Human Gene PER1 (uc002gkd.3) Description and Page Index
  Description: Homo sapiens period circadian clock 1 (PER1), mRNA.
RefSeq Summary (NM_002616): This gene is a member of the Period family of genes and is expressed in a circadian pattern in the suprachiasmatic nucleus, the primary circadian pacemaker in the mammalian brain. Genes in this family encode components of the circadian rhythms of locomotor activity, metabolism, and behavior. This gene is upregulated by CLOCK/ARNTL heterodimers but then represses this upregulation in a feedback loop using PER/CRY heterodimers to interact with CLOCK/ARNTL. Polymorphisms in this gene may increase the risk of getting certain cancers. Alternative splicing has been observed in this gene; however, these variants have not been fully described. [provided by RefSeq, Jan 2014]. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: AF022991.1, AK291061.1 [ECO:0000332] RNAseq introns :: mixed/partial sample support SAMEA1965299, SAMEA1966682 [ECO:0000350] ##Evidence-Data-END## ##RefSeq-Attributes-START## MANE Ensembl match :: ENST00000317276.9/ ENSP00000314420.4 RefSeq Select criteria :: based on conservation, expression, longest protein ##RefSeq-Attributes-END##
Transcript (Including UTRs)
   Position: hg19 chr17:8,043,788-8,055,753 Size: 11,966 Total Exon Count: 23 Strand: -
Coding Region
   Position: hg19 chr17:8,044,386-8,054,024 Size: 9,639 Coding Exon Count: 22 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-15

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr17:8,043,788-8,055,753)mRNA (may differ from genome)Protein (1290 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
neXtProtOMIMPubMedReactomeStanford SOURCETreefam

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Period circadian protein homolog 1; Short=hPER1; AltName: Full=Circadian clock protein PERIOD 1; AltName: Full=Circadian pacemaker protein Rigui;
FUNCTION: Component of the circadian clock mechanism which is essential for generating circadian rhythms. Negative element in the circadian transcriptional loop. Influences clock function by interacting with other circadian regulatory proteins and transporting them to the nucleus. Negatively regulates CLOCK|NPAS2-BMAL1|BMAL2-induced transactivation. Can bind heme (By similarity).
SUBUNIT: Homodimer (By similarity). Component of the circadian core oscillator, which includes the CRY proteins, CLOCK or NPAS2, BMAL1 or 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. Interaction with CSNK1D or CSNK1E promotes nuclear location of PER proteins. Interacts with GPRASP1 (By similarity). Binding to CSNK1G2 triggers proteasomal degradation.
SUBCELLULAR LOCATION: Nucleus (By similarity). Cytoplasm (By similarity). Note=Mainly nuclear. 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 or by interaction with CSNK1E and/or phosphorylation which appears to mask the PER1 nuclear localization signal. Also translocated to the nucleus by CRY1 or CRY2 (By similarity).
TISSUE SPECIFICITY: Widely expressed. Found in heart, brain, placenta, lung, liver, skeletal muscle, pancreas, kidney, spleen, thymus, prostate, testis, ovary and small intestine. Highest level in skeletal muscle. Low level in kidney.
INDUCTION: Serum-induced levels in fibroblasts show circadian oscillations. Maximum levels after 1 hour stimulation, minimum levels after 12 hours. Another peak is then observed after 20 hours. Protein levels show maximum levels at 6 hours, decrease to reach minimum levels at 20 hours, and increase again to reach a second peak after 26 hours. Levels then decrease slightly and then increase to maximum levels at 32 hours. Levels of phosphorylated form increase between 3 hours and 12 hours.
PTM: Phosphorylated on serine residues by CSNK1E. Also can be phosphorylated by the delta isoform. Phosphorylation by CSNK1 retains PER1 in the cytoplasm and leads to its ubiquitination and subsequent degradation. Phosphorylated upon DNA damage, probably by ATM or ATR.
PTM: Ubiquitinated (By similarity).
SIMILARITY: Contains 1 PAC (PAS-associated C-terminal) domain.
SIMILARITY: Contains 2 PAS (PER-ARNT-SIM) domains.
SEQUENCE CAUTION: Sequence=BAC06326.2; Type=Erroneous initiation;

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): PER1
CDC HuGE Published Literature: PER1
Positive Disease Associations: autism , delayed sleep phase syndrome
Related Studies:
  1. autism
    Nicholas, B. et al. 2007, Association of Per1 and Npas2 with autistic disorder, Mol Psychiatry 2007. [PubMed 17264841]
  2. delayed sleep phase syndrome
    Ebisawa, T. et al. 2001, Association of structural polymorphisms in the human period3 gene with delayed sleep phase syndrome., EMBO reports. 2001 Apr;2(4):342-6. [PubMed 11306557]
    Our results suggest that structural polymorphisms in the hPer3 gene may be implicated in the pathogenesis of DSPS.

-  MalaCards Disease Associations
  MalaCards Gene Search: PER1
Diseases sorted by gene-association score: periodic limb movement disorder (9), advanced sleep phase syndrome (8), autistic disorder (1)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 118.39 RPKM in Skin - Not Sun Exposed (Suprapubic)
Total median expression: 2452.30 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -94.53238-0.397 Picture PostScript Text
3' UTR -237.80598-0.398 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR001610 - PAC
IPR000014 - PAS
IPR013655 - PAS_fold_3
IPR022728 - Period_circadian-like_C

Pfam Domains:
PF08447 - PAS fold
PF12114 - Period protein 2/3C-terminal region
PF14598 - PAS domain

SCOP Domains:
55785 - PYP-like sensor domain (PAS domain)

Protein Data Bank (PDB) 3-D Structure
MuPIT help

- Model

ModBase Predicted Comparative 3D Structure on O15534
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserGenome BrowserNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 Protein SequenceProtein Sequence   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000976 transcription regulatory region sequence-specific DNA binding
GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding
GO:0000989 transcription factor activity, transcription factor binding
GO:0005515 protein binding
GO:0008134 transcription factor binding
GO:0019900 kinase binding
GO:0031490 chromatin DNA binding
GO:0031625 ubiquitin protein ligase binding
GO:0070888 E-box binding

Biological Process:
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0002028 regulation of sodium ion transport
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0007623 circadian rhythm
GO:0009416 response to light stimulus
GO:0009649 entrainment of circadian clock
GO:0010608 posttranscriptional regulation of gene expression
GO:0032922 circadian regulation of gene expression
GO:0042634 regulation of hair cycle
GO:0042752 regulation of circadian rhythm
GO:0043124 negative regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043153 entrainment of circadian clock by photoperiod
GO:0043966 histone H3 acetylation
GO:0043967 histone H4 acetylation
GO:0045892 negative regulation of transcription, DNA-templated
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0046329 negative regulation of JNK cascade
GO:0048511 rhythmic process
GO:0051591 response to cAMP
GO:0070932 histone H3 deacetylation
GO:0097167 circadian regulation of translation
GO:1900015 regulation of cytokine production involved in inflammatory response
GO:1900744 regulation of p38MAPK cascade
GO:2000323 negative regulation of glucocorticoid receptor signaling pathway

Cellular Component:
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005829 cytosol

-  Descriptions from all associated GenBank mRNAs
  AB088477 - Homo sapiens KIAA0482 mRNA for KIAA0482 protein.
AF022991 - Homo sapiens Rigui (RIGUI) mRNA, complete cds.
JD109162 - Sequence 90186 from Patent EP1572962.
JD271965 - Sequence 252989 from Patent EP1572962.
JD423797 - Sequence 404821 from Patent EP1572962.
JD055334 - Sequence 36358 from Patent EP1572962.
JD559056 - Sequence 540080 from Patent EP1572962.
JD092382 - Sequence 73406 from Patent EP1572962.
JD518232 - Sequence 499256 from Patent EP1572962.
AK291061 - Homo sapiens cDNA FLJ77255 complete cds, highly similar to Homo sapiens period homolog 1 (Drosophila) (PER1), mRNA.
BC137346 - Homo sapiens period homolog 1 (Drosophila), mRNA (cDNA clone MGC:168967 IMAGE:9021344), complete cds.
BC144593 - Homo sapiens cDNA clone IMAGE:9053123.
JD100158 - Sequence 81182 from Patent EP1572962.
JD308072 - Sequence 289096 from Patent EP1572962.
JD157271 - Sequence 138295 from Patent EP1572962.
JD414210 - Sequence 395234 from Patent EP1572962.
JD320301 - Sequence 301325 from Patent EP1572962.
AB002107 - Homo sapiens hPer mRNA, complete cds.
AB383894 - Synthetic construct DNA, clone: pF1KSDA0482, Homo sapiens PER1 gene for period circadian protein homolog 1, complete cds, without stop codon, in Flexi system.
BC150151 - Homo sapiens cDNA clone IMAGE:40134409.
BC028207 - Homo sapiens period homolog 1 (Drosophila), mRNA (cDNA clone IMAGE:5215552).
AK295410 - Homo sapiens cDNA FLJ59327 complete cds, highly similar to Period circadian protein 1.
KJ901631 - Synthetic construct Homo sapiens clone ccsbBroadEn_11025 PER1 gene, encodes complete protein.
CU688426 - Synthetic construct Homo sapiens gateway clone IMAGE:100019891 5' read PER1 mRNA.
BC072458 - Homo sapiens period homolog 1 (Drosophila), mRNA (cDNA clone IMAGE:6200422), complete cds.
KJ901632 - Synthetic construct Homo sapiens clone ccsbBroadEn_11026 PER1 gene, encodes complete protein.
CU687240 - Synthetic construct Homo sapiens gateway clone IMAGE:100022889 5' read PER1 mRNA.
JD290426 - Sequence 271450 from Patent EP1572962.
JD541562 - Sequence 522586 from Patent EP1572962.
JD174925 - Sequence 155949 from Patent EP1572962.
JD131642 - Sequence 112666 from Patent EP1572962.
JD522112 - Sequence 503136 from Patent EP1572962.
JD211282 - Sequence 192306 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04710 - Circadian rhythm - mammal

BioCarta from NCI Cancer Genome Anatomy Project
h_circadianPathway - Circadian Rhythms

Reactome (by CSHL, EBI, and GO)

Protein O15534 (Reactome details) participates in the following event(s):

R-HSA-400219 Beta-TrCP1 binds phosphorylated PER proteins
R-HSA-400382 CSNK1E,CSNK1D phosphorylate CRY and PER proteins
R-HSA-400256 CRY:PER heterodimer binds the BMAL1:CLOCK/NPAS2 heterodimer
R-HSA-400253 Circadian Clock

-  Other Names for This Gene
  Alternate Gene Symbols: B2RPA8, D3DTR3, KIAA0482, NM_002616, NP_002607, O15534, PER, PER1_HUMAN, RIGUI
UCSC ID: uc002gkd.3
RefSeq Accession: NM_002616
Protein: O15534 (aka PER1_HUMAN)
CCDS: CCDS11131.1

-  Gene Model Information
category: coding nonsense-mediated-decay: no RNA accession: NM_002616.2
exon count: 23CDS single in 3' UTR: no RNA size: 4717
ORF size: 3873CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 7711.00frame shift in genome: no % Coverage: 99.83
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.