CLOCK Recombinant Monoclonal Antibody

說明書

中文名稱：

CLOCK Recombinant Monoclonal Antibody
貨號：

CSB-RA100602A0HU
規格：

￥1320
圖片：
Immunofluorescence staining of A431 cell with CSB-RA100602A0HU at 1:50, counter-stained with DAPI. The cells were fixed in 4% formaldehyde, permeabilized using 0.2% Triton X-100 and blocked in 10% normal Goat Serum. The cells were then incubated with the antibody overnight at 4°C. The secondary antibody was Alexa Fluor 488-congugated AffiniPure Goat Anti-Rabbit IgG(H+L).

Overlay Peak curve showing 786-O cells stained with CSB-RA100602A0HU (red line) at 1:100. The cells were fixed in 4% formaldehyde and permeated by 0.2% TritonX-100 for 10min. Then 10% normal goat serum to block non-specific protein-protein interactions followed by the antibody (1ug/1*10⁶cells) for 45min at 4℃. The secondary antibody used was FITC-conjugated goat anti-rabbit IgG (H+L) at 1/200 dilution for 35min at 4℃.Control antibody (green line) was Rabbit IgG (1ug/1*10⁶cells) used under the same conditions. Acquisition of >10,000 events was performed.
其他：

產品詳情
產品評價
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靶點詳情

產品詳情

Uniprot No.：

O15516
基因名：

CLOCK
別名：

Circadian locomoter output cycles protein kaput (hCLOCK) (EC 2.3.1.48) (Class E basic helix-loop-helix protein 8) (bHLHe8), CLOCK, BHLHE8 KIAA0334
反應種屬：

Human
免疫原：

A synthesized peptide from human CLOCK protein
免疫原種屬：

Homo sapiens (Human)
標記方式：

Non-conjugated
克隆類型：

Monoclonal
抗體亞型：

Rabbit IgG
純化方式：

Affinity-chromatography
克隆號：

10A9
濃度：

It differs from different batches. Please contact us to confirm it.
保存緩沖液：

Preservative: 0.03% Proclin 300
Constituents: 50% Glycerol, 0.01M PBS, PH 7.4
產品提供形式：

Liquid
應用范圍：

ELISA, IF, FC

推薦稀釋比：

Application	Recommended Dilution
IF	1:50-1:200
FC	1:50-1:200

Protocols：

ELISA Protocol
Immunofluorescence (IF) Protocol
Flow cytometry (FC) Protocol
儲存條件：

Upon receipt, store at -20°C or -80°C. Avoid repeated freeze.
貨期：

Basically, we can dispatch the products out in 1-3 working days after receiving your orders. Delivery time maybe differs from different purchasing way or location, please kindly consult your local distributors for specific delivery time.
用途：

For Research Use Only. Not for use in diagnostic or therapeutic procedures.

產品評價

靶點詳情

功能：

Transcriptional activator which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, ARNTL/BMAL1, ARNTL2/BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and ARNTL/BMAL1 or ARNTL2/BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-ARNTL/BMAL1|ARNTL2/BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress ARNTL/BMAL1 transcription, respectively. Regulates the circadian expression of ICAM1, VCAM1, CCL2, THPO and MPL and also acts as an enhancer of the transactivation potential of NF-kappaB. Plays an important role in the homeostatic regulation of sleep. The CLOCK-ARNTL/BMAL1 heterodimer regulates the circadian expression of SERPINE1/PAI1, VWF, B3, CCRN4L/NOC, NAMPT, DBP, MYOD1, PPARGC1A, PPARGC1B, SIRT1, GYS2, F7, NGFR, GNRHR, BHLHE40/DEC1, ATF4, MTA1, KLF10 and also genes implicated in glucose and lipid metabolism. Promotes rhythmic chromatin opening, regulating the DNA accessibility of other transcription factors. The CLOCK-ARNTL2/BMAL2 heterodimer activates the transcription of SERPINE1/PAI1 and BHLHE40/DEC1. The preferred binding motif for the CLOCK-ARNTL/BMAL1 heterodimer is 5'-CACGTGA-3', which contains a flanking Ala residue in addition to the canonical 6-nucleotide E-box sequence. CLOCK specifically binds to the half-site 5'-CAC-3', while ARNTL binds to the half-site 5'-GTGA-3'. The CLOCK-ARNTL/BMAL1 heterodimer also recognizes the non-canonical E-box motifs 5'-AACGTGA-3' and 5'-CATGTGA-3'. CLOCK has an intrinsic acetyltransferase activity, which enables circadian chromatin remodeling by acetylating histones and nonhistone proteins, including its own partner ARNTL/BMAL1. Represses glucocorticoid receptor NR3C1/GR-induced transcriptional activity by reducing the association of NR3C1/GR to glucocorticoid response elements (GREs) via the acetylation of multiple lysine residues located in its hinge region. The acetyltransferase activity of CLOCK is as important as its transcription activity in circadian control. Acetylates metabolic enzymes IMPDH2 and NDUFA9 in a circadian manner. Facilitated by BMAL1, rhythmically interacts and acetylates argininosuccinate synthase 1 (ASS1) leading to enzymatic inhibition of ASS1 as well as the circadian oscillation of arginine biosynthesis and subsequent ureagenesis. Drives the circadian rhythm of blood pressure through transcriptional activation of ATP1B1.
基因功能參考文獻：
1. As a novel CLOCK-dependent diurnal gene, TIMP3 inhibits the expression of inflammatory cytokines that are up-regulated by UV irradiation in human keratinocytes. PMID: 29180440
2. the CLOCK gene polymorphism is one of factors determining elastic properties of vascular wall PMID: 28290876
3. Rhythmic luciferase activity from clock gene luciferase reporter cells lines was used to test the effect of p38 MAPK inhibition on clock properties as determined using the damped sine fit and Levenberg-Marquardt algorithm.Glioma treatment with p38 MAPK inhibitors may be more effective and less toxic if administered at the appropriate time of the day. PMID: 29316898
4. data suggest that SNP variability in the CLOCK gene for rs6850524 and rs11932595 is associated with idiopathic recurrent spontaneous abortion in pregnancies from Slovenia and Serbia PMID: 29768442
5. Results indicated that inhibiting the circadian gene Clock expression can reverse the cisplatin resistance of ovarian cancer SKOV3/DDP cell lines by affecting the protein expression of drug resistance genes during which autophagy plays an important role. PMID: 28514207
6. Low expression of CLOCK protein is associated with kidney tumor. PMID: 29271044
7. Association between HCRTR2, ADH4,CLOCK gene polymorphisms and cluster headache was not significant in the present study. PMID: 29318394
8. No association between 3111T/C Clock gene polymorphism and complaints of patients with insomnia was detected. PMID: 28853078
9. Study found three gene variants (CLOCK-rs4864548, PEMT-rs936108, and GHRELIN-rs696217) that exhibited uncorrected gene-by-sleep duration interactions in relation to BMI z-scores in a cohort of New Zealand European children. However, no interactions were identified in percentage body fat differences. Notably, these interactions are evident without detectable effects on sleep duration. PMID: 28899534
10. These findings suggest that upregulation of the circadian gene hClock plays an important role in metastasis of colorectal cancer. PMID: 28498393
11. results of this study suggest that genetic variability in the ARNTL and CLOCK genes might be associated with risk for multiple sclerosis PMID: 29324865
12. Evening chronotype is associated with higher obesity in severely obese subjects and with lower weight loss effectiveness after bariatric surgery. In addition, circadian preferences interact with CLOCK 3111T/C for obesity. The circadian and genetic assessment could provide tailored weight loss recommendations in subjects who underwent bariatric surgery. PMID: 27339606
13. CLOCK regulates the expression of genes involved in neuronal migration, and a functional assay showed that CLOCK knockdown increased neuronal migratory distance. PMID: 29196536
14. Our findings suggest that CLOCK and CRY1 polymorphisms might be involved in individual susceptibility to abdominal obesity in Chinese Han population. PMID: 26923944
15. Our results suggest that the circadian gene human Clock may play an important role in carcinogenesis by inhibiting apoptotic cell death via attenuating proapoptotic signaling PMID: 25976934
16. ASS1 acetylation by CLOCK exhibits circadian oscillation in human cells and mouse liver, possibly caused by rhythmic interaction between CLOCK and ASS1, leading to the circadian regulation of ASS1 and ureagenesis. PMID: 28985504
17. CLOCK SNP rs2070062 is associated with shorter sleep duration. PMID: 28645331
18. This study showed that Lack of Association between Genetic Polymorphism of clock gene with Late Onset Depression and Alzheimer's Disease in a Sample of a Brazilian Population This study showed that Lack of Association between Genetic Polymorphism of PER2 gene with Late Onset Depression and Alzheimer's Disease in a Sample of a Brazilian Population PMID: 27335043
19. CLOCK gene expression mean was significantly higher in morning than in evening during Shabaan PMID: 28384165
20. found that overexpression of both Clock and Bmal1 suppressed cell growth PMID: 26370682
21. Clock circadian regulator (CLOCK) gene single nucleotide polymorphism rs1801260 minor allele C showed a significantly higher association with the prevalence of diabetes in the Japanese population independent of body mass index (BMI). PMID: 26374515
22. a novel mechanism of action of CLOCK in human umbilical vein endothelial cells, is reported. PMID: 28058089
23. Low Clock gene expression is associated with colorectal liver metastases. PMID: 27492458
24. The possession of CLOCK rs3749474 may influence the effect of reducing the percentage intake of dietary fat on obesity-associated variables and carrying this SNP might benefit more than others from weight loss treatment involving dietary fat restriction. PMID: 26690565
25. CLOCK gene variation is associated with incidence of type-2 diabetes and cardiovascular diseases in type-2 diabetic subjects. Suggest diet-gene interaction. PMID: 26739996
26. Clock gene variants associated with obesity and sleep duration. [review] PMID: 26553137
27. CLOCK rs1801260 modulated the relationship between early stress, adult history of attempted suicide and current suicide ideation PMID: 26204460
28. The CLOCK 3111T > C polymorphism could be an independent risk factor for irregular menstrual cycles, irrespective of psychological distress and endocrine or metabolic conditions in Korean adolescents. PMID: 26453284
29. Findings indicate that CLOCK protein plays an important role in fertility and its knockdown leads to reduction in reproduction and increased miscarriage risk. PMID: 26390085
30. when overexpressed, c-MYC is able to repress Per1 transactivation by BMAL1/CLOCK via targeting selective E-box sequences. Importantly, upon serum stimulation, MYC was detected in BMAL1 protein complexes PMID: 26850841
31. Variants of the CLOCK gene are associated with idiopathic male infertility and therefore may be applied as a risk factor of male infertility. PMID: 26181468
32. CLOCK, ARNTL, and NPAS2 gene polymorphisms may have a role in seasonal variations in mood and behavior PMID: 26134245
33. minor polymorphisms of CLOCK may be associated with poor morning gastric motility, and may have a combinatorial effect with PER3. PMID: 25775462
34. CLOCK 3111 T/C SNP interacts with emotional eating behavior to modulate total weight loss. PMID: 24905098
35. these findings suggest that sumoylation plays a critical role in the spatiotemporal co-activation of CLOCK-BMAL1 by CBP for immediate-early Per induction and the resetting of the circadian clock. PMID: 26164627
36. the circadian gene hClock promoted CRC progression and inhibit tumor cell apoptosis in vitro and in vivo, while silencing hClock was able to reverse this effect. PMID: 25625359
37. PASD1 is a circadian bHLH-PAS paralog repressor of CLOCK protein expression. PMID: 25936801
38. The observed interaction effects provide converging evidence that the clock gene and OXT/AVP systems are intertwined and contribute to human prosociality. PMID: 25309987
39. There is not a significant difference in the expression of CLOCK, BMAL1, and PER1 in buccal epithelial cells of patients with essential arterial hypertension regardless of patient genotype. PMID: 25070164
40. The CLOCK 3111T/C polymorphism was not significantly associated with overweight or sleep duration. PMID: 24818524
41. CLOCK polymorphisms are associated with increased susceptibility of schizophrenic patients to restless legs syndrome PMID: 24824748
42. The results of this study present no evidence for an association of CLOCK polymorphisms with juvenile myoclonic epilepsy. PMID: 24892753
43. Data suggest that influence of obesity-associated CLOCK SNPs (rs12649507, rs6858749) on sleep duration and macronutrient intake can be ameliorated via habitual longer sleep duration and favorable dietary profile (lower protein; higher PUFA). PMID: 25527757
44. Two single nucleotide polymorphisms in RORA were associated with breast cancer in the whole sample and among postmenopausal women, and we also reported an association with CLOCK, RORA, and NPAS2 in the analyses at the gene level PMID: 24919398
45. A population specific variation of MTHFR and hCLOCK genes also highlights ethnicity specific risk management. PMID: 24510388
46. SNP (rs6855837) in the CLOCK gene is significant correlation with genotype and allele frequency in lung cancer. PMID: 24821610
47. E2 promoted the binding of ERalpha to the EREs (estrogen-response elements) of CLOCK promoter, thereby up-regulating the transcription of CLOCK PMID: 24789043
48. data support the notion that a chronic consumption of a healthy diet may play a contributing role in triggering glucose metabolism by interacting with the rs1801260 SNP at CLOCK gene locus in metabolic syndrome patients PMID: 24328727
49. No association with SNPs or haplotypes of the CLOCK gene was observed in prophylactic lithium response. PMID: 24636202
50. This study failed to show a mediating role of evening preference, ongoing efforts are needed to identify the mechanisms by which the CLOCK gene determines ADHD-related traits. PMID: 24068320
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亞細胞定位：

Nucleus. Cytoplasm. Cytoplasm, cytosol.
組織特異性：

Hair follicles (at protein level). Expressed in all tissues examined including spleen, thymus, prostate, testis, ovary, small intestine, colon, leukocytes, heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Highest levels in testis
數據庫鏈接：

HGNC: 2082

OMIM: 601851

KEGG: hsa:9575

STRING: 9606.ENSP00000308741

UniGene: Hs.436975

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