Homo sapiens Protein: ARNTL2
InnateDB Protein IDBP-24495.7
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol ARNTL2
Protein Name aryl hydrocarbon receptor nuclear translocator-like 2
Species Homo sapiens
Ensembl Protein ENSP00000312247
InnateDB Gene IDBG-24491 (ARNTL2)
Protein Structure
UniProt Annotation
Function 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 CLOCKNPAS2-ARNTL/BMAL1ARNTL2/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. {ECO:0000269PubMed:11018023, ECO:0000269PubMed:12738229, ECO:0000269PubMed:14672706}.
Subcellular Localization Nucleus {ECO:0000255PROSITE- ProRule:PRU00981, ECO:0000269PubMed:10964693}.
Disease Associations
Tissue Specificity Expressed in fetal brain. Highly expressed in brain and placenta. Lower levels in heart, liver, thymus, kidney and lung. Located to endothelial cells and neuronal cells of the suprachiasmatic nucleus (SCN). Also detected in endothelial cells of the heart, lung and kidney. In the brain, specifically expressed in the thalamus, hippocampus and amygdala. {ECO:0000269PubMed:10864977, ECO:0000269PubMed:10964693, ECO:0000269PubMed:11018023}.
Number of Interactions This gene and/or its encoded proteins are associated with 4 experimentally validated interaction(s) in this database.
Experimentally validated
Total 4 [view]
Protein-Protein 4 [view]
Protein-DNA 0
Protein-RNA 0
Gene Ontology

Molecular Function
Accession GO Term
GO:0000982 RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity
GO:0003700 sequence-specific DNA binding transcription factor activity
GO:0004871 signal transducer activity
GO:0005515 protein binding
GO:0046983 protein dimerization activity
GO:0070888 E-box binding
Biological Process
GO:0006355 regulation of transcription, DNA-templated
GO:0006357 regulation of transcription from RNA polymerase II promoter
GO:0006366 transcription from RNA polymerase II promoter
GO:0007165 signal transduction
GO:0007623 circadian rhythm
GO:0009649 entrainment of circadian clock
GO:0042753 positive regulation of circadian rhythm
GO:0045893 positive regulation of transcription, DNA-templated
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
Cellular Component
GO:0005634 nucleus
GO:0005667 transcription factor complex
GO:0005730 nucleolus
GO:0005737 cytoplasm
Protein Structure and Domains
InterPro IPR000014 PAS domain
IPR001067 Nuclear translocator
IPR011598 Myc-type, basic helix-loop-helix (bHLH) domain
IPR013655 PAS fold-3
IPR013767 PAS fold
PFAM PF13188
Post-translational Modifications
SwissProt Q8WYA1
PhosphoSite PhosphoSite-Q8WYA1
UniProt Splice Variant
Entrez Gene 56938
UniGene Hs.445447
RefSeq NP_001234931
OMIM 614517
HPRD 16507
EMBL AB039921 AC068794 AC092829 AF231338 AF231339 AF246960 AF246961 AF246962 AF246963 AF256215 AK296706 BC000172 BC125061 BC125062
GenPept AAF71306 AAF71307 AAG34652 AAH00172 AAI25062 AAI25063 AAL50339 AAL50340 AAL50341 AAL50342 BAB01485 BAH12415