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Protein

Period circadian protein homolog 1

Gene

Per1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Transcriptional repressor which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, ARNTL/BMAL1, ARNTL2/BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and ARNTL/BMAL1 or ARNTL2/BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-ARNTL/BMAL1|ARNTL2/BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress ARNTL/BMAL1 transcription, respectively. Regulates circadian target genes expression at post-transcriptional levels, but may not be required for the repression at transcriptional level. Controls PER2 protein decay. Represses CRY2 preventing its repression on CLOCK/ARNTL target genes such as FXYD5 and SCNN1A in kidney and PPARA in liver. Besides its involvement in the maintenance of the circadian clock, has an important function in the regulation of several processes. Participates in the repression of glucocorticoid receptor NR3C1/GR-induced transcriptional activity by reducing the association of NR3C1/GR to glucocorticoid response elements (GREs) by ARNTL:CLOCK. Plays a role in the modulation of the neuroinflammatory state via the regulation of inflammatory mediators release, such as CCL2 and IL6. In spinal astrocytes, negatively regulates the MAPK14/p38 and MAPK8/JNK MAPK cascades as well as the subsequent activation of NFkappaB. Coordinately regulates the expression of multiple genes that are involved in the regulation of renal sodium reabsorption. Can act as gene expression activator in a gene and tissue specific manner, in kidney enhances WNK1 and SLC12A3 expression in collaboration with CLOCK. Modulates hair follicle cycling. Represses the CLOCK-ARNTL/BMAL1 induced transcription of BHLHE40/DEC1.1 Publication

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Biological rhythms, Transcription, Transcription regulation

Names & Taxonomyi

Protein namesi
Recommended name:
Period circadian protein homolog 1
Short name:
rPER1
Alternative name(s):
Circadian clock protein PERIOD 1
Gene namesi
Name:Per1Imported
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi727863. Per1.

Subcellular locationi

  • Nucleus By similarity
  • Cytoplasm By similarity

  • Note: Nucleocytoplasmic shuttling is effected by interaction with other circadian core oscillator proteins and/or by phosphorylation. Retention of PER1 in the cytoplasm occurs through PER1-PER2 heterodimer formation. Translocate to the nucleus after phosphorylation by CSNK1D or CSNK1E. Also translocated to the nucleus by CRY1 or CRY2 (By similarity).By similarity

GO - Cellular componenti

  • cytoplasm Source: UniProtKB-SubCell
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 12931293Period circadian protein homolog 1PRO_0000162629Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei121 – 1211Phosphothreonine; by CSNK1ESequence analysis
Modified residuei122 – 1221Phosphoserine; by CSNK1ESequence analysis
Modified residuei126 – 1261Phosphoserine; by CSNK1ESequence analysis
Modified residuei660 – 6601PhosphoserineBy similarity
Modified residuei662 – 6621PhosphoserineBy similarity
Modified residuei703 – 7031PhosphoserineBy similarity
Modified residuei814 – 8141PhosphoserineBy similarity
Modified residuei975 – 9751PhosphoserineBy similarity
Modified residuei976 – 9761PhosphoserineBy similarity

Post-translational modificationi

Phosphorylated on serine residues by CSNK1D, CSNK1E and probably also by CSNK1G2. Phosphorylation by CSNK1D or CSNK1E promotes nuclear location of PER proteins as well as ubiquitination and subsequent degradation. May be dephosphorylated by PP1.By similarity
Ubiquitinated; requires phosphorylation by CSNK1E and interaction with BTRC and FBXW11. Deubiquitinated by USP2.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ8CHI5.
PRIDEiQ8CHI5.

Expressioni

Tissue specificityi

Expressed in pancreas. In the CNS, highly expressed in the SCN, internal granular layer of granular cells of the olfactory bulb, tuberculum olfactorium, piriform cortex, gyrus dentatus of the hippocampus, cerebellum, pars tuberalis/median eminence, and pituitary, and moderately in the tenia tecta, caudate putamen, accumbens nucleus, spinal cord, superior and inferior colliculus and pineal gland.3 Publications

Inductioni

In pancreas, expression exhibits a circadian rhythm in the presence of light/dark cycles.1 Publication

Interactioni

Subunit structurei

Homodimer. Component of the circadian core oscillator, which includes the CRY proteins, CLOCK or NPAS2, ARNTL/BMAL1 or ARNTL2/BMAL2, CSNK1D and/or CSNK1E, TIMELESS, and the PER proteins. Interacts directly with TIMELESS, PER2, PER3 and, through a C-terminal domain, with CRY1 and CRY2. Interacts with ARNTL/BMAL1 and CLOCK. Interacts with GPRASP1. Interacts (phosphorylated) with BTRC and FBXW11; the interactions trigger proteasomal degradation. Interacts with NONO, WDR5 and SFPQ. Interacts with USP2 (By similarity).By similarity2 Publications

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000053964.

Structurei

3D structure databases

ProteinModelPortaliQ8CHI5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini208 – 27568PAS 1PROSITE-ProRule annotationAdd
BLAST
Domaini348 – 41467PAS 2PROSITE-ProRule annotationAdd
BLAST
Domaini422 – 46544PACSequence analysisAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 151151Interaction with BTRCBy similarityAdd
BLAST
Regioni596 – 814219Required for phosphorylation by CSNK1EBy similarityAdd
BLAST
Regioni1145 – 1293149CRY binding domainBy similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi138 – 14710Nuclear export signal 1By similarity
Motifi489 – 49810Nuclear export signal 2By similarity
Motifi823 – 83917Nuclear localization signalBy similarityAdd
BLAST
Motifi978 – 9858Nuclear export signal 3By similarity
Motifi1039 – 10435LXXLL

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi49 – 12981Ser-richAdd
BLAST
Compositional biasi844 – 968125Pro-richAdd
BLAST
Compositional biasi1026 – 110075Ser-richAdd
BLAST
Compositional biasi1221 – 126343Gly-richAdd
BLAST
Compositional biasi1272 – 12754Poly-Glu
Compositional biasi1279 – 12824Poly-Ser

Sequence similaritiesi

Contains 2 PAS (PER-ARNT-SIM) domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG410IMRF. Eukaryota.
ENOG410ZBUP. LUCA.
HOGENOMiHOG000231111.
HOVERGENiHBG008167.
InParanoidiQ8CHI5.
KOiK02633.
OMAiAPGCHHG.
OrthoDBiEOG7TJ3H5.
PhylomeDBiQ8CHI5.
TreeFamiTF318445.

Family and domain databases

InterProiIPR000014. PAS.
IPR013655. PAS_fold_3.
IPR022728. Period_circadian-like_C.
[Graphical view]
PfamiPF08447. PAS_3. 1 hit.
PF12114. Period_C. 1 hit.
[Graphical view]
SMARTiSM00091. PAS. 2 hits.
[Graphical view]
SUPFAMiSSF55785. SSF55785. 1 hit.
PROSITEiPS50112. PAS. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q8CHI5-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSGPLEGADG GGDPRPGEPF CPGGVPSPGA PQHRPCPGPS LADDTDANSN
60 70 80 90 100
GSSGNESNGH ESRGASQRSS HSSSSGNGKD SALLETTESS KSTNSQSPSP
110 120 130 140 150
PSSSIAYSLL SASSEQDNPS TSGCSSEQSA RARTQKELMT ALRELKLRLP
160 170 180 190 200
PERRGKGRSG TLATLQYALA CVKQVQANQE YYQQWSLEEG EPCAMDMSTY
210 220 230 240 250
TLEELEHITS EYTLRNQDTF SVAVSFLTGR IVYISEQAGV LLRCKRDVFR
260 270 280 290 300
GARFSELLAP QDVGVFYGST TPSRLPTWGT GTSAGSGLKD FTQEKSVFCR
310 320 330 340 350
IRGGPDRDPG PRYQPFRLTP YVTKIRVSDG APAQPCCLLI AERIHSGYEA
360 370 380 390 400
PRIPPDKRIF TTRHTPSCLF QDVDERAAPL LGYLPQDLLG APVLLFLHPE
410 420 430 440 450
DRPLMLAIHK KILQLAGQPF DHSPIRFCAR NGEYVTMDTS WAGFVHPWSR
460 470 480 490 500
KVAFVLGRHK VRTAPLNEDV FTPPVPSPAP SLDSDIQELS EQIHRLLLQP
510 520 530 540 550
VHSSSTTGLC GVGPLMSPGP LHSPGSSSDS NGGDAEGPGP PAPVTFQQIC
560 570 580 590 600
KDVHLVKHQG QQLFIESRAK PPPRPRLLAT GTFKAKVLPC QSPNPELEVA
610 620 630 640 650
PAPDQASLAL APEEPERKES SGCSYQQINC LDSILRYLES CNIPNTTKRK
660 670 680 690 700
CASSSCTASS ASDDDKQRAG PVPVGAKKDT SSAVLSGEGA TPRKEPVVGG
710 720 730 740 750
TLSPLALANK AESVVSVTSQ CSFSSTIVHV GDKKPPESDI IMMEDLPGLA
760 770 780 790 800
PGPAPSPAPS PTVAPDPAPD AYRPVGLTKA VLSLHTQKEE QAFLSRFRDL
810 820 830 840 850
GRLRGLDTSS VAPSAPGCHH GPIPSGRRHH CRSKAKRSRH HQTPRPETPC
860 870 880 890 900
YVSHPSPVPS SGPWPPPPAT TPFPAVVQPY PLPVFSPRGG PQPLPPAPTS
910 920 930 940 950
VSPATFPSPL VTPMVALVLP NYLFPSPTSY PYGVSQAPVE GPPTPASHSP
960 970 980 990 1000
SPSLPPPPPS PPHRPDSPLF NSRCSSPLQL NLLQLEESPR TEGGAAAGGP
1010 1020 1030 1040 1050
GSSAGPLPPS EESAEPEPRL VEVTESSNQD ALSGSSDLLE LLLQEDSRSG
1060 1070 1080 1090 1100
TGSAASGSLG SGLGSGSGSG SHEGGSTSAS ITRSSQSSHT SKYFGSIDSS
1110 1120 1130 1140 1150
EAEAGAAQAR TEPGDQVIKY VLQDPIWLLM ANADQHVMMT YQVPSRDAAS
1160 1170 1180 1190 1200
VLKQDRERLR AMQKQQPRFS EDQRRELGAV HSWVRKGQLP QALDVTACVD
1210 1220 1230 1240 1250
CGSSVQDPGH SDDPLFSELD GLGLEPMEEG GGEGGGVGGG GGGVGGGGGD
1260 1270 1280 1290
GGEEAQTQIG TKGSSSQDSA MEEEEQGGSS SSPALPAEEN GTS
Length:1,293
Mass (Da):136,164
Last modified:November 28, 2006 - v2
Checksum:i3A9DAB0C539AB175
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti1242 – 12443GGV → SCR in BAC53666 (Ref. 2) Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY903228 mRNA. Translation: AAX85358.1.
AY903229 mRNA. Translation: AAX85359.1.
AY903230 mRNA. Translation: AAX85360.1.
AB092976 mRNA. Translation: BAC53666.1.
RefSeqiNP_001029297.1. NM_001034125.1.
XP_006246675.1. XM_006246613.2.
XP_006246676.1. XM_006246614.2.
UniGeneiRn.34433.

Genome annotation databases

GeneIDi287422.
KEGGirno:287422.
UCSCiRGD:727863. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY903228 mRNA. Translation: AAX85358.1.
AY903229 mRNA. Translation: AAX85359.1.
AY903230 mRNA. Translation: AAX85360.1.
AB092976 mRNA. Translation: BAC53666.1.
RefSeqiNP_001029297.1. NM_001034125.1.
XP_006246675.1. XM_006246613.2.
XP_006246676.1. XM_006246614.2.
UniGeneiRn.34433.

3D structure databases

ProteinModelPortaliQ8CHI5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000053964.

Proteomic databases

PaxDbiQ8CHI5.
PRIDEiQ8CHI5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi287422.
KEGGirno:287422.
UCSCiRGD:727863. rat.

Organism-specific databases

CTDi5187.
RGDi727863. Per1.

Phylogenomic databases

eggNOGiENOG410IMRF. Eukaryota.
ENOG410ZBUP. LUCA.
HOGENOMiHOG000231111.
HOVERGENiHBG008167.
InParanoidiQ8CHI5.
KOiK02633.
OMAiAPGCHHG.
OrthoDBiEOG7TJ3H5.
PhylomeDBiQ8CHI5.
TreeFamiTF318445.

Miscellaneous databases

PROiQ8CHI5.

Family and domain databases

InterProiIPR000014. PAS.
IPR013655. PAS_fold_3.
IPR022728. Period_circadian-like_C.
[Graphical view]
PfamiPF08447. PAS_3. 1 hit.
PF12114. Period_C. 1 hit.
[Graphical view]
SMARTiSM00091. PAS. 2 hits.
[Graphical view]
SUPFAMiSSF55785. SSF55785. 1 hit.
PROSITEiPS50112. PAS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Positional cloning of rat hd."
    Liska F., Blachut S., Gosele C., Kren V., Krenova D., Hubner N.
    Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: BN-Lx/Cub, SHR/OlaIpcv and Wistar Hd.
    Tissue: Testis.
  2. Suzuki S., Oishi K., Sakamoto K., Ishida N.
    Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-1244.
    Tissue: BrainImported.
  3. "Distribution of the rhythm-related genes rPERIOD1, rPERIOD2, and rCLOCK, in the rat brain."
    Shieh K.-R.
    Neuroscience 118:831-843(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  4. "A novel protein interacts with a clock-related protein, rPer1."
    Matsuki T., Kiyama A., Kawabuchi M., Okada M., Nagai K.
    Brain Res. 916:1-10(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH GPRASP1.
  5. "Indication of circadian oscillations in the rat pancreas."
    Muehlbauer E., Wolgast S., Finckh U., Peschke D., Peschke E.
    FEBS Lett. 564:91-96(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, INDUCTION.
  6. "PERIOD1-associated proteins modulate the negative limb of the mammalian circadian oscillator."
    Brown S.A., Ripperger J., Kadener S., Fleury-Olela F., Vilbois F., Rosbash M., Schibler U.
    Science 308:693-696(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH NONO AND WDR5.
  7. "Clock gene Per1 regulates the production of CCL2 and interleukin-6 through p38, JNK1 and NF-kappaB activation in spinal astrocytes."
    Sugimoto T., Morioka N., Zhang F.F., Sato K., Abe H., Hisaoka-Nakashima K., Nakata Y.
    Mol. Cell. Neurosci. 59C:37-46(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN INFLAMMATION, TISSUE SPECIFICITY.

Entry informationi

Entry nameiPER1_RAT
AccessioniPrimary (citable) accession number: Q8CHI5
Secondary accession number(s): Q2KMM8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 15, 2005
Last sequence update: November 28, 2006
Last modified: June 8, 2016
This is version 112 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.