BMAL1_RAT
ID BMAL1_RAT Reviewed; 626 AA.
AC Q9EPW1; O88337; O88810; Q499M8;
DT 15-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2007, sequence version 4.
DT 25-MAY-2022, entry version 159.
DE RecName: Full=Aryl hydrocarbon receptor nuclear translocator-like protein 1;
DE AltName: Full=Brain and muscle ARNT-like 1;
DE AltName: Full=Tic;
GN Name=Arntl; Synonyms=Bmal1, Tic;
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] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=9735336; DOI=10.1006/bbrc.1998.9275;
RA Honma S., Ikeda M., Abe H., Tanahashi Y., Namihira M., Honma K., Nomura M.;
RT "Circadian oscillation of BMAL1, a partner of a mammalian clock gene clock,
RT in rat suprachiasmatic nucleus.";
RL Biochem. Biophys. Res. Commun. 250:83-87(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=9585435; DOI=10.1007/s003359900797;
RA Wolting C.D., McGlade C.J.;
RT "Cloning and chromosomal localization of a new member of the bHLH/PAS
RT transcription factor family.";
RL Mamm. Genome 9:463-468(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RC STRAIN=Wistar; TISSUE=Brain;
RA Jac M., Sladek M., Sauman I.;
RT "Sequence of Rat BMAL1g' cDNA.";
RL Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Prostate;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=22356123; DOI=10.1111/j.1365-2826.2012.02302.x;
RA Matagne V., Kim J.G., Ryu B.J., Hur M.K., Kim M.S., Kim K., Park B.S.,
RA Damante G., Smiley G., Lee B.J., Ojeda S.R.;
RT "Thyroid transcription factor 1, a homeodomain containing transcription
RT factor, contributes to regulating periodic oscillations in GnRH gene
RT expression.";
RL J. Neuroendocrinol. 24:916-929(2012).
RN [6]
RP FUNCTION.
RX PubMed=23596172; DOI=10.1152/ajpcell.00008.2013;
RA Chen H., Zhao L., Kumazawa M., Yamauchi N., Shigeyoshi Y., Hashimoto S.,
RA Hattori M.A.;
RT "Downregulation of core clock gene Bmal1 attenuates expression of
RT progesterone and prostaglandin biosynthesis-related genes in rat
RT luteinizing granulosa cells.";
RL Am. J. Physiol. 304:C1131-C1140(2013).
CC -!- FUNCTION: Transcriptional activator which forms a core component of the
CC circadian clock. The circadian clock, an internal time-keeping system,
CC regulates various physiological processes through the generation of
CC approximately 24 hour circadian rhythms in gene expression, which are
CC translated into rhythms in metabolism and behavior. It is derived from
CC the Latin roots 'circa' (about) and 'diem' (day) and acts as an
CC important regulator of a wide array of physiological functions
CC including metabolism, sleep, body temperature, blood pressure,
CC endocrine, immune, cardiovascular, and renal function. Consists of two
CC major components: the central clock, residing in the suprachiasmatic
CC nucleus (SCN) of the brain, and the peripheral clocks that are present
CC in nearly every tissue and organ system. Both the central and
CC peripheral clocks can be reset by environmental cues, also known as
CC Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the
CC central clock is light, which is sensed by retina and signals directly
CC to the SCN. The central clock entrains the peripheral clocks through
CC neuronal and hormonal signals, body temperature and feeding-related
CC cues, aligning all clocks with the external light/dark cycle. Circadian
CC rhythms allow an organism to achieve temporal homeostasis with its
CC environment at the molecular level by regulating gene expression to
CC create a peak of protein expression once every 24 hours to control when
CC a particular physiological process is most active with respect to the
CC solar day. Transcription and translation of core clock components
CC (CLOCK, NPAS2, ARNTL/BMAL1, ARNTL2/BMAL2, PER1, PER2, PER3, CRY1 and
CC CRY2) plays a critical role in rhythm generation, whereas delays
CC imposed by post-translational modifications (PTMs) are important for
CC determining the period (tau) of the rhythms (tau refers to the period
CC of a rhythm and is the length, in time, of one complete cycle). A
CC diurnal rhythm is synchronized with the day/night cycle, while the
CC ultradian and infradian rhythms have a period shorter and longer than
CC 24 hours, respectively. Disruptions in the circadian rhythms contribute
CC to the pathology of cardiovascular diseases, cancer, metabolic
CC syndromes and aging. A transcription/translation feedback loop (TTFL)
CC forms the core of the molecular circadian clock mechanism.
CC Transcription factors, CLOCK or NPAS2 and ARNTL/BMAL1 or ARNTL2/BMAL2,
CC form the positive limb of the feedback loop, act in the form of a
CC heterodimer and activate the transcription of core clock genes and
CC clock-controlled genes (involved in key metabolic processes), harboring
CC E-box elements (5'-CACGTG-3') within their promoters. The core clock
CC genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form
CC the negative limb of the feedback loop and interact with the
CC CLOCK|NPAS2-ARNTL/BMAL1|ARNTL2/BMAL2 heterodimer inhibiting its
CC activity and thereby negatively regulating their own expression. This
CC heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G,
CC which form a second feedback loop and which activate and repress
CC ARNTL/BMAL1 transcription, respectively. ARNTL/BMAL1 positively
CC regulates myogenesis and negatively regulates adipogenesis via the
CC transcriptional control of the genes of the canonical Wnt signaling
CC pathway. Plays a role in normal pancreatic beta-cell function;
CC regulates glucose-stimulated insulin secretion via the regulation of
CC antioxidant genes NFE2L2/NRF2 and its targets SESN2, PRDX3, CCLC and
CC CCLM. Negatively regulates the mTORC1 signaling pathway; regulates the
CC expression of MTOR and DEPTOR. Controls diurnal oscillations of Ly6C
CC inflammatory monocytes; rhythmic recruitment of the PRC2 complex
CC imparts diurnal variation to chemokine expression that is necessary to
CC sustain Ly6C monocyte rhythms. Regulates the expression of HSD3B2,
CC STAR, PTGS2, CYP11A1, CYP19A1 and LHCGR in the ovary and also the genes
CC involved in hair growth. Plays an important role in adult hippocampal
CC neurogenesis by regulating the timely entry of neural stem/progenitor
CC cells (NSPCs) into the cell cycle and the number of cell divisions that
CC take place prior to cell-cycle exit. Regulates the circadian expression
CC of CIART and KLF11. The CLOCK-ARNTL/BMAL1 heterodimer regulates the
CC circadian expression of SERPINE1/PAI1, VWF, B3, CCRN4L/NOC, NAMPT, DBP,
CC MYOD1, PPARGC1A, PPARGC1B, SIRT1, GYS2, F7, NGFR, GNRHR, BHLHE40/DEC1,
CC ATF4, MTA1, KLF10 and also genes implicated in glucose and lipid
CC metabolism. Promotes rhythmic chromatin opening, regulating the DNA
CC accessibility of other transcription factors. May play a role in
CC spermatogenesis; contributes to the chromatoid body assembly and
CC physiology. The NPAS2-ARNTL/BMAL1 heterodimer positively regulates the
CC expression of MAOA, F7 and LDHA and modulates the circadian rhythm of
CC daytime contrast sensitivity by regulating the rhythmic expression of
CC adenylate cyclase type 1 (ADCY1) in the retina. The preferred binding
CC motif for the CLOCK-ARNTL/BMAL1 heterodimer is 5'-CACGTGA-3', which
CC contains a flanking Ala residue in addition to the canonical 6-
CC nucleotide E-box sequence (By similarity). CLOCK specifically binds to
CC the half-site 5'-CAC-3', while ARNTL binds to the half-site 5'-GTGA-3'
CC (By similarity). The CLOCK-ARNTL/BMAL1 heterodimer also recognizes the
CC non-canonical E-box motifs 5'-AACGTGA-3' and 5'-CATGTGA-3'. Essential
CC for the rhythmic interaction of CLOCK with ASS1 and plays a critical
CC role in positively regulating CLOCK-mediated acetylation of ASS1 (By
CC similarity). Plays a role in protecting against lethal sepsis by
CC limiting the expression of immune checkpoint protein CD274 in
CC macrophages in a PKM2-dependent manner (By similarity). Regulates the
CC diurnal rhythms of skeletal muscle metabolism via transcriptional
CC activation of genes promoting triglyceride synthesis (DGAT2) and
CC metabolic efficiency (COQ10B) (By similarity).
CC {ECO:0000250|UniProtKB:O00327, ECO:0000250|UniProtKB:Q9WTL8,
CC ECO:0000269|PubMed:22356123, ECO:0000269|PubMed:23596172}.
CC -!- SUBUNIT: Component of the circadian clock oscillator which includes the
CC CRY1/2 proteins, CLOCK or NPAS2, ARNTL/BMAL1 or ARNTL2/BMAL2, CSNK1D
CC and/or CSNK1E, TIMELESS and the PER1/2/3 proteins (By similarity).
CC Forms a heterodimer with CLOCK (By similarity). The CLOCK-ARNTL/BMAL1
CC heterodimer is required for E-box-dependent transactivation, for CLOCK
CC nuclear translocation and degradation, and, for phosphorylation of both
CC CLOCK and ARNTL/BMAL1 (By similarity). Part of a nuclear complex which
CC also includes RACK1 and PRKCA; RACK1 and PRKCA are recruited to the
CC complex in a circadian manner (By similarity). Interacts with NPAS2 (By
CC similarity). Interacts with EZH2 (By similarity). Interacts with SUMO3
CC (By similarity). Interacts with SIRT1 (By similarity). Interacts with
CC AHR (By similarity). Interacts with ID1, ID2 and ID3 (By similarity).
CC Interacts with DDX4 (By similarity). Interacts with OGT (By
CC similarity). Interacts with EED and SUZ12 (By similarity). Interacts
CC with MTA1 (By similarity). Interacts with CIART (By similarity).
CC Interacts with HSP90 (By similarity). Interacts with KAT2B and EP300
CC (By similarity). Interacts with BHLHE40/DEC1 and BHLHE41/DEC2 (By
CC similarity). Interacts with RELB and the interaction is enhanced in the
CC presence of CLOCK (By similarity). Interacts with PER1, PER2, CRY1 and
CC CRY2 and this interaction requires a translocation to the nucleus (By
CC similarity). Interaction of the CLOCK-ARNTL/BMAL1 heterodimer with PER
CC or CRY inhibits transcription activation (By similarity). Interaction
CC of the CLOCK-ARNTL/BMAL1 with CRY1 is independent of DNA but with PER2
CC is off DNA (By similarity). The CLOCK-ARNTL/BMAL1 heterodimer interacts
CC with GSK3B (By similarity). Interacts with KDM5A (By similarity).
CC Interacts with KMT2A; in a circadian manner (By similarity). Interacts
CC with UBE3A (By similarity). Interacts with PRKCG (By similarity).
CC Interacts with MAGEL2 (By similarity). Interacts with NCOA2 (By
CC similarity). Interacts with THRAP3 (By similarity). The CLOCK-
CC ARNTL/BMAL1 heterodimer interacts with PASD1 (By similarity). Interacts
CC with PASD1 (By similarity). Interacts with USP9X (By similarity).
CC Interacts with PIWIL2 (via PIWI domain) (By similarity). Interacts with
CC HDAC3 (By similarity). Interacts with HNF4A (By similarity).
CC {ECO:0000250|UniProtKB:O00327, ECO:0000250|UniProtKB:Q9WTL8}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00981,
CC ECO:0000269|PubMed:22356123}. Cytoplasm {ECO:0000250|UniProtKB:Q9WTL8}.
CC Nucleus, PML body {ECO:0000250|UniProtKB:Q9WTL8}. Note=Shuttles between
CC the nucleus and the cytoplasm and this nucleocytoplasmic shuttling is
CC essential for the nuclear accumulation of CLOCK, target gene
CC transcription and the degradation of the CLOCK-ARNTL/BMAL1 heterodimer.
CC The sumoylated form localizes in the PML body. Sequestered to the
CC cytoplasm in the presence of ID2. {ECO:0000250|UniProtKB:Q9WTL8}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=b;
CC IsoId=Q9EPW1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9EPW1-2; Sequence=VSP_007997;
CC Name=3; Synonyms=g';
CC IsoId=Q9EPW1-3; Sequence=VSP_007998, VSP_007999;
CC -!- PTM: Ubiquitinated, leading to its proteasomal degradation.
CC Deubiquitinated by USP9X. {ECO:0000250|UniProtKB:Q9WTL8}.
CC -!- PTM: O-glycosylated; contains O-GlcNAc. O-glycosylation by OGT prevents
CC protein degradation by inhibiting ubiquitination. It also stabilizes
CC the CLOCK-ARNTL/BMAL1 heterodimer thereby increasing CLOCK-ARNTL/BMAL1-
CC mediated transcription of genes in the negative loop of the circadian
CC clock such as PER1/2/3 and CRY1/2. {ECO:0000250|UniProtKB:Q9WTL8}.
CC -!- PTM: Acetylated on Lys-538 by CLOCK during the repression phase of the
CC circadian cycle. Acetylation facilitates recruitment of CRY1 protein
CC and initiates the repression phase of the circadian cycle. Acetylated
CC at Lys-538 by KAT5 during the activation phase of the cycle, leading to
CC recruitment of the positive transcription elongation factor b (P-TEFb)
CC and BRD4, followed by productive elongation of circadian transcripts.
CC Deacetylated by SIRT1, which may result in decreased protein stability.
CC {ECO:0000250|UniProtKB:Q9WTL8}.
CC -!- PTM: Phosphorylated upon dimerization with CLOCK. Phosphorylation
CC enhances the transcriptional activity, alters the subcellular
CC localization and decreases the stability of the CLOCK-ARNTL/BMAL1
CC heterodimer by promoting its degradation. Phosphorylation shows
CC circadian variations in the liver with a peak between CT10 to CT14.
CC Phosphorylation at Ser-90 by CK2 is essential for its nuclear
CC localization, its interaction with CLOCK and controls CLOCK nuclear
CC entry. Dephosphorylation at Ser-78 is important for dimerization with
CC CLOCK and transcriptional activity. {ECO:0000250|UniProtKB:O00327,
CC ECO:0000250|UniProtKB:Q9WTL8}.
CC -!- PTM: Sumoylated on Lys-259 upon dimerization with CLOCK. Predominantly
CC conjugated to poly-SUMO2/3 rather than SUMO1 and the level of these
CC conjugates undergo rhythmic variation, peaking at CT9-CT12. Sumoylation
CC localizes it exclusively to the PML body and promotes its
CC ubiquitination in the PML body, ubiquitin-dependent proteasomal
CC degradation and the transcriptional activity of the CLOCK-ARNTL/BMAL1
CC heterodimer. {ECO:0000250|UniProtKB:Q9WTL8}.
CC -!- PTM: Undergoes lysosome-mediated degradation in a time-dependent manner
CC in the liver. {ECO:0000250|UniProtKB:Q9WTL8}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC21449.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB012600; BAA33450.1; -; mRNA.
DR EMBL; AF015953; AAC21449.1; ALT_INIT; mRNA.
DR EMBL; AF317669; AAG34180.2; -; mRNA.
DR EMBL; BC099833; AAH99833.1; -; mRNA.
DR RefSeq; NP_077338.2; NM_024362.2.
DR RefSeq; XP_006230091.1; XM_006230029.3.
DR AlphaFoldDB; Q9EPW1; -.
DR SMR; Q9EPW1; -.
DR STRING; 10116.ENSRNOP00000042830; -.
DR PhosphoSitePlus; Q9EPW1; -.
DR PRIDE; Q9EPW1; -.
DR GeneID; 29657; -.
DR KEGG; rno:29657; -.
DR UCSC; RGD:62003; rat. [Q9EPW1-1]
DR CTD; 406; -.
DR RGD; 62003; Arntl.
DR eggNOG; KOG3561; Eukaryota.
DR InParanoid; Q9EPW1; -.
DR OrthoDB; 331262at2759; -.
DR PhylomeDB; Q9EPW1; -.
DR PRO; PR:Q9EPW1; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0034751; C:aryl hydrocarbon receptor complex; IBA:GO_Central.
DR GO; GO:0033391; C:chromatoid body; ISS:UniProtKB.
DR GO; GO:1990513; C:CLOCK-BMAL transcription complex; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0016604; C:nuclear body; ISO:RGD.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
DR GO; GO:0005667; C:transcription regulator complex; ISS:UniProtKB.
DR GO; GO:0017162; F:aryl hydrocarbon receptor binding; ISO:RGD.
DR GO; GO:0043425; F:bHLH transcription factor binding; ISO:RGD.
DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; ISO:RGD.
DR GO; GO:0070888; F:E-box binding; ISS:UniProtKB.
DR GO; GO:0051879; F:Hsp90 protein binding; ISO:RGD.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:RGD.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:RGD.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISS:UniProtKB.
DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0007623; P:circadian rhythm; IEP:RGD.
DR GO; GO:0060137; P:maternal process involved in parturition; ISO:RGD.
DR GO; GO:0120163; P:negative regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0045599; P:negative regulation of fat cell differentiation; ISS:UniProtKB.
DR GO; GO:2000323; P:negative regulation of glucocorticoid receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0032007; P:negative regulation of TOR signaling; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0090403; P:oxidative stress-induced premature senescence; ISS:UniProtKB.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; ISS:UniProtKB.
DR GO; GO:0042753; P:positive regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:1901985; P:positive regulation of protein acetylation; ISS:UniProtKB.
DR GO; GO:2001016; P:positive regulation of skeletal muscle cell differentiation; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0006606; P:protein import into nucleus; ISO:RGD.
DR GO; GO:0051726; P:regulation of cell cycle; ISS:UniProtKB.
DR GO; GO:2000772; P:regulation of cellular senescence; ISS:UniProtKB.
DR GO; GO:0042634; P:regulation of hair cycle; ISS:UniProtKB.
DR GO; GO:0050796; P:regulation of insulin secretion; ISS:UniProtKB.
DR GO; GO:0050767; P:regulation of neurogenesis; ISS:UniProtKB.
DR GO; GO:0042176; P:regulation of protein catabolic process; ISO:RGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:2000074; P:regulation of type B pancreatic cell development; ISS:UniProtKB.
DR GO; GO:0051775; P:response to redox state; ISS:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; ISS:UniProtKB.
DR CDD; cd00130; PAS; 2.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR InterPro; IPR001067; Nuc_translocat.
DR InterPro; IPR001610; PAC.
DR InterPro; IPR000014; PAS.
DR InterPro; IPR035965; PAS-like_dom_sf.
DR InterPro; IPR013767; PAS_fold.
DR Pfam; PF00010; HLH; 1.
DR Pfam; PF00989; PAS; 1.
DR PRINTS; PR00785; NCTRNSLOCATR.
DR SMART; SM00353; HLH; 1.
DR SMART; SM00086; PAC; 1.
DR SMART; SM00091; PAS; 2.
DR SUPFAM; SSF47459; SSF47459; 1.
DR SUPFAM; SSF55785; SSF55785; 2.
DR TIGRFAMs; TIGR00229; sensory_box; 1.
DR PROSITE; PS50888; BHLH; 1.
DR PROSITE; PS50112; PAS; 2.
PE 2: Evidence at transcript level;
KW Acetylation; Activator; Alternative splicing; Biological rhythms;
KW Cytoplasm; DNA-binding; Isopeptide bond; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Transcription; Transcription regulation;
KW Ubl conjugation.
FT CHAIN 1..626
FT /note="Aryl hydrocarbon receptor nuclear translocator-like
FT protein 1"
FT /id="PRO_0000127159"
FT DOMAIN 72..125
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT DOMAIN 143..215
FT /note="PAS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 326..396
FT /note="PAS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 401..444
FT /note="PAC"
FT REGION 1..58
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 459..492
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 508..588
FT /note="Interaction with CIART"
FT /evidence="ECO:0000250|UniProtKB:Q9WTL8"
FT REGION 511..595
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 36..41
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:Q9WTL8"
FT MOTIF 142..152
FT /note="Nuclear export signal 1"
FT /evidence="ECO:0000250|UniProtKB:Q9WTL8"
FT MOTIF 361..369
FT /note="Nuclear export signal 2"
FT /evidence="ECO:0000250|UniProtKB:Q9WTL8"
FT COMPBIAS 1..37
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 38..58
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 512..532
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 77
FT /note="Interaction with E-box DNA"
FT /evidence="ECO:0000250|UniProtKB:O00327"
FT SITE 80
FT /note="Interaction with E-box DNA"
FT /evidence="ECO:0000250|UniProtKB:O00327"
FT SITE 81
FT /note="Interaction with E-box DNA"
FT /evidence="ECO:0000250|UniProtKB:O00327"
FT SITE 85
FT /note="Interaction with E-box DNA"
FT /evidence="ECO:0000250|UniProtKB:O00327"
FT SITE 125
FT /note="Important for interaction with CLOCK"
FT /evidence="ECO:0000250|UniProtKB:O00327"
FT MOD_RES 17
FT /note="Phosphoserine; by GSK3-beta"
FT /evidence="ECO:0000250|UniProtKB:Q9WTL8"
FT MOD_RES 21
FT /note="Phosphothreonine; by GSK3-beta"
FT /evidence="ECO:0000250|UniProtKB:Q9WTL8"
FT MOD_RES 78
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O00327"
FT MOD_RES 90
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000250|UniProtKB:Q9WTL8"
FT MOD_RES 538
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9WTL8"
FT CROSSLNK 252
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2 and SUMO3)"
FT /evidence="ECO:0000250|UniProtKB:Q9WTL8"
FT CROSSLNK 259
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9WTL8"
FT CROSSLNK 259
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:O00327"
FT VAR_SEQ 154..263
FT /note="AADGFLFVVGCDRGKILFVSESVFKILNYSQNDLIGQSLFDYLHPKDIAKVK
FT EQLSSSDTAPRERLIDAKTGLPVKTDITPGPSRLCSGARRSFFCRMKCNRPSVKVEDK
FT -> DVTEGRSSLSPNLSSRSSIIARMTLLARVCSTTCIQKILPKLRNSYLPRTLHLGSS
FT RSSIIARMTLLARVCSTTCIQKILPKLRNSYLPRTLHLGSDSSMRRLDFRLKRI (in
FT isoform 3)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_007998"
FT VAR_SEQ 154..184
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9585435"
FT /id="VSP_007997"
FT VAR_SEQ 264..626
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_007999"
FT CONFLICT 141
FT /note="S -> F (in Ref. 2; AAC21449, 3; AAG34180 and 4;
FT AAH99833)"
FT /evidence="ECO:0000305"
FT CONFLICT 505
FT /note="E -> G (in Ref. 1; BAA33450)"
FT /evidence="ECO:0000305"
FT CONFLICT 603
FT /note="I -> T (in Ref. 1; BAA33450)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 626 AA; 68616 MW; 512746E8F87659F5 CRC64;
MADQRMDISS TISDFMSPGP TDLLSGSLST SGVDCNRKRK GSATDYQESM DTDKDDPHGR
LEYAEHQGRI KNAREAHSQI EKRRRDKMNS FIDELASLVP TCNAMSRKLD KLTVLRMAVQ
HMKTLRGATN PYTEANYKPT SLSDDELKHL ILRAADGFLF VVGCDRGKIL FVSESVFKIL
NYSQNDLIGQ SLFDYLHPKD IAKVKEQLSS SDTAPRERLI DAKTGLPVKT DITPGPSRLC
SGARRSFFCR MKCNRPSVKV EDKDFASTCS KKKADRKSFC TIHSTGYLKS WPPTKMGLDE
DSEPDNEGCN LSCLVAIGRL HSHMVPQPVN GEIRVKSMEY VSRHAIDGKF VFVDQRATAI
LAYLPQELLG TSCYEYFHQD DIGHLAECHR QVLQTREKIT TNCYKFKIKD GSFITLRSRW
FSFMNPWTKE VEYIVSTNTV VLANVLEGGD PTFPQLTASP HSMDSMLPSG EGGPKRTHPT
VPGIPGGTRA GAGKIGRMIA EEIMEIHRIR GSSPSSCGSS PLNITSTPPP DASSPGGKKI
LNGGTPDIPS AGLLPGQAQE TPGYPYSDSS SILGENPHIG IDMIDNDQGS SSPSNDEAAM
AVIMSLLEAD AGLGGPVDFS DLPWPL
