BHE41_RAT
ID BHE41_RAT Reviewed; 410 AA.
AC O35779;
DT 05-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 05-MAR-2002, sequence version 2.
DT 03-AUG-2022, entry version 129.
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=Enhancer-of-split and hairy-related protein 1;
DE Short=SHARP-1;
GN Name=Bhlhb3; Synonyms=Sharp1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Cerebellum;
RX PubMed=9532582; DOI=10.1006/mcne.1997.0640;
RA Rossner M.J., Doerr J., Gass P., Schwab M.H., Nave K.-A.;
RT "SHARPs: mammalian enhancer-of-split- and hairy-related proteins coupled to
RT neuronal stimulation.";
RL Mol. Cell. Neurosci. 10:460-475(1997).
RN [2]
RP INDUCTION, AND TISSUE SPECIFICITY.
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).
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 (By similarity). Inhibits HNF1A-mediated
CC transactivation of CYP1A2, CYP2E1 AND CYP3A11 (By similarity).
CC {ECO:0000250|UniProtKB:Q99PV5}.
CC -!- SUBUNIT: Homodimer (By similarity). Heterodimer with BHLHE40/DEC1 (By
CC similarity). Interacts with CIART (By similarity). Interacts with
CC ARNTL/BMAL1 and RXRA (By similarity). Interacts with NR0B2 and HNF1A
CC (By similarity). {ECO:0000250|UniProtKB:Q99PV5,
CC ECO:0000250|UniProtKB:Q9C0J9}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00380,
CC ECO:0000255|PROSITE-ProRule:PRU00981}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the caudate putamen, pineal
CC gland, granular cell layer of the cerebellum, olfactory bulb, piriform
CC cortex, hippocampus and hypothalamic nuclei. Moderately expressed in
CC skeletal muscle, heart. Weakly expressed in lung.
CC {ECO:0000269|PubMed:12397359}.
CC -!- INDUCTION: Expressed in a circadian manner in the suprachiasmatic
CC nucleus (SCN) of the brain. {ECO:0000269|PubMed:12397359}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB63586.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF009329; AAB63586.1; ALT_FRAME; mRNA.
DR AlphaFoldDB; O35779; -.
DR PhosphoSitePlus; O35779; -.
DR RGD; 70900; Bhlhb3.
DR InParanoid; O35779; -.
DR PhylomeDB; O35779; -.
DR PRO; PR:O35779; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0043425; F:bHLH transcription factor binding; ISO:RGD.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0070888; F:E-box binding; ISO:RGD.
DR GO; GO:0042826; F:histone deacetylase binding; ISO:RGD.
DR GO; GO:0043426; F:MRF binding; ISO:RGD.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:RGD.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:RGD.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IBA:GO_Central.
DR GO; GO:0032922; P:circadian regulation of gene expression; ISO:RGD.
DR GO; GO:0007623; P:circadian rhythm; IEP:UniProtKB.
DR GO; GO:0010832; P:negative regulation of myotube differentiation; ISO:RGD.
DR GO; GO:0010944; P:negative regulation of transcription by competitive promoter binding; ISO:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0007399; P:nervous system development; NAS:RGD.
DR GO; GO:0050767; P:regulation of neurogenesis; IBA:GO_Central.
DR GO; GO:0048168; P:regulation of neuronal synaptic plasticity; IEP:RGD.
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 2: Evidence at transcript 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_0000127149"
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..251
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 371..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; 43917 MW; 829705CA3A013127 CRC64;
MDEGIPHLQE RQLLEHRDFI GLDYSSLYMC KPKRSLKRDD TKDTYKLPHR LIEKKRRDRI
NECIAQLKDL LPEHLKLTTL GHLEKAVVLE LTLKHLKALT ALTEQQHQKI IALQNGERSL
KSPVQADLDA FHSGFQTCAK EVLQYLARFE SWTPREPRCA QLVSHLHAVA TQLLTPQVTP
GRGPGRAPCS AGAAAASGSE RVARCVPVIQ RTQPGTEPEH DTDTDSGYGG EAEQGRAAVK
QEPPGDPSAA PKRLKLEARG ALLGPEPALL GSLVALGGGA PFAQPAAAPF CLPFYLLSPS
AAAYVQPWLD KSGLDKYLYP AAAAPFPLLY PGIPAAAAAA AAAAFPCLSS VLSPPPEKAG
SAAGAPFLAH EVAPPGSLRP QHAHSRTHLP HAVNPESSQE DATQPAKDAP
