Gene Symbol: Cry2
Description: cryptochrome circadian regulator 2
Alias: cryptochrome-2, cryptochrome 2 (photolyase-like), cryptochrome circadian clock 2
Species: rat
Products:     Cry2

Top Publications

  1. 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
    ..human gene whose amino acid sequence displays 73% identity to the first one and have named the two genes CRY1 and CRY2, respectively...
  2. Duong H, Robles M, Knutti D, Weitz C. A molecular mechanism for circadian clock negative feedback. Science. 2011;332:1436-9 pubmed publisher
    ..These findings provide a function for the PER complex and a molecular mechanism for circadian clock negative feedback. ..
  3. 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
    ..Using green fluorescent protein fused peptides we showed that the C-terminal region of the mouse CRY2 protein contains a unique nuclear localization signal, which is absent in the CRY1 protein...
  4. 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
    ..The mammalian proteins Cryl and Cry2, which are members of the family of plant blue-light receptors (cryptochromes) and photolyases, have been proposed ..
  5. Partch C, Clarkson M, Ozgur S, Lee A, Sancar A. Role of structural plasticity in signal transduction by the cryptochrome blue-light photoreceptor. Biochemistry. 2005;44:3795-805 pubmed
    ..Collectively, these findings provide the first biochemical evidence for the proposed conformational rearrangement of cryptochromes upon light exposure. ..
  6. 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
    Cryptochrome (Cry) 1 and Cry2 are regarded as critical components for circadian rhythm generation in mammals...
  7. 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
    ..These results reveal a specific mechanism through which cryptochromes couple the activity of clock and receptor target genes to complex genomic circuits underpinning normal metabolic homeostasis. ..
  8. Ozber N, Baris I, Tatlici G, Gur I, Kilinc S, Unal E, et al. Identification of two amino acids in the C-terminal domain of mouse CRY2 essential for PER2 interaction. BMC Mol Biol. 2010;11:69 pubmed publisher
    ..Our results identify mCRY2 amino acid residues that interact with the mPER2 binding region and suggest the potential for rational drug design to inhibit CRYs for specific therapeutic approaches. ..
  9. 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. ..

More Information


  1. Ozgur S, Sancar A. Purification and properties of human blue-light photoreceptor cryptochrome 2. Biochemistry. 2003;42:2926-32 pubmed
    ..In this study, we purified cryptochrome 2 (hCRY2) from human cells and characterized it...
  2. Xing W, Busino L, Hinds T, Marionni S, Saifee N, Bush M, et al. SCF(FBXL3) ubiquitin ligase targets cryptochromes at their cofactor pocket. Nature. 2013;496:64-8 pubmed publisher
    ..Here we report crystal structures of mammalian CRY2 in its apo, FAD-bound and FBXL3-SKP1-complexed forms...
  3. 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 receptors ..
  4. Goriki A, Hatanaka F, Myung J, Kim J, Yoritaka T, Tanoue S, et al. A novel protein, CHRONO, functions as a core component of the mammalian circadian clock. PLoS Biol. 2014;12:e1001839 pubmed publisher
    ..clock component of an unsuspected negative circadian feedback loop that is independent of another negative regulator, Cry2, and that integrates behavioral stress and epigenetic control for efficient metabolic integration of the clock.
  5. Eun B, Lee B, Kang H. Cloning and expression of cryptochrome2 cDNA in the rat. Mol Cells. 2001;12:286-91 pubmed
    ..Therefore, we isolated and characterized cry2 cDNA from the rat brain...
  6. 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. ..
  7. 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
    ..Collectively, these data indicate that Cry deficiency results in an increased vulnerability to high-fat diet-induced obesity that might be mediated by increased insulin secretion and lipid storage in adipose tissues. ..
  8. Kurabayashi N, Hirota T, Sakai M, Sanada K, Fukada Y. DYRK1A and glycogen synthase kinase 3beta, a dual-kinase mechanism directing proteasomal degradation of CRY2 for circadian timekeeping. Mol Cell Biol. 2010;30:1757-68 pubmed publisher
    ..Although CRY2 undergoes rhythmic phosphorylation in its C-terminal tail, structurally distinct from the CRY1 tail, little is ..
  9. Sakakida Y, Miyamoto Y, Nagoshi E, Akashi M, Nakamura T, Mamine T, et al. Importin alpha/beta mediates nuclear transport of a mammalian circadian clock component, mCRY2, together with mPER2, through a bipartite nuclear localization signal. J Biol Chem. 2005;280:13272-8 pubmed
    ..These results suggest that the importin alpha/beta system is involved in nuclear entry of mammalian clock components, which is indispensable to transcriptional oscillation of clock genes. ..
  10. 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
    ..Transcription assays with a 2.1-kb mPer1 promoter revealed that CRY2 inhibited the transactivation mediated by BMAL1-CLOCK more strongly than that by BMAL2-CLOCK...
  11. Ishibashi K, Miyamoto K, Taketani Y, Morita K, Takeda E, Sasaki S, et al. Molecular cloning of a second human stanniocalcin homologue (STC2). Biochem Biophys Res Commun. 1998;250:252-8 pubmed
    ..We have cloned a widely expressed new human stanniocalcin homologue which suppressed the expression of renal Na-phosphate cotransporter. ..
  12. Quintela T, Sousa C, Patriarca F, Goncalves I, Santos C. Gender associated circadian oscillations of the clock genes in rat choroid plexus. Brain Struct Funct. 2015;220:1251-62 pubmed publisher
    ..We show that there is a 24-h rhythm in the expression of Per2 and Cry2 in males and females. Bmal1 and Per1 expression also varied along the day, but only in females...
  13. 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. ..
  14. 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(Afh) to ..
  15. 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. ..
  16. 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. ..
  17. 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
    ..Therefore, these data suggest a new role for the C-terminal tail of CRY1 in which phosphorylation rhythmically regulates CRY1 stability and contributes to the proper circadian period length. ..
  18. 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. ..
  19. 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. ..
  20. 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. ..
  21. 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. ..
  22. 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...