Homo sapiens Protein: CRY1
InnateDB Protein IDBP-55049.5
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol CRY1
Protein Name cryptochrome 1 (photolyase-like)
Synonyms PHLL1;
Species Homo sapiens
Ensembl Protein ENSP00000008527
InnateDB Gene IDBG-55047 (CRY1)
Protein Structure
UniProt Annotation
Function 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 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. CRY1 and CRY2 have redundant functions but also differential and selective contributions at least in defining the pace of the SCN circadian clock and its circadian transcriptional outputs. More potent transcriptional repressor in cerebellum and liver than CRY2, though more effective in lengthening the period of the SCN oscillator. On its side, CRY2 seems to play a critical role in tuning SCN circadian period by opposing the action of CRY1. With CRY2, is dispensable for circadian rhythm generation but necessary for the development of intercellular networks for rhythm synchrony. Capable of translocating circadian clock core proteins such as PER proteins to the nucleus. Interacts with CLOCK:BMAL1 independently of PER proteins and is found at CLOCK:BMAL1-bound sites, suggesting that CRY may act as a molecular gatekeeper to maintain CLOCK:BMAL1 in a poised and repressed state until the proper time for transcriptional activation. Represses the CLOCK-ARNTL/BMAL1 induced transcription of BHLHE40/DEC1, ATF4 and MTA1. May repress circadian target genes expression in collaboration with HDAC1 and HDAC2 through histone deacetylation. Mediates the clock-control activation of ATR and modulates ATR-mediated DNA damage checkpoint. In liver, mediates circadian regulation of cAMP signaling and gluconeogenesis by binding to membrane-coupled G proteins and blocking glucagon-mediated increases in intracellular cAMP concentrations and CREB1 phosphorylation. Besides its role in the maintenance of the circadian clock, is also involved in the regulation of other processes. Represses glucocorticoid receptor NR3C1/GR-induced transcriptional activity by binding to glucocorticoid response elements (GREs). Plays a key role in glucose and lipid metabolism modulation, in part, through the transcriptional regulation of genes involved in these pathways, such as LEP or ACSL4. {ECO:0000269PubMed:10531061, ECO:0000269PubMed:14672706, ECO:0000269PubMed:22170608, ECO:0000269PubMed:23133559}.
Subcellular Localization Cytoplasm. Nucleus. Note=Translocated to the nucleus through interaction with other Clock proteins such as PER2 or ARNTL/BMAL1. {ECO:0000250}.
Disease Associations
Tissue Specificity
Number of Interactions This gene and/or its encoded proteins are associated with 29 experimentally validated interaction(s) in this database.
They are also associated with 25 interaction(s) predicted by orthology.
Experimentally validated
Total 29 [view]
Protein-Protein 27 [view]
Protein-DNA 1 [view]
Protein-RNA 0
DNA-DNA 1 [view]
Predicted by orthology
Total 25 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0000166 nucleotide binding
GO:0000989 transcription factor binding transcription factor activity
GO:0001047 core promoter binding
GO:0003677 DNA binding
GO:0003690 double-stranded DNA binding
GO:0003913 DNA photolyase activity
GO:0005515 protein binding
GO:0008134 transcription factor binding
GO:0009882 blue light photoreceptor activity
GO:0019900 kinase binding
GO:0019901 protein kinase binding
GO:0019902 phosphatase binding
GO:0035257 nuclear hormone receptor binding
GO:0042826 histone deacetylase binding
GO:0043130 ubiquitin binding
Biological Process
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0006094 gluconeogenesis
GO:0006281 DNA repair
GO:0006351 transcription, DNA-templated
GO:0006975 DNA damage induced protein phosphorylation
GO:0007623 circadian rhythm
GO:0009785 blue light signaling pathway
GO:0018298 protein-chromophore linkage
GO:0019915 lipid storage
GO:0031397 negative regulation of protein ubiquitination
GO:0032868 response to insulin
GO:0032922 circadian regulation of gene expression
GO:0033762 response to glucagon
GO:0042593 glucose homeostasis
GO:0042752 regulation of circadian rhythm
GO:0042754 negative regulation of circadian rhythm
GO:0043153 entrainment of circadian clock by photoperiod
GO:0045744 negative regulation of G-protein coupled receptor protein signaling pathway
GO:0045892 negative regulation of transcription, DNA-templated
GO:2000001 regulation of DNA damage checkpoint
GO:2000323 negative regulation of glucocorticoid receptor signaling pathway
GO:2000850 negative regulation of glucocorticoid secretion
Cellular Component
GO:0005634 nucleus
GO:0005730 nucleolus
GO:0005737 cytoplasm
GO:0005739 mitochondrion
Protein Structure and Domains
InterPro IPR005101 DNA photolyase, FAD-binding/Cryptochrome, C-terminal
IPR006050 DNA photolyase, N-terminal
PFAM PF03441
Post-translational Modifications
SwissProt Q16526
PhosphoSite PhosphoSite-Q16526
UniProt Splice Variant
Entrez Gene 1407
UniGene Hs.739819
RefSeq NP_004066
OMIM 601933
HPRD 09050
EMBL AC007541 AC078929 AK290552 BC030519 CH471054 D83702 D84657 EF015898
GenPept AAH30519 ABM64209 BAA12068 BAA12710 BAF83241 EAW97795 EAW97797