Q9R194 (CRY2_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified July 9, 2014. Version 108. History...
Names and origin
|Protein names||Recommended name:|
|Organism||Mus musculus (Mouse) [Reference proteome]|
|Taxonomic identifier||10090 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus|
|Sequence length||592 AA.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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 CLOCK|NPAS2-ARNTL/BMAL1|ARNTL2/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. Less potent transcriptional repressor in cerebellum and liver than CRY1, though less effective in lengthening the period of the SCN oscillator. Seems to play a critical role in tuning SCN circadian period by opposing the action of CRY1. With CRY1, dispensable for circadian rhythm generation but necessary for the development of intercellular networks for rhythm synchrony. May mediate circadian regulation of cAMP signaling and gluconeogenesis by blocking glucagon-mediated increases in intracellular cAMP concentrations and in CREB1 phosphorylation. Besides its role in the maintenance of the circadian clock, is also involved in the regulation of other processes. 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. Represses glucocorticoid receptor NR3C1/GR-induced transcriptional activity by binding to glucocorticoid response elements (GREs). Ref.1 Ref.11 Ref.14 Ref.18 Ref.19 Ref.20 Ref.21 Ref.25 Ref.26
Binds 1 FAD per subunit. Only a minority of the protein molecules contain bound FAD. Contrary to the situation in photolyases, the FAD is bound in a shallow, surface-exposed pocket. Ref.30
Binds 1 5,10-methenyltetrahydrofolate non-covalently per subunit By similarity. Ref.30
Component of the circadian core oscillator, which includes the CRY proteins, CLOCK or NPAS2, ARNTL or ARNTL2, CSNK1D and/or CSNK1E, TIMELESS, and the PER proteins. Interacts directly with PER1 and PER2 C-terminal domains. Interaction with PER2 inhibits its ubiquitination and vice versa. Interacts with NFIL3. Interacts with FBXL3 and FBXL21. FBXL3, PER2 and the cofactor FAD compete for overlapping binding sites. FBXL3 cannot bind CRY2 that interacts already with PER2 or that contains bound FAD. Interacts with PPP5C (via TPR repeats); the interaction downregulates the PPP5C phosphatase activity on CSNK1E. AR, NR1D1, NR3C1/GR, RORA and RORC; the interaction, at least, with NR3C1/GR is ligand dependent. Interacts with PRKDC. Ref.1 Ref.8 Ref.9 Ref.11 Ref.12 Ref.13 Ref.15 Ref.16 Ref.19 Ref.20 Ref.22 Ref.23 Ref.24 Ref.30
Shows no clear circadian oscillation pattern in testis, cerebellum nor liver. In skeletal muscle, under constant darkness and 12 hours light:12 hours dark conditions, levels peak between ZT6 and ZT9. Ref.1 Ref.6 Ref.15
Phosphorylation on Ser-265 by MAPK is important for the inhibition of CLOCK-ARNTL-mediated transcriptional activity. Phosphorylation by CSKNE requires interaction with PER1 or PER2. Phosphorylated in a circadian manner at Ser-553 and Ser-557 in the suprachiasmatic nucleus (SCN) and liver. Phosphorylation at Ser-557 by DYRK1A promotes subsequent phosphorylation at Ser-553 by GSK3-beta: the two-step phosphorylation at the neighboring Ser residues leads to its proteasomal degradation. Ref.7 Ref.8 Ref.10 Ref.17
Ubiquitinated by the SCF(FBXL3) and SCF(FBXL21) complexes, regulating the balance between degradation and stabilization. The SCF(FBXL3) complex is mainly nuclear and mediates ubiquitination and subsequent degradation of CRY2. In contrast, cytoplasmic SCF(FBXL21) complex-mediated ubiquitination leads to stabilize CRY2 and counteract the activity of the SCF(FBXL3) complex. The SCF(FBXL3) and SCF(FBXL21) complexes probably mediate ubiquitination at different Lys residues. The SCF(FBXL3) complex recognizes and binds CRY2 phosphorylated at Ser-553 and Ser-557. Ubiquitination may be inhibited by PER2. Ref.7 Ref.8 Ref.10 Ref.17
Animals show longer circadian periods. Double knockouts of CRY1 and CRY2 show slightly decrease body weight and lose the cycling rhythmicity of feeding behavior, energy expenditure and glucocorticorids expression. Glucose homeostasis is severely disrupted and animals exhibit elevated blood glucose in response to acute feeding after an overnight fast as well as severely impaired glucose clearance in a glucose tolerance test. When challenged with high-fat diet, animals rapidly gain weight and surpass that of wild-type mice, despite displaying hypophagia. They exhibit hyperinsulinemia and selective insulin resistance in the liver and muscle but show high insulin sensitivity in adipose tissue and consequent increased lipid uptake. Mice display enlarged gonadal, subcutaneous and perirenal fat deposits with adipocyte hypertrophy and increased lipied accumulation in liver. Ref.18 Ref.19 Ref.21 Ref.25
Belongs to the DNA photolyase class-1 family.
Contains 1 photolyase/cryptochrome alpha/beta domain.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 592||592||Cryptochrome-2||PRO_0000261149|
|Domain||21 – 150||130||Photolyase/cryptochrome alpha/beta|
|Nucleotide binding||405 – 407||3||FAD|
|Region||389 – 488||100||Required for inhibition of CLOCK-ARNTL-mediated transcription By similarity|
|Compositional bias||2 – 5||4||Poly-Ala|
|Binding site||270||1||FAD; via amide nitrogen|
|Binding site||307||1||FAD By similarity|
Amino acid modifications
|Modified residue||265||1||Phosphoserine; by MAPK Ref.7|
|Modified residue||553||1||Phosphoserine; by GSK3-beta Ref.17|
|Modified residue||557||1||Phosphoserine; by DYRK1A and MAPK Ref.7 Ref.10 Ref.17|
|Cross-link||125||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.23|
|Cross-link||241||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.23|
|Cross-link||347||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.23|
|Cross-link||474||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.23|
|Cross-link||503||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.23|
|Mutagenesis||265||1||S → A: Reduced in vitro MAPK-catalyzed phosphorylation. No effect on inhibition of CLOCK-ARNTL-mediated transcriptional activity. Very little in vitro MAPK-catalyzed phosphorylation; when associated with A-557. Ref.7|
|Mutagenesis||265||1||S → D: Reduced inhibition of CLOCK-ARNTL-mediated transcriptional activity. No effect on nuclear localization nor on protein stability. Ref.7|
|Mutagenesis||310||1||W → A: Decreases FBXL3 binding. Strongly decreases CRY2 degradation. Ref.30|
|Mutagenesis||339||1||D → R: Strongly reduces PER1 binding. Ref.30|
|Mutagenesis||376||1||R → A: Impairs protein folding. Abolishes binding of ARNTL, PER1 and FBXL3. Strongly reduces SKP1 binding. Ref.30|
|Mutagenesis||428||1||F → D: Abolishes binding of FBXL3 and SKP1. Strongly decreases CRY2 degradation. Ref.30|
|Mutagenesis||499||1||I → D: Abolishes binding of FBXL3 and SKP1. Strongly decreases CRY2 degradation. Ref.30|
|Mutagenesis||501||1||R → Q: Inhibits interaction with PER2. Does not suppress its nuclear localization. Inhibits its repression activity on CLOCK|NPAS2-ARNTL-driven transcription. Ref.16|
|Mutagenesis||503||1||K → R: Inhibits interaction with PER2. Does not suppress its nuclear localization. Inhibits its repression activity on CLOCK|NPAS2-ARNTL-driven transcription. Ref.16|
|Mutagenesis||517||1||L → D: Decreases FBXL3 binding. Strongly decreases CRY2 degradation. Ref.30|
|Mutagenesis||553||1||S → A: Shorter circadian rhythm; when associated with A-557. Ref.17|
|Mutagenesis||557||1||S → A: Reduced in vitro MAPK-catalyzed phosphorylation. No effect on inhibition of CLOCK-ARNTL-mediated transcriptional activity. Very little in vitro MAPK-catalyzed phosphorylation; when associated with A-265. Shorter circadian rhythm; when associated with A-553. Ref.7 Ref.17|
|Mutagenesis||557||1||S → D: Reduced inhibition of CLOCK-ARNTL-mediated transcriptional activity. No effect on nuclear localization nor on protein stability. Ref.7 Ref.17|
|Sequence conflict||191 – 192||2||QQ → SR in BAA19864. Ref.5|
|Sequence conflict||202||1||E → K in BAA19864. Ref.5|
|Sequence conflict||327||1||M → V in BAA19864. Ref.5|
Helix Strand Turn
|Beta strand||22 – 26||5|
|Beta strand||32 – 35||4|
|Helix||37 – 43||7|
|Beta strand||47 – 55||9|
|Helix||59 – 61||3|
|Helix||67 – 85||19|
|Turn||86 – 88||3|
|Beta strand||91 – 96||6|
|Helix||98 – 109||12|
|Beta strand||113 – 117||5|
|Helix||122 – 137||16|
|Beta strand||141 – 145||5|
|Beta strand||148 – 151||4|
|Helix||153 – 159||7|
|Turn||160 – 162||3|
|Helix||168 – 176||9|
|Helix||190 – 194||5|
|Helix||204 – 208||5|
|Turn||213 – 217||5|
|Helix||232 – 242||11|
|Helix||245 – 251||7|
|Helix||259 – 262||4|
|Helix||270 – 274||5|
|Helix||280 – 294||15|
|Beta strand||295 – 297||3|
|Helix||302 – 305||4|
|Helix||306 – 318||13|
|Turn||322 – 325||4|
|Helix||342 – 350||9|
|Helix||356 – 368||13|
|Helix||373 – 383||11|
|Turn||384 – 388||5|
|Helix||392 – 402||11|
|Helix||408 – 418||11|
|Beta strand||421 – 423||3|
|Helix||435 – 440||6|
|Helix||445 – 450||6|
|Helix||452 – 454||3|
|Helix||459 – 462||4|
|Helix||465 – 467||3|
|Helix||470 – 475||6|
|Turn||480 – 482||3|
|Helix||491 – 507||17|
|Beta strand||517 – 521||5|
|||"mCRY1 and mCRY2 are essential components of the negative limb of the circadian clock feedback loop."|
Kume K., Zylka M.J., Sriram S., Shearman L.P., Weaver D.R., Jin X., Maywood E.S., Hastings M.H., Reppert S.M.
Cell 98:193-205(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, INDUCTION, INTERACTION WITH PER1; PER2; PER3 AND TIMELESS.
|||"The transcriptional landscape of the mammalian genome."|
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Embryo, Fetal brain and Thymus.
|||"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."|
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6 and CD-1.
Tissue: Brain and Neural stem cell.
|||"Prediction of the coding sequences of mouse homologues of KIAA gene: IV. The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries."|
Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S., Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H., Nagase T., Ohara O., Koga H.
DNA Res. 11:205-218(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 9-592.
Tissue: Fetal brain.
|||"Characterization of photolyase/blue-light receptor homologs in mouse and human cells."|
Kobayashi K., Kanno S., Smit B., van der Horst G.T.J., Takao M., Yasui A.
Nucleic Acids Res. 26:5086-5092(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 24-592, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
|||"Circadian regulation of cryptochrome genes in the mouse."|
Miyamoto Y., Sancar A.
Brain Res. Mol. Brain Res. 71:238-243(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, INDUCTION.
|||"Serine phosphorylation of mCRY1 and mCRY2 by mitogen-activated protein kinase."|
Sanada K., Harada Y., Sakai M., Todo T., Fukada Y.
Genes Cells 9:697-708(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-265 AND SER-557, MUTAGENESIS OF SER-265 AND SER-557.
|||"The circadian regulatory proteins BMAL1 and cryptochromes are substrates of casein kinase Iepsilon."|
Eide E.J., Vielhaber E.L., Hinz W.A., Virshup D.M.
J. Biol. Chem. 277:17248-17254(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PER1 AND PER2, PHOSPHORYLATION, SUBCELLULAR LOCATION.
|||"Direct association between mouse PERIOD and CKIepsilon is critical for a functioning circadian clock."|
Lee C., Weaver D.R., Reppert S.M.
Mol. Cell. Biol. 24:584-594(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PER1; PER2 AND PER3.
|||"Ser-557-phosphorylated mCRY2 is degraded upon synergistic phosphorylation by glycogen synthase kinase-3 beta."|
Harada Y., Sakai M., Kurabayashi N., Hirota T., Fukada Y.
J. Biol. Chem. 280:31714-31721(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-557, SUBCELLULAR LOCATION.
|||"Post-translational regulation of circadian transcriptional CLOCK(NPAS2)/BMAL1 complex by CRYPTOCHROMES."|
Kondratov R.V., Kondratova A.A., Lee C., Gorbacheva V.Y., Chernov M.V., Antoch M.P.
Cell Cycle 5:890-895(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CLOCK-ARNTL COMPLEX, FUNCTION.
|||"The negative transcription factor E4BP4 is associated with circadian clock protein PERIOD2."|
Ohno T., Onishi Y., Ishida N.
Biochem. Biophys. Res. Commun. 354:1010-1015(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NFIL3.
|||"Circadian mutant Overtime reveals F-box protein FBXL3 regulation of cryptochrome and period gene expression."|
Siepka S.M., Yoo S.H., Park J., Song W., Kumar V., Hu Y., Lee C., Takahashi J.S.
Cell 129:1011-1023(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FBXL3, UBIQUITINATION.
|||"CIPC is a mammalian circadian clock protein without invertebrate homologues."|
Zhao W.N., Malinin N., Yang F.C., Staknis D., Gekakis N., Maier B., Reischl S., Kramer A., Weitz C.J.
Nat. Cell Biol. 9:268-275(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
|||"Rhythmic PER abundance defines a critical nodal point for negative feedback within the circadian clock mechanism."|
Chen R., Schirmer A., Lee Y., Lee H., Kumar V., Yoo S.H., Takahashi J.S., Lee C.
Mol. Cell 36:417-430(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ARNTL AND CLOCK, INDUCTION.
|||"Identification of two amino acids in the C-terminal domain of mouse CRY2 essential for PER2 interaction."|
Ozber N., Baris I., Tatlici G., Gur I., Kilinc S., Unal E.B., Kavakli I.H.
BMC Mol. Biol. 11:69-69(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ARNTL AND PER2, SUBCELLULAR LOCATION, MUTAGENESIS OF ARG-501 AND LYS-503.
|||"DYRK1A and glycogen synthase kinase 3beta, a dual-kinase mechanism directing proteasomal degradation of CRY2 for circadian timekeeping."|
Kurabayashi N., Hirota T., Sakai M., Sanada K., Fukada Y.
Mol. Cell. Biol. 30:1757-1768(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-553 AND SER-557, MUTAGENESIS OF SER-553 AND SER-557.
|||"Cryptochrome mediates circadian regulation of cAMP signaling and hepatic gluconeogenesis."|
Zhang E.E., Liu Y., Dentin R., Pongsawakul P.Y., Liu A.C., Hirota T., Nusinow D.A., Sun X., Landais S., Kodama Y., Brenner D.A., Montminy M., Kay S.A.
Nat. Med. 16:1152-1156(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN GLUCONEOGENESIS, DISRUPTION PHENOTYPE.
|||"Cryptochromes mediate rhythmic repression of the glucocorticoid receptor."|
Lamia K.A., Papp S.J., Yu R.T., Barish G.D., Uhlenhaut N.H., Jonker J.W., Downes M., Evans R.M.
Nature 480:552-556(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS NR3C1 REPRESSOR, INTERACTION WITH AR AND NR3C1, DISRUPTION PHENOTYPE.
|||"A role for the circadian clock protein Per1 in the regulation of aldosterone levels and renal Na+ retention."|
Richards J., Cheng K.Y., All S., Skopis G., Jeffers L., Lynch I.J., Wingo C.S., Gumz M.L.
Am. J. Physiol. 305:F1697-F1704(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS TRANSCRIPTIONAL REPRESSOR, INTERACTION WITH PER1, TISSUE SPECIFICITY.
|||"High-fat diet-induced hyperinsulinemia and tissue-specific insulin resistance in Cry-deficient mice."|
Barclay J.L., Shostak A., Leliavski A., Tsang A.H., Johren O., Muller-Fielitz H., Landgraf D., Naujokat N., van der Horst G.T., Oster H.
Am. J. Physiol. 304:E1053-E1063(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN METABOLISM, DISRUPTION PHENOTYPE.
|||"Competing E3 ubiquitin ligases govern circadian periodicity by degradation of CRY in nucleus and cytoplasm."|
Yoo S.H., Mohawk J.A., Siepka S.M., Shan Y., Huh S.K., Hong H.K., Kornblum I., Kumar V., Koike N., Xu M., Nussbaum J., Liu X., Chen Z., Chen Z.J., Green C.B., Takahashi J.S.
Cell 152:1091-1105(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION BY THE SCF(FBXL3) AND SCF(FBXL21) COMPLEXES, INTERACTION WITH FBXL3 AND FBXL21.
|||"FBXL21 regulates oscillation of the circadian clock through ubiquitination and stabilization of cryptochromes."|
Hirano A., Yumimoto K., Tsunematsu R., Matsumoto M., Oyama M., Kozuka-Hata H., Nakagawa T., Lanjakornsiripan D., Nakayama K.I., Fukada Y.
Cell 152:1106-1118(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION BY THE SCF(FBXL3) AND SCF(FBXL21) COMPLEXES, UBIQUITINATION AT LYS-125; LYS-241; LYS-347; LYS-474 AND LYS-503, INTERACTION WITH FBXL3 AND FBXL21.
|||"Phosphorylation of the cryptochrome 1 C-terminal tail regulates circadian period length."|
Gao P., Yoo S.H., Lee K.J., Rosensweig C., Takahashi J.S., Chen B.P., Green C.B.
J. Biol. Chem. 288:35277-35286(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PRKDC.
|||"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."|
Anand S.N., Maywood E.S., Chesham J.E., Joynson G., Banks G.T., Hastings M.H., Nolan P.M.
J. Neurosci. 33:7145-7153(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CIRCADIAN CLOCK, DISRUPTION PHENOTYPE.
|||"Cryptochromes are critical for the development of coherent circadian rhythms in the mouse suprachiasmatic nucleus."|
Ono D., Honma S., Honma K.
Nat. Commun. 4:1666-1666(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CIRCADIAN RHYTHM MAINTENANCE.
|||"Metabolism and the circadian clock converge."|
Eckel-Mahan K., Sassone-Corsi P.
Physiol. Rev. 93:107-135(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
|||"Molecular architecture of the mammalian circadian clock."|
Partch C.L., Green C.B., Takahashi J.S.
Trends Cell Biol. 24:90-99(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
|||"Crystal structure of mammalian cryptochrome in complex with a small molecule competitor of its ubiquitin ligase."|
Nangle S., Xing W., Zheng N.
Cell Res. 23:1417-1419(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.94 ANGSTROMS) OF 1-512 IN COMPLEX WITH UBIQUITIN LIGASE SYNTHETIC INHIBITOR.
|||"SCF(FBXL3) ubiquitin ligase targets cryptochromes at their cofactor pocket."|
Xing W., Busino L., Hinds T.R., Marionni S.T., Saifee N.H., Bush M.F., Pagano M., Zheng N.
Nature 496:64-68(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1-512 IN COMPLEXES WITH FAD; SKP1 AND FBXL3, IDENTIFICATION IN A COMPLEX WITH SKP1 AND FBXL3, COFACTOR, IDENTIFICATION BY MASS SPECTROMETRY, MUTAGENESIS OF TRP-310; ASP-339; ARG-376; PHE-428; ILE-499 AND LEU-517.
|+||Additional computationally mapped references.|
|AF156987 mRNA. Translation: AAD46561.1.|
AK041696 mRNA. Translation: BAC31037.1.
AK133781 mRNA. Translation: BAE21836.1.
BC054794 mRNA. Translation: AAH54794.1.
BC066799 mRNA. Translation: AAH66799.1.
AK172994 mRNA. Translation: BAD32272.1.
AB003433 mRNA. Translation: BAA19864.1.
|RefSeq||NP_034093.1. NM_009963.4. |
3D structure databases
|SMR||Q9R194. Positions 21-512. |
Protein-protein interaction databases
|BioGrid||198907. 15 interactions.|
|IntAct||Q9R194. 13 interactions.|
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSMUST00000090559; ENSMUSP00000088047; ENSMUSG00000068742. |
ENSMUST00000111278; ENSMUSP00000106909; ENSMUSG00000068742.
|UCSC||uc008kxy.2. mouse. |
|MGI||MGI:1270859. Cry2. |
Enzyme and pathway databases
|Reactome||REACT_200794. Mus musculus biological processes. |
Gene expression databases
Family and domain databases
|Gene3D||184.108.40.2060. 1 hit. |
|InterPro||IPR006050. DNA_photolyase_N. |
|Pfam||PF00875. DNA_photolyase. 1 hit. |
PF03441. FAD_binding_7. 1 hit.
|SUPFAM||SSF48173. SSF48173. 1 hit. |
SSF52425. SSF52425. 1 hit.
|PROSITE||PS51645. PHR_CRY_ALPHA_BETA. 1 hit. |
|Accession||Primary (citable) accession number: Q9R194|
Secondary accession number(s): O08706, Q6A024
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|