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Protein

Class E basic helix-loop-helix protein 41

Gene

BHLHE41

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 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.6 Publications

GO - Molecular functioni

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-1368108 BMAL1:CLOCK,NPAS2 activates circadian gene expression
R-HSA-400253 Circadian Clock
SignaLinkiQ9C0J9
SIGNORiQ9C0J9

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:BHLHE41
Synonyms:BHLHB3, DEC2, SHARP1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000123095.5
HGNCiHGNC:16617 BHLHE41
MIMi606200 gene
neXtProtiNX_Q9C0J9

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

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi70 – 71LL → AA: Abolishes RXRA repression. 1 Publication2

Organism-specific databases

DisGeNETi79365
MalaCardsiBHLHE41
MIMi612975 phenotype
OpenTargetsiENSG00000123095
PharmGKBiPA164716636

Polymorphism and mutation databases

BioMutaiBHLHE41
DMDMi20137459

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001271471 – 482Class E basic helix-loop-helix protein 41Add BLAST482

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki31Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki121Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki210Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki266Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources

Keywords - PTMi

Isopeptide bond, Ubl conjugation

Proteomic databases

EPDiQ9C0J9
MaxQBiQ9C0J9
PaxDbiQ9C0J9
PeptideAtlasiQ9C0J9
PRIDEiQ9C0J9
ProteomicsDBi80065
TopDownProteomicsiQ9C0J9

PTM databases

iPTMnetiQ9C0J9
PhosphoSitePlusiQ9C0J9

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000123095 Expressed in 221 organ(s), highest expression level in spinal cord
ExpressionAtlasiQ9C0J9 baseline and differential
GenevisibleiQ9C0J9 HS

Organism-specific databases

HPAiHPA056035

Interactioni

Subunit structurei

Homodimer. Heterodimer with BHLHE40/DEC1. Interacts with CIART and ARNTL/BMAL1 (By similarity). Interacts with RXRA.By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
HIF1AQ166652EBI-10988877,EBI-447269

GO - Molecular functioni

Protein-protein interaction databases

BioGridi122654, 38 interactors
DIPiDIP-59904N
IntActiQ9C0J9, 10 interactors
STRINGi9606.ENSP00000242728

Structurei

3D structure databases

ProteinModelPortaliQ9C0J9
SMRiQ9C0J9
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini44 – 99bHLHPROSITE-ProRule annotationAdd BLAST56
Domaini131 – 166OrangePROSITE-ProRule annotationAdd BLAST36

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni67 – 71Necessary for interaction with RXRA and repressor activity towards RXRA1 Publication5

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi297 – 431Ala/Gly-richAdd BLAST135

Phylogenomic databases

eggNOGiKOG4304 Eukaryota
ENOG4111F0X LUCA
GeneTreeiENSGT00510000046898
HOGENOMiHOG000234381
HOVERGENiHBG050685
InParanoidiQ9C0J9
KOiK03730
OMAiLYMCKSK
OrthoDBiEOG091G0D3I
PhylomeDBiQ9C0J9
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.

Q9C0J9-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MDEGIPHLQE RQLLEHRDFI GLDYSSLYMC KPKRSMKRDD TKDTYKLPHR
60 70 80 90 100
LIEKKRRDRI NECIAQLKDL LPEHLKLTTL GHLEKAVVLE LTLKHLKALT
110 120 130 140 150
ALTEQQHQKI IALQNGERSL KSPIQSDLDA FHSGFQTCAK EVLQYLSRFE
160 170 180 190 200
SWTPREPRCV QLINHLHAVA TQFLPTPQLL TQQVPLSKGT GAPSAAGSAA
210 220 230 240 250
APCLERAGQK LEPLAYCVPV IQRTQPSAEL AAENDTDTDS GYGGEAEARP
260 270 280 290 300
DREKGKGAGA SRVTIKQEPP GEDSPAPKRM KLDSRGGGSG GGPGGGAAAA
310 320 330 340 350
AAALLGPDPA AAAALLRPDA ALLSSLVAFG GGGGAPFPQP AAAAAPFCLP
360 370 380 390 400
FCFLSPSAAA AYVQPFLDKS GLEKYLYPAA AAAPFPLLYP GIPAPAAAAA
410 420 430 440 450
AAAAAAAAAA AFPCLSSVLS PPPEKAGAAA ATLLPHEVAP LGAPHPQHPH
460 470 480
GRTHLPFAGP REPGNPESSA QEDPSQPGKE AP
Length:482
Mass (Da):50,498
Last modified:June 1, 2001 - v1
Checksum:i2BECDC2FDEB7CE14
GO

Polymorphismi

Genetic variations in BHLHE41 are associated with the short sleep phenotype [MIMi:612975]. Individuals with this trait require less sleep in any 24-hour period than is typical for their age group.1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_063259384P → R Associated with short sleep phenotype. 1 PublicationCorresponds to variant dbSNP:rs121912617EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB044088 mRNA Translation: BAB21502.1
EF015896 Genomic DNA Translation: ABM64207.1
CH471094 Genomic DNA Translation: EAW96527.1
CCDSiCCDS8706.1
PIRiJC7583
RefSeqiNP_110389.1, NM_030762.2
UniGeneiHs.177841

Genome annotation databases

EnsembliENST00000242728; ENSP00000242728; ENSG00000123095
GeneIDi79365
KEGGihsa:79365
UCSCiuc001rhb.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB044088 mRNA Translation: BAB21502.1
EF015896 Genomic DNA Translation: ABM64207.1
CH471094 Genomic DNA Translation: EAW96527.1
CCDSiCCDS8706.1
PIRiJC7583
RefSeqiNP_110389.1, NM_030762.2
UniGeneiHs.177841

3D structure databases

ProteinModelPortaliQ9C0J9
SMRiQ9C0J9
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122654, 38 interactors
DIPiDIP-59904N
IntActiQ9C0J9, 10 interactors
STRINGi9606.ENSP00000242728

PTM databases

iPTMnetiQ9C0J9
PhosphoSitePlusiQ9C0J9

Polymorphism and mutation databases

BioMutaiBHLHE41
DMDMi20137459

Proteomic databases

EPDiQ9C0J9
MaxQBiQ9C0J9
PaxDbiQ9C0J9
PeptideAtlasiQ9C0J9
PRIDEiQ9C0J9
ProteomicsDBi80065
TopDownProteomicsiQ9C0J9

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000242728; ENSP00000242728; ENSG00000123095
GeneIDi79365
KEGGihsa:79365
UCSCiuc001rhb.4 human

Organism-specific databases

CTDi79365
DisGeNETi79365
EuPathDBiHostDB:ENSG00000123095.5
GeneCardsiBHLHE41
HGNCiHGNC:16617 BHLHE41
HPAiHPA056035
MalaCardsiBHLHE41
MIMi606200 gene
612975 phenotype
neXtProtiNX_Q9C0J9
OpenTargetsiENSG00000123095
PharmGKBiPA164716636
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4304 Eukaryota
ENOG4111F0X LUCA
GeneTreeiENSGT00510000046898
HOGENOMiHOG000234381
HOVERGENiHBG050685
InParanoidiQ9C0J9
KOiK03730
OMAiLYMCKSK
OrthoDBiEOG091G0D3I
PhylomeDBiQ9C0J9
TreeFamiTF330859

Enzyme and pathway databases

ReactomeiR-HSA-1368108 BMAL1:CLOCK,NPAS2 activates circadian gene expression
R-HSA-400253 Circadian Clock
SignaLinkiQ9C0J9
SIGNORiQ9C0J9

Miscellaneous databases

ChiTaRSiBHLHE41 human
GeneWikiiBHLHB3
GenomeRNAii79365
PROiPR:Q9C0J9
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000123095 Expressed in 221 organ(s), highest expression level in spinal cord
ExpressionAtlasiQ9C0J9 baseline and differential
GenevisibleiQ9C0J9 HS

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 nameiBHE41_HUMAN
AccessioniPrimary (citable) accession number: Q9C0J9
Secondary accession number(s): A2I2N8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 5, 2002
Last sequence update: June 1, 2001
Last modified: November 7, 2018
This is version 151 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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