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
ID:PER1_HUMAN 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
autism Nicholas, B. et al. 2007, Association of Per1 and Npas2 with autistic disorder, Mol Psychiatry 2007.
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.
Our results suggest that structural polymorphisms in the hPer3 gene may be implicated in the pathogenesis of DSPS.
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.
ModBase Predicted Comparative 3D Structure on O15534
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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.
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