Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q9C0J9 (BHE41_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 117. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Class E basic helix-loop-helix protein 41

Short name=bHLHe41
Alternative name(s):
Class B basic helix-loop-helix protein 3
Short name=bHLHb3
Differentially expressed in chondrocytes protein 2
Short name=hDEC2
Enhancer-of-split and hairy-related protein 1
Short name=SHARP-1
Gene names
Name:BHLHE41
Synonyms:BHLHB3, DEC2, SHARP1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length482 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 and in turn is repressed by PER1/2 and CRY1/2. Represses the activity of the circadian transcriptional activator: CLOCK-ARNTL/BMAL1 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/B/G, NR1H3/LXRA, NR1H4 and VDR transactivation activity. Ref.4 Ref.5 Ref.6 Ref.7 Ref.8 Ref.9

Subunit structure

Homodimer. Heterodimer with BHLHE40/DEC1. Interacts with CIART and ARNTL/BMAL1 By similarity. Interacts with RXRA. Ref.6 Ref.9

Subcellular location

Nucleus By similarity.

Tissue specificity

Highly expressed in skeletal muscle and brain, moderately expressed in pancreas and heart, weakly expressed in placenta, lung, liver and kidney.

Polymorphism

Genetic variations in BHLHE41 are associated with the short sleep phenotype [MIM:612975]. Individuals with this trait require less sleep in any 24-hour period than is typical for their age group.

Sequence similarities

Contains 1 bHLH (basic helix-loop-helix) domain.

Contains 1 Orange domain.

Ontologies

Keywords
   Biological processBiological rhythms
Transcription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityPolymorphism
   LigandDNA-binding
   Molecular functionRepressor
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell differentiation

Non-traceable author statement Ref.1. Source: UniProtKB

cell proliferation

Non-traceable author statement Ref.1. Source: UniProtKB

circadian regulation of gene expression

Inferred from electronic annotation. Source: Ensembl

negative regulation of myotube differentiation

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of transcription by competitive promoter binding

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of transcription from RNA polymerase II promoter

Inferred from direct assay Ref.5Ref.6. Source: BHF-UCL

negative regulation of transcription, DNA-templated

Inferred from sequence or structural similarity. Source: UniProtKB

organ morphogenesis

Non-traceable author statement Ref.1. Source: UniProtKB

   Cellular_componentnucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionE-box binding

Inferred from direct assay Ref.5Ref.6. Source: BHF-UCL

MRF binding

Inferred from sequence or structural similarity. Source: BHF-UCL

RNA polymerase II activating transcription factor binding

Inferred from sequence or structural similarity. Source: BHF-UCL

RNA polymerase II core promoter proximal region sequence-specific DNA binding

Inferred from sequence or structural similarity. Source: BHF-UCL

RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription

Inferred from sequence or structural similarity. Source: BHF-UCL

RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity

Inferred from sequence or structural similarity. Source: BHF-UCL

RNA polymerase II transcription factor binding transcription factor activity involved in negative regulation of transcription

Inferred from sequence or structural similarity. Source: BHF-UCL

bHLH transcription factor binding

Inferred from physical interaction Ref.6. Source: BHF-UCL

histone deacetylase binding

Inferred from sequence or structural similarity. Source: BHF-UCL

protein heterodimerization activity

Inferred from physical interaction Ref.6. Source: BHF-UCL

protein homodimerization activity

Inferred from sequence or structural similarity. Source: BHF-UCL

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 482482Class E basic helix-loop-helix protein 41
PRO_0000127147

Regions

Domain44 – 9956bHLH
Domain131 – 16636Orange
Region67 – 715Necessary for its interaction with RXRA and repressor activity towards RXRA
Compositional bias297 – 431135Ala/Gly-rich

Natural variations

Natural variant3841P → R Associated with short sleep phenotype. Ref.10
VAR_063259

Experimental info

Mutagenesis70 – 712LL → AA: Abolishes RXRA repression. Ref.9

Sequences

Sequence LengthMass (Da)Tools
Q9C0J9 [UniParc].

Last modified June 1, 2001. Version 1.
Checksum: 2BECDC2FDEB7CE14

FASTA48250,498
        10         20         30         40         50         60 
MDEGIPHLQE RQLLEHRDFI GLDYSSLYMC KPKRSMKRDD TKDTYKLPHR LIEKKRRDRI 

        70         80         90        100        110        120 
NECIAQLKDL LPEHLKLTTL GHLEKAVVLE LTLKHLKALT ALTEQQHQKI IALQNGERSL 

       130        140        150        160        170        180 
KSPIQSDLDA FHSGFQTCAK EVLQYLSRFE SWTPREPRCV QLINHLHAVA TQFLPTPQLL 

       190        200        210        220        230        240 
TQQVPLSKGT GAPSAAGSAA APCLERAGQK LEPLAYCVPV IQRTQPSAEL AAENDTDTDS 

       250        260        270        280        290        300 
GYGGEAEARP DREKGKGAGA SRVTIKQEPP GEDSPAPKRM KLDSRGGGSG GGPGGGAAAA 

       310        320        330        340        350        360 
AAALLGPDPA AAAALLRPDA ALLSSLVAFG GGGGAPFPQP AAAAAPFCLP FCFLSPSAAA 

       370        380        390        400        410        420 
AYVQPFLDKS GLEKYLYPAA AAAPFPLLYP GIPAPAAAAA AAAAAAAAAA AFPCLSSVLS 

       430        440        450        460        470        480 
PPPEKAGAAA ATLLPHEVAP LGAPHPQHPH GRTHLPFAGP REPGNPESSA QEDPSQPGKE 


AP 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning and characterization of DEC2, a new member of basic helix-loop-helix proteins."
Fujimoto K., Shen M., Noshiro M., Matsubara K., Shingu S., Honda K., Yoshida E., Suardita K., Matsuda Y., Kato Y.
Biochem. Biophys. Res. Commun. 280:164-171(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]NHLBI resequencing and genotyping service (RS&G)
Submitted (SEP-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The basic helix-loop-helix protein, SHARP-1, represses transcription by a histone deacetylase-dependent and histone deacetylase-independent mechanism."
Garriga-Canut M., Roopra A., Buckley N.J.
J. Biol. Chem. 276:14821-14828(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[5]"A novel autofeedback loop of Dec1 transcription involved in circadian rhythm regulation."
Kawamoto T., Noshiro M., Sato F., Maemura K., Takeda N., Nagai R., Iwata T., Fujimoto K., Furukawa M., Miyazaki K., Honma S., Honma K.I., Kato Y.
Biochem. Biophys. Res. Commun. 313:117-124(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[6]"DNA binding, but not interaction with Bmal1, is responsible for DEC1-mediated transcription regulation of the circadian gene mPer1."
Li Y., Song X., Ma Y., Liu J., Yang D., Yan B.
Biochem. J. 382:895-904(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, HETERODIMERIZATION WITH BHLHE40/DEC1.
[7]"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: FUNCTION.
[8]"DEC1 modulates the circadian phase of clock gene expression."
Nakashima A., Kawamoto T., Honda K.K., Ueshima T., Noshiro M., Iwata T., Fujimoto K., Kubo H., Honma S., Yorioka N., Kohno N., Kato Y.
Mol. Cell. Biol. 28:4080-4092(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[9]"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, INTERACTION WITH RXRA, MUTAGENESIS OF 70-LEU-LEU-71.
[10]"The transcriptional repressor DEC2 regulates sleep length in mammals."
He Y., Jones C.R., Fujiki N., Xu Y., Guo B., Holder J.L. Jr., Rossner M.J., Nishino S., Fu Y.H.
Science 325:866-870(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ARG-384, ASSOCIATION OF VARIANT ARG-384 WITH SHORT SLEEP PHENOTYPE.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB044088 mRNA. Translation: BAB21502.1.
EF015896 Genomic DNA. Translation: ABM64207.1.
CH471094 Genomic DNA. Translation: EAW96527.1.
CCDSCCDS8706.1.
PIRJC7583.
RefSeqNP_110389.1. NM_030762.2.
UniGeneHs.177841.

3D structure databases

ProteinModelPortalQ9C0J9.
SMRQ9C0J9. Positions 36-99.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid122654. 11 interactions.
DIPDIP-59904N.
STRING9606.ENSP00000242728.

PTM databases

PhosphoSiteQ9C0J9.

Polymorphism databases

DMDM20137459.

Proteomic databases

PaxDbQ9C0J9.
PRIDEQ9C0J9.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000242728; ENSP00000242728; ENSG00000123095.
GeneID79365.
KEGGhsa:79365.
UCSCuc001rhb.3. human.

Organism-specific databases

CTD79365.
GeneCardsGC12M026272.
HGNCHGNC:16617. BHLHE41.
MIM606200. gene.
612975. phenotype.
neXtProtNX_Q9C0J9.
PharmGKBPA164716636.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG235394.
HOGENOMHOG000234381.
HOVERGENHBG050685.
InParanoidQ9C0J9.
KOK03730.
OMAAYKLPHR.
OrthoDBEOG75XGKZ.
PhylomeDBQ9C0J9.
TreeFamTF330859.

Enzyme and pathway databases

ReactomeREACT_24941. Circadian Clock.
SignaLinkQ9C0J9.

Gene expression databases

BgeeQ9C0J9.
GenevestigatorQ9C0J9.

Family and domain databases

Gene3D4.10.280.10. 1 hit.
InterProIPR011598. bHLH_dom.
IPR003650. Orange.
IPR018352. Orange_subgr.
[Graphical view]
PfamPF07527. Hairy_orange. 1 hit.
PF00010. HLH. 1 hit.
[Graphical view]
SMARTSM00353. HLH. 1 hit.
SM00511. ORANGE. 1 hit.
[Graphical view]
SUPFAMSSF47459. SSF47459. 1 hit.
PROSITEPS50888. BHLH. 1 hit.
PS51054. ORANGE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSBHLHE41. human.
GeneWikiBHLHB3.
GenomeRNAi79365.
NextBio68333.
PROQ9C0J9.
SOURCESearch...

Entry information

Entry nameBHE41_HUMAN
AccessionPrimary (citable) accession number: Q9C0J9
Secondary accession number(s): A2I2N8
Entry history
Integrated into UniProtKB/Swiss-Prot: March 5, 2002
Last sequence update: June 1, 2001
Last modified: July 9, 2014
This is version 117 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM