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   24-JAN-2024, entry version 163.
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 BMAL1.
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-BMAL1 heterodimer by
CC       competing for the binding to E-box elements (5'-CACGTG-3') found within
CC       the promoters of its target genes. Negatively regulates its own
CC       expression and the expression of DBP and BHLHE41/DEC2. Acts as a
CC       corepressor of RXR and the RXR-LXR heterodimers and represses the
CC       ligand-induced RXRA/B/G, NR1H3/LXRA, NR1H4 and VDR transactivation
CC       activity. Inhibits HNF1A-mediated transactivation of CYP1A2, CYP2E1 and
CC       CYP3A11 (PubMed:30555544). {ECO:0000269|PubMed:12397359,
CC       ECO:0000269|PubMed:14672706, ECO:0000269|PubMed:18411297,
CC       ECO:0000269|PubMed:19786558, ECO:0000269|PubMed:24736997,
CC       ECO:0000269|PubMed:30555544}.
CC   -!- SUBUNIT: Homodimer (PubMed:15560782). Heterodimer with BHLHE40/DEC1
CC       (PubMed:15560782). Interacts with CIART (PubMed:24736997). Interacts
CC       with BMAL1 (PubMed:12397359). Interacts with RXRA (By similarity).
CC       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; 10090-ENSMUSP00000032386; -.
DR   ProteomicsDB; 273682; -.
DR   Antibodypedia; 24289; 529 antibodies from 32 providers.
DR   DNASU; 79362; -.
DR   Ensembl; ENSMUST00000032386.11; ENSMUSP00000032386.5; ENSMUSG00000030256.12.
DR   GeneID; 79362; -.
DR   KEGG; mmu:79362; -.
DR   UCSC; uc009ert.2; mouse.
DR   AGR; MGI:1930704; -.
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; KKPKMNW; -.
DR   OrthoDB; 2968390at2759; -.
DR   PhylomeDB; Q99PV5; -.
DR   TreeFam; TF330859; -.
DR   BioGRID-ORCS; 79362; 2 hits in 79 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 111 other cell types or tissues.
DR   ExpressionAtlas; Q99PV5; baseline and differential.
DR   GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
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:0045892; P:negative regulation of DNA-templated transcription; IDA: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:0050767; P:regulation of neurogenesis; IBA:GO_Central.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   CDD; cd19750; bHLH-O_DEC2; 1.
DR   Gene3D; 6.10.250.980; -; 1.
DR   Gene3D; 4.10.280.10; Helix-loop-helix DNA-binding domain; 1.
DR   InterPro; IPR011598; bHLH_dom.
DR   InterPro; IPR036638; HLH_DNA-bd_sf.
DR   InterPro; IPR003650; Orange_dom.
DR   PANTHER; PTHR10985; BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTOR, HES-RELATED; 1.
DR   PANTHER; PTHR10985:SF76; CLASS E BASIC HELIX-LOOP-HELIX PROTEIN 41; 1.
DR   Pfam; PF07527; Hairy_orange; 1.
DR   Pfam; PF00010; HLH; 1.
DR   SMART; SM00353; HLH; 1.
DR   SMART; SM00511; ORANGE; 1.
DR   SUPFAM; SSF47459; HLH, helix-loop-helix DNA-binding domain; 1.
DR   SUPFAM; SSF158457; Orange domain-like; 1.
DR   PROSITE; PS50888; BHLH; 1.
DR   PROSITE; PS51054; ORANGE; 1.
DR   Genevisible; Q99PV5; MM.
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
//