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 24-JAN-2024, entry version 159. 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, BMAL1, BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a CC critical role in rhythm generation, whereas delays imposed by post- CC translational modifications (PTMs) are important for determining the CC period (tau) of the rhythms (tau refers to the period of a rhythm and CC is the length, in time, of one complete cycle). A diurnal rhythm is CC synchronized with the day/night cycle, while the ultradian and CC infradian rhythms have a period shorter and longer than 24 hours, CC respectively. Disruptions in the circadian rhythms contribute to the CC pathology of cardiovascular diseases, cancer, metabolic syndrome and CC aging. A transcription/translation feedback loop (TTFL) forms the core CC of the molecular circadian clock mechanism. Transcription factors, CC CLOCK or NPAS2 and BMAL1 or BMAL2, form the positive limb of the CC 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-BMAL1|BMAL2 heterodimer CC inhibiting its activity and thereby negatively regulating their own CC expression. This heterodimer also activates nuclear receptors NR1D1/2 CC and RORA/B/G, which form a second feedback loop and which activate and CC repress BMAL1 transcription, respectively. PER1 and PER2 proteins CC transport CRY1 and CRY2 into the nucleus with appropriate circadian CC timing, but also contribute directly to repression of clock-controlled CC target genes through interaction with several classes of RNA-binding CC proteins, helicases and others transcriptional repressors. PER appears CC to regulate circadian control of transcription by at least three CC different modes. First, interacts directly with the CLOCK-BMAL1 at the CC tail end of the nascent transcript peak to recruit complexes containing CC the SIN3-HDAC that remodel chromatin to repress transcription. Second, CC brings H3K9 methyltransferases such as SUV39H1 and SUV39H2 to the E-box CC elements of the circadian target genes, like PER2 itself or PER1. The CC recruitment of each repressive modifier to the DNA seems to be very CC precisely temporally orchestrated by the large PER complex, the CC deacetylases acting before than the methyltransferases. Additionally, CC large PER complexes are also recruited to the target genes 3' CC termination site through interactions with RNA-binding proteins and CC helicases that may play a role in transcription termination to regulate CC transcription independently of CLOCK-BMAL1 interactions. Recruitment of CC large PER complexes to the elongating polymerase at PER and CRY CC termination sites inhibited SETX action, impeding RNA polymerase II CC release and thereby repressing transcriptional reinitiation. May CC propagate clock information to metabolic pathways via the interaction CC with nuclear receptors. Coactivator of PPARA and corepressor of NR1D1, CC binds rhythmically at the promoter of nuclear receptors target genes CC like BMAL1 or G6PC1. Directly and specifically represses PPARG CC proadipogenic activity by blocking PPARG recruitment to target CC promoters and thereby transcriptional activation. Required for fatty CC acid and lipid metabolism, is involved as well in the regulation of CC circulating insulin levels. Plays an important role in the maintenance CC of 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-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, BMAL1 or BMAL2, CSNK1D CC and/or CSNK1E, TIMELESS, and the PER proteins. Interacts with CLOCK- CC BMAL1 (off DNA). Interacts directly with PER1 and PER3, and through a CC C-terminal domain, with CRY1 and CRY2. Interacts (via PAS 2 domain) CC with TIMELESS. Interacts with NFIL3. Different large complexes have CC been identified with different repressive functions. The core of PER CC complexes is composed of at least PER1, PER2, PER3, CRY1, CRY2, CSNK1D CC and/or CSNK1E. The large PER complex involved in the repression of CC transcriptional termination is composed of at least PER2, CDK9, DDX5, CC DHX9, NCBP1 and POLR2A (active). The large PER complex involved in the CC histone deacetylation is composed of at least HDAC1, PER2, SFPQ and CC SIN3A. The large PER complex involved in the histone methylation is CC composed of at least PER2, CBX3, TRIM28, SUV39H1 and/or SUV39H2; CBX3 CC mediates the formation of the complex. Interacts with SETX; the CC interaction inhibits termination of circadian target genes. Interacts CC with the nuclear receptors HNF4A, NR1D1, NR4A2, RORA, PPARA, PPARG and CC THRA; the interaction with at least PPARG is ligand dependent. CC Interacts with PML. Interacts (phosphorylated) with BTRC and FBXW11; CC the interactions trigger proteasomal degradation. Interacts with NONO CC and SFPQ. Interacts with CAVIN3 (By similarity). Interacts with MAGEL2 CC (By similarity). Interacts with MAP1LC3B (By similarity). Interacts CC with HNF4A (By similarity). {ECO:0000250|UniProtKB:O15055, CC ECO:0000250|UniProtKB:O54943, ECO:0000269|PubMed:11112428, CC ECO:0000269|PubMed:11533252, 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 10116-ENSRNOP00000027507; -. DR Ensembl; ENSRNOT00000027506.6; ENSRNOP00000027507.4; ENSRNOG00000020254.8. DR Ensembl; ENSRNOT00055016243; ENSRNOP00055013051; ENSRNOG00055009603. DR Ensembl; ENSRNOT00060015508; ENSRNOP00060012104; ENSRNOG00060009201. DR GeneID; 63840; -. DR KEGG; rno:63840; -. DR AGR; RGD:61945; -. 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; ENCSMGR; -. DR OrthoDB; 2971905at2759; -. 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 cell types or tissues. 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; ISO: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:0006338; P:chromatin remodeling; ISS:UniProtKB. 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:0019249; P:lactate biosynthetic process; ISS:UniProtKB. DR GO; GO:0042754; P:negative regulation of circadian rhythm; ISS:UniProtKB. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:UniProtKB. 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:0060567; P:negative regulation of termination of DNA-templated transcription; ISO:RGD. 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: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 Gene3D; 3.30.450.20; PAS domain; 2. DR InterPro; IPR000014; PAS. DR InterPro; IPR035965; PAS-like_dom_sf. DR InterPro; IPR013655; PAS_fold_3. DR InterPro; IPR048814; Per1-3_PAS-A. DR InterPro; IPR022728; Period_circadian-like_C. DR PANTHER; PTHR11269; PERIOD CIRCADIAN PROTEIN; 1. DR PANTHER; PTHR11269:SF9; PERIOD CIRCADIAN PROTEIN HOMOLOG 2; 1. DR Pfam; PF08447; PAS_3; 1. DR Pfam; PF21353; Per3-like_PAS-A; 1. DR Pfam; PF12114; Period_C; 1. DR SMART; SM00091; PAS; 2. DR SUPFAM; SSF55785; PYP-like sensor domain (PAS domain); 1. DR PROSITE; PS50112; PAS; 1. DR Genevisible; Q9Z301; RN. 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 FT 478-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 //