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Gene Symbol |
CLOCK |
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Aliases |
KAT13D, bHLHe8 |
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Entrez Gene ID |
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Gene Name |
Clock circadian regulator |
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Chromosomal Location |
4q12 |
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HGNC ID |
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Summary |
The protein encoded by this gene plays a central role in the regulation of circadian rhythms. The protein encodes a transcription factor of the basic helix-loop-helix (bHLH) family and contains DNA binding histone acetyltransferase activity. The encoded protein forms a heterodimer with ARNTL (BMAL1) that binds E-box enhancer elements upstream of Period (PER1, PER2, PER3) and Cryptochrome (CRY1, CRY2) genes and activates transcription of these genes. PER and CRY proteins heterodimerize and repress their own transcription by interacting in a feedback loop with CLOCK/ARNTL complexes. Polymorphisms in this gene may be associated with behavioral changes in certain populations and with obesity and metabolic syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]
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e!Ensembl
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Gene Ontology (GO)
| GO ID |
Ontology |
Function |
Evidence |
Reference |
| GO:0000077 |
Biological process |
DNA damage checkpoint |
IMP |
21659603 |
| GO:0006357 |
Biological process |
Regulation of transcription by RNA polymerase II |
TAS |
10198158 |
| GO:0006473 |
Biological process |
Protein acetylation |
IDA |
28985504 |
| GO:0007165 |
Biological process |
Signal transduction |
TAS |
10198158 |
| GO:0009648 |
Biological process |
Photoperiodism |
TAS |
10198158 |
| GO:0032922 |
Biological process |
Circadian regulation of gene expression |
IDA |
24005054 |
| GO:0032922 |
Biological process |
Circadian regulation of gene expression |
IMP |
21980503, 28985504 |
| GO:0042634 |
Biological process |
Regulation of hair cycle |
IMP |
24005054 |
| GO:0045893 |
Biological process |
Positive regulation of transcription, DNA-templated |
IDA |
23785138 |
| GO:0045944 |
Biological process |
Positive regulation of transcription by RNA polymerase II |
IGI |
9576906 |
| GO:0051775 |
Biological process |
Response to redox state |
IDA |
11441146 |
| GO:0071479 |
Biological process |
Cellular response to ionizing radiation |
IDA |
21659603 |
| GO:0005634 |
Cellular component |
Nucleus |
IDA |
14645221, 28985504 |
| GO:0005667 |
Cellular component |
Transcription factor complex |
IPI |
9576906 |
| GO:0005694 |
Cellular component |
Chromosome |
IDA |
21659603 |
| GO:0005829 |
Cellular component |
Cytosol |
IDA |
28985504 |
| GO:0000978 |
Molecular function |
RNA polymerase II proximal promoter sequence-specific DNA binding |
IDA |
18411297 |
| GO:0000981 |
Molecular function |
DNA-binding transcription factor activity, RNA polymerase II-specific |
ISM |
19274049 |
| GO:0000981 |
Molecular function |
DNA-binding transcription factor activity, RNA polymerase II-specific |
NAS |
19274049 |
| GO:0003677 |
Molecular function |
DNA binding |
IDA |
11441146 |
| GO:0004402 |
Molecular function |
Histone acetyltransferase activity |
IMP |
21980503, 28985504 |
| GO:0005515 |
Molecular function |
Protein binding |
IPI |
14645221, 20861012, 21960634, 21980503, 28903391, 28985504, 30530698 |
| GO:0070888 |
Molecular function |
E-box binding |
IDA |
18411297, 23785138 |
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| Protein Information |
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Protein Name |
Circadian locomoter output cycles protein kaput, circadian locomoter output cycles kaput protein, class E basic helix-loop-helix protein 8, clock homolog |
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Function |
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UniProt |
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PDB |
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Interactions |
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| STRING |
MINT |
IntAct |
| ENSP00000334592 |
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View interactions
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Associated Diseases
| Disease group | Disease Name | References |
| Endocrine System Diseases |
| PCOS |
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| Psychiatric/Brain disorders |
| Bipolar Disorder |
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| Mental Depression |
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| Seasonal Affective Disorder |
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| Mood Disorders |
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| Schizophrenia |
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| Delirium |
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References |
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| Chen Minghui, Xu Yanwen, Miao Benyu, Zhao Hui, Luo Lu, Shi Huijuan, Zhou Canquan |
| Reproductive Medicine Center, The First Affiliated Hospital of Sun Yat-sen University, 58 2nd Zhongshan Road, Guangzhou, GD510080, People's Republic of China.| Guangdong Provincial Key Laboratory of Reproductive Medicine, The First Affiliated Hospital of Sun Yat-sen University, 58 2nd Zhongshan Road, Guangzhou, GD510080, People's Republic of China.| Reproductive Medicine Center, The First Affiliated Hospital of Sun Yat-sen University, 58 2nd Zhongshan Road, Guangzhou, GD510080, People's Republic of China.| Guangdong Provincial Key Laboratory of Reproductive Medicine, The First Affiliated Hospital of Sun Yat-sen University, 58 2nd Zhongshan Road, Guangzhou, GD510080, People's Republic of China.| Reproductive Medicine Center, The First Affiliated Hospital of Sun Yat-sen University, 58 2nd Zhongshan Road, Guangzhou, GD510080, People's Republic of China.| Guangdong Provincial Key Laboratory of Reproductive Medicine, The First Affiliated Hospital of Sun Yat-sen University, 58 2nd Zhongshan Road, Guangzhou, GD510080, People's Republic of China.| Department of Hepatic Surgery, The Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Guangzhou, GD510630, People's Republic of China.| Reproductive Medicine Center, The First Affiliated Hospital of Sun Yat-sen University, 58 2nd Zhongshan Road, Guangzhou, GD510080, People's Republic of China.| Guangdong Provincial Key Laboratory of Reproductive Medicine, The First Affiliated Hospital of Sun Yat-sen University, 58 2nd Zhongshan Road, Guangzhou, GD510080, People's Republic of China.| Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, 58 2nd Zhongshan Road, Guangzhou, GD510080, People's Republic of China.| Reproductive Medicine Center, The First Affiliated Hospital of Sun Yat-sen University, 58 2nd Zhongshan Road, Guangzhou, GD510080, People's Republic of China. zhoucanquan@hotmail.com.| Guangdong Provincial Key Laboratory of Reproductive Medicine, The First Affiliated Hospital of Sun Yat-sen University, 58 2nd Zhongshan Road, Guangzhou, GD510080, People's Republic of China. zhoucanquan@hotmail.com. |
| J Ovarian Res. 2016 Sep 10;9(1):56. doi: 10.1186/s13048-016-0264-5. |
Abstract
BACKGROUND: Previous studies have shown that circadian genes might be involved in the development of polycystic ovarian syndrome (PCOS). Hyperandrogenism is a hallmark feature of PCOS. However, the effect of hyperandrogenism on circadian gene expression in human granulosa cells is unknown, and the general expression pattern of circadian genes in the human ovary is unclear. METHODS: Expression of the circadian proteins CLOCK and PER2 in human ovaries was observed by immunohistochemistry. The mRNA expression patterns of the circadian genes CLOCK, PER2, and BMAL1, and the steroidogenesis-related genes STAR, CYP11A1, HSD3B2, and CYP19A1 in cultured human luteinized granulosa cells were analyzed over the course of 48 h after testosterone treatment by quantitative polymerase chain reaction. RESULTS: Immunostaining of CLOCK and PER2 protein was detected in the granulosa cells of dominant antral follicles but was absent in the primordial, primary, or preantral follicles of human ovaries. After testosterone stimulation, expression of PER2 showed an oscillating pattern, with two peaks occurring at the 24th and 44th hours; expression of CLOCK increased significantly to the peak at the 24th hour, whereas expression of BMAL1 did not change significantly over time in human luteinized granulosa cells. Among the four steroidogenesis-related genes evaluated, only STAR displayed an oscillating expression pattern with two peaks occurring at the 24th and 40th hours after testosterone stimulation. CONCLUSIONS: Circadian genes are expressed in the dominant antral follicles of the human ovary. Oscillating expression of the circadian gene PER2 can be induced by testosterone in human granulosa cells in vitro. Expression of STAR also displayed an oscillating pattern after testosterone stimulation. Our results indicate a potential relationship between the circadian clock and steroidogenesis in the human ovary, and demonstrate the effect of testosterone on circadian gene expression in granulosa cells. |
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| © 2019, Biomedical Informatics Centre, NIRRH |
National Institute for Research in Reproductive Health, Jehangir Merwanji Street, Parel, Mumbai-400 012
Tel: 91-22-24192104, Fax No: 91-22-24139412
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