CRY1
CRY1 (cryptochrome circadian regulator 1, also known as PHLL1) is a flavin adenine dinucleotide-binding transcriptional repressor and a core component of the circadian clock. It forms part of the negative limb of the feedback loop that generates roughly 24-hour rhythms in gene expression. Browse Assay Genie's current range of CRY1 research reagents below, or read on for the biology behind the target.
CRY1 is a transcriptional repressor at the heart of the molecular circadian clock. The clock rests on a transcription/translation feedback loop. CLOCK or NPAS2 form a heterodimer with BMAL1 or BMAL2 and activate genes carrying E-box elements in their promoters. The repressors PER1/2/3 and CRY1/2 form the negative limb: they interact with the CLOCK|NPAS2-BMAL1|BMAL2 heterodimer, inhibit its activity and so suppress their own expression. CRY1 binds CLOCK-BMAL1 independently of PER proteins and may act as a gatekeeper, holding the complex in a poised, repressed state until the correct time for activation. It can also carry PER proteins into the nucleus.
CRY1 and CRY2 have redundant functions but contribute differently to the pace of the suprachiasmatic nucleus clock. CRY1 is a more potent repressor than CRY2 in cerebellum and liver and is more effective at lengthening the period of the SCN oscillator, whereas CRY2 appears to oppose it in tuning period. Beyond the clock, CRY1 represses CLOCK-BMAL1-driven transcription of targets such as BHLHE40/DEC1, ATF4, MTA1, KLF10 and NAMPT. In liver it binds membrane-coupled G proteins, blocking glucagon-driven increases in cAMP and CREB1 phosphorylation, and lowers nuclear FOXO1 to restrain gluconeogenesis. It also represses glucocorticoid receptor activity, PPARD in skeletal muscle, and is needed for circadian rhythms in the retina.
The CRY1 gene encodes a protein that is widely conserved across plants and animals and belongs to the DNA photolyase class-1 family. Earlier names include cryptochrome 1 (photolyase-like). NCBI notes that polymorphisms in the gene have been associated with altered sleep patterns, and that loss of the related gene in mouse shortens the circadian cycle in complete darkness. More broadly, disrupted circadian rhythms contribute to cardiovascular disease, cancer, metabolic syndromes and ageing.
CRY1 is a core repressor in the CLOCK-BMAL1 feedback loop, making it central to studies of how 24-hour rhythms in gene expression are generated.
Polymorphisms in the CRY1 gene have been associated with altered sleep patterns, and clock output regulates sleep and body temperature.
CRY1 restrains hepatic gluconeogenesis and regulates genes such as LEP and ACSL4, linking the clock to metabolic control.
CRY1 helps set the period of the suprachiasmatic nucleus oscillator and is essential for generating circadian rhythms in the retina.
CRY1 is a transcriptional repressor in the circadian clock. It interacts with the CLOCK-BMAL1 heterodimer to inhibit its activity, closing the negative feedback loop. It also regulates hepatic gluconeogenesis, glucose and lipid metabolism, and glucocorticoid receptor signalling.
The HGNC name is cryptochrome circadian regulator 1, and UniProt lists the protein as Cryptochrome-1. The gene was previously known as PHLL1, cryptochrome 1 (photolyase-like) and cryptochrome circadian clock 1. It is in the cryptochrome circadian regulator family of flavoproteins.
The encoded protein is widely conserved across plants and animals, and mouse and rat both have a Cry1 ortholog. Check the datasheet of any product for its validated reactivity. Polymorphisms are associated with altered sleep patterns, and circadian disruption more generally contributes to cardiovascular, metabolic and oncological disease.
CRY2, the closest cryptochrome partner of CRY1, along with other crystallin-named proteins that are listed on the site.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q16526; product specifications from Assay Genie datasheets.