PER2_RAT
ID PER2_RAT Reviewed; 1257 AA.
AC Q9Z301;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Period circadian protein homolog 2;
DE Short=rPER2;
DE AltName: Full=Circadian clock protein PERIOD 2;
GN Name=Per2 {ECO:0000312|RGD:61945};
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] {ECO:0000305, ECO:0000312|EMBL:BAA34187.1}
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND INDUCTION.
RC STRAIN=Sprague-Dawley {ECO:0000312|EMBL:BAA34187.1};
RC TISSUE=Brain {ECO:0000312|EMBL:BAA34187.1};
RX PubMed=9765215; DOI=10.1074/jbc.273.42.27039;
RA Sakamoto K., Nagase T., Fukui H., Horikawa K., Okada T., Tanaka H.,
RA Sato K., Miyake Y., Ohara O., Kako K., Ishida N.;
RT "Multitissue circadian expression of rat period homologue (rPer2) mRNA is
RT governed by the mammalian circadian clock, the suprachiasmatic nucleus in
RT the brain.";
RL J. Biol. Chem. 273:27039-27042(1998).
RN [2] {ECO:0000305}
RP INTERACTION WITH TIMELESS.
RX PubMed=11112428; DOI=10.1006/bbrc.2000.3927;
RA Sakamoto S., Miyazaki K., Fukui H., Oishi K., Hayasaka N., Okada M.,
RA Kamakura M., Taniguchi T., Nagai K., Ishida N.;
RT "Molecular characterization and nuclear localization of rat timeless-like
RT gene product.";
RL Biochem. Biophys. Res. Commun. 279:131-138(2000).
RN [3]
RP INTERACTION WITH CRY1, CRY BINDING DOMAIN, NUCLEAR LOCALIZATION SIGNAL, AND
RP SUBCELLULAR LOCATION.
RX PubMed=11533252; DOI=10.1128/mcb.21.19.6651-6659.2001;
RA Miyazaki K., Mesaki M., Ishida N.;
RT "Nuclear entry mechanism of rat PER2 (rPER2): role of rPER2 in nuclear
RT localization of CRY protein.";
RL Mol. Cell. Biol. 21:6651-6659(2001).
RN [4] {ECO:0000305}
RP TISSUE SPECIFICITY.
RX PubMed=12710990; DOI=10.1016/s0306-4522(03)00004-6;
RA Shieh K.-R.;
RT "Distribution of the rhythm-related genes rPERIOD1, rPERIOD2, and rCLOCK,
RT in the rat brain.";
RL Neuroscience 118:831-843(2003).
RN [5]
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 [6] {ECO:0000305}
RP TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=15094047; DOI=10.1016/s0014-5793(04)00322-9;
RA Muehlbauer E., Wolgast S., Finckh U., Peschke D., Peschke E.;
RT "Indication of circadian oscillations in the rat pancreas.";
RL FEBS Lett. 564:91-96(2004).
RN [7]
RP INTERACTION WITH BTRC AND FBXW11, AND MUTAGENESIS OF 93-SER--SER-97 AND
RP 478-SER--SER-482.
RX PubMed=18782782; DOI=10.1093/jb/mvn112;
RA Ohsaki K., Oishi K., Kozono Y., Nakayama K., Nakayama K.I., Ishida N.;
RT "The role of {beta}-TrCP1 and {beta}-TrCP2 in circadian rhythm generation
RT by mediating degradation of clock protein PER2.";
RL J. Biochem. 144:609-618(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-693 AND SER-697, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Transcriptional repressor 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 syndrome
CC and aging. A transcription/translation feedback loop (TTFL) forms the
CC core of the molecular circadian clock mechanism. Transcription factors,
CC CLOCK or NPAS2 and ARNTL/BMAL1 or ARNTL2/BMAL2, form the positive limb
CC of the feedback loop, act in the form of a heterodimer and activate the
CC transcription of core clock genes and clock-controlled genes (involved
CC in key metabolic processes), harboring E-box elements (5'-CACGTG-3')
CC within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which
CC are transcriptional repressors form the negative limb of the feedback
CC loop and interact with the CLOCK|NPAS2-ARNTL/BMAL1|ARNTL2/BMAL2
CC heterodimer inhibiting its activity and thereby negatively regulating
CC their own expression. This heterodimer also activates nuclear receptors
CC NR1D1/2 and RORA/B/G, which form a second feedback loop and which
CC activate and repress ARNTL/BMAL1 transcription, respectively. PER1 and
CC PER2 proteins transport CRY1 and CRY2 into the nucleus with appropriate
CC circadian timing, but also contribute directly to repression of clock-
CC controlled target genes through interaction with several classes of
CC RNA-binding proteins, helicases and others transcriptional repressors.
CC PER appears to regulate circadian control of transcription by at least
CC three different modes. First, interacts directly with the CLOCK-
CC ARTNL/BMAL1 at the tail end of the nascent transcript peak to recruit
CC complexes containing the SIN3-HDAC that remodel chromatin to repress
CC transcription. Second, brings H3K9 methyltransferases such as SUV39H1
CC and SUV39H2 to the E-box elements of the circadian target genes, like
CC PER2 itself or PER1. The recruitment of each repressive modifier to the
CC DNA seems to be very precisely temporally orchestrated by the large PER
CC complex, the deacetylases acting before than the methyltransferases.
CC Additionally, large PER complexes are also recruited to the target
CC genes 3' termination site through interactions with RNA-binding
CC proteins and helicases that may play a role in transcription
CC termination to regulate transcription independently of CLOCK-
CC ARTNL/BMAL1 interactions. Recruitment of large PER complexes to the
CC elongating polymerase at PER and CRY termination sites inhibited SETX
CC action, impeding RNA polymerase II release and thereby repressing
CC transcriptional reinitiation. May propagate clock information to
CC metabolic pathways via the interaction with nuclear receptors.
CC Coactivator of PPARA and corepressor of NR1D1, binds rhythmically at
CC the promoter of nuclear receptors target genes like ARNTL or G6PC1.
CC Directly and specifically represses PPARG proadipogenic activity by
CC blocking PPARG recruitment to target promoters and thereby
CC transcriptional activation. Required for fatty acid and lipid
CC metabolism, is involved as well in the regulation of circulating
CC insulin levels. Plays an important role in the maintenance of
CC cardiovascular functions through the regulation of NO and
CC vasodilatatory prostaglandins production in aortas. Controls circadian
CC glutamate uptake in synaptic vesicles through the regulation of VGLUT1
CC expression. May also be involved in the regulation of inflammatory
CC processes. Represses the CLOCK-ARNTL/BMAL1 induced transcription of
CC BHLHE40/DEC1 and ATF4. Negatively regulates the formation of the
CC TIMELESS-CRY1 complex by competing with TIMELESS for binding to CRY1.
CC {ECO:0000269|PubMed:14672706}.
CC -!- SUBUNIT: Homodimer. Component of the circadian core oscillator, which
CC includes the CRY proteins, CLOCK or NPAS2, ARTNL/BMAL1 or ARTNL2/BMAL2,
CC CSNK1D and/or CSNK1E, TIMELESS, and the PER proteins. Interacts with
CC CLOCK-ARNTL/BMAL1 (off DNA). Interacts directly with PER1 and PER3, and
CC through a C-terminal domain, with CRY1 and CRY2. Interacts, via its
CC second PAS domain, with TIMELESS in vitro. Interacts with NFIL3.
CC Different large complexes have been identified with different
CC repressive functions. The core of PER complexes is composed of at least
CC PER1, PER2, PER3, CRY1, CRY2, CSNK1D and/or CSNK1E. The large PER
CC complex involved in the repression of transcriptional termination is
CC composed of at least PER2, CDK9, DDX5, DHX9, NCBP1 and POLR2A (active).
CC The large PER complex involved in the histone deacetylation is composed
CC of at least HDAC1, PER2, SFPQ and SIN3A. The large PER complex involved
CC in the histone methylation is composed of at least PER2, CBX3, TRIM28,
CC SUV39H1 and/or SUV39H2; CBX3 mediates the formation of the complex.
CC Interacts with SETX; the interaction inhibits termination of circadian
CC target genes. Interacts with the nuclear receptors HNF4A, NR1D1, NR4A2,
CC RORA, PPARA, PPARG and THRA; the interaction with at least PPARG is
CC ligand dependent. Interacts with PML. Interacts (phosphorylated) with
CC BTRC and FBXW11; the interactions trigger proteasomal degradation.
CC Interacts with NONO and SFPQ. Interacts with CAVIN3 (By similarity).
CC Interacts with MAGEL2 (By similarity). Interacts with MAP1LC3B (By
CC similarity). Interacts with HNF4A (By similarity).
CC {ECO:0000250|UniProtKB:O15055, ECO:0000250|UniProtKB:O54943,
CC ECO:0000269|PubMed:11112428, ECO:0000269|PubMed:11533252,
CC ECO:0000269|PubMed:18782782}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11533252}. Cytoplasm
CC {ECO:0000269|PubMed:11533252}. Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:O54943}. Note=Nucleocytoplasmic shuttling is
CC effected by interaction with other circadian core oscillator proteins
CC and/or by phosphorylation. Translocate to the nucleus after
CC phosphorylation by CSNK1D or CSNK1E. Also translocated to the nucleus
CC by CRY1 or CRY2. PML regulates its nuclear localization (By
CC similarity). {ECO:0000250|UniProtKB:O54943}.
CC -!- TISSUE SPECIFICITY: Expressed in all tissues examined including eye,
CC brain, heart, lung, spleen, liver, pancreas and kidney. In the CNS,
CC highly expressed in the SCN, internal granular layer of granular cells
CC of the olfactory bulb, tuberculum olfactorium, piriform cortex, gyrus
CC dentatus of the hippocampus, cerebellum, pars tuberalis/median
CC eminence, and pituitary, and moderately in the tenia tecta, caudate
CC putamen, accumbens nucleus, superior and inferior colliculus and pineal
CC gland. {ECO:0000269|PubMed:12710990, ECO:0000269|PubMed:15094047,
CC ECO:0000269|PubMed:9765215}.
CC -!- INDUCTION: In eye, brain, heart, lung, spleen, liver, pancreas and
CC kidney, expression exhibits a circadian rhythm in the presence of
CC light/dark cycles. {ECO:0000269|PubMed:15094047,
CC ECO:0000269|PubMed:9765215}.
CC -!- PTM: Acetylated. Deacetylated by SIRT1, resulting in decreased protein
CC stability. Deacetylated by SIRT6, preventing its degradation by the
CC proteasome, resulting in increased protein stability.
CC {ECO:0000250|UniProtKB:O54943}.
CC -!- PTM: Phosphorylated by CSNK1E and CSNK1D. Phosphorylation results in
CC PER2 protein degradation. May be dephosphorylated by PP1 (By
CC similarity). {ECO:0000250|UniProtKB:O54943}.
CC -!- PTM: Ubiquitinated, leading to its proteasomal degradation.
CC Ubiquitination may be inhibited by CRY1.
CC {ECO:0000250|UniProtKB:O54943}.
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DR EMBL; AB016532; BAA34187.1; -; mRNA.
DR PIR; T13957; T13957.
DR RefSeq; NP_113866.1; NM_031678.1.
DR RefSeq; XP_006245538.1; XM_006245476.3.
DR RefSeq; XP_017452107.1; XM_017596618.1.
DR AlphaFoldDB; Q9Z301; -.
DR SMR; Q9Z301; -.
DR BioGRID; 248899; 2.
DR CORUM; Q9Z301; -.
DR STRING; 10116.ENSRNOP00000027507; -.
DR iPTMnet; Q9Z301; -.
DR PhosphoSitePlus; Q9Z301; -.
DR PaxDb; Q9Z301; -.
DR Ensembl; ENSRNOT00000027506; ENSRNOP00000027507; ENSRNOG00000020254.
DR GeneID; 63840; -.
DR KEGG; rno:63840; -.
DR CTD; 8864; -.
DR RGD; 61945; Per2.
DR eggNOG; KOG3753; Eukaryota.
DR GeneTree; ENSGT00940000156342; -.
DR HOGENOM; CLU_006667_0_0_1; -.
DR InParanoid; Q9Z301; -.
DR OMA; ESQPCSV; -.
DR OrthoDB; 145617at2759; -.
DR PhylomeDB; Q9Z301; -.
DR TreeFam; TF318445; -.
DR PRO; PR:Q9Z301; -.
DR Proteomes; UP000002494; Chromosome 9.
DR Bgee; ENSRNOG00000020254; Expressed in skeletal muscle tissue and 19 other tissues.
DR Genevisible; Q9Z301; RN.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:RGD.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; ISO:RGD.
DR GO; GO:0042826; F:histone deacetylase binding; ISO:RGD.
DR GO; GO:1990226; F:histone methyltransferase binding; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0019900; F:kinase binding; ISO:RGD.
DR GO; GO:0016922; F:nuclear receptor binding; ISO:RGD.
DR GO; GO:0036002; F:pre-mRNA binding; ISO:RGD.
DR GO; GO:0070063; F:RNA polymerase binding; ISO:RGD.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISS:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; ISS:UniProtKB.
DR GO; GO:0001222; F:transcription corepressor binding; ISO:RGD.
DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0097167; P:circadian regulation of translation; ISS:UniProtKB.
DR GO; GO:0007623; P:circadian rhythm; IEP:UniProtKB.
DR GO; GO:0043153; P:entrainment of circadian clock by photoperiod; IBA:GO_Central.
DR GO; GO:0006631; P:fatty acid metabolic process; ISS:UniProtKB.
DR GO; GO:0006094; P:gluconeogenesis; ISS:UniProtKB.
DR GO; GO:0005978; P:glycogen biosynthetic process; ISS:UniProtKB.
DR GO; GO:0070932; P:histone H3 deacetylation; ISS:UniProtKB.
DR GO; GO:0019249; P:lactate biosynthetic process; ISS:UniProtKB.
DR GO; GO:0042754; P:negative regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:0060567; P:negative regulation of DNA-templated transcription, termination; ISO:RGD.
DR GO; GO:0070345; P:negative regulation of fat cell proliferation; ISS:UniProtKB.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:2000678; P:negative regulation of transcription regulatory region DNA binding; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0051726; P:regulation of cell cycle; ISS:UniProtKB.
DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:0051946; P:regulation of glutamate uptake involved in transmission of nerve impulse; 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:0019229; P:regulation of vasoconstriction; ISS:UniProtKB.
DR GO; GO:0002931; P:response to ischemia; ISS:UniProtKB.
DR GO; GO:0050872; P:white fat cell differentiation; ISS:UniProtKB.
DR CDD; cd00130; PAS; 1.
DR InterPro; IPR000014; PAS.
DR InterPro; IPR035965; PAS-like_dom_sf.
DR InterPro; IPR013655; PAS_fold_3.
DR InterPro; IPR022728; Period_circadian-like_C.
DR Pfam; PF08447; PAS_3; 1.
DR Pfam; PF12114; Period_C; 1.
DR SMART; SM00091; PAS; 2.
DR SUPFAM; SSF55785; SSF55785; 1.
DR PROSITE; PS50112; PAS; 1.
PE 1: Evidence at protein level;
KW Acetylation; Biological rhythms; Cytoplasm; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Transcription; Transcription regulation;
KW Ubl conjugation.
FT CHAIN 1..1257
FT /note="Period circadian protein homolog 2"
FT /id="PRO_0000162632"
FT DOMAIN 179..246
FT /note="PAS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 319..385
FT /note="PAS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 393..436
FT /note="PAC"
FT /evidence="ECO:0000255"
FT REGION 1..59
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 471..567
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 478..482
FT /note="Important for protein stability"
FT /evidence="ECO:0000269|PubMed:18782782"
FT REGION 510..709
FT /note="CSNK1E binding domain"
FT /evidence="ECO:0000250|UniProtKB:O54943"
FT REGION 678..706
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 757..833
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 882..1067
FT /note="Interaction with PPARG"
FT /evidence="ECO:0000250|UniProtKB:O54943"
FT REGION 993..1044
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1070..1108
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1157..1257
FT /note="CRY binding domain"
FT /evidence="ECO:0000269|PubMed:11533252"
FT REGION 1226..1257
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 109..118
FT /note="Nuclear export signal 1"
FT /evidence="ECO:0000250|UniProtKB:O54943"
FT MOTIF 306..310
FT /note="LXXLL"
FT MOTIF 460..469
FT /note="Nuclear export signal 2"
FT /evidence="ECO:0000250|UniProtKB:O54943"
FT MOTIF 778..794
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:11533252"
FT MOTIF 983..990
FT /note="Nuclear export signal 3"
FT /evidence="ECO:0000250|UniProtKB:O54943"
FT MOTIF 1051..1055
FT /note="LXXLL"
FT COMPBIAS 1..52
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 475..503
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 514..562
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 818..832
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 999..1019
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1237..1257
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 525
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O54943"
FT MOD_RES 528
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O54943"
FT MOD_RES 531
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O54943"
FT MOD_RES 538
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O54943"
FT MOD_RES 544
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O54943"
FT MOD_RES 554
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O54943"
FT MOD_RES 659
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O15055"
FT MOD_RES 693
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 697
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 706
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O54943"
FT MOD_RES 758
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O54943"
FT MOD_RES 763
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O54943"
FT MOD_RES 858
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O54943"
FT MOD_RES 939
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O54943"
FT MOD_RES 964
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O54943"
FT MOD_RES 971
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O54943"
FT MOD_RES 1126
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O54943"
FT MUTAGEN 93..97
FT /note="SGCSS->IGCSI: No effect on interaction with BTRC and
FT FBXW11. Strongly decreases interaction with BTRC and FBXW11
FT and increases protein stability; when associated with 478-
FT N--N-482."
FT /evidence="ECO:0000269|PubMed:18782782"
FT MUTAGEN 478..482
FT /note="SGYGS->NGYGN: Strongly decreases interaction with
FT BTRC and FBXW11 and increases protein stability. Strongly
FT decreases interaction with BTRC and FBXW11 and increases
FT protein stability; when associated with 93-I--I-97."
FT /evidence="ECO:0000269|PubMed:18782782"
SQ SEQUENCE 1257 AA; 136028 MW; A772E3C453E63CED CRC64;
MNGYVDFSPS PTSPTQEPGE PQPTQAVLQE DVDMSSGSSG NENCSTGRDS QGSDCDDSGK
ELRMLVESSN THPSPDDTFR LMMTEAEHNP STSGCSSEQS AKADAHKELI RTLRELKVHL
PADKKAKGKA STLATLKYAL RSVKQVKANE EYYQLLMSSE SQPCSVDVPS YTMEQVEGIT
SEYIVKNSDM FAVAVSLVSG KILYISNQVA PIFHCKKDAF SDAKFVEFLA PHDVSVFHSY
TTPYKLPPWS VSSGLDSFTQ ECMEEKSFFC RVSVGKHHEN EIRYQPFRMT PYLVKVQEQK
GAASQLCCLL LAERVHSGYE APRIPPEKRI FTTTHTPNCL FQDVDERAVP LLGYLPQDLI
ETPVLVQLHP SDRPLMLAIH KKILQASGQP FDYSPIRFRT RNGEYITLDT SWSSFINPWS
RKISFIIGRH KVRVGPLNED VFAASPCPEE KTPHPSVQEL TEQIHRLLMQ PVPHSGSSGY
GSLGSNGSHE HLMSQTSSSD SNGQEESHWR RSGIFKTSGK SQSKSHFSPE SGGQKEASVA
EMQSSPPAQV RSVTTMERDS SGASLPKASF PEELTYKSQP PCSYQQISCL DSVIRYLESC
NEAATLKRKC EFPANIPSRK ATVSPGLHSG EAARSSKVTS HTEVSAHLSS LALPGKAESV
VSLTSQCSYS STIVHVGDKK PQPELETVED VASGPESQDD AAGGLSQEKG SLQKLGLTKE
VLAAHTQREE QGFLQRFREV SRLGALQAHC QNYLQERSRA PASDRGLRNA SGIESSWKKT
GKNRKLKSKR VKTRDSSEST GSGGPVSHRP PLVGLNATAW SPSDTSQSSC PSAPFPAPVP
AYPLPVFPAP GIVSTPGTVV APPAAAHTGF TMPVVPMGTQ PEFAVQPLPF AAPLAPVMAF
MLPSYPFPPA TPNLPQAFFP SQPHFPAHPT LASEITPASQ AEFPSRTSML RQPCACPVTP
PAGTVALGRA SPPLFQSRGS SPLQLNLLQL EEAPESSTGA AGTLGTTGTA ASGLDCTSGA
SRDRQPKAPP TCSEPSDTQN SDAISTSSDL LNLLLGEDLC SATGSALSRS GASATSDSLG
SSSLGCDTSR SGAGSSDTSH TSKYFGSIDS SENNHKAKMI TDTEESEQFI KYVLQDPIWL
LMANTDDNIM MTYQLPSRDL QAVLKEDQEK LKLLQRSQPH FTEGQRRELR EVHPWVHTGG
LPTAIDVTGC VYCESEEKGN LCLPYEEDSP SLGLCDTSEA KEEESGQLAN PRKEAQT
