CLOCK Antibody (PACO51438)
- SKU:
- PACO51438
- Product type:
- Antibody
- Reactivity:
- Human
- Host Species:
- Rabbit
- Isotype:
- IgG
- Application:
- ELISA
- Application:
- WB
- Application:
- IHC
- Application:
- IF
- Antibody type:
- Polyclonal
- Conjugation:
- Unconjugated
Description
抗体名: | CLOCK Antibody (PACO51438) |
抗体コード: | PACO51438 |
サイズ: | 50ug |
宿主種: | Rabbit |
申し込み: | ELISA, WB, IHC, IF |
推奨される希釈: | ELISA:1:2000-1:10000, WB:1:500-1:5000, IHC:1:20-1:200, IF:1:50-1:200 |
反応性: | Human |
免疫原: | Recombinant Human Circadian locomoter output cycles protein kaput protein (577-846AA) |
憲法: | Liquid |
ストレージバッファ: | Preservative: 0.03% Proclin 300 Constituents: 50% Glycerol, 0.01M PBS, pH 7.4 |
精製方法: | >95%, Protein G purified |
抗体のクローン性: | Polyclonal |
アイソタイプ: | IgG |
Conjugate: | Non-conjugated |
Western Blot. Positive WB detected in: Hela whole cell lysate. All lanes: CLOCK antibody at 3.5µg/ml. Secondary. Goat polyclonal to rabbit IgG at 1/50000 dilution. Predicted band size: 96 kDa. Observed band size: 96 kDa.. | |
Immunofluorescent analysis of Hela cells using PACO51438 at dilution of 1:100 and Alexa Fluor 488-congugated AffiniPure Goat Anti-Rabbit IgG(H+L). | |
Immunohistochemistry of paraffin-embedded human brain tissue using PACO51438 at dilution of 1:100. |
バックグラウンド: | 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. CLOCK has an intrinsic acetyltransferase activity, which enables circadian chromatin remodeling by acetylating histones and nonhistone proteins, including its own partner ARNTL/BMAL1. 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. 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. 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. |
シノニム: | Circadian locomoter output cycles protein kaput (hCLOCK) (EC 2.3.1.48) (Class E basic helix-loop-helix protein 8) (bHLHe8), CLOCK, BHLHE8 KIAA0334 |
Uniprot
UniProt Protein Function: | CLOCK: ARNTL/2-CLOCK heterodimers activate E-box element (3'- CACGTG-5') transcription of a number of proteins of the circadian clock. Activates transcription of PER1 and PER2. This transcription is inhibited in a feedback loop by PER and CRY proteins. Has intrinsic histone acetyltransferase activity and this enzymatic function contributes to chromatin-remodeling events implicated in circadian control of gene expression. Acetylates primarily histones H3 and H4. Acetylates also a non-histone substrate: ARNTL. Plays a role in DNA damage response (DDR) signaling during the S phase. Component of the circadian clock oscillator which includes the CRY proteins, CLOCK or NPAS2, ARNTL or ARNTL2, CSNK1D and/or CSNK1E, TIMELESS and the PER proteins. Efficient DNA binding requires dimerization with another bHLH protein. Heterodimerization with ARNTL is required for E-box-dependent transactivation, for CLOCK nuclear translocation and degradation, and, for phosphorylation of both CLOCK and ARNTL. Interaction with PER and CRY proteins requires translocation to the nucleus. Interaction of the CLOCK-ARNTL heterodimer with PER or CRY inhibits transcription activation. Binds weakly ARNTL and ARNTL2 to form heterodimers which bind poorly to the E-box motif. 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 and skeletal muscle. Low levels in thymus, lung and liver. Expressed in all brain regions with highest levels in cerebellum. Highly expressed in the suprachiasmatic nucleus (SCN). |
UniProt Protein Details: | Protein type:EC 2.3.1.48; DNA-binding; Acetyltransferase; Transcription factor Chromosomal Location of Human Ortholog: 4q12 Cellular Component: chromosome; intracellular membrane-bound organelle; nucleoplasm; nucleus; transcription factor complex Molecular Function:chromatin DNA binding; DNA binding; histone acetyltransferase activity; protein binding; sequence-specific DNA binding; transcription factor activity Biological Process: activation of NF-kappaB transcription factor; circadian regulation of gene expression; circadian rhythm; DNA damage checkpoint; negative regulation of transcription, DNA-dependent; photoperiodism; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription, DNA-dependent; proteasomal ubiquitin-dependent protein catabolic process; regulation of hair cycle; regulation of insulin secretion; regulation of transcription from RNA polymerase II promoter; regulation of transcription, DNA-dependent; response to redox state; signal transduction; spermatogenesis |
NCBI 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] |
UniProt Code: | O15516 |
NCBI GenInfo Identifier: | 6166009 |
NCBI Gene ID: | 9575 |
NCBI Accession: | O15516.1 |
UniProt Secondary Accession: | O15516,O14516, Q9UIT8, A0AV01, A2I2N9, |
UniProt Related Accession: | O15516 |
Molecular Weight: | 95,304 Da |
NCBI Full Name: | Circadian locomoter output cycles protein kaput |
NCBI Synonym Full Names: | clock circadian regulator |
NCBI Official Symbol: | CLOCK |
NCBI Official Synonym Symbols: | KAT13D; bHLHe8 |
NCBI Protein Information: | circadian locomoter output cycles protein kaput |
UniProt Protein Name: | Circadian locomoter output cycles protein kaput |
UniProt Synonym Protein Names: | Class E basic helix-loop-helix protein 8; bHLHe8 |
Protein Family: | Clock-controlled protein |
UniProt Gene Name: | CLOCK |
UniProt Entry Name: | CLOCK_HUMAN |
Antibodies | ELISA Kits |
Anti-CLOCK Antibody (CAB5633) | Clock Colorimetric Cell-Based ELISA |
CLOCK Antibody (PACO00614) |
Secondary Antibody |
Anti-HRP Goat Anti-Rabbit IgG (H+L) Antibody (CABS014) |
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