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Protein

Class E basic helix-loop-helix protein 40

Gene

BHLHE40

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: -Experimental evidence at transcript 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 be involved in the regulation of chondrocyte differentiation via the cAMP pathway (By similarity).By similarity

GO - Molecular functioni

GO - Biological processi

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
Gene namesi
Name:BHLHE40
Synonyms:BHLHB2
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 22

Organism-specific databases

VGNCiVGNC:26486 BHLHE40

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

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003546861 – 412Class E basic helix-loop-helix protein 40Add BLAST412

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
Cross-linki167Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)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
Cross-linki288Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei383PhosphoserineBy similarity1

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

PaxDbiQ5EA15
PRIDEiQ5EA15

Expressioni

Gene expression databases

BgeeiENSBTAG00000009863 Expressed in 10 organ(s), highest expression level in skeletal muscle tissue

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

STRINGi9913.ENSBTAP00000013008

Structurei

3D structure databases

ProteinModelPortaliQ5EA15
SMRiQ5EA15
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
GeneTreeiENSGT00510000046898
HOGENOMiHOG000234381
InParanoidiQ5EA15
KOiK03729
OMAiAGQEMFC
OrthoDBiEOG091G0D3I
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.

Q5EA15-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MERIPSAQPP PTCLPKAPGL EPGDLSGMDF AHMYQVYKSR RGIKRSEDSK
60 70 80 90 100
ETYKLPHRLI EKKRRDRINE CIAQLKDLLP EHLKLTTLGH LEKAVVLELT
110 120 130 140 150
LKHVKALTNL IDQQQQKIIA LQSGLQAGDL SGRNVEAGQE MFCSGFQTCA
160 170 180 190 200
REVLQYLAKH ENTRDLKSSQ LVTHLHRVVS ELLQGGTSRK PSDPAPKAMD
210 220 230 240 250
FKEKPSSLAK GSEGPGKNCV PVIQRTFAHS SGEQSGSDTD TDSGYGGESE
260 270 280 290 300
KSELRVEQPY FKSDHGRRFT MGERISAIKQ ESEEPPMKKS RMQLSDDEGP
310 320 330 340 350
FTSTDLISSP FLGPHPHQPP FCLPFYLIPP SATAYLPMLE KCWYPTSVPV
360 370 380 390 400
LYQGLNASAA ALSSFMNPDK ISAPLLMPQR LPSPLPTHPA IDSSALLQAL
410
KQIPPLNLET KD
Length:412
Mass (Da):45,621
Last modified:March 15, 2005 - v1
Checksum:iFC272344E54F79BD
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BT020754 mRNA Translation: AAX08771.1
RefSeqiNP_001020100.1, NM_001024929.1
UniGeneiBt.23123

Genome annotation databases

EnsembliENSBTAT00000013008; ENSBTAP00000013008; ENSBTAG00000009863
GeneIDi506945
KEGGibta:506945

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BT020754 mRNA Translation: AAX08771.1
RefSeqiNP_001020100.1, NM_001024929.1
UniGeneiBt.23123

3D structure databases

ProteinModelPortaliQ5EA15
SMRiQ5EA15
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000013008

Proteomic databases

PaxDbiQ5EA15
PRIDEiQ5EA15

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000013008; ENSBTAP00000013008; ENSBTAG00000009863
GeneIDi506945
KEGGibta:506945

Organism-specific databases

CTDi8553
VGNCiVGNC:26486 BHLHE40

Phylogenomic databases

eggNOGiKOG4304 Eukaryota
ENOG4111F0X LUCA
GeneTreeiENSGT00510000046898
HOGENOMiHOG000234381
InParanoidiQ5EA15
KOiK03729
OMAiAGQEMFC
OrthoDBiEOG091G0D3I
TreeFamiTF330859

Gene expression databases

BgeeiENSBTAG00000009863 Expressed in 10 organ(s), highest expression level in skeletal muscle tissue

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
ProtoNetiSearch...

Entry informationi

Entry nameiBHE40_BOVIN
AccessioniPrimary (citable) accession number: Q5EA15
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 25, 2008
Last sequence update: March 15, 2005
Last modified: September 12, 2018
This is version 88 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
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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