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ARNTL Antibody

  • 货号：
    CSB-PA555899
  • 规格：
    ￥2024
  • 图片：
    • Western blot analysis of extracts from mouse brain tissue using BMAL1 antibody.
    • Western blot analysis of extracts from HL60、THP-1
  • 其他：

产品详情

  • 产品名称：
    Rabbit anti-Homo sapiens (Human) ARNTL Polyclonal antibody
  • Uniprot No.：
    O00327
  • 基因名：
    ARNTL
  • 宿主：
    Rabbit
  • 反应种属：
    Human,Mouse,Rat
  • 免疫原：
    Peptide sequence around aa.569~573 (S-S-S-I-L) derived from Human BMAL1.
  • 免疫原种属：
    Homo sapiens (Human)
  • 克隆类型：
    Polyclonal
  • 纯化方式：
    Antibodies were produced by immunizing rabbits with synthetic peptide and KLH conjugates. Antibodies were purified by affinity-chromatography using epitope-specific peptide.
  • 浓度：
    It differs from different batches. Please contact us to confirm it.
  • 产品提供形式：
    Liquid
  • 应用范围：
    ELISA,WB
  • 推荐稀释比：
    Application Recommended Dilution
    WB 1:500-1:3000
  • Protocols：
  • 储存条件：
    Upon receipt, store at -20°C or -80°C. Avoid repeated freeze.
  • 货期：
    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.

产品评价

靶点详情

  • 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. ARNTL/BMAL1 positively regulates myogenesis and negatively regulates adipogenesis via the transcriptional control of the genes of the canonical Wnt signaling pathway. Plays a role in normal pancreatic beta-cell function; regulates glucose-stimulated insulin secretion via the regulation of antioxidant genes NFE2L2/NRF2 and its targets SESN2, PRDX3, CCLC and CCLM. Negatively regulates the mTORC1 signaling pathway; regulates the expression of MTOR and DEPTOR. Controls diurnal oscillations of Ly6C inflammatory monocytes; rhythmic recruitment of the PRC2 complex imparts diurnal variation to chemokine expression that is necessary to sustain Ly6C monocyte rhythms. Regulates the expression of HSD3B2, STAR, PTGS2, CYP11A1, CYP19A1 and LHCGR in the ovary and also the genes involved in hair growth. Plays an important role in adult hippocampal neurogenesis by regulating the timely entry of neural stem/progenitor cells (NSPCs) into the cell cycle and the number of cell divisions that take place prior to cell-cycle exit. Regulates the circadian expression of CIART and KLF11. 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 NPAS2-ARNTL/BMAL1 heterodimer positively regulates the expression of MAOA, F7 and LDHA and modulates the circadian rhythm of daytime contrast sensitivity by regulating the rhythmic expression of adenylate cyclase type 1 (ADCY1) in the retina. 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'. Essential for the rhythmic interaction of CLOCK with ASS1 and plays a critical role in positively regulating CLOCK-mediated acetylation of ASS1. Plays a role in protecting against lethal sepsis by limiting the expression of immune checkpoint protein CD274 in macrophages in a PKM2-dependent manner. Regulates the diurnal rhythms of skeletal muscle metabolism via transcriptional activation of genes promoting triglyceride synthesis (DGAT2) and metabolic efficiency (COQ10B).
  • 基因功能参考文献：
    1. BMAL1 Deficiency Contributes to Mandibular Dysplasia by Upregulating MMP3. PMID: 29276151
    2. ARNTL rs7107287 was associated with a cyclothymic temperament, depressive and stress symptoms PMID: 28708003
    3. NR1D1 and BMAL1 mRNA and protein levels were significantly reduced in OA compared to normal cartilage. In cultured human chondrocytes, a clear circadian rhythmicity was observed for NR1D1 and BMAL1. PMID: 27884645
    4. These results suggest that the circadian clock system can be recovered through BMAL1 expression induced by aza-dC within a day. PMID: 28487473
    5. Determined a novel role of TNF-alpha in inducing Bmal1 via dual calcium dependent pathways; Roralpha was up-regulated in the presence of Ca(2+) influx and Rev-erbalpha was down-regulated in the absence of that. PMID: 29217191
    6. results of this study suggest that genetic variability in the ARNTL and CLOCK genes might be associated with risk for multiple sclerosis PMID: 29324865
    7. PI3K-PTEN upregulated-mTORC1 and mTORC2 complex plays a critical role in controlling BMAL1, establishing a connection between PI3K signaling and the regulation of circadian rhythm, ultimately resulting in deregulated BMAL1 in tumor cells with disrupted PI3K signaling PMID: 27285754
    8. M. tuberculosis infection caused enhanced MMP-1, -9, and miR-223 expression, with inhibited BMAL1 expression. MiR-223 modulated BMAL1 expression via the direct binding of BMAL1 3'-UTR. PMID: 28543681
    9. research describes an association between changes in the methylation of the BMAL1 gene with the intervention and the effects of a weight loss intervention on blood lipids levels PMID: 26873744
    10. Study found rhythmic methylation of BMAL1 was altered in Alzheimer's disease brains and fibroblasts and correlated with transcription cycles. Results indicate that cycles of DNA methylation contribute to the regulation of BMAL1 rhythms in the brain. PMID: 27883893
    11. TFEB regulates PER3 expression via glucose-dependent effects on CLOCK/BMAL1 PMID: 27373683
    12. found that overexpression of both Clock and Bmal1 suppressed cell growth PMID: 26370682
    13. our results identified Bmal1 as a novel tumor suppressor gene that elevates the sensitivity of cancer cells to paclitaxel, with potential implications as a chronotherapy timing biomarker in tongue squamous cell carcinoma PMID: 27821487
    14. The level of BMAL1 expression in granulosa cells the polycystic ovary syndrome (PCOS) group was lower than that of the group without PCOS. We also analyzed estrogen synthesis and aromatase expression in KGN cell lines. Both were downregulated after BMAL1 and SIRT1 knock-down and, conversely, upregulated after overexpression treatments of these two genes in KGN cells. PMID: 27117143
    15. this study shows that BMAL1 can regulate cellular innate immunity against specific RNA viruses PMID: 27913791
    16. Bmal1 is a key clock gene to involve in cartilage homeostasis mediated through sirt1. PMID: 27253997
    17. The BMAL1 rs2278749 T/C was associated with Alzheimer disease (AD) risk, and T carriers in BMAL1 rs2278749 T/C showed a higher risk of AD than did non-carriers. PMID: 26782499
    18. Our results indicate that activation of TGF-beta1 promotes the transcriptional induction of BMAL1. PMID: 26753996
    19. possible circadian rhythm in full-term placental expression PMID: 26247999
    20. Synchronized cells exhibit an autonomous ultradian mitochondrial respiratory activity which is abrogated by silencing the master clock gene BMAL1. PMID: 27060253
    21. decreased expression of Bmal1 is correlated with tumor progression and poor prognosis in pancreatic ductal adenocarcinoma, with potential to be used as a biomarker for diagnosis and prognosis PMID: 26915801
    22. ARNTL and PER1 were associated with PD. PMID: 26507264
    23. define a regulatory mechanism that links chondrocyte BMAL1 to the maintenance and repair of cartilage PMID: 26657859
    24. 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
    25. Bmal1 could directly bind to the p53 gene promoter and thereby transcriptionally activate the downstream tumor suppressor pathway in a p53-dependent manner in pancreatic tumors. PMID: 26683776
    26. Data suggest that cryptochromes mediate periodic binding of Ck2b (casein kinase 2beta) to Bmal1 (aryl hydrocarbon receptor nuclear translocator-like protein) and thus inhibit Bmal1-Ser90 phosphorylation by Ck2a (casein kinase 2alpha). [SYNOPSIS] PMID: 26562283
    27. a 4-locus CSNK1E haplotype encompassing the rs1534891 SNP (Z-score=2.685, permuted p=0.0076) and a 3-locus haplotype in ARNTL (Z-score=3.269, permuted p=0.0011) showed a significant association with Bipolar Disorder PMID: 26283580
    28. CLOCK, ARNTL, and NPAS2 gene polymorphisms may have a role in seasonal variations in mood and behavior PMID: 26134245
    29. rs2290036-C variant of ARNTL was over-represented in psychosis patients, and the variants rs934945-G and rs10462023-G of PER2 were associated with a more severe psychotic disorder PMID: 25799324
    30. 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
    31. In men undergoing acute total sleep deprivation, BMAL1 gene expression was decreased in skeletal muscle compared with controls. PMID: 26168277
    32. Data indicate that the inner nuclear membrane protein MAN1 directly binds the transcription activator BMAL1 promoter and enhances its transcription. PMID: 25182847
    33. Bmal1-dependent oscillators of arginine vasopressin neurons modulate the coupling of the suprachiasmatic nucleus. PMID: 25741730
    34. PER1 and BMAL1 operate as cell-autonomous modulators of human pigmentation and may be targeted for future therapeutic strategies PMID: 25310406
    35. These results suggested that ARNTL may be a tumor suppressor and is epigenetically silenced in ovarian cancer. PMID: 25175925
    36. temporal signals of fasting and refeeding hormones regulate the transcription of Bmal1, a key transcription activator of molecular clock, in the liver PMID: 25480789
    37. 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
    38. FAL1 associates with the epigenetic repressor BMI1 and regulates its stability in order to modulate the transcription of a number of genes including CDKN1A. PMID: 25203321
    39. The results of this study suggest that the ARNTL gene may be associated with the lithium prophylactic response in bipolar illness. PMID: 24636202
    40. The SNPs most strongly associated in the single-marker analysis of the combined Danish samples were rs4757144 in ARNTL (P=3.78 x 10-6) and rs8057927 in CDH13. PMID: 23358160
    41. The progression-free survival of patients with high Bmal1 expression is significantly longer than that of patients with low Bmal1 expression. PMID: 24277452
    42. The rhythm of Bmal1 mRNA in human plaque-derived vascular smooth muscle cells is altered. PMID: 24418196
    43. These results suggest that DNA methylation of the BMAL1 gene is critical for interfering with circadian rhythms. PMID: 24103761
    44. Knockdown of either BMAL1 or Period1 in human anagen hair follicles significantly prolonged anagen. PMID: 24005054
    45. there is significant daily variation in PER2, PER3, and ARNTL1 expression with earlier timing of expression in women than in men PMID: 23606611
    46. Bmal1 is a tumor suppressor, capable of suppressing cancer cell growth and invasiveness. PMID: 23563360
    47. The data suggest that the impairment of the BMAL1 clock gene expression is closely associated with GDM susceptibility. PMID: 23206673
    48. O-GlcNAc transferase (OGT) promotes expression of BMAL1/CLOCK target genes and affects circadian oscillation of clock genes in vitro and in vivo. PMID: 23395176
    49. Variants in ARNTL have been associated with seasonality and seasonal affective disorder, phenotypes that could reflect circadian rhythm disruption. PMID: 23449886
    50. The phospho-mimicking S78E mutant of BMAL1 efficiently blocks DNA binding, which provides a molecular rationale for the possibility of rhythmic binding of CLOCK-BMAL1 during circadian cycle. PMID: 23229515

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  • 亚细胞定位：
    Nucleus. Cytoplasm. Nucleus, PML body.
  • 组织特异性：
    Hair follicles (at protein level). Highly expressed in the adult brain, skeletal muscle and heart.
  • 数据库链接：

    HGNC: 701

    OMIM: 602550

    KEGG: hsa:406

    STRING: 9606.ENSP00000374357

    UniGene: Hs.65734