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Q9R194

- CRY2_MOUSE

UniProt

Q9R194 - CRY2_MOUSE

Protein

Cryptochrome-2

Gene

Cry2

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 110 (01 Oct 2014)
      Sequence version 1 (01 May 2000)
      Previous versions | rss
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    Functioni

    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). Represses the CLOCK-ARNTL/BMAL1 induced transcription of BHLHE40/DEC1.9 Publications

    Cofactori

    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.1 Publication
    Binds 1 5,10-methenyltetrahydrofolate non-covalently per subunit.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei270 – 2701FAD; via amide nitrogen
    Binding sitei307 – 3071FADBy similarity
    Binding sitei373 – 3731FAD

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi405 – 4073FAD

    GO - Molecular functioni

    1. damaged DNA binding Source: Ensembl
    2. DNA photolyase activity Source: InterPro
    3. FAD binding Source: UniProtKB
    4. kinase binding Source: UniProtKB
    5. nuclear hormone receptor binding Source: UniProtKB
    6. photoreceptor activity Source: UniProtKB-KW
    7. protein binding Source: UniProtKB
    8. protein kinase binding Source: UniProtKB
    9. single-stranded DNA binding Source: Ensembl
    10. transcription factor binding transcription factor activity Source: Ensembl
    11. transcription regulatory region sequence-specific DNA binding Source: UniProtKB
    12. ubiquitin binding Source: UniProtKB

    GO - Biological processi

    1. circadian regulation of gene expression Source: UniProtKB
    2. circadian rhythm Source: UniProtKB
    3. DNA repair Source: InterPro
    4. entrainment of circadian clock by photoperiod Source: UniProtKB
    5. glucose homeostasis Source: UniProtKB
    6. lipid storage Source: UniProtKB
    7. negative regulation of circadian rhythm Source: UniProtKB
    8. negative regulation of glucocorticoid receptor signaling pathway Source: UniProtKB
    9. negative regulation of glucocorticoid secretion Source: UniProtKB
    10. negative regulation of phosphoprotein phosphatase activity Source: Ensembl
    11. negative regulation of transcription, DNA-templated Source: UniProtKB
    12. negative regulation of transcription from RNA polymerase II promoter Source: Ensembl
    13. protein-chromophore linkage Source: UniProtKB-KW
    14. protein import into nucleus Source: MGI
    15. regulation of circadian rhythm Source: UniProtKB
    16. regulation of sodium-dependent phosphate transport Source: Ensembl
    17. response to insulin Source: UniProtKB
    18. transcription, DNA-templated Source: UniProtKB-KW

    Keywords - Molecular functioni

    Photoreceptor protein, Receptor, Repressor

    Keywords - Biological processi

    Biological rhythms, Sensory transduction, Transcription, Transcription regulation

    Keywords - Ligandi

    Chromophore, FAD, Flavoprotein, Nucleotide-binding

    Enzyme and pathway databases

    ReactomeiREACT_198620. BMAL1:CLOCK,NPAS2 activates circadian gene expression.
    REACT_24972. Circadian Clock.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cryptochrome-2
    Gene namesi
    Name:Cry2
    Synonyms:Kiaa0658
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 2

    Organism-specific databases

    MGIiMGI:1270859. Cry2.

    Subcellular locationi

    Cytoplasm. Nucleus
    Note: Translocated to the nucleus through interaction with other Clock proteins such as PER2 or ARNTL.

    GO - Cellular componenti

    1. cytosol Source: Reactome
    2. extracellular region Source: Ensembl
    3. mitochondrion Source: UniProtKB
    4. nucleoplasm Source: Reactome
    5. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Disruption phenotypei

    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.4 Publications

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi265 – 2651S → 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. 1 Publication
    Mutagenesisi265 – 2651S → D: Reduced inhibition of CLOCK-ARNTL-mediated transcriptional activity. No effect on nuclear localization nor on protein stability. 1 Publication
    Mutagenesisi310 – 3101W → A: Decreases FBXL3 binding. Strongly decreases CRY2 degradation. 1 Publication
    Mutagenesisi339 – 3391D → R: Strongly reduces PER1 binding. 1 Publication
    Mutagenesisi376 – 3761R → A: Impairs protein folding. Abolishes binding of ARNTL, PER1 and FBXL3. Strongly reduces SKP1 binding. 1 Publication
    Mutagenesisi428 – 4281F → D: Abolishes binding of FBXL3 and SKP1. Strongly decreases CRY2 degradation. 1 Publication
    Mutagenesisi499 – 4991I → D: Abolishes binding of FBXL3 and SKP1. Strongly decreases CRY2 degradation. 1 Publication
    Mutagenesisi501 – 5011R → Q: Inhibits interaction with PER2. Does not suppress its nuclear localization. Inhibits its repression activity on CLOCK|NPAS2-ARNTL-driven transcription. 1 Publication
    Mutagenesisi503 – 5031K → R: Inhibits interaction with PER2. Does not suppress its nuclear localization. Inhibits its repression activity on CLOCK|NPAS2-ARNTL-driven transcription. 1 Publication
    Mutagenesisi517 – 5171L → D: Decreases FBXL3 binding. Strongly decreases CRY2 degradation. 1 Publication
    Mutagenesisi553 – 5531S → A: Shorter circadian rhythm; when associated with A-557. 1 Publication
    Mutagenesisi557 – 5571S → 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. 2 Publications
    Mutagenesisi557 – 5571S → D: Reduced inhibition of CLOCK-ARNTL-mediated transcriptional activity. No effect on nuclear localization nor on protein stability. 2 Publications

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 592592Cryptochrome-2PRO_0000261149Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Cross-linki125 – 125Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
    Cross-linki241 – 241Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
    Modified residuei265 – 2651Phosphoserine; by MAPK2 Publications
    Cross-linki347 – 347Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
    Cross-linki474 – 474Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
    Cross-linki503 – 503Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
    Modified residuei553 – 5531Phosphoserine; by GSK3-beta2 Publications
    Modified residuei557 – 5571Phosphoserine; by DYRK1A and MAPK4 Publications

    Post-translational modificationi

    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.4 Publications
    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 PER2.6 Publications

    Keywords - PTMi

    Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    PaxDbiQ9R194.
    PRIDEiQ9R194.

    PTM databases

    PhosphoSiteiQ9R194.

    Expressioni

    Tissue specificityi

    Expressed in all tissues examined including heart, brain, spleen, lung, liver, skeletal muscle, kidney and testis. Weak expression in spleen.3 Publications

    Inductioni

    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 ZT9.3 Publications

    Gene expression databases

    ArrayExpressiQ9R194.
    BgeeiQ9R194.
    CleanExiMM_CRY2.
    GenevestigatoriQ9R194.

    Interactioni

    Subunit structurei

    Component of the circadian core oscillator, which includes the CRY proteins, CLOCK or NPAS2, ARNTL/BMAL1 or ARNTL2/BMAL2, 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 and CIART.16 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    ArntlQ9WTL86EBI-1266619,EBI-644534
    Fbxl21Q8BFZ44EBI-1266619,EBI-6898235
    Fbxl3Q8C4V46EBI-1266619,EBI-1266589
    Per2O549434EBI-1266619,EBI-1266779

    Protein-protein interaction databases

    BioGridi198907. 15 interactions.
    DIPiDIP-38517N.
    IntActiQ9R194. 13 interactions.
    STRINGi10090.ENSMUSP00000106909.

    Structurei

    Secondary structure

    1
    592
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi22 – 265
    Beta strandi32 – 354
    Helixi37 – 437
    Beta strandi47 – 559
    Helixi59 – 613
    Helixi67 – 8519
    Turni86 – 883
    Beta strandi91 – 966
    Helixi98 – 10912
    Beta strandi113 – 1175
    Helixi122 – 13716
    Beta strandi141 – 1455
    Beta strandi148 – 1514
    Helixi153 – 1597
    Turni160 – 1623
    Helixi168 – 1769
    Helixi190 – 1945
    Helixi204 – 2085
    Turni213 – 2175
    Helixi232 – 24211
    Helixi245 – 2517
    Helixi259 – 2624
    Helixi270 – 2745
    Helixi280 – 29415
    Beta strandi295 – 2973
    Helixi302 – 3054
    Helixi306 – 31813
    Turni322 – 3254
    Helixi342 – 3509
    Helixi356 – 36813
    Helixi373 – 38311
    Turni384 – 3885
    Helixi392 – 40211
    Helixi408 – 41811
    Beta strandi421 – 4233
    Helixi435 – 4406
    Helixi445 – 4506
    Helixi452 – 4543
    Helixi459 – 4624
    Helixi465 – 4673
    Helixi470 – 4756
    Turni480 – 4823
    Helixi491 – 50717
    Beta strandi517 – 5215

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    4I6EX-ray2.70A1-512[»]
    4I6GX-ray2.20A/B1-512[»]
    4I6JX-ray2.70A1-544[»]
    4MLPX-ray1.94A/B/C/D1-512[»]
    ProteinModelPortaliQ9R194.
    SMRiQ9R194. Positions 21-512.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini21 – 150130Photolyase/cryptochrome alpha/betaAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni389 – 488100Required for inhibition of CLOCK-ARNTL-mediated transcriptionBy similarityAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi2 – 54Poly-Ala

    Sequence similaritiesi

    Belongs to the DNA photolyase class-1 family.Curated

    Phylogenomic databases

    eggNOGiCOG0415.
    GeneTreeiENSGT00500000044813.
    HOGENOMiHOG000245622.
    HOVERGENiHBG053470.
    InParanoidiQ9R194.
    KOiK02295.
    OMAiIQENHDD.
    OrthoDBiEOG7QG43M.
    PhylomeDBiQ9R194.
    TreeFamiTF323191.

    Family and domain databases

    Gene3Di3.40.50.620. 1 hit.
    InterProiIPR006050. DNA_photolyase_N.
    IPR005101. Photolyase_FAD-bd/Cryptochr_C.
    IPR014729. Rossmann-like_a/b/a_fold.
    [Graphical view]
    PfamiPF00875. DNA_photolyase. 1 hit.
    PF03441. FAD_binding_7. 1 hit.
    [Graphical view]
    SUPFAMiSSF48173. SSF48173. 1 hit.
    SSF52425. SSF52425. 1 hit.
    PROSITEiPS51645. PHR_CRY_ALPHA_BETA. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q9R194-1 [UniParc]FASTAAdd to Basket

    « Hide

    MAAAAVVAAT VPAQSMGADG ASSVHWFRKG LRLHDNPALL AAVRGARCVR    50
    CVYILDPWFA ASSSVGINRW RFLLQSLEDL DTSLRKLNSR LFVVRGQPAD 100
    VFPRLFKEWG VTRLTFEYDS EPFGKERDAA IMKMAKEAGV EVVTENSHTL 150
    YDLDRIIELN GQKPPLTYKR FQALISRMEL PKKPAVAVSS QQMESCRAEI 200
    QENHDDTYGV PSLEELGFPT EGLGPAVWQG GETEALARLD KHLERKAWVA 250
    NYERPRMNAN SLLASPTGLS PYLRFGCLSC RLFYYRLWDL YKKVKRNSTP 300
    PLSLFGQLLW REFFYTAATN NPRFDRMEGN PICIQIPWDR NPEALAKWAE 350
    GKTGFPWIDA IMTQLRQEGW IHHLARHAVA CFLTRGDLWV SWESGVRVFD 400
    ELLLDADFSV NAGSWMWLSC SAFFQQFFHC YCPVGFGRRT DPSGDYIRRY 450
    LPKLKGFPSR YIYEPWNAPE SVQKAAKCII GVDYPRPIVN HAETSRLNIE 500
    RMKQIYQQLS RYRGLCLLAS VPSCVEDLSH PVAEPGSSQA GSISNTGPRA 550
    LSSGPASPKR KLEAAEEPPG EELTKRARVT EMPTQEPASK DS 592
    Length:592
    Mass (Da):66,850
    Last modified:May 1, 2000 - v1
    Checksum:i4D6E7B199C392CBB
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti191 – 1922QQ → SR in BAA19864. (PubMed:9801304)Curated
    Sequence conflicti202 – 2021E → K in BAA19864. (PubMed:9801304)Curated
    Sequence conflicti327 – 3271M → V in BAA19864. (PubMed:9801304)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSiCCDS16447.1.
    RefSeqiNP_034093.1. NM_009963.4.
    UniGeneiMm.254181.

    Genome annotation databases

    EnsembliENSMUST00000090559; ENSMUSP00000088047; ENSMUSG00000068742.
    ENSMUST00000111278; ENSMUSP00000106909; ENSMUSG00000068742.
    GeneIDi12953.
    KEGGimmu:12953.
    UCSCiuc008kxy.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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 .
    CCDSi CCDS16447.1.
    RefSeqi NP_034093.1. NM_009963.4.
    UniGenei Mm.254181.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    4I6E X-ray 2.70 A 1-512 [» ]
    4I6G X-ray 2.20 A/B 1-512 [» ]
    4I6J X-ray 2.70 A 1-544 [» ]
    4MLP X-ray 1.94 A/B/C/D 1-512 [» ]
    ProteinModelPortali Q9R194.
    SMRi Q9R194. Positions 21-512.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 198907. 15 interactions.
    DIPi DIP-38517N.
    IntActi Q9R194. 13 interactions.
    STRINGi 10090.ENSMUSP00000106909.

    PTM databases

    PhosphoSitei Q9R194.

    Proteomic databases

    PaxDbi Q9R194.
    PRIDEi Q9R194.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000090559 ; ENSMUSP00000088047 ; ENSMUSG00000068742 .
    ENSMUST00000111278 ; ENSMUSP00000106909 ; ENSMUSG00000068742 .
    GeneIDi 12953.
    KEGGi mmu:12953.
    UCSCi uc008kxy.2. mouse.

    Organism-specific databases

    CTDi 1408.
    MGIi MGI:1270859. Cry2.
    Rougei Search...

    Phylogenomic databases

    eggNOGi COG0415.
    GeneTreei ENSGT00500000044813.
    HOGENOMi HOG000245622.
    HOVERGENi HBG053470.
    InParanoidi Q9R194.
    KOi K02295.
    OMAi IQENHDD.
    OrthoDBi EOG7QG43M.
    PhylomeDBi Q9R194.
    TreeFami TF323191.

    Enzyme and pathway databases

    Reactomei REACT_198620. BMAL1:CLOCK,NPAS2 activates circadian gene expression.
    REACT_24972. Circadian Clock.

    Miscellaneous databases

    NextBioi 282666.
    PROi Q9R194.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9R194.
    Bgeei Q9R194.
    CleanExi MM_CRY2.
    Genevestigatori Q9R194.

    Family and domain databases

    Gene3Di 3.40.50.620. 1 hit.
    InterProi IPR006050. DNA_photolyase_N.
    IPR005101. Photolyase_FAD-bd/Cryptochr_C.
    IPR014729. Rossmann-like_a/b/a_fold.
    [Graphical view ]
    Pfami PF00875. DNA_photolyase. 1 hit.
    PF03441. FAD_binding_7. 1 hit.
    [Graphical view ]
    SUPFAMi SSF48173. SSF48173. 1 hit.
    SSF52425. SSF52425. 1 hit.
    PROSITEi PS51645. PHR_CRY_ALPHA_BETA. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "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.
      Strain: C57BL/6.
    2. "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.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: C57BL/6J.
      Tissue: Embryo, Fetal brain and Thymus.
    3. "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.
    4. "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.
    5. "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.
      Tissue: Liver.
    6. "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.
    7. "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.
    8. "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.
    9. "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.
    10. "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.
    11. "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.
    12. "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.
    13. "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.
    14. "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.
    15. "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.
    16. "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.
    17. "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.
    18. "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.
    19. "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.
    20. "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.
    21. "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.
    22. "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.
    23. "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.
    24. "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.
    25. "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.
    26. "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.
    27. "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.
    28. Cited for: INTERACTION WITH CIART.
    29. "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.
    30. "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.
    31. "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.

    Entry informationi

    Entry nameiCRY2_MOUSE
    AccessioniPrimary (citable) accession number: Q9R194
    Secondary accession number(s): O08706, Q6A024
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 28, 2006
    Last sequence update: May 1, 2000
    Last modified: October 1, 2014
    This is version 110 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3