BHE41_MOUSE
ID BHE41_MOUSE Reviewed; 410 AA.
AC Q99PV5;
DT 05-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Class E basic helix-loop-helix protein 41;
DE Short=bHLHe41;
DE AltName: Full=Class B basic helix-loop-helix protein 3;
DE Short=bHLHb3;
DE AltName: Full=Differentially expressed in chondrocytes protein 2;
DE Short=mDEC2;
GN Name=Bhlhe41; Synonyms=Bhlhb3, Dec2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11162494; DOI=10.1006/bbrc.2000.4133;
RA Fujimoto K., Shen M., Noshiro M., Matsubara K., Shingu S., Honda K.,
RA Yoshida E., Suardita K., Matsuda Y., Kato Y.;
RT "Molecular cloning and characterization of DEC2, a new member of basic
RT helix-loop-helix proteins.";
RL Biochem. Biophys. Res. Commun. 280:164-171(2001).
RN [2]
RP FUNCTION, AND INTERACTION WITH ARNTL.
RX PubMed=12397359; DOI=10.1038/nature01123;
RA Honma S., Kawamoto T., Takagi Y., Fujimoto K., Sato F., Noshiro M.,
RA Kato Y., Honma K.I.;
RT "Dec1 and Dec2 are regulators of the mammalian molecular clock.";
RL Nature 419:841-844(2002).
RN [3]
RP FUNCTION.
RX PubMed=14672706; DOI=10.1016/j.bbrc.2003.11.099;
RA Kawamoto T., Noshiro M., Sato F., Maemura K., Takeda N., Nagai R.,
RA Iwata T., Fujimoto K., Furukawa M., Miyazaki K., Honma S., Honma K.I.,
RA Kato Y.;
RT "A novel autofeedback loop of Dec1 transcription involved in circadian
RT rhythm regulation.";
RL Biochem. Biophys. Res. Commun. 313:117-124(2004).
RN [4]
RP SUBUNIT, AND HETERODIMERIZATION WITH BHLHE40.
RX PubMed=15560782; DOI=10.1111/j.1432-1033.2004.04379.x;
RA Sato F., Kawamoto T., Fujimoto K., Noshiro M., Honda K.K., Honma S.,
RA Honma K., Kato Y.;
RT "Functional analysis of the basic helix-loop-helix transcription factor
RT DEC1 in circadian regulation. Interaction with BMAL1.";
RL Eur. J. Biochem. 271:4409-4419(2004).
RN [5]
RP FUNCTION.
RX PubMed=18411297; DOI=10.1128/mcb.02168-07;
RA Nakashima A., Kawamoto T., Honda K.K., Ueshima T., Noshiro M., Iwata T.,
RA Fujimoto K., Kubo H., Honma S., Yorioka N., Kohno N., Kato Y.;
RT "DEC1 modulates the circadian phase of clock gene expression.";
RL Mol. Cell. Biol. 28:4080-4092(2008).
RN [6]
RP FUNCTION, AND INDUCTION.
RX PubMed=19786558; DOI=10.1124/mol.109.057000;
RA Cho Y., Noshiro M., Choi M., Morita K., Kawamoto T., Fujimoto K., Kato Y.,
RA Makishima M.;
RT "The basic helix-loop-helix proteins differentiated embryo chondrocyte
RT (DEC) 1 and DEC2 function as corepressors of retinoid X receptors.";
RL Mol. Pharmacol. 76:1360-1369(2009).
RN [7]
RP TRANSGENIC MICE.
RX PubMed=19679812; DOI=10.1126/science.1174443;
RA He Y., Jones C.R., Fujiki N., Xu Y., Guo B., Holder J.L. Jr., Rossner M.J.,
RA Nishino S., Fu Y.H.;
RT "The transcriptional repressor DEC2 regulates sleep length in mammals.";
RL Science 325:866-870(2009).
RN [8]
RP FUNCTION, AND INTERACTION WITH CIART.
RX PubMed=24736997; DOI=10.1371/journal.pbio.1001839;
RA Goriki A., Hatanaka F., Myung J., Kim J.K., Yoritaka T., Tanoue S., Abe T.,
RA Kiyonari H., Fujimoto K., Kato Y., Todo T., Matsubara A., Forger D.,
RA Takumi T.;
RT "A novel protein, CHRONO, functions as a core component of the mammalian
RT circadian clock.";
RL PLoS Biol. 12:E1001839-E1001839(2014).
RN [9]
RP FUNCTION, AND INTERACTION WITH NR0B2 AND HNF1A.
RX PubMed=30555544; DOI=10.7150/thno.28676;
RA Zhang T., Yu F., Guo L., Chen M., Yuan X., Wu B.;
RT "Small heterodimer partner regulates circadian cytochromes p450 and drug-
RT induced hepatotoxicity.";
RL Theranostics 8:5246-5258(2018).
CC -!- FUNCTION: Transcriptional repressor involved in the regulation of the
CC circadian rhythm by negatively regulating the activity of the clock
CC genes and clock-controlled genes. Acts as the negative limb of a novel
CC autoregulatory feedback loop (DEC loop) which differs from the one
CC formed by the PER and CRY transcriptional repressors (PER/CRY loop).
CC Both these loops are interlocked as it represses the expression of PER1
CC and in turn is repressed by PER1/2 and CRY1/2. Represses the activity
CC of the circadian transcriptional activator: CLOCK-ARNTL/BMAL1
CC heterodimer by competing for the binding to E-box elements (5'-CACGTG-
CC 3') found within the promoters of its target genes. Negatively
CC regulates its own expression and the expression of DBP and
CC BHLHE41/DEC2. Acts as a corepressor of RXR and the RXR-LXR heterodimers
CC and represses the ligand-induced RXRA/B/G, NR1H3/LXRA, NR1H4 and VDR
CC transactivation activity. Inhibits HNF1A-mediated transactivation of
CC CYP1A2, CYP2E1 AND CYP3A11 (PubMed:30555544).
CC {ECO:0000269|PubMed:12397359, ECO:0000269|PubMed:14672706,
CC ECO:0000269|PubMed:18411297, ECO:0000269|PubMed:19786558,
CC ECO:0000269|PubMed:24736997, ECO:0000269|PubMed:30555544}.
CC -!- SUBUNIT: Homodimer (PubMed:15560782). Heterodimer with BHLHE40/DEC1
CC (PubMed:15560782). Interacts with CIART (PubMed:24736997). Interacts
CC with ARNTL/BMAL1 (PubMed:12397359). Interacts with RXRA (By
CC similarity). Interacts with NR0B2 and HNF1A (PubMed:30555544).
CC {ECO:0000250|UniProtKB:Q9C0J9, ECO:0000269|PubMed:12397359,
CC ECO:0000269|PubMed:15560782, ECO:0000269|PubMed:24736997,
CC ECO:0000269|PubMed:30555544}.
CC -!- INTERACTION:
CC Q99PV5; P28033: Cebpb; NbExp=5; IntAct=EBI-6143801, EBI-1029979;
CC Q99PV5; Q3TQ03: Ciart; NbExp=2; IntAct=EBI-6143801, EBI-16101489;
CC Q99PV5; Q16665: HIF1A; Xeno; NbExp=3; IntAct=EBI-6143801, EBI-447269;
CC Q99PV5; P25789: PSMA4; Xeno; NbExp=2; IntAct=EBI-6143801, EBI-359310;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00380,
CC ECO:0000255|PROSITE-ProRule:PRU00981}.
CC -!- TISSUE SPECIFICITY: Expressed in skeletal muscle, brain and lung.
CC -!- INDUCTION: Expressed in a circdadian manner in the liver with a peak at
CC ZT10. {ECO:0000269|PubMed:19786558}.
CC -!- MISCELLANEOUS: Activity profiles and sleep recordings of transgenic
CC mice carrying the mutation Arg-325 show increased vigilance time and
CC less sleep time than control mice in a zeitgeber time- and sleep
CC deprivation-dependent manner.
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DR EMBL; AB044090; BAB21503.1; -; mRNA.
DR CCDS; CCDS20697.1; -.
DR PIR; JC7584; JC7584.
DR RefSeq; NP_001258697.1; NM_001271768.1.
DR RefSeq; NP_077789.1; NM_024469.2.
DR AlphaFoldDB; Q99PV5; -.
DR BioGRID; 219755; 3.
DR DIP; DIP-57696N; -.
DR IntAct; Q99PV5; 25.
DR MINT; Q99PV5; -.
DR STRING; 10090.ENSMUSP00000032386; -.
DR iPTMnet; Q99PV5; -.
DR PhosphoSitePlus; Q99PV5; -.
DR MaxQB; Q99PV5; -.
DR PaxDb; Q99PV5; -.
DR PRIDE; Q99PV5; -.
DR ProteomicsDB; 273682; -.
DR Antibodypedia; 24289; 460 antibodies from 32 providers.
DR DNASU; 79362; -.
DR Ensembl; ENSMUST00000032386; ENSMUSP00000032386; ENSMUSG00000030256.
DR GeneID; 79362; -.
DR KEGG; mmu:79362; -.
DR UCSC; uc009ert.2; mouse.
DR CTD; 79365; -.
DR MGI; MGI:1930704; Bhlhe41.
DR VEuPathDB; HostDB:ENSMUSG00000030256; -.
DR eggNOG; KOG4304; Eukaryota.
DR GeneTree; ENSGT00940000161014; -.
DR HOGENOM; CLU_049895_0_0_1; -.
DR InParanoid; Q99PV5; -.
DR OMA; PLYMCKS; -.
DR OrthoDB; 629563at2759; -.
DR PhylomeDB; Q99PV5; -.
DR TreeFam; TF330859; -.
DR BioGRID-ORCS; 79362; 2 hits in 74 CRISPR screens.
DR ChiTaRS; Bhlhe41; mouse.
DR PRO; PR:Q99PV5; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q99PV5; protein.
DR Bgee; ENSMUSG00000030256; Expressed in retinal neural layer and 109 other tissues.
DR ExpressionAtlas; Q99PV5; baseline and differential.
DR Genevisible; Q99PV5; MM.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0017053; C:transcription repressor complex; TAS:MGI.
DR GO; GO:0043425; F:bHLH transcription factor binding; IDA:BHF-UCL.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:BHF-UCL.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:BHF-UCL.
DR GO; GO:0070888; F:E-box binding; IDA:BHF-UCL.
DR GO; GO:0042826; F:histone deacetylase binding; IDA:BHF-UCL.
DR GO; GO:0043426; F:MRF binding; IDA:BHF-UCL.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:BHF-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:BHF-UCL.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:BHF-UCL.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IDA:BHF-UCL.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0003714; F:transcription corepressor activity; TAS:MGI.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IBA:GO_Central.
DR GO; GO:0032922; P:circadian regulation of gene expression; IMP:BHF-UCL.
DR GO; GO:0007623; P:circadian rhythm; IEP:UniProtKB.
DR GO; GO:0010832; P:negative regulation of myotube differentiation; IDA:BHF-UCL.
DR GO; GO:0010944; P:negative regulation of transcription by competitive promoter binding; IDA:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0050767; P:regulation of neurogenesis; IBA:GO_Central.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR InterPro; IPR003650; Orange_dom.
DR Pfam; PF07527; Hairy_orange; 1.
DR Pfam; PF00010; HLH; 1.
DR SMART; SM00353; HLH; 1.
DR SMART; SM00511; ORANGE; 1.
DR SUPFAM; SSF47459; SSF47459; 1.
DR PROSITE; PS50888; BHLH; 1.
DR PROSITE; PS51054; ORANGE; 1.
PE 1: Evidence at protein level;
KW Biological rhythms; DNA-binding; Isopeptide bond; Nucleus;
KW Reference proteome; Repressor; Transcription; Transcription regulation;
KW Ubl conjugation.
FT CHAIN 1..410
FT /note="Class E basic helix-loop-helix protein 41"
FT /id="PRO_0000127148"
FT DOMAIN 44..99
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT DOMAIN 131..166
FT /note="Orange"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00380"
FT REGION 209..255
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 360..410
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CROSSLNK 31
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9C0J9"
FT CROSSLNK 121
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9C0J9"
FT CROSSLNK 240
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9C0J9"
SQ SEQUENCE 410 AA; 43946 MW; 40A87281B08E233D CRC64;
MDEGIPHLQE RQLLEHRDFI GLDYSSLYMC KPKRSLKRDD TKDTYKLPHR LIEKKRRDRI
NECIAQLKDL LPEHLKLTTL GHLEKAVVLE LTLKHLKALT ALTEQQHQKI IALQNGERSL
KSPVQADLDA FHSGFQTCAK EVLQYLARFE SWTPREPRCA QLVSHLHAVA TQLLTPQVPS
GRGSGRAPCS AGAAAASGPE RVARCVPVIQ RTQPGTEPEH DTDTDSGYGG EAEQGRAAVK
QEPPGDSSPA PKRPKLEARG ALLGPEPALL GSLVALGGGA PFAQPAAAPF CLPFYLLSPS
AAAYVQPWLD KSGLDKYLYP AAAAPFPLLY PGIPAAAAAA AAAAFPCLSS VLSPPPEKAG
ATAGAPFLAH EVAPPGPLRP QHAHSRTHLP RAVNPESSQE DATQPAKDAP
