UniProtKB - Q9C0J9 (BHE41_HUMAN)
Protein
Class E basic helix-loop-helix protein 41
Gene
BHLHE41
Organism
Homo sapiens (Human)
Status
Functioni
Transcriptional repressor involved in the regulation of the circadian rhythm by negatively regulating the activity of the clock genes and clock-controlled genes (PubMed:11278948, PubMed:14672706, PubMed:15193144, PubMed:15560782, PubMed:18411297, PubMed:19786558, PubMed:25083013). 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 (PubMed:25083013). 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. Inhibits HNF1A-mediated transactivation of CYP1A2, CYP2E1 AND CYP3A11 (By similarity).By similarity7 Publications
GO - Molecular functioni
- bHLH transcription factor binding Source: BHF-UCL
- DNA-binding transcription factor activity, RNA polymerase II-specific Source: BHF-UCL
- DNA-binding transcription repressor activity, RNA polymerase II-specific Source: GO_Central
- E-box binding Source: BHF-UCL
- histone deacetylase binding Source: BHF-UCL
- MRF binding Source: BHF-UCL
- protein heterodimerization activity Source: BHF-UCL
- protein homodimerization activity Source: BHF-UCL
- RNA polymerase II activating transcription factor binding Source: BHF-UCL
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: BHF-UCL
- sequence-specific double-stranded DNA binding Source: ARUK-UCL
GO - Biological processi
- anterior/posterior pattern specification Source: GO_Central
- circadian regulation of gene expression Source: GO_Central
- negative regulation of myotube differentiation Source: BHF-UCL
- negative regulation of transcription, DNA-templated Source: UniProtKB
- negative regulation of transcription by competitive promoter binding Source: BHF-UCL
- negative regulation of transcription by RNA polymerase II Source: BHF-UCL
- regulation of neurogenesis Source: GO_Central
- regulation of transcription by RNA polymerase II Source: GO_Central
Keywordsi
Molecular function | DNA-binding, Repressor |
Biological process | Biological rhythms, Transcription, Transcription regulation |
Enzyme and pathway databases
PathwayCommonsi | Q9C0J9 |
Reactomei | R-HSA-1368108, BMAL1:CLOCK,NPAS2 activates circadian gene expression R-HSA-400253, Circadian Clock |
SignaLinki | Q9C0J9 |
SIGNORi | Q9C0J9 |
Names & Taxonomyi
Protein namesi | Recommended name: Class E basic helix-loop-helix protein 41CuratedShort 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 | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:16617, BHLHE41 |
MIMi | 606200, gene |
neXtProti | NX_Q9C0J9 |
VEuPathDBi | HostDB:ENSG00000123095.5 |
Subcellular locationi
Nucleus
- Nucleus PROSITE-ProRule annotation
Nucleus
- nuclear chromatin Source: NTNU_SB
- nucleus Source: GO_Central
Keywords - Cellular componenti
NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 70 – 71 | LL → AA: Abolishes RXRA repression. 1 Publication | 2 |
Organism-specific databases
DisGeNETi | 79365 |
MalaCardsi | BHLHE41 |
MIMi | 612975, phenotype |
OpenTargetsi | ENSG00000123095 |
PharmGKBi | PA164716636 |
Miscellaneous databases
Pharosi | Q9C0J9, Tbio |
Genetic variation databases
BioMutai | BHLHE41 |
DMDMi | 20137459 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000127147 | 1 – 482 | Class E basic helix-loop-helix protein 41Add BLAST | 482 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Cross-linki | 31 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources | ||
Cross-linki | 121 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources | ||
Cross-linki | 210 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources | ||
Cross-linki | 266 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources |
Keywords - PTMi
Isopeptide bond, Ubl conjugationProteomic databases
EPDi | Q9C0J9 |
jPOSTi | Q9C0J9 |
MassIVEi | Q9C0J9 |
MaxQBi | Q9C0J9 |
PaxDbi | Q9C0J9 |
PeptideAtlasi | Q9C0J9 |
PRIDEi | Q9C0J9 |
ProteomicsDBi | 80065 |
TopDownProteomicsi | Q9C0J9 |
PTM databases
iPTMneti | Q9C0J9 |
PhosphoSitePlusi | Q9C0J9 |
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
Bgeei | ENSG00000123095, Expressed in spinal cord and 232 other tissues |
ExpressionAtlasi | Q9C0J9, baseline and differential |
Genevisiblei | Q9C0J9, HS |
Organism-specific databases
HPAi | ENSG00000123095, Tissue enhanced (skeletal) |
Interactioni
Subunit structurei
Binary interactionsi
Q9C0J9
With | #Exp. | IntAct |
---|---|---|
HIF1A [Q16665] | 2 | EBI-10988877,EBI-447269 |
GO - Molecular functioni
- bHLH transcription factor binding Source: BHF-UCL
- histone deacetylase binding Source: BHF-UCL
- MRF binding Source: BHF-UCL
- protein heterodimerization activity Source: BHF-UCL
- protein homodimerization activity Source: BHF-UCL
- RNA polymerase II activating transcription factor binding Source: BHF-UCL
Protein-protein interaction databases
BioGRIDi | 122654, 38 interactors |
DIPi | DIP-59904N |
IntActi | Q9C0J9, 10 interactors |
STRINGi | 9606.ENSP00000242728 |
Miscellaneous databases
RNActi | Q9C0J9, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 44 – 99 | bHLHPROSITE-ProRule annotationAdd BLAST | 56 | |
Domaini | 131 – 166 | OrangePROSITE-ProRule annotationAdd BLAST | 36 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 67 – 71 | Necessary for interaction with RXRA and repressor activity towards RXRA1 Publication | 5 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 297 – 431 | Ala/Gly-richAdd BLAST | 135 |
Phylogenomic databases
eggNOGi | KOG4304, Eukaryota |
GeneTreei | ENSGT00940000161014 |
HOGENOMi | CLU_049895_0_0_1 |
InParanoidi | Q9C0J9 |
OMAi | LYMCKSK |
OrthoDBi | 629563at2759 |
PhylomeDBi | Q9C0J9 |
TreeFami | TF330859 |
Family and domain databases
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 |
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 |
i Sequence
Sequence statusi: Complete.
Q9C0J9-1 [UniParc]FASTAAdd to basket
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
Polymorphismi
Genetic variations in BHLHE41 are associated with the familial natural short sleep 1 (FNSS1) phenotype, an autosomal dominant trait [MIMi:612975]. Individuals with this trait require less sleep in any 24-hour period than is typical for their age group.2 Publications
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_082585 | 362 | Y → H Associated with short sleep phenotype; abolishes inhibition of CLOCK-ARNTL/BMAL1 and NPAS2/BMAL1 transactivation activities. 1 Publication | 1 | |
Natural variantiVAR_082586 | 384 | P → Q Associated with short sleep phenotype; heterogeneous phenotype; increases inhibition of CLOCK-ARNTL/BMAL1 and NPAS2/BMAL1 transactivation activities. 1 PublicationCorresponds to variant dbSNP:rs121912617EnsemblClinVar. | 1 | |
Natural variantiVAR_063259 | 384 | P → R Associated with short sleep phenotype; abolishes inhibition of CLOCK-ARNTL/BMAL1 and NPAS2/BMAL1 transactivation activities. 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 |
CCDSi | CCDS8706.1 |
PIRi | JC7583 |
RefSeqi | NP_110389.1, NM_030762.2 |
Genome annotation databases
Ensembli | ENST00000242728; ENSP00000242728; ENSG00000123095 |
GeneIDi | 79365 |
KEGGi | hsa:79365 |
UCSCi | uc001rhb.4, human |
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 |
CCDSi | CCDS8706.1 |
PIRi | JC7583 |
RefSeqi | NP_110389.1, NM_030762.2 |
3D structure databases
SMRi | Q9C0J9 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 122654, 38 interactors |
DIPi | DIP-59904N |
IntActi | Q9C0J9, 10 interactors |
STRINGi | 9606.ENSP00000242728 |
PTM databases
iPTMneti | Q9C0J9 |
PhosphoSitePlusi | Q9C0J9 |
Genetic variation databases
BioMutai | BHLHE41 |
DMDMi | 20137459 |
Proteomic databases
EPDi | Q9C0J9 |
jPOSTi | Q9C0J9 |
MassIVEi | Q9C0J9 |
MaxQBi | Q9C0J9 |
PaxDbi | Q9C0J9 |
PeptideAtlasi | Q9C0J9 |
PRIDEi | Q9C0J9 |
ProteomicsDBi | 80065 |
TopDownProteomicsi | Q9C0J9 |
Protocols and materials databases
Antibodypediai | 24289, 408 antibodies |
Genome annotation databases
Ensembli | ENST00000242728; ENSP00000242728; ENSG00000123095 |
GeneIDi | 79365 |
KEGGi | hsa:79365 |
UCSCi | uc001rhb.4, human |
Organism-specific databases
CTDi | 79365 |
DisGeNETi | 79365 |
GeneCardsi | BHLHE41 |
HGNCi | HGNC:16617, BHLHE41 |
HPAi | ENSG00000123095, Tissue enhanced (skeletal) |
MalaCardsi | BHLHE41 |
MIMi | 606200, gene 612975, phenotype |
neXtProti | NX_Q9C0J9 |
OpenTargetsi | ENSG00000123095 |
PharmGKBi | PA164716636 |
VEuPathDBi | HostDB:ENSG00000123095.5 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG4304, Eukaryota |
GeneTreei | ENSGT00940000161014 |
HOGENOMi | CLU_049895_0_0_1 |
InParanoidi | Q9C0J9 |
OMAi | LYMCKSK |
OrthoDBi | 629563at2759 |
PhylomeDBi | Q9C0J9 |
TreeFami | TF330859 |
Enzyme and pathway databases
PathwayCommonsi | Q9C0J9 |
Reactomei | R-HSA-1368108, BMAL1:CLOCK,NPAS2 activates circadian gene expression R-HSA-400253, Circadian Clock |
SignaLinki | Q9C0J9 |
SIGNORi | Q9C0J9 |
Miscellaneous databases
BioGRID-ORCSi | 79365, 11 hits in 895 CRISPR screens |
ChiTaRSi | BHLHE41, human |
GeneWikii | BHLHB3 |
GenomeRNAii | 79365 |
Pharosi | Q9C0J9, Tbio |
PROi | PR:Q9C0J9 |
RNActi | Q9C0J9, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000123095, Expressed in spinal cord and 232 other tissues |
ExpressionAtlasi | Q9C0J9, baseline and differential |
Genevisiblei | Q9C0J9, HS |
Family and domain databases
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 |
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... |
MobiDBi | Search... |
Entry informationi
Entry namei | BHE41_HUMAN | |
Accessioni | Q9C0J9Primary (citable) accession number: Q9C0J9 Secondary accession number(s): A2I2N8 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | March 5, 2002 |
Last sequence update: | June 1, 2001 | |
Last modified: | February 10, 2021 | |
This is version 168 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
Reference proteomeDocuments
- Human chromosome 12
Human chromosome 12: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot