Gene Symbol: Cry1
Description: cryptochrome circadian regulator 1
Alias: cryptochrome-1, cryptochrome 1 (photolyase-like), cryptochrome circadian clock 1
Species: rat
Products:     Cry1

Top Publications

  1. Sasaki M, Yoshitane H, Du N, Okano T, Fukada Y. Preferential inhibition of BMAL2-CLOCK activity by PER2 reemphasizes its negative role and a positive role of BMAL2 in the circadian transcription. J Biol Chem. 2009;284:25149-59 pubmed publisher
    ..Collectively, it is strongly suggested that BMAL2 plays an active role in the circadian transcription. ..
  2. van der Horst G, Muijtjens M, Kobayashi K, Takano R, Kanno S, Takao M, et al. Mammalian Cry1 and Cry2 are essential for maintenance of circadian rhythms. Nature. 1999;398:627-30 pubmed
    ..This suggests that, in addition to a possible photoreceptor and antagonistic clock-adjusting function, both proteins are essential for the maintenance of circadian rhythmicity. ..
  3. Yagita K, Tamanini F, Yasuda M, Hoeijmakers J, van der Horst G, Okamura H. Nucleocytoplasmic shuttling and mCRY-dependent inhibition of ubiquitylation of the mPER2 clock protein. EMBO J. 2002;21:1301-14 pubmed
    ..On the basis of these data we propose a model in which shuttling mPER2 is ubiquitylated and degraded by the proteasome unless it is retained in the nucleus by mCRY proteins. ..
  4. Lamia K, Sachdeva U, DiTacchio L, Williams E, Alvarez J, Egan D, et al. AMPK regulates the circadian clock by cryptochrome phosphorylation and degradation. Science. 2009;326:437-40 pubmed publisher
    ..adenosine monophosphate-activated protein kinase (AMPK) phosphorylates and destabilizes the clock component cryptochrome 1 (CRY1)...
  5. Ukai Tadenuma M, Yamada R, Xu H, Ripperger J, Liu A, Ueda H. Delay in feedback repression by cryptochrome 1 is required for circadian clock function. Cell. 2011;144:268-81 pubmed publisher
    ..b>Cryptochrome 1 (Cry1), an essential clock component, displays evening-time expression and serves as a strong repressor at ..
  6. Engelen E, Janssens R, Yagita K, Smits V, van der Horst G, Tamanini F. Mammalian TIMELESS is involved in period determination and DNA damage-dependent phase advancing of the circadian clock. PLoS ONE. 2013;8:e56623 pubmed publisher
    ..Furthermore, we reveal that the N-terminus of TIM is sufficient for interaction with CRY1 and CHK1 as well for homodimerization, and the C-terminus is necessary for nuclear localization...
  7. Kume K, Zylka M, Sriram S, Shearman L, Weaver D, Jin X, et al. mCRY1 and mCRY2 are essential components of the negative limb of the circadian clock feedback loop. Cell. 1999;98:193-205 pubmed
    ..Luciferase reporter gene assays show that mCRY1 or mCRY2 alone abrogates CLOCK:BMAL1-E box-mediated transcription. The mPER and mCRY proteins appear to inhibit the transcriptional complex differentially. ..
  8. Zhang E, Liu Y, Dentin R, Pongsawakul P, Liu A, Hirota T, et al. Cryptochrome mediates circadian regulation of cAMP signaling and hepatic gluconeogenesis. Nat Med. 2010;16:1152-6 pubmed publisher
    ..of gene expression is achieved by two transcriptional activators, Clock and Bmal1, which stimulate cryptochrome (Cry1 and Cry2) and Period (Per1, Per2 and Per3) repressors that feed back on Clock-Bmal1 activity...
  9. Naruse Y, Oh hashi K, Iijima N, Naruse M, Yoshioka H, Tanaka M. Circadian and light-induced transcription of clock gene Per1 depends on histone acetylation and deacetylation. Mol Cell Biol. 2004;24:6278-87 pubmed
    ..Mouse CRY1 (mCRY1) repressed transcription with HDACs and mSin3B, which was relieved by the HDAC inhibitor trichostatin A (TSA)..

More Information


  1. Ye R, Selby C, Ozturk N, Annayev Y, Sancar A. Biochemical analysis of the canonical model for the mammalian circadian clock. J Biol Chem. 2011;286:25891-902 pubmed publisher
    ..These findings support some aspects of the canonical model, but also suggest that some key features of the model need to be revised. ..
  2. Kang T, Leem S. Modulation of ATR-mediated DNA damage checkpoint response by cryptochrome 1. Nucleic Acids Res. 2014;42:4427-34 pubmed publisher
    ..Here we show that Cry1 modulates the ATR-mediated DNA damage checkpoint (DDC) response by interacting with Timeless (Tim) in a time-of-day-..
  3. Dudley C, Erbel Sieler C, Estill S, Reick M, Franken P, Pitts S, et al. Altered patterns of sleep and behavioral adaptability in NPAS2-deficient mice. Science. 2003;301:379-83 pubmed
    ..Our results indicate that NPAS2 plays a substantive role in maintaining circadian behaviors in normal LD and feeding conditions and that NPAS2 is critical for adaptability to food restriction. ..
  4. Anand S, Maywood E, Chesham J, Joynson G, Banks G, Hastings M, et al. Distinct and separable roles for endogenous CRY1 and CRY2 within the circadian molecular clockwork of the suprachiasmatic nucleus, as revealed by the Fbxl3(Afh) mutation. J Neurosci. 2013;33:7145-53 pubmed publisher
    ..To determine the differential contributions of CRY1 and CRY2 within circadian timing in vivo, we exploited the N-ethyl-N-nitrosourea-induced afterhours mutant Fbxl3(..
  5. Gao P, Yoo S, Lee K, Rosensweig C, Takahashi J, Chen B, et al. Phosphorylation of the cryptochrome 1 C-terminal tail regulates circadian period length. J Biol Chem. 2013;288:35277-86 pubmed publisher
    ..We then identified serine 588 in the C-terminal tail of mouse CRY1 as a potential DNA-PK phosphorylation site but surprisingly found that the phosphomimetic mutation S588D also ..
  6. Preitner N, Damiola F, Lopez Molina L, Zakany J, Duboule D, Albrecht U, et al. The orphan nuclear receptor REV-ERBalpha controls circadian transcription within the positive limb of the mammalian circadian oscillator. Cell. 2002;110:251-60 pubmed
    ..While REV-ERBalpha influences the period length and affects the phase-shifting properties of the clock, it is not required for circadian rhythm generation. ..
  7. Annayev Y, Adar S, Chiou Y, Lieb J, Sancar A, Ye R. Gene model 129 (Gm129) encodes a novel transcriptional repressor that modulates circadian gene expression. J Biol Chem. 2014;289:5013-24 pubmed publisher
    ..ChIP analysis revealed that the CLOCK·BMAL1·CRY1 complex strongly occupies the promoter region of Gm129...
  8. Kobayashi K, Kanno S, Smit B, van der Horst G, Takao M, Yasui A. Characterization of photolyase/blue-light receptor homologs in mouse and human cells. Nucleic Acids Res. 1998;26:5086-92 pubmed
    ..C-terminal region of the mouse CRY2 protein contains a unique nuclear localization signal, which is absent in the CRY1 protein. The N-terminal region of CRY1 was shown to contain the mitochondrial transport signal...
  9. Zhao S, Sancar A. Human blue-light photoreceptor hCRY2 specifically interacts with protein serine/threonine phosphatase 5 and modulates its activity. Photochem Photobiol. 1997;66:727-31 pubmed
    ..We found that hCRY2, but not the highly homologous (6-4) photolyase, inhibits the phosphatase activity of PP5. This inhibition may be on the pathway of blue-light signal transduction reaction in humans. ..
  10. Ramsey K, Yoshino J, Brace C, Abrassart D, Kobayashi Y, Marcheva B, et al. Circadian clock feedback cycle through NAMPT-mediated NAD+ biosynthesis. Science. 2009;324:651-4 pubmed publisher
    ..In turn, the circadian transcription factor CLOCK binds to and up-regulates Nampt, thus completing a feedback loop involving NAMPT/NAD+ and SIRT1/CLOCK:BMAL1. ..
  11. Zhao W, Malinin N, Yang F, Staknis D, Gekakis N, Maier B, et al. CIPC is a mammalian circadian clock protein without invertebrate homologues. Nat Cell Biol. 2007;9:268-75 pubmed
    ..Our results suggest that negative feedback in the mammalian circadian clock is divided into distinct pathways, and that the addition of new genes has contributed to the complexity of vertebrate clocks. ..
  12. Ando H, Ushijima K, Yanagihara H, Hayashi Y, Takamura T, Kaneko S, et al. Clock gene expression in the liver and adipose tissues of non-obese type 2 diabetic Goto-Kakizaki rats. Clin Exp Hypertens. 2009;31:201-7 pubmed publisher
    ..In this study, we show that the rhythmic mRNA expression of clock genes (Clock, Bmal1, Cry1, and Dbp) is not attenuated in the liver and visceral adipose tissues of Goto-Kakizaki rats, a model of nonobese, ..
  13. Boone D, Sell S, Micci M, Crookshanks J, Parsley M, Uchida T, et al. Traumatic brain injury-induced dysregulation of the circadian clock. PLoS ONE. 2012;7:e46204 pubmed publisher
    ..Dysregulated expression of key circadian clock genes, such as Bmal1 and Cry1, was detected, suggesting perturbation of transcriptional-translational feedback loops that are central to ..
  14. Cheng M, Bullock C, Li C, Lee A, Bermak J, Belluzzi J, et al. Prokineticin 2 transmits the behavioural circadian rhythm of the suprachiasmatic nucleus. Nature. 2002;417:405-10 pubmed
    ..The high expression of PKR2 mRNA within the SCN and the positive feedback of PK2 on its own transcription through activation of PKR2 suggest that PK2 may also function locally within the SCN to synchronize output. ..
  15. Lamia K, Papp S, Yu R, Barish G, Uhlenhaut N, Jonker J, et al. Cryptochromes mediate rhythmic repression of the glucocorticoid receptor. Nature. 2011;480:552-6 pubmed publisher
    ..In mice, genetic loss of cryptochrome 1 and/or 2 results in glucose intolerance and constitutively high levels of circulating corticosterone, ..
  16. Devos J, Weselake S, Wevrick R. Magel2, a Prader-Willi syndrome candidate gene, modulates the activities of circadian rhythm proteins in cultured cells. J Circadian Rhythms. 2011;9:12 pubmed publisher
  17. Na J, Lee K, Kim H, Shin J, Na W, Jeong H, et al. Role of type II protein arginine methyltransferase 5 in the regulation of Circadian Per1 gene. PLoS ONE. 2012;7:e48152 pubmed publisher
    ..In this study, we identified the type II protein arginine methyltransferase 5 (PRMT5) as an interacting molecule of CRY1. Although the Prmt5 gene was constitutively expressed, increased interaction of PRMT5 with CRY1 was observed when ..
  18. Park K, Kang H. Cloning and circadian expression of rat Cry1. Mol Cells. 2004;18:256-60 pubmed
    ..2001)]. We report here the cloning of another cryptochrome gene, Cry1, from rat brain by reverse-transcription coupled to polymerase chain reaction (RT-PCR), together with rapid-..
  19. Koyanagi S, Hamdan A, Horiguchi M, Kusunose N, Okamoto A, Matsunaga N, et al. cAMP-response element (CRE)-mediated transcription by activating transcription factor-4 (ATF4) is essential for circadian expression of the Period2 gene. J Biol Chem. 2011;286:32416-23 pubmed publisher
    ..These results suggest that ATF4 is a component responsible for sustaining circadian oscillation of CRE-mediated gene expression and also constitute a molecular link connecting cAMP-dependent signaling to the circadian clock. ..
  20. Li D, Pakala S, Reddy S, Peng S, Balasenthil S, Deng C, et al. Metastasis-associated protein 1 is an integral component of the circadian molecular machinery. Nat Commun. 2013;4:2545 pubmed publisher
    ..MTA1, in turn, interacts with and recruits CLOCK-BMAL1 at its own and CRY1 promoters and promotes their transcription...
  21. Schoenhard J, Smith L, Painter C, Eren M, Johnson C, Vaughan D. Regulation of the PAI-1 promoter by circadian clock components: differential activation by BMAL1 and BMAL2. J Mol Cell Cardiol. 2003;35:473-81 pubmed
    ..In this way, fundamental circadian clock components may drive circadian variation in PAI-1, which in turn influences the pathogenesis, timing, and treatment of acute atherothrombotic events. ..
  22. Ono D, Honma S, Honma K. Cryptochromes are critical for the development of coherent circadian rhythms in the mouse suprachiasmatic nucleus. Nat Commun. 2013;4:1666 pubmed publisher
    ..Nevertheless, cultured suprachiasmatic nucleus (SCN) of neonatal Cry double deficient (Cry1(-/-)/Cry2(-/-)) mice exhibit circadian rhythms that damp out in several cycles...
  23. Honma S, Kawamoto T, Takagi Y, Fujimoto K, Sato F, Noshiro M, et al. Dec1 and Dec2 are regulators of the mammalian molecular clock. Nature. 2002;419:841-4 pubmed
    ..A brief light pulse induced Dec1 but not Dec2 expression in the suprachiasmic nucleus in a phase-dependent manner. Dec1 and Dec2 are regulators of the mammalian molecular clock, and form a fifth clock-gene family. ..
  24. Hirayama J, Nakamura H, Ishikawa T, Kobayashi Y, Todo T. Functional and structural analyses of cryptochrome. Vertebrate CRY regions responsible for interaction with the CLOCK:BMAL1 heterodimer and its nuclear localization. J Biol Chem. 2003;278:35620-8 pubmed
    ..These findings show that both nuclear localization and interaction with the CLOCK:BMAL heterodimer are essential for transcriptional repression by CRY. ..
  25. Hara Y, Onishi Y, Oishi K, Miyazaki K, Fukamizu A, Ishida N. Molecular characterization of Mybbp1a as a co-repressor on the Period2 promoter. Nucleic Acids Res. 2009;37:1115-26 pubmed publisher
    ..We purified mouse CRY1 (mCRY1) protein complexes from Sarcoma 180 cells to determine their roles in circadian gene expression and ..
  26. Kawamoto T, Noshiro M, Sato F, Maemura K, Takeda N, Nagai R, et al. A novel autofeedback loop of Dec1 transcription involved in circadian rhythm regulation. Biochem Biophys Res Commun. 2004;313:117-24 pubmed
    ..The autofeedback loop of Dec1 may be interlocked with the core feedback loop of Per in some situations. ..
  27. Fang M, Zhang X, Zarbl H. Methylselenocysteine resets the rhythmic expression of circadian and growth-regulatory genes disrupted by nitrosomethylurea in vivo. Cancer Prev Res (Phila). 2010;3:640-52 pubmed publisher
    ..Here, we report that NMU disrupted the expression of core circadian genes (Per1, Per2, Cry1, Cry2, and RevErbAalpha) and circadian-controlled genes, including melatonin receptor 1alpha (MTNR1A), estrogen ..
  28. Kojima S, Matsumoto K, Hirose M, Shimada M, Nagano M, Shigeyoshi Y, et al. LARK activates posttranscriptional expression of an essential mammalian clock protein, PERIOD1. Proc Natl Acad Sci U S A. 2007;104:1859-64 pubmed
    ..These data indicate that mLARKs are novel posttranscriptional regulators of mammalian circadian clocks. ..
  29. Mattam U, Jagota A. Differential role of melatonin in restoration of age-induced alterations in daily rhythms of expression of various clock genes in suprachiasmatic nucleus of male Wistar rats. Biogerontology. 2014;15:257-68 pubmed publisher
    ..We report here differential restoration of daily rhythm, phase, levels and stoichiometric interaction of m-RNA expression of these genes in various age groups in rat SCN with melatonin treatment...
  30. Bellet M, Zocchi L, Sassone Corsi P. The RelB subunit of NF?B acts as a negative regulator of circadian gene expression. Cell Cycle. 2012;11:3304-11 pubmed publisher
    ..Notably, RelB -/- fibroblasts have profound alterations of circadian genes expression. These findings reveal a previously unforeseen function for RelB as an important regulator of the mammalian circadian system in fibroblasts. ..
  31. Barclay J, Shostak A, Leliavski A, Tsang A, Jöhren O, Müller Fielitz H, et al. High-fat diet-induced hyperinsulinemia and tissue-specific insulin resistance in Cry-deficient mice. Am J Physiol Endocrinol Metab. 2013;304:E1053-63 pubmed publisher
    ..The CRYPTOCHROMEs are critical interaction partners of PERs, and simultaneous deletion of Cry1 and -2 results in behavioral and molecular circadian arrhythmicity...
  32. Hamaguchi H, Fujimoto K, Kawamoto T, Noshiro M, Maemura K, Takeda N, et al. Expression of the gene for Dec2, a basic helix-loop-helix transcription factor, is regulated by a molecular clock system. Biochem J. 2004;382:43-50 pubmed
    ..In addition, Cry and Per may also modulate Dec2 transcription. ..
  33. Han D, Lee Y, Kim K, Kim C, Cho S. Modulation of glucocorticoid receptor induction properties by core circadian clock proteins. Mol Cell Endocrinol. 2014;383:170-80 pubmed publisher
    ..Accordingly, we observe that PER1 and CRY1, the primary targets of CLOCK/BMAL1 action, reduce maximal GR transactivation while not affecting the efficacy...
  34. Hsu D, Zhao X, Zhao S, Kazantsev A, Wang R, Todo T, et al. Putative human blue-light photoreceptors hCRY1 and hCRY2 are flavoproteins. Biochemistry. 1996;35:13871-7 pubmed
    ..a second human gene whose amino acid sequence displays 73% identity to the first one and have named the two genes CRY1 and CRY2, respectively...
  35. Bertolucci C, Cavallari N, Colognesi I, Aguzzi J, Chen Z, Caruso P, et al. Evidence for an overlapping role of CLOCK and NPAS2 transcription factors in liver circadian oscillators. Mol Cell Biol. 2008;28:3070-5 pubmed publisher
    ..heterodimers were (i) comparable (a fourfold increase), (ii) dampened by the negative circadian regulators PER2 and CRY1, and (iii) abolished upon E-box mutagenesis...