ID   PER2_CHICK              Reviewed;        1344 AA.
AC   Q8QGQ8;
DT   28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2002, sequence version 1.
DT   24-JAN-2024, entry version 105.
DE   RecName: Full=Period circadian protein homolog 2;
DE            Short=cPER2;
DE   AltName: Full=Circadian clock protein PERIOD 2;
GN   Name=PER2;
OS   Gallus gallus (Chicken).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC   Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC   Phasianinae; Gallus.
OX   NCBI_TaxID=9031;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND INDUCTION.
RC   TISSUE=Pineal gland;
RX   PubMed=11554928; DOI=10.1046/j.1365-2443.2001.00462.x;
RA   Okano T., Yamamoto K., Okano K., Hirota T., Kasahara T., Sasaki M.,
RA   Takanaka Y., Fukada Y.;
RT   "Chicken pineal clock genes: implication of BMAL2 as a bidirectional
RT   regulator in circadian clock oscillation.";
RL   Genes Cells 6:825-836(2001).
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 (By
CC       similarity). {ECO:0000250|UniProtKB:O54943,
CC       ECO:0000269|PubMed:11554928}.
CC   -!- SUBUNIT: Component of the circadian clock oscillator which includes the
CC       CRY proteins, CLOCK or NPAS2, BMAL1 or BMAL2, CSNK1E, and the PER
CC       proteins. Interacts directly with PER3, and through a C-terminal
CC       domain, with CRY1 and CRY2. {ECO:0000250|UniProtKB:O54943}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:O54943}. Cytoplasm
CC       {ECO:0000250|UniProtKB:O54943}. Note=Mainly nuclear. Nucleocytoplasmic
CC       shuttling is effected by interaction with other circadian core
CC       oscillator proteins and/or by phosphorylation. Retention of PER1 in the
CC       cytoplasm occurs through PER1-PER2 heterodimer formation or by
CC       interaction with CSNK1E and/or phosphorylation which appears to mask
CC       the PER1 nuclear localization signal. Also translocated to the nucleus
CC       by CRY1 or CRY2 (By similarity). {ECO:0000250|UniProtKB:O54943}.
CC   -!- INDUCTION: Exhibits circadian rhythm expression. Peak levels in early
CC       morning and low levels at early night. {ECO:0000269|PubMed:11554928}.
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DR   EMBL; AF246956; AAL98705.1; -; mRNA.
DR   RefSeq; NP_989593.1; NM_204262.1.
DR   AlphaFoldDB; Q8QGQ8; -.
DR   SMR; Q8QGQ8; -.
DR   STRING; 9031.ENSGALP00000047397; -.
DR   PaxDb; 9031-ENSGALP00000008844; -.
DR   GeneID; 374116; -.
DR   KEGG; gga:374116; -.
DR   CTD; 8864; -.
DR   VEuPathDB; HostDB:geneid_374116; -.
DR   eggNOG; KOG3753; Eukaryota.
DR   InParanoid; Q8QGQ8; -.
DR   PhylomeDB; Q8QGQ8; -.
DR   PRO; PR:Q8QGQ8; -.
DR   Proteomes; UP000000539; Unassembled WGS sequence.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0000976; F:transcription cis-regulatory region binding; IBA:GO_Central.
DR   GO; GO:0001222; F:transcription corepressor binding; IBA:GO_Central.
DR   GO; GO:0032922; P:circadian regulation of gene expression; IBA:GO_Central.
DR   GO; GO:0007623; P:circadian rhythm; IDA:UniProtKB.
DR   GO; GO:0043153; P:entrainment of circadian clock by photoperiod; IBA:GO_Central.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central.
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.
PE   2: Evidence at transcript level;
KW   Biological rhythms; Cytoplasm; Nucleus; Reference proteome; Repeat;
KW   Transcription; Transcription regulation.
FT   CHAIN           1..1344
FT                   /note="Period circadian protein homolog 2"
FT                   /id="PRO_0000261154"
FT   DOMAIN          231..298
FT                   /note="PAS 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT   DOMAIN          371..437
FT                   /note="PAS 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT   DOMAIN          445..488
FT                   /note="PAC"
FT   REGION          1..21
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          42..112
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          531..609
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          661..686
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          823..894
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1038..1065
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1107..1126
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1149..1197
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1244..1344
FT                   /note="CRY binding domain"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Z301"
FT   MOTIF           161..170
FT                   /note="Nuclear export signal 1"
FT                   /evidence="ECO:0000250|UniProtKB:O54943"
FT   MOTIF           358..362
FT                   /note="LXXLL"
FT   MOTIF           512..521
FT                   /note="Nuclear export signal 2"
FT                   /evidence="ECO:0000250|UniProtKB:O54943"
FT   MOTIF           851..865
FT                   /note="Nuclear localization signal"
FT                   /evidence="ECO:0000250|UniProtKB:O54943"
FT   MOTIF           1138..1142
FT                   /note="LXXLL"
FT   COMPBIAS        42..56
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        74..96
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        97..112
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        531..562
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        563..597
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        663..686
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1041..1065
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1149..1195
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   1344 AA;  147942 MW;  A34EC8265066A2A0 CRC64;
     MDCIEVRGFY SSTEEQNPEQ QADISENISS LFSLKEQQKM SEYSGLASNH SQMIAEDSEI
     QPKPEHSPEV LQEDIEMSSG SSGNDFSGNE TNENYSSGHD SHGHESDENG KDSAMLMESS
     DCHKSSSSNA FSLMIANSEH NQSSSGCSSE QSTKAKTQKE LLKTLQELKA HLPAEKRIKG
     KSSVLTTLKY ALKSIKQVKA NEEYYQLLMI NESQPSGLNV SSYTVEEVET ITSEYIMKNA
     DMFAVAVSLI TGKIVYISDQ AAAILRCKRS YFKNAKFVEL LAPQDVSVFY TSTTPYRLPS
     WNICSRAESS TQDCMEEKSF FCRISAGKER ENEICYHPFR MTPYLIKVQD PEVAEDQLCC
     VLLAEKVHSG YEAPRIPPDK RIFTTTHTPT CLFQDVDERA VPLLGYLPQD LIGTPVLVHL
     HPNDRPLMLA IHKKILQYGG QPFDYSPIRF CTRNGDYITM DTSWSSFINP WSRKVSFIIG
     RHKVRTGPLN EDVFAAPNYT EDRILHPSVQ EITEQIYRLL LQPVHNSGSS GYGSLGSNGS
     HEHLMSVASS SDSTGNNNDD TQKDKTISQD ARKVKTKGQH IFTENKGKLE YKREPSAEKQ
     NGPGGQVKDV IGKDTTATAA PKNVATEELA WKEQPVYSYQ QISCLDSVIR YLESCNVPGT
     AKRKCEPSSS VNSSVHEQKA SVNAIQPLGD STVLKSSGKS SGPPVVGAHL TSLALPGKPE
     SVVSLTSQCS YSSTIVHVGD KKPQPELEMI EDGPSGAEVL DTQLPAPPPS STHVNQEKES
     FKKLGLTKEV LAVHTQKEEQ SFLNKFKEIK RFNIFQSHCN YYLQDKPKGR PGERGGRGQR
     NGTSGMDQPW KKSGKNRKSK RIKPQESSDS TTSGTKFPHR FPLQGLNTTA WSPSDTSQAS
     YSAMSFPTVM PAYPLPVFPA AAGTVPPAPE TSVSGFNQLP DSGNTCSMQP SQFSAPLMTP
     VVALVLPNYV YPEMNNSLPQ TLYHSQANFP THPAFSSQTV FPAQPPFTTP SPFPQQAFFP
     MQPFHYNPPA EIEKVPVTET RNEPSRSCTP QSVGPQDQAS PPLFQSRCSS PLNLLQLEEN
     TKTVESGAPA GLHGALNEEG TIGKIMTTDA GSGKGSLPAE SPMDAQNSDA LSMSSVLLDI
     LLQEDACSGT GSASSGSGVS AAAESLGSGS NGCDMSGSRT GSSETSHTSK YFGSIDSSEN
     HHKTKMKAEI EESEHFIKYV LQDPIWLLMA NTDDTVMMTY QLPSRDLETV LKEDKLKLKQ
     MQKLQPKFTE DQKRELIEVH PWIQQGGLPK TVANSECIFC EDNIQSNFYT SYDEEIHEMD
     LNEMIEDSGE NNLVPLSQVN EEQT
//