ARNTL2 - Aryl hydrocarbon receptor nuclear translocator-like protein 2 - human protein (Function)
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ARNTL2 »  Aryl hydrocarbon receptor nuclear translocator-like protein 2
Protein also known as:  Class E basic helix-loop-helix protein 6 (bHLHe6).
Gene name:  ARNTL2
Entry whose protein(s) existence is based on evidence at protein level
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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, NR1D2, RORA, RORB and RORG, 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.  
  • CuratedUniProtKB
GO molecular function 
E-box bindingdefinition[GO:0070888]  
  • IDAUniProtKB
Protein dimerization activitydefinition[GO:0046983] silver  
  • IEAInterPro 2 GO
RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activitydefinition[GO:0000982]  
Sequence-specific DNA binding transcription factor activitydefinition[GO:0003700]  
  • NASUniProtKB
Signal transducer activitydefinition[GO:0004871] silver  
  • IEAInterPro 2 GO
GO biological process 
Circadian rhythmdefinition[GO:0007623]  
Entrainment of circadian clockdefinition[GO:0009649]  
  • NASUniProtKB
Positive regulation of circadian rhythmdefinition[GO:0042753]  
  • ISSOrtholog Curator
Positive regulation of transcription from RNA polymerase II promoterdefinition[GO:0045944]  
Positive regulation of transcription, DNA-templateddefinition[GO:0045893]  
  • IDAUniProtKB
Regulation of transcription from RNA polymerase II promoterdefinition[GO:0006357]  
Regulation of transcription, DNA-templateddefinition[GO:0006355]  
  • NASUniProtKB
Signal transductiondefinition[GO:0007165] silver  
  • IEAInterPro 2 GO
Transcription from RNA polymerase II promoterdefinition[GO:0006366]  
According to Reactome, this protein belongs to the following pathway:
BMAL1:CLOCK,NPAS2 activates circadian gene expression  REACT_111118  


Biological process 
Biological rhythms  definition   [KW-0090]
Transcription  definition   [KW-0804]
Transcription regulation  definition   [KW-0805]
Molecular function 
Activator  definition   [KW-0010]
Technical term 
Reference proteome  definition   [KW-1185]

Further external links

GeneWiki: ARNTL2
GenomeRNAi: 56938