtoNetiSearch...

Entry informationi

Entry nameiBHE40_RAT
AccessioniPrimary (citable) accession number: O35780
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 5, 2002
Last sequence update: January 1, 1998
Last modified: May 10, 2017
This is version 121 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

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 one 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.