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 function as a transcriptional factor for neuronal differentiation (By similarity).By similarity

GO - Molecular functionⁱ

E-box binding Source: UniProtKB
protein dimerization activity Source: InterPro
transcription corepressor activity Source: UniProtKB

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

circadian rhythm
Source: UniProtKB
Inferred from expression patternⁱ
- 12397359
negative regulation of transcription, DNA-templated Source: UniProtKB
negative regulation of transcription by RNA polymerase II
Source: RGD
Inferred from mutant phenotypeⁱ
- 12954728
nervous system development
Source: RGD
Non-traceable author statementⁱ
- 9532582
regulation of neuronal synaptic plasticity
Source: RGD
Inferred from expression patternⁱ
- 9532582
response to light stimulus
Source: UniProtKB
Inferred from direct assayⁱ
- 12397359
transcription, DNA-templated Source: UniProtKB-KW

View the complete GO annotation on QuickGO ...

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 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
Organismⁱ	Rattus norvegicus (Rat)
Taxonomic identifierⁱ	10116 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus
Proteomesⁱ	UP000002494 Componentⁱ: Unplaced

Organism-specific databases

Rat genome database More...RGDⁱ	68439 Bhlhe40

RGDⁱ

68439 Bhlhe40

Keywords - Cellular componentⁱ

Cytoplasm, Nucleus

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	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

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

PaxDbⁱ	O35780
PRIDEⁱ	O35780

PTM databases

iPTMnetⁱ	O35780
PhosphoSitePlusⁱ	O35780

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 dimerization activity Source: InterPro

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

STRINGⁱ	10116.ENSRNOP00000009564

STRINGⁱ

10116.ENSRNOP00000009564

Structureⁱ

3D structure databases

ProteinModelPortalⁱ	O35780
SMRⁱ	O35780
ModBaseⁱ	Search...
MobiDBⁱ	Search...

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	75 – 79	Necessary for interaction with RXRA and repressor activity against RXRABy similarity		5

Phylogenomic databases

eggNOGⁱ	KOG4304 Eukaryota ENOG4111F0X LUCA
HOGENOMⁱ	HOG000234381
InParanoidⁱ	O35780
KEGG Orthology (KO) More...KOⁱ	K03729
PhylomeDBⁱ	O35780

Family and domain databases

Conserved Domains Database More...CDDⁱ	cd00083 HLH, 1 hit
Gene3Dⁱ	4.10.280.10, 1 hit
InterProⁱ	View protein in InterPro IPR011598 bHLH_dom IPR036638 HLH_DNA-bd_sf IPR003650 Orange_dom
Pfam protein domain database More...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

Sequenceⁱ

Sequence statusⁱ: Complete.

O35780-1 [UniParc]FASTA Add 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
NCBI Reference Sequences More...RefSeqⁱ	NP_445780.1, NM_053328.1
UniGeneⁱ	Rn.81055

Genome annotation databases

GeneIDⁱ	79431
KEGGⁱ	rno:79431
UCSC genome browser More...UCSCⁱ	RGD:68439 rat

Similar proteinsⁱ

90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length
O35780	Class E basic helix-loop-helix protein 40		FUKDA		503
Basic helix-loop-helix family member e40		PANPA		414
UPI0004545E47		CRIGR		412
class E basic helix-loop-helix protein 40		DIPOR		412
UPI00038C4AA0		MICOH		411
+6

Protein	Similar proteins		Species	Score	Length
O35780	Class E basic helix-loop-helix protein 40		HUMAN		412
BHLHE40 isoform 1		PANTR		412
Basic helix-loop-helix family member e40		GORGO		412
UPI00057BC7D3		CAMDR		508
Basic helix-loop-helix family member e40		AILME		416
+114

Cross-referencesⁱ

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	AF009330 mRNA Translation: AAB63587.1
NCBI Reference Sequences More...RefSeqⁱ	NP_445780.1, NM_053328.1
UniGeneⁱ	Rn.81055

3D structure databases

ProteinModelPortalⁱ	O35780
SMRⁱ	O35780
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

STRINGⁱ	10116.ENSRNOP00000009564

STRINGⁱ

10116.ENSRNOP00000009564

PTM databases

iPTMnetⁱ	O35780
PhosphoSitePlusⁱ	O35780

Proteomic databases

PaxDbⁱ	O35780
PRIDEⁱ	O35780

Protocols and materials databases

Structural Biology Knowledgebase	Search...

Structural Biology Knowledgebase

Search...

Genome annotation databases

GeneIDⁱ	79431
KEGGⁱ	rno:79431
UCSC genome browser More...UCSCⁱ	RGD:68439 rat

Organism-specific databases

CTDⁱ	8553
Rat genome database More...RGDⁱ	68439 Bhlhe40

Phylogenomic databases

eggNOGⁱ	KOG4304 Eukaryota ENOG4111F0X LUCA
HOGENOMⁱ	HOG000234381
InParanoidⁱ	O35780
KEGG Orthology (KO) More...KOⁱ	K03729
PhylomeDBⁱ	O35780

Miscellaneous databases

Protein Ontology More...PROⁱ	PR:O35780

PROⁱ

PR:O35780

Family and domain databases

Conserved Domains Database More...CDDⁱ	cd00083 HLH, 1 hit
Gene3Dⁱ	4.10.280.10, 1 hit
InterProⁱ	View protein in InterPro IPR011598 bHLH_dom IPR036638 HLH_DNA-bd_sf IPR003650 Orange_dom
Pfam protein domain database More...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
ProtoNetⁱ	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:	May 23, 2018
	This is version 127 of the entry and version 1 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program

Miscellaneousⁱ

Keywords - Technical termⁱ

Complete proteome, Reference proteome

UniProtKB

UniParc

Help

UniRef

Proteomes

Annotation systems

Supporting data

UniProtKB - O35780 (BHE40_RAT)

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Class E basic helix-loop-helix protein 40

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<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Biological processi

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Nucleus

Other locations

Nucleus

Other locations

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Region

Phylogenomic databases

Family and domain databases

Sequence databases

Genome annotation databases

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Miscellaneous databases

Family and domain databases

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

PTM / Processingⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ