BHE40_PONAB
ID BHE40_PONAB Reviewed; 412 AA.
AC Q5RAI7;
DT 25-NOV-2008, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 25-MAY-2022, entry version 87.
DE RecName: Full=Class E basic helix-loop-helix protein 40;
DE Short=bHLHe40;
DE AltName: Full=Class B basic helix-loop-helix protein 2;
DE Short=bHLHb2;
GN Name=BHLHE40; Synonyms=BHLHB2;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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
CC PER1/2 and in turn is repressed by PER1/2 and CRY1/2. Represses the
CC activity of the circadian transcriptional activator: CLOCK-
CC ARNTL/BMAL1|ARNTL2/BMAL2 heterodimer by competing for the binding to E-
CC box elements (5'-CACGTG-3') found within the promoters of its target
CC genes. Negatively regulates its own expression and the expression of
CC DBP and BHLHE41/DEC2. Acts as a corepressor of RXR and the RXR-LXR
CC heterodimers and represses the ligand-induced RXRA and NR1H3/LXRA
CC transactivation activity. May be involved in the regulation of
CC chondrocyte differentiation via the cAMP pathway (By similarity).
CC Represses the transcription of NR0B2 and attentuates the
CC transactivation of NR0B2 by the CLOCK-ARNTL/BMAL1 complex (By
CC similarity). Drives the circadian rhythm of blood pressure through
CC transcriptional repression of ATP1B1 in the cardiovascular system (By
CC similarity). {ECO:0000250|UniProtKB:O14503,
CC ECO:0000250|UniProtKB:O35185}.
CC -!- SUBUNIT: Homodimer. Heterodimer with BHLHE41/DEC2. Interacts with
CC TCF3/E47. Interacts with ubiquitin-conjugating enzyme UBE2I/UBC9.
CC Interacts with HDAC1, SUMO1, RXRA and ARNTL/BMAL1 (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O14503}. Nucleus
CC {ECO:0000250|UniProtKB:O14503}. Note=Predominantly localized in the
CC nucleus (By similarity). {ECO:0000250|UniProtKB:O14503}.
CC -!- PTM: Ubiquitinated; which may lead to proteasomal degradation.
CC {ECO:0000250}.
CC -!- PTM: Sumoylation inhibits its ubiquitination and promotes its negative
CC regulation of the CLOCK-ARNTL/BMAL1 heterodimer transcriptional
CC activator activity. {ECO:0000250}.
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DR EMBL; CR859028; CAH91223.1; -; mRNA.
DR RefSeq; NP_001125722.1; NM_001132250.1.
DR AlphaFoldDB; Q5RAI7; -.
DR SMR; Q5RAI7; -.
DR STRING; 9601.ENSPPYP00000015316; -.
DR GeneID; 100172646; -.
DR KEGG; pon:100172646; -.
DR CTD; 8553; -.
DR eggNOG; KOG4304; Eukaryota.
DR InParanoid; Q5RAI7; -.
DR OrthoDB; 629563at2759; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0070888; F:E-box binding; ISS:UniProtKB.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0007623; P:circadian rhythm; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
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; Cytoplasm; DNA-binding; Isopeptide bond; Nucleus;
KW Phosphoprotein; Reference proteome; Repressor; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..412
FT /note="Class E basic helix-loop-helix protein 40"
FT /id="PRO_0000354687"
FT DOMAIN 52..107
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT DOMAIN 142..175
FT /note="Orange"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00380"
FT REGION 1..139
FT /note="Essential for interaction with ARNTL/BMAL1, E-box
FT binding and repressor activity against the CLOCK-
FT ARNTL/BMAL1 heterodimer"
FT /evidence="ECO:0000250"
FT REGION 75..79
FT /note="Necessary for interaction with RXRA and repressor
FT activity against RXRA"
FT /evidence="ECO:0000250"
FT REGION 183..259
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 275..309
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 224..243
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 244..259
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 275..298
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 235
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O14503"
FT MOD_RES 383
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35185"
FT CROSSLNK 159
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1, SUMO2 and SUMO3)"
FT /evidence="ECO:0000250"
FT CROSSLNK 167
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O14503"
FT CROSSLNK 279
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1); alternate"
FT /evidence="ECO:0000250|UniProtKB:O14503"
FT CROSSLNK 279
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1, SUMO2 and SUMO3); alternate"
FT /evidence="ECO:0000250"
FT CROSSLNK 279
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:O14503"
FT CROSSLNK 288
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O14503"
SQ SEQUENCE 412 AA; 45516 MW; A5A94B23DBF77205 CRC64;
MERIPSAQPP PACLPKAPGL EHGDLPGMYP AHMYQVYKSR RGIKRSEDSK ETYKLPHRLI
EKKRRDRINE CIAQLKDLLP EHLKLTTLGH LEKAVVLELT LKHVKALTNL IDQQQQKIIA
LQSGLQAGEL SGRNVETGQE MFCSGFQTCA REVLQYLAKH ENTRDLKSSQ LVTHLHRVVS
ELLQGGTSRK SSDPAPKVMD FKEKPSSPAK GSEGPGKNCV PVIQRTFAHS SGEQSGSDTD
TDSGYGGESE KGDLRSEQLC FKSDHGRRFT MGERIGAIKQ ESEEPPTKKN RMQLSDDEGH
FTSSDLISSP FLGPHPHQPP FCLPFYLIPP SATAYLPMLE KCWYPTSVPV LYPGLNASAA
ALSSFMNPDK ISAPLLMPQR LPSPLPAHPS VDSSVLLQAL KPIPPLNLET KD
