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The 19 function of PAS of the protein

S.NOUniprot IDProtein Name Sequence LengthPAS Repeated RegionFunction
1 Q8IUM7 Neuronal PAS domain-containing protein 4 802"Transcription factor expressed in neurons of the brain that regulates the excitatory-inhibitory balance within neural circuits and is required for contextual memory in the hyppocampus (By similarity).
Plays a key role in the structural and functional plasticity of neurons (By similarity).
Acts as an early-response transcription factor in both excitatory and inhibitory neurons, where it induces distinct but overlapping sets of late-response genes in these two types of neurons, allowing the synapses that form on inhibitory and excitatory neurons to be modified by neuronal activity in a manner specific to their function within a circuit, thereby facilitating appropriate circuit responses to sensory experience (By similarity).
In excitatory neurons, activates transcription of BDNF, which in turn controls the number of GABA-releasing synapses that form on excitatory neurons, thereby promoting an increased number of inhibitory synapses on excitatory neurons (By similarity).
In inhibitory neurons, regulates a distinct set of target genes that serve to increase excitatory input onto somatostatin neurons, probably resulting in enhanced feedback inhibition within cortical circuits (By similarity).
The excitatory and inhibitory balance in neurons affects a number of processes, such as short-term and long-term memory, acquisition of experience, fear memory, response to stress and social behavior (By similarity).
Acts as a regulator of dendritic spine development in olfactory bulb granule cells in a sensory-experience-dependent manner by regulating expression of MDM2 (By similarity).
Efficient DNA binding requires dimerization with another bHLH protein, such as ARNT, ARNT2 or BMAL1 (PubMed:14701734).
Can activate the CME (CNS midline enhancer) element (PubMed:14701734)".
2 P81133 Single-minded homolog 1 766Transcriptional factor that may have pleiotropic effects during embryogenesis and in the adult.
3 Q14190 Single-minded homolog 2 667Transcription factor that may be a master gene of CNS development in cooperation with Arnt.
It may have pleiotropic effects in the tissues expressed during development.
4 Q8WYA1 Aryl hydrocarbon receptor nuclear translocator-like protein 2 636"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.
The CLOCK-ARNTL2/BMAL2 heterodimer activates the transcription of SERPINE1/PAI1 and BHLHE40/DEC1".
5 Q96RG2 PAS domain-containing serine/threonine-protein kinase 1323"Serine/threonine-protein kinase involved in energy homeostasis and protein translation.
Phosphorylates EEF1A1, GYS1, PDX1 and RPS6.
Probably plays a role under changing environmental conditions (oxygen, glucose, nutrition), rather than under standard conditions.
Acts as a sensor involved in energy homeostasis: regulates glycogen synthase synthesis by mediating phosphorylation of GYS1, leading to GYS1 inactivation.
May be involved in glucose-stimulated insulin production in pancreas and regulation of glucagon secretion by glucose in alpha cells; however such data require additional evidences.
May play a role in regulation of protein translation by phosphorylating EEF1A1, leading to increase translation efficiency.
May also participate to respiratory regulation".
6 P56645 Period circadian protein homolog 3 1201"Originally described as 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, NR1D2, RORA, RORB and RORG, which form a second feedback loop and which activate and repress ARNTL/BMAL1 transcription, respectively.
Has a redundant role with the other PER proteins PER1 and PER2 and is not essential for the circadian rhythms maintenance.
In contrast, plays an important role in sleep-wake timing and sleep homeostasis probably through the transcriptional regulation of sleep homeostasis-related genes, without influencing circadian parameters.
Can bind heme".
7 Q9Y2N7 Hypoxia-inducible factor 3-alpha 669"Acts as a transcriptional regulator in adaptive response to low oxygen tension.
Acts as a regulator of hypoxia-inducible gene expression (PubMed:11573933, PubMed:16126907, PubMed:19694616, PubMed:20416395, PubMed:21069422).
Functions as an inhibitor of angiogenesis in hypoxic cells of the cornea.
Plays a role in the development of the cardiorespiratory system.
May also be involved in apoptosis (By similarity).
; Isoform 2: Attenuates the ability of transcription factor HIF1A to bind to hypoxia-responsive elements (HRE) located within the enhancer/promoter of hypoxia-inducible target genes and hence inhibits HRE-driven transcriptional activation.
Also inhibits hypoxia-inducible ARNT-mediated gene expression.
; Isoform 3: Attenuates the ability of transcription factor HIF1A to bind to hypoxia-responsive elements (HRE) located within the enhancer/promoter of hypoxia-inducible target genes and hence inhibits HRE-driven transcriptional activation.
; isoform 4: Attenuates the ability of transcription factor HIF1A and EPAS1/HIF2A to bind to hypoxia-responsive elements (HRE) located within the enhancer/promoter of hypoxia-inducible target genes and hence inhibits HRE-driven transcriptional activation (PubMed:16126907, PubMed:17998805, PubMed:19694616, PubMed:20416395).
May act as a tumor suppressor and inhibits malignant cell transformation (PubMed:17998805).
; Isoform 5: Attenuates the ability of transcription factor HIF1A to bind to hypoxia-responsive elements (HRE) located within the enhancer/promoter of hypoxia-inducible target genes and hence inhibits HRE-driven transcriptional activation".
8 Q99814 Endothelial PAS domain-containing protein 1 870Transcription factor involved in the induction of oxygen regulated genes.
Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters (By similarity).
Regulates the vascular endothelial growth factor (VEGF) expression and seems to be implicated in the development of blood vessels and the tubular system of lung.
May also play a role in the formation of the endothelium that gives rise to the blood brain barrier.
Potent activator of the Tie-2 tyrosine kinase expression.
Activation requires recruitment of transcriptional coactivators such as CREBBP and probably EP300.
Interaction with redox regulatory protein APEX seems to activate CTAD (By similarity).
9 Q16665 Hypoxia-inducible factor 1-alpha 826"Functions as a master transcriptional regulator of the adaptive response to hypoxia.
Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia.
Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease.
Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters (By similarity).
Activation requires recruitment of transcriptional coactivators such as CREBBP and EP300.
Activity is enhanced by interaction with both, NCOA1 or NCOA2.
Interaction with redox regulatory protein APEX seems to activate CTAD and potentiates activation by NCOA1 and CREBBP.
Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia".
10 O15055 Period circadian protein homolog 2 1255"Transcriptional repressor 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 syndrome 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.
PER1 and PER2 proteins transport CRY1 and CRY2 into the nucleus with appropriate circadian timing, but also contribute directly to repression of clock-controlled target genes through interaction with several classes of RNA-binding proteins, helicases and others transcriptional repressors.
PER appears to regulate circadian control of transcription by at least three different modes.
First, interacts directly with the CLOCK-ARTNL/BMAL1 at the tail end of the nascent transcript peak to recruit complexes containing the SIN3-HDAC that remodel chromatin to repress transcription.
Second, brings H3K9 methyltransferases such as SUV39H1 and SUV39H2 to the E-box elements of the circadian target genes, like PER2 itself or PER1.
The recruitment of each repressive modifier to the DNA seems to be very precisely temporally orchestrated by the large PER complex, the deacetylases acting before than the methyltransferases.
Additionally, large PER complexes are also recruited to the target genes 3' termination site through interactions with RNA-binding proteins and helicases that may play a role in transcription termination to regulate transcription independently of CLOCK-ARTNL/BMAL1 interactions.
Recruitment of large PER complexes to the elongating polymerase at PER and CRY termination sites inhibited SETX action, impeding RNA polymerase II release and thereby repressing transcriptional reinitiation.
May propagate clock information to metabolic pathways via the interaction with nuclear receptors.
Coactivator of PPARA and corepressor of NR1D1, binds rhythmically at the promoter of nuclear receptors target genes like ARNTL or G6PC.
Directly and specifically represses PPARG proadipogenic activity by blocking PPARG recruitment to target promoters and thereby inhibiting transcriptional activation.
Required for fatty acid and lipid metabolism, is involved as well in the regulation of circulating insulin levels.
Plays an important role in the maintenance of cardiovascular functions through the regulation of NO and vasodilatatory prostaglandins production in aortas.
Controls circadian glutamate uptake in synaptic vesicles through the regulation of VGLUT1 expression.
May also be involved in the regulation of inflammatory processes.
Represses the CLOCK-ARNTL/BMAL1 induced transcription of BHLHE40/DEC1 and ATF4.
Negatively regulates the formation of the TIMELESS-CRY1 complex by competing with TIMELESS for binding to CRY1".
11 O15534 Period circadian protein homolog 1 1290"Transcriptional repressor 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 circadian target genes expression at post-transcriptional levels, but may not be required for the repression at transcriptional level.
Controls PER2 protein decay.
Represses CRY2 preventing its repression on CLOCK/ARNTL target genes such as FXYD5 and SCNN1A in kidney and PPARA in liver.
Besides its involvement in the maintenance of the circadian clock, has an important function in the regulation of several processes.
Participates in the repression of glucocorticoid receptor NR3C1/GR-induced transcriptional activity by reducing the association of NR3C1/GR to glucocorticoid response elements (GREs) by ARNTL:CLOCK.
Plays a role in the modulation of the neuroinflammatory state via the regulation of inflammatory mediators release, such as CCL2 and IL6.
In spinal astrocytes, negatively regulates the MAPK14/p38 and MAPK8/JNK MAPK cascades as well as the subsequent activation of NFkappaB.
Coordinately regulates the expression of multiple genes that are involved in the regulation of renal sodium reabsorption.
Can act as gene expression activator in a gene and tissue specific manner, in kidney enhances WNK1 and SLC12A3 expression in collaboration with CLOCK.
Modulates hair follicle cycling.
Represses the CLOCK-ARNTL/BMAL1 induced transcription of BHLHE40/DEC1".
12 P35869 Aryl hydrocarbon receptor 848Ligand-activated transcriptional activator.
Binds to the XRE promoter region of genes it activates.
Activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene).
Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons.
Involved in cell-cycle regulation.
Likely to play an important role in the development and maturation of many tissues.
Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1.
Inhibits PER1 by repressing the CLOCK-ARNTL/BMAL1 heterodimer mediated transcriptional activation of PER1.
The heterodimer ARNT:AHR binds to core DNA sequence 5'-TGCGTG-3' within the dioxin response element (DRE) of target gene promoters and activates their transcription (PubMed:28602820).
13 O15516 Circadian locomoter output cycles protein kaput 846"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 (PubMed:23229515).
CLOCK specifically binds to the half-site 5'-CAC-3', while ARNTL binds to the half-site 5'-GTGA-3' (PubMed:23229515).
The CLOCK-ARNTL/BMAL1 heterodimer also recognizes the non-canonical E-box motifs 5'-AACGTGA-3' and 5'-CATGTGA-3' (PubMed:23229515).
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 (PubMed:21980503).
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 (PubMed:28985504)".
14 Q99742 Neuronal PAS domain-containing protein 1 590May control regulatory pathways relevant to schizophrenia and to psychotic illness.
May play a role in late central nervous system development by modulating EPO expression in response to cellular oxygen level (By similarity).
Forms a heterodimer that binds core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) leading to transcriptional repression on its target gene TH (By similarity).
15 Q8IXF0 Neuronal PAS domain-containing protein 3 933May play a broad role in neurogenesis.
May control regulatory pathways relevant to schizophrenia and to psychotic illness (By similarity).
16 Q9HBZ2 Aryl hydrocarbon receptor nuclear translocator 2 717"Transcription factor that plays a role in the development of the hypothalamo-pituitary axis, postnatal brain growth, and visual and renal function (PubMed:24022475).
Specifically recognizes the xenobiotic response element (XRE)".
17 O00327 Aryl hydrocarbon receptor nuclear translocator-like protein 1 626"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 (PubMed:23229515).
CLOCK specifically binds to the half-site 5'-CAC-3', while ARNTL binds to the half-site 5'-GTGA-3' (PubMed:23229515).
The CLOCK-ARNTL/BMAL1 heterodimer also recognizes the non-canonical E-box motifs 5'-AACGTGA-3' and 5'-CATGTGA-3' (PubMed:23229515).
Essential for the rhythmic interaction of CLOCK with ASS1 and plays a critical role in positively regulating CLOCK-mediated acetylation of ASS1 (PubMed:28985504)".
18 P27540 Aryl hydrocarbon receptor nuclear translocator 789Required for activity of the Ah (dioxin) receptor.
This protein is required for the ligand-binding subunit to translocate from the cytosol to the nucleus after ligand binding.
The complex then initiates transcription of genes involved in the activation of PAH procarcinogens.
The heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters and functions as a transcriptional regulator of the adaptive response to hypoxia (By similarity).
The heterodimer ARNT:AHR binds to core DNA sequence 5'-TGCGTG-3' within the dioxin response element (DRE) of target gene promoters and activates their transcription (PubMed:28396409).
19 Q99743 Neuronal PAS domain-containing protein 2 824"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.
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.
NPAS2 plays an important role in sleep homeostasis and in maintaining circadian behaviors in normal light/dark and feeding conditions and in the effective synchronization of feeding behavior with scheduled food availability.
Regulates the gene transcription of key metabolic pathways in the liver and is involved in DNA damage response by regulating several cell cycle and DNA repair genes".