ID PER3_RAT Reviewed; 1119 AA.
AC Q8CJE2;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 24-JAN-2024, entry version 116.
DE RecName: Full=Period circadian protein homolog 3;
DE Short=rPER3;
DE AltName: Full=Circadian clock protein PERIOD 3;
GN Name=Per3;
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].
RC TISSUE=Brain;
RA Suzuki S., Oishi K., Sakamoto K., Ishida N.;
RT "Cloning and circadian expression of rat period3 gene.";
RL Submitted (SEP-2002) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Originally described as a core component of the circadian
CC clock. The circadian clock, an internal time-keeping system, regulates
CC various physiological processes through the generation of approximately
CC 24 hour circadian rhythms in gene expression, which are translated into
CC rhythms in metabolism and behavior. It is derived from the Latin roots
CC 'circa' (about) and 'diem' (day) and acts as an important regulator of
CC a wide array of physiological functions including metabolism, sleep,
CC body temperature, blood pressure, endocrine, immune, cardiovascular,
CC and renal function. Consists of two major components: the central
CC clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and
CC the peripheral clocks that are present in nearly every tissue and organ
CC system. Both the central and peripheral clocks can be reset by
CC environmental cues, also known as Zeitgebers (German for 'timegivers').
CC The predominant Zeitgeber for the central clock is light, which is
CC sensed by retina and signals directly to the SCN. The central clock
CC entrains the peripheral clocks through neuronal and hormonal signals,
CC body temperature and feeding-related cues, aligning all clocks with the
CC external light/dark cycle. Circadian rhythms allow an organism to
CC achieve temporal homeostasis with its environment at the molecular
CC level by regulating gene expression to create a peak of protein
CC expression once every 24 hours to control when a particular
CC physiological process is most active with respect to the solar day.
CC Transcription and translation of core clock components (CLOCK, NPAS2,
CC BMAL1, BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in
CC rhythm generation, whereas delays imposed by post-translational
CC modifications (PTMs) are important for determining the period (tau) of
CC the rhythms (tau refers to the period of a rhythm and is the length, in
CC time, of one complete cycle). A diurnal rhythm is synchronized with the
CC day/night cycle, while the ultradian and infradian rhythms have a
CC period shorter and longer than 24 hours, respectively. Disruptions in
CC the circadian rhythms contribute to the pathology of cardiovascular
CC diseases, cancer, metabolic syndromes and aging. A
CC transcription/translation feedback loop (TTFL) forms the core of the
CC molecular circadian clock mechanism. Transcription factors, CLOCK or
CC NPAS2 and BMAL1 or BMAL2, form the positive limb of the feedback loop,
CC act in the form of a heterodimer and activate the transcription of core
CC clock genes and clock-controlled genes (involved in key metabolic
CC processes), harboring E-box elements (5'-CACGTG-3') within their
CC promoters. The core clock genes: PER1/2/3 and CRY1/2 which are
CC transcriptional repressors form the negative limb of the feedback loop
CC and interact with the CLOCK|NPAS2-BMAL1|BMAL2 heterodimer inhibiting
CC its activity and thereby negatively regulating their own expression.
CC This heterodimer also activates nuclear receptors NR1D1, NR1D2, RORA,
CC RORB and RORG, which form a second feedback loop and which activate and
CC repress BMAL1 transcription, respectively. Has a redundant role with
CC the other PER proteins PER1 and PER2 and is not essential for the
CC circadian rhythms maintenance. In contrast, plays an important role in
CC sleep-wake timing and sleep homeostasis probably through the
CC transcriptional regulation of sleep homeostasis-related genes, without
CC influencing circadian parameters. Can bind heme.
CC {ECO:0000250|UniProtKB:O70361, ECO:0000250|UniProtKB:P56645}.
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 directly with
CC PER1, PER2, CRY1, CRY2, and TIMELESS; interaction with CRY1 and CRY2 is
CC weak and not rhythmic. Interacts with FBXW11 and BTRC.
CC {ECO:0000250|UniProtKB:O70361, ECO:0000250|UniProtKB:P56645}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O70361}. Nucleus
CC {ECO:0000250|UniProtKB:O70361}. Note=Mainly cytoplasmic. Translocates
CC to the nucleus through binding PER1, PER2, CRY1 or CRY2, but not
CC TIMELESS. {ECO:0000250|UniProtKB:O70361}.
CC -!- PTM: Phosphorylation by CSNK1E is weak and appears to require
CC association with PER1 and translocation to the nucleus.
CC {ECO:0000250|UniProtKB:O70361}.
CC -!- PTM: Ubiquitinated. {ECO:0000250|UniProtKB:O70361}.
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DR EMBL; AB092512; BAC16806.1; -; mRNA.
DR RefSeq; NP_076468.2; NM_023978.2.
DR AlphaFoldDB; Q8CJE2; -.
DR SMR; Q8CJE2; -.
DR STRING; 10116.ENSRNOP00000076026; -.
DR PhosphoSitePlus; Q8CJE2; -.
DR PaxDb; 10116-ENSRNOP00000024932; -.
DR GeneID; 78962; -.
DR KEGG; rno:78962; -.
DR UCSC; RGD:621581; rat.
DR AGR; RGD:621581; -.
DR CTD; 8863; -.
DR RGD; 621581; Per3.
DR eggNOG; KOG3753; Eukaryota.
DR InParanoid; Q8CJE2; -.
DR OrthoDB; 2971905at2759; -.
DR PhylomeDB; Q8CJE2; -.
DR PRO; PR:Q8CJE2; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0019900; F:kinase binding; ISO:RGD.
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:0031625; F:ubiquitin protein ligase binding; ISO:RGD.
DR GO; GO:0032922; P:circadian regulation of gene expression; IBA:GO_Central.
DR GO; GO:0007623; P:circadian rhythm; ISO:RGD.
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; ISS:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; ISS:UniProtKB.
DR GO; GO:0045187; P:regulation of circadian sleep/wake cycle, sleep; 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:SF13; PERIOD CIRCADIAN PROTEIN HOMOLOG 3; 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; Phosphoprotein; Reference proteome;
KW Repeat; Transcription; Transcription regulation; Ubl conjugation.
FT CHAIN 1..1119
FT /note="Period circadian protein homolog 3"
FT /id="PRO_0000261155"
FT DOMAIN 120..187
FT /note="PAS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 259..325
FT /note="PAS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 334..377
FT /note="PAC"
FT REGION 1..48
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 419..449
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 483..530
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 551..750
FT /note="CSNK1E binding domain"
FT /evidence="ECO:0000250"
FT REGION 718..744
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 878..910
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 947..1011
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1037..1119
FT /note="CRY binding domain"
FT /evidence="ECO:0000250"
FT MOTIF 54..63
FT /note="Nuclear export signal 1"
FT /evidence="ECO:0000250"
FT MOTIF 400..409
FT /note="Nuclear export signal 3"
FT /evidence="ECO:0000250"
FT MOTIF 720..739
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT MOTIF 913..920
FT /note="Nuclear export signal 2"
FT /evidence="ECO:0000250"
FT COMPBIAS 19..35
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 487..530
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 882..904
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 947..998
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 907
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P56645"
SQ SEQUENCE 1119 AA; 122686 MW; 38FD286377CD234E CRC64;
MDPCGNPAVP GGDCPQTRGP GLQGSSGQEG PLQGICVDSS HSEHEDRNRM SEELIMVVQE
MKKYFPAERH TKPSTLDALN YALRCVHSVQ ANSEFFQSLS PRGARQAEAT VYNLEELTSL
ASEHTSKNTD TFVAVFSFLS GRLVHISEQA AWILNSKKGF LKSLHFVDLL APRDVRVFYA
HTAPTQLPFW NTWTQRASQY ECAPVKPFFC RICGGGDREQ KRHYSPFRIL PYLVHVHSPA
QPEPEPCCLT LVEKIHSGYE APRIPVDKRV FTTTHTPGCV FLEVDERAVP LLGFLPQDLI
GTSILTYLHP EDRPLMVAVH QKVLKYVGHP PFEHSPIRFC TQNGDYVILD SSWSSFVNPW
SRKVSFIIGR HKVRTSPLNE DVFATRIKKA TSHDEDITEL QEQIHRLLLQ PVHASASSGY
GSLGSSGSQE QHISVTSSSE SSGHCVEEAQ QEQMTLQQVY ASVNKIKNVG QQLYIESMAR
SSVKPVMETC TEPQGSDEQK DFSSSQTLKN KSTDTGSGGD LRPEQHSSSY QQMNCIDSVI
RYLTSYSFPA LKRKCISCTN TSSSSEEAKP NPEADGSLRD TEQLLDIPEQ ETTTPSADAE
GGVARTLSTA ALSMASGVSQ CSCSSTTDHV PPLQSESVAG ACEPWALRTK AHVTAEGFKP
VGLTAAVLSA HTQKEEQNYV DRFREKILTS PYGCYLQQEG RNHAKYACVV GAGATPKHSR
CAGSERRKHK RKKLPTPVDS SSSSAHLCPH VRGLLPDVQH WSASVTSPCA TGLALPSALV
VPNQTPYLLS SFPLQDMAPH GVGDSAPWGA AAECPPLSAG PHPVSTFPSA YMGTFMTVLL
HNSPLFPLWP ASFSPYPFLG ATGPSQMAPL VPAMAPDLEP TPSDHGPRRV EENWETHSEE
EHPFISSRSS SPLQLNLLQE EMPAPSEYAD ALRRGACPDA KQLCVTGNSG SRSPPCATGE
LATASVQQES PSAAASGSSA SSVHGSGSDY TSEVSENGQR SQDTHRDRAF SGAAEESIWR
MIERTPQCVL MTYQVPERGR DTVLREDLEK LHSMERQRPQ FSSAQKEELA KVRSWIHSHP
APEERQLQRA MSPVKTEVQL VTLQRPVNSV QQKTPVEQL
//
