| + |
CSNK1E | down-regulates quantity by destabilization 
phosphorylation
|
PER2 |
0.902 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277419 |
Ser480 |
PVPHSGSsGYGSLGS |
in vitro |
|
| pmid |
sentence |
| 30425162 |
Priming-independent clusters located in the C-terminal portion of PER2’s PAS domains are targeted by CK1ε/δ and are required for ubiquitin ligase–mediated degradation of PER2 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-276065 |
|
|
in vitro |
|
| pmid |
sentence |
| 17525164 |
AMPK enhances mPer2 degradation and CKIɛ activity by phosphorylating Ser-389 of CKIɛ. One of the regulators of the period length is casein kinase Iepsilon (CKIepsilon), which by phosphorylating and inducing the degradation of the circadian clock component, mPer2, shortens the period length. AMPK phosphorylates Ser-389 of CKIepsilon, resulting in increased CKIepsilon activity and degradation of mPer2. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267995 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 15767683 |
The mammalian circadian regulatory proteins PER1 and PER2 undergo a daily cycle of accumulation followed by phosphorylation and degradation. CKIepsilon-mediated phosphorylation of PER2 recruits the ubiquitin ligase adapter protein beta-TrCP to a specific site, and dominant negative beta-TrCP blocks phosphorylation-dependent degradation of mPER2. These results provide a biochemical mechanism and functional relevance for the observed phosphorylation-degradation cycle of mammalian PER2. |
|
| Publications: |
3 |
Organism: |
In Vitro, Mus Musculus |
| Pathways: | Circadian clock |
| + |
CSNK1D | down-regulates quantity by destabilization
phosphorylation
|
PER2 |
0.869 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277420 |
Ser480 |
PVPHSGSsGYGSLGS |
in vitro |
|
| pmid |
sentence |
| 30425162 |
Priming-independent clusters located in the C-terminal portion of PER2’s PAS domains are targeted by CK1ε/δ and are required for ubiquitin ligase–mediated degradation of PER2 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268000 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11165242 |
Human casein kinase Idelta phosphorylation of human circadian clock proteins period 1 and 2. We have now extended our previous studies to show that human casein kinase Idelta (hCKIdelta), the closest homologue to hCKIepsilon, associates with and phosphorylates hPER1 and causes protein instability. Furthermore, we observed that both hCKIdelta and hCKIepsilon phosphorylated and caused protein instability of human period 2 protein (hPER2). |
|
| Publications: |
2 |
Organism: |
In Vitro, Homo Sapiens |
| Pathways: | Circadian clock |
| + |
PER2 | down-regulates activity
binding
|
CLOCK/BMAL1 |
0.763 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267977 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20817722 |
The mammalian clock is regulated at the cellular level by a transcriptional/translational feedback loop. BMAL1/clock (or NPAS2) heterodimers activate the expression of the period (PER) and cryptochrome (CRY) genes acting as transcription factors directed to the PER and CRY promoters via E-box elements. PER and CRY proteins form heterodimers and suppress the activity of the BMAL1/clock (or NPAS2) completing the feedback loop. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Circadian clock |
| + |
PER2 | up-regulates 
|
Apoptosis |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256370 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22260161 |
We have previously shown that PER2 is a downstream CCAAT-enhancer-binding protein (C/EBP)-target gene, and its disruption might be involved in the initiation and progression of acute myelogenous leukemia (AML) |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PER2 | down-regulates 
|
Proliferation |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256371 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22260161 |
We have previously shown that PER2 is a downstream CCAAT-enhancer-binding protein (C/EBP)-target gene, and its disruption might be involved in the initiation and progression of acute myelogenous leukemia (AML) |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PER2 | down-regulates quantity by repression
transcriptional regulation
|
TWIST1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-254153 |
|
|
Homo sapiens |
MCF-10A Cell |
| pmid |
sentence |
| 23836662 |
We further demonstrated that PER2 served as a transcriptional corepressor, which recruited polycomb proteins EZH2 and SUZ12 as well as HDAC2 to octamer transcription factor 1 (OCT1) (POU2F1) binding sites of the TWIST1 and SLUG promoters to repress expression of these EMT genes. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SCF-betaTRCP | down-regulates quantity by destabilization
ubiquitination
|
PER2 |
0.487 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268055 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 17876059 |
Here, the authors show that the F-box protein beta-transducin repeat containing protein 1 (beta-TrCP1) as part of the E3 ubiquitin ligase complex is an essential component of the mammalian circadian oscillator. Down-regulation of endogenous beta-TrCP1 as well as expression of a dominant-negative form both result in lengthening of the circadian period in oscillating fibroblasts. These phenotypes are due to an impaired degradation of PERIOD (PER) proteins, since expression of beta-TrCP interaction-deficient PER2 variants--but not wild-type PER2--results in a dramatic stabilization of PER2 protein as well as in the disruption of circadian rhythmicity. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Circadian clock |
| + |
CLOCK/BMAL1 | up-regulates quantity by expression
transcriptional regulation
|
PER2 |
0.763 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253682 |
|
|
|
|
| pmid |
sentence |
| 22750052 |
Mammalian clocks are primarily based on a transcription and translation feedback loop in which a heterodimeric complex of the transcription factors CLOCK (circadian locomotor output cycles kaput) and BMAL1 (brain and muscle Arnt-like protein 1) activates the expression of its own repressors, the period (PER1-3) and cryptochrome (CRY1,2) proteins. |
|
| Publications: |
1 |
| Pathways: | Circadian clock |
| + |
RAI1 | up-regulates quantity by expression
transcriptional regulation
|
PER2 |
0.309 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-266840 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 22578325 |
Data further show that haploinsufficiency of RAI1 and Rai1 in SMS fibroblasts and the mouse hypothalamus, respectively, results in the transcriptional dysregulation of the circadian clock and causes altered expression and regulation of multiple circadian genes, including PER2, PER3, CRY1, BMAL1, and others. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Circadian clock |
| + |
PER2 | down-regulates activity
binding
|
POU2F1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-254148 |
|
|
Homo sapiens |
MCF-10A Cell |
| pmid |
sentence |
| 23836662 |
This PER2-OCT1 interaction effectively converted OCT1 sites, which normally activate expression, into repressor sites by recruitment of a polycomb repressor complex including EZH2 and SUZ12, as well as HDAC2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SIK3 | down-regulates quantity by destabilization
phosphorylation
|
PER2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-279570 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 29227248 |
In the current study, we found that SIK3 promotes phosphorylation of PER2 and regulates the abundance of the protein by accelerating its degradation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MDM2 | down-regulates quantity by destabilization
polyubiquitination
|
PER2 |
0.357 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277421 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 30425162 |
We identified PER2 as a previously uncharacterized substrate for the ubiquitin ligase mouse double minute 2 homolog (MDM2) and found that MDM2 targeted PER2 for degradation in a manner independent of PER2 phosphorylation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
BMAL1/NPAS2 | up-regulates quantity by expression 
transcriptional regulation
|
PER2 |
0.751 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267969 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20817722 |
The mammalian clock is regulated at the cellular level by a transcriptional/translational feedback loop. BMAL1/clock (or NPAS2) heterodimers activate the expression of the period (PER) and cryptochrome (CRY) genes acting as transcription factors directed to the PER and CRY promoters via E-box elements. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Circadian clock |
| + |
CEBPA | up-regulates quantity by expression
transcriptional regulation
|
PER2 |
0.425 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256369 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22260161 |
We have previously shown that PER2 is a downstream CCAAT-enhancer-binding protein (C/EBP)-target gene, and its disruption might be involved in the initiation and progression of acute myelogenous leukemia (AML) |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PER2 | down-regulates activity
binding
|
BMAL1/NPAS2 |
0.751 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267973 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20817722 |
The mammalian clock is regulated at the cellular level by a transcriptional/translational feedback loop. BMAL1/clock (or NPAS2) heterodimers activate the expression of the period (PER) and cryptochrome (CRY) genes acting as transcription factors directed to the PER and CRY promoters via E-box elements. PER and CRY proteins form heterodimers and suppress the activity of the BMAL1/clock (or NPAS2) completing the feedback loop. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Circadian clock |
| + |
BHLHE40 | down-regulates quantity by repression
transcriptional regulation
|
PER2 |
0.472 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253717 |
|
|
Mus musculus |
NIH-3T3 Cell |
| pmid |
sentence |
| 14672706 |
Forced expression of Clock/Bmal increased endogenous Dec1 mRNA level, and overexpression of Dec1 resulted in suppression of Dec2, Per2, and Dbp expression |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
CLOCK | up-regulates quantity by expression
transcriptional regulation
|
PER2 |
0.778 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253634 |
|
|
|
|
| pmid |
sentence |
| 22750052 |
Mammalian clocks are primarily based on a transcription and translation feedback loop in which a heterodimeric complex of the transcription factors CLOCK (circadian locomotor output cycles kaput) and BMAL1 (brain and muscle Arnt-like protein 1) activates the expression of its own repressors, the period (PER1-3) and cryptochrome (CRY1,2) proteins. |
|
| Publications: |
1 |
| Pathways: | Circadian clock |
| + |
NR3C1 | up-regulates quantity by expression
transcriptional regulation
|
PER2 |
0.498 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268049 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 19805059 |
GR directly regulates transcription of circadian clock components in mouse and human primary MSCs. Per2, E4bp4, Per1, and Timeless rapidly respond to glucocorticoid stimulation. Primary glucocorticoid receptor (GR) target genes are those at which GR occupies a nearby genomic glucocorticoid response element (GRE) and regulates target gene transcription |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Circadian clock |
| + |
ARNTL | up-regulates quantity by expression
transcriptional regulation
|
PER2 |
0.748 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253629 |
|
|
|
|
| pmid |
sentence |
| 22750052 |
Mammalian clocks are primarily based on a transcription and translation feedback loop in which a heterodimeric complex of the transcription factors CLOCK (circadian locomotor output cycles kaput) and BMAL1 (brain and muscle Arnt-like protein 1) activates the expression of its own repressors, the period (PER1-3) and cryptochrome (CRY1,2) proteins. |
|
| Publications: |
1 |
| Pathways: | Circadian clock |
| + |
PER2 | down-regulates quantity by repression
transcriptional regulation
|
SNAI2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-254147 |
|
|
Homo sapiens |
MCF-10A Cell |
| pmid |
sentence |
| 23836662 |
PER2 Suppresses TWIST1 and SLUG Transcription by Recruiting EZH2, SUZ12, and HDAC2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
3.0
PER2
- 
- 