PER1_SPAJD
ID PER1_SPAJD Reviewed; 1285 AA.
AC Q8K3T3;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 80.
DE RecName: Full=Period circadian protein homolog 1;
DE Short=sPER1;
DE AltName: Full=Circadian clock protein PERIOD 1;
GN Name=PER1;
OS Spalax judaei (Judean Mountains blind mole rat) (Nannospalax judaei).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Spalacidae; Spalacinae; Nannospalax.
OX NCBI_TaxID=134510;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND INDUCTION.
RC TISSUE=Brain;
RX PubMed=12193657; DOI=10.1073/pnas.182423299;
RA Avivi A., Oster H., Joel A., Albrecht U., Nevo E.;
RT "Circadian genes in a blind subterranean mammal II: conservation and
RT uniqueness of the three Period homologs in the blind subterranean mole rat,
RT Spalax ehrenbergi superspecies.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:11718-11723(2002).
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
CC syndromes and aging. A transcription/translation feedback loop (TTFL)
CC forms the core of the molecular circadian clock mechanism.
CC Transcription factors, CLOCK or NPAS2 and ARNTL/BMAL1 or ARNTL2/BMAL2,
CC form the positive limb of the feedback loop, act in the form of a
CC heterodimer and activate the transcription of core clock genes and
CC clock-controlled genes (involved in key metabolic processes), harboring
CC E-box elements (5'-CACGTG-3') within their promoters. The core clock
CC genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form
CC the negative limb of the feedback loop and interact with the
CC CLOCK|NPAS2-ARNTL/BMAL1|ARNTL2/BMAL2 heterodimer inhibiting its
CC activity and thereby negatively regulating their own expression. This
CC heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G,
CC which form a second feedback loop and which activate and repress
CC ARNTL/BMAL1 transcription, respectively. Regulates circadian target
CC genes expression at post-transcriptional levels, but may not be
CC required for the repression at transcriptional level. Controls PER2
CC protein decay. Represses CRY2 preventing its repression on CLOCK/ARNTL
CC target genes such as FXYD5 and SCNN1A in kidney and PPARA in liver.
CC Besides its involvement in the maintenance of the circadian clock, has
CC an important function in the regulation of several processes.
CC Participates in the repression of glucocorticoid receptor NR3C1/GR-
CC induced transcriptional activity by reducing the association of
CC NR3C1/GR to glucocorticoid response elements (GREs) by ARNTL:CLOCK.
CC Plays a role in the modulation of the neuroinflammatory state via the
CC regulation of inflammatory mediators release, such as CCL2 and IL6. In
CC spinal astrocytes, negatively regulates the MAPK14/p38 and MAPK8/JNK
CC MAPK cascades as well as the subsequent activation of NFkappaB.
CC Coordinately regulates the expression of multiple genes that are
CC involved in the regulation of renal sodium reabsorption. Can act as
CC gene expression activator in a gene and tissue specific manner, in
CC kidney enhances WNK1 and SLC12A3 expression in collaboration with
CC CLOCK. Modulates hair follicle cycling. Represses the CLOCK-ARNTL/BMAL1
CC induced transcription of BHLHE40/DEC1. {ECO:0000250|UniProtKB:O35973}.
CC -!- SUBUNIT: Homodimer (By similarity). Component of the circadian core
CC oscillator, which includes the CRY proteins, CLOCK or NPAS2,
CC ARNTL/BMAL1 or ARNTL2/BMAL2, CSNK1D and/or CSNK1E, TIMELESS, and the
CC PER proteins (By similarity). Interacts directly with TIMELESS, PER2,
CC PER3, CRY1 and CRY2 (By similarity). Interacts with ARNTL/BMAL1 and
CC CLOCK (By similarity). Interacts with GPRASP1 (By similarity).
CC Interacts (phosphorylated) with BTRC and FBXW11; the interactions
CC trigger proteasomal degradation (By similarity). Interacts with NONO,
CC WDR5 and SFPQ (By similarity). Interacts with USP2 (By similarity).
CC Interacts with HNF4A (By similarity). {ECO:0000250|UniProtKB:O15534,
CC ECO:0000250|UniProtKB:O35973, ECO:0000250|UniProtKB:Q8CHI5}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Cytoplasm {ECO:0000250}.
CC Note=Nucleocytoplasmic shuttling is effected by interaction with other
CC circadian core oscillator proteins and/or by phosphorylation. Retention
CC of PER1 in the cytoplasm occurs through PER1-PER2 heterodimer
CC formation. Translocate to the nucleus after phosphorylation by CSNK1D
CC or CSNK1E. Also translocated to the nucleus by CRY1 or CRY2 (By
CC similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in the brain, mainly in the
CC suprachiasmatic nucleus (SCN). Expression also found in the harderian
CC gland, lung, eye, intestine, liver and skeletal muscle.
CC {ECO:0000269|PubMed:12193657}.
CC -!- INDUCTION: Exhibits circadian rhythm expression. In the SCN and
CC harderian gland, maximum levels at ZT6. Maximum levels in the eye and
CC liver at ZT12. Under constant darkness, maximum levels, in SCN and
CC harderian gland, during subjective day at CT6. In the eye, maximum
CC levels at CT12. PER1 is highly light-inducible at ZT14 and ZT22.
CC {ECO:0000269|PubMed:12193657}.
CC -!- PTM: Phosphorylated on serine residues by CSNK1D, CSNK1E and probably
CC also by CSNK1G2. Phosphorylation by CSNK1D or CSNK1E promotes nuclear
CC location of PER proteins as well as ubiquitination and subsequent
CC degradation. May be dephosphorylated by PP1.
CC {ECO:0000250|UniProtKB:O35973}.
CC -!- PTM: Ubiquitinated; requires phosphorylation by CSNK1E and interaction
CC with BTRC and FBXW11. Deubiquitinated by USP2.
CC {ECO:0000250|UniProtKB:O35973}.
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DR EMBL; AJ345059; CAC95146.1; -; mRNA.
DR AlphaFoldDB; Q8K3T3; -.
DR SMR; Q8K3T3; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0031490; F:chromatin DNA binding; 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:0043153; P:entrainment of circadian clock by photoperiod; ISS:UniProtKB.
DR GO; GO:0070932; P:histone H3 deacetylation; ISS:UniProtKB.
DR GO; GO:2000323; P:negative regulation of glucocorticoid receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0046329; P:negative regulation of JNK cascade; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0010608; P:post-transcriptional regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:1900015; P:regulation of cytokine production involved in inflammatory response; ISS:UniProtKB.
DR GO; GO:0042634; P:regulation of hair cycle; ISS:UniProtKB.
DR GO; GO:1900744; P:regulation of p38MAPK cascade; ISS:UniProtKB.
DR GO; GO:0002028; P:regulation of sodium ion transport; 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 2: Evidence at transcript level;
KW Biological rhythms; Cytoplasm; Nucleus; Phosphoprotein; Repeat;
KW Transcription; Transcription regulation; Ubl conjugation.
FT CHAIN 1..1285
FT /note="Period circadian protein homolog 1"
FT /id="PRO_0000261152"
FT DOMAIN 208..275
FT /note="PAS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 348..414
FT /note="PAS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 422..465
FT /note="PAC"
FT REGION 1..151
FT /note="Interaction with BTRC"
FT /evidence="ECO:0000250|UniProtKB:O15534"
FT REGION 1..134
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 503..544
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 592..811
FT /note="Required for phosphorylation by CSNK1E"
FT /evidence="ECO:0000250"
FT REGION 643..694
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 802..867
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 931..1030
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1045..1091
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1142..1285
FT /note="CRY binding domain"
FT /evidence="ECO:0000250"
FT REGION 1202..1285
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 138..147
FT /note="Nuclear export signal 1"
FT /evidence="ECO:0000250|UniProtKB:O54943"
FT MOTIF 489..498
FT /note="Nuclear export signal 2"
FT /evidence="ECO:0000250|UniProtKB:O35973"
FT MOTIF 820..836
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:O35973"
FT MOTIF 975..982
FT /note="Nuclear export signal 3"
FT /evidence="ECO:0000250|UniProtKB:O54943"
FT MOTIF 1036..1040
FT /note="LXXLL"
FT COMPBIAS 42..134
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 643..663
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 820..840
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 850..867
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 940..963
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 966..983
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1252..1285
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 121
FT /note="Phosphothreonine; by CSNK1E"
FT /evidence="ECO:0000255"
FT MOD_RES 122
FT /note="Phosphoserine; by CSNK1E"
FT /evidence="ECO:0000255"
FT MOD_RES 126
FT /note="Phosphoserine; by CSNK1E"
FT /evidence="ECO:0000255"
FT MOD_RES 657
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35973"
FT MOD_RES 659
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35973"
FT MOD_RES 700
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O15534"
FT MOD_RES 811
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O15534"
FT MOD_RES 972
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O15534"
FT MOD_RES 973
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O15534"
SQ SEQUENCE 1285 AA; 135988 MW; D0494840FE9828D1 CRC64;
MSGPLEGADG GGDPRPGESF CSGGVPSPGA PQHRSCPGPS LADDTDANSN GSSGNESNGH
ESRGASQRSS HSSSSGNGKD SALLETTESS KSTNSQSPSP PSSSIAYSLL SASSEQDNPS
TSGCSSEQSA RARTQKELMT ALRELKLRLP PGHRGKGRSG TLATLQYALA CVKQVQANQE
YYQQWSLEEG EPCAMDMSTY TLEELEHITS EYTLRNQDTF SVAVSFLTGR IVYISEQAGV
LLRCKRDVFR GARFSELLAP QDVGVFYGST APFRLPTWGT GTSAGSGLKD FTQEKSVFCR
IRGGPDRDPG PRYHPFRLTP YVTKIRVSDG APAQPCCLLI AERIHSGYEA PRIPPDKRIF
TTRHTPSCLF QDVDERAAPL LGYLPQDLLG APVLLFLHPE DRPLMLAIHK KILQLAGQPF
DHSPIRFCAR NGEYVTMDTS WAGFVHPWSR KVAFVLGRHK VRTAPLNEDV FTPPAPSPAP
SLDSDIQELS EQIHRLLLQP VHSSSPTGPC GIGPLMSPRP LHSPGSSSDS NGGDAEGPGP
PAPVTFQQIC KDVHLVKHQG QQLFIESRAR PPPRPRLLGK AKGLPCQSLD PELEVVPMPN
QAPLALALEE AERKEASSCS YQQINCLDSI LRYLESCNIP STTKRKCASS SSCTASSASD
DDKQRTGPVP VGAKKDPSST VLSGEGASPR KEPVVGGTLS PLTLANKAES VVSITSQCSF
SSTIVHVGDK KPPESDIIMM EDLPGLAPGP VPSPAPSPTV APDPAPDAYR PVGLTKAVLS
LHTQKEEQAF LSRFKDLGRL RGLDSSSATP SAPGCHHGPV PPGRRHHCRS KAKRSRHHHT
PRAEAPCCVS HPSPVPPSGP WPPPPSTTPF PAVVQPYPLP VFSARGGPQP LPPAPTPMPP
ATFPTPLVTP MVALVLPNYL FPTPPSYPYG LSQAPVEEPP SPASHSPSPS LTPLTPSPPH
HPDSPLFNSR CSSPLQLNLL QLEESPRTEG GAVAGGPGSS AGPPPPTEEA AEPEARLVEV
TESSNQDALS GSSDLLELLL QEDSRSGTGS AASGSLGSGL GSGSGSGSHE GGSTSASITR
SSQSSHTSKY FGSIDSSEAE AGAVQARIEL GDQVIKYVLQ DPIWLLMANA DQHVMMTYQV
PSRDRASVLK QDRERLRTMQ KQQPRFSEDQ RRELGAVHSW VRKGQLPQAL DVMACVDCSS
SIQDPGHSDD PLFSELDGLG LEPMEEGGGE GGGGGGGGGE GEGGEEAQAH IGVKVSSSQD
SAMDEEEQGG SSSSPALPAE ENSTS
