Npas2
entrez
18143
canonical
uniprot
P97460
canonical
ensembl
ENSMUSG00000026077
resolver
ensp
ENSMUSP00000054719
resolver
ensp
ENSMUSP00000281575
resolver
enst
ENSMUST00000056815
resolver
genesymbol
Npas2
resolver
uniprot
G3X9B7
resolver
uniprot
Q32ME6
resolver
uniprot_entry
G3X9B7_MOUSE
resolver
uniprot_entry
NPAS2_MOUSE
resolver
uniprot_entry
Q32ME6_MOUSE
resolver
activity_regulation
ACTIVITY REGULATION: Carbon monoxide (CO) and the redox state of the cell can modulate the transcriptional activity of the NPAS2-BMAL1 heterodimer. NADH and NADPH enhance the DNA-binding activity of the heterodimer whereas CO binds the heme group in NPAS2 and inhibits the DNA-binding activity of the heterodimer. {ECO:0000269|PubMed:15797872, ECO:0000269|PubMed:23831463}.
uniprot
proteins
amino_acid_sequence
MDEDEKDRAKRASRNKSEKKRRDQFNVLIKELSSMLPGNTRKMDKTTVLEKVIGFLQKHNEVSAQTEICDIQQDWKPSFLSNEEFTQLMLEALDGFVIVVTTDGSIIYVSDSITPLLGHLPADVMDQNLLNFLPEQEHSEVYKILSSHMLVTDSPSPEFLKSDNDLEFYCHLLRGSLNPKEFPTYEYIKFVGNFRSYNNVPSPSCNGFDNTLSRPCHVPLGKDVCFIATVRLATPQFLKEMCVADEPLEEFTSRHSLEWKFLFLDHRAPPIIGYLPFEVLGTSGYNYYHIDDLELLARCHQHLMQFGKGKSCCYRFLTKGQQWIWLQTHYYITYHQWNSKPEFIVCTHSVVSYADVRVERRQELALEDPPTEAMHPSAVKEKDSSLEPPQPFNALDMGASGLPSSPSPSASSRSSHKSSHTAMSEPTSTPTKLMAENSTTALPRPATLPQELPVQGLSQAATMPTALHSSASCDLTKQLLLQSLPQTGLQSPPAPVTQFSAQFSMFQTIKDQLEQRTRILQANIRWQQEELHKIQEQLCLVQDSNVQMFLQQPAVSLSFSSTQRPAAQQQLQQRPAAPSQPQLVVNTPLQGQITSTQVTNQHLLRESNVISAQGPKPMRSSQLLPASGRSLSSLPSQFSSTASVLPPGLSLTTIAPTPQDDSQCQPSPDFGHDRQLRLLLSQPIQPMMPGSCDARQPSEVSRTGRQVKYAQSQVMFPSPDSHPTNSSASTPVLLMGQAVLHPSFPASRPSPLQPAQAQQQPPPYLQAPTSLHSEQPDSLLLSTFSQQPGTLGYAATQSTPPQPPRPSRRVSRLSES
uniprot
proteins
function
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, BMAL1, 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 BMAL1 or 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-BMAL1|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 BMAL1 transcription, respectively. The NPAS2-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. Controls the circadian rhythm of NR0B2 expression by binding rhythmically to its promoter (PubMed:25212631). Mediates the diurnal variation in the expression of GABARA1 receptor in the brain and contributes to the regulation of anxiety-like behaviors and GABAergic neurotransmission in the ventral striatum (PubMed:29163035). {ECO:0000269|PubMed:12843397, ECO:0000269|PubMed:16628007, ECO:0000269|PubMed:16636276, ECO:0000269|PubMed:17417633, ECO:0000269|PubMed:18230344, ECO:0000269|PubMed:18316400, ECO:0000269|PubMed:18439826, ECO:0000269|PubMed:20026146, ECO:0000269|PubMed:24048828, ECO:0000269|PubMed:24067359, ECO:0000269|PubMed:25212631, ECO:0000269|PubMed:29163035}.
uniprot
proteins
mass_dalton
90916
uniprot
proteins
mutagenesis
MUTAGEN 119; /note="H->A: Significant decrease in DNA binding affinity resulting in a loss of the transcriptional activity."; /evidence="ECO:0000269|PubMed:18230344"; MUTAGEN 171; /note="H->A: Significant decrease in DNA binding affinity resulting in a loss of the transcriptional activity."; /evidence="ECO:0000269|PubMed:18230344
uniprot
proteins
pubmed
12843397
uniprot
proteins
pubmed
14645221
uniprot
proteins
pubmed
15797872
uniprot
proteins
pubmed
16628007
uniprot
proteins
pubmed
16636276
uniprot
proteins
pubmed
17417633
uniprot
proteins
pubmed
18230344
uniprot
proteins
pubmed
18316400
uniprot
proteins
pubmed
18439826
uniprot
proteins
pubmed
19147932
uniprot
proteins
pubmed
20026146
uniprot
proteins
pubmed
22245004
uniprot
proteins
pubmed
23831463
uniprot
proteins
pubmed
24048828
uniprot
proteins
pubmed
24067359
uniprot
proteins
pubmed
25212631
uniprot
proteins
pubmed
29163035
uniprot
proteins
pubmed
9012850
uniprot
proteins
sequence_length
816
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00981, ECO:0000269|PubMed:16628007}.
uniprot
proteins