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P97784

- CRY1_MOUSE

UniProt

P97784 - CRY1_MOUSE

Protein

Cryptochrome-1

Gene

Cry1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 118 (01 Oct 2014)
      Sequence version 1 (01 May 1997)
      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. 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 ACSL4.19 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 By similarity.By similarity
    Binds 1 5,10-methenyltetrahydrofolate non-covalently per subunit.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei252 – 2521FAD; via amide nitrogenBy similarity
    Binding sitei289 – 2891FADBy similarity
    Binding sitei355 – 3551FADBy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi387 – 3893FADBy similarity

    GO - Molecular functioni

    1. core promoter binding Source: UniProtKB
    2. core promoter sequence-specific DNA binding Source: UniProtKB
    3. DNA photolyase activity Source: InterPro
    4. double-stranded DNA binding Source: UniProtKB
    5. histone deacetylase binding Source: UniProtKB
    6. kinase binding Source: UniProtKB
    7. nuclear hormone receptor binding Source: UniProtKB
    8. nucleotide binding Source: UniProtKB-KW
    9. photoreceptor activity Source: UniProtKB-KW
    10. protein binding Source: UniProtKB
    11. protein kinase binding Source: UniProtKB
    12. transcription factor binding Source: UniProtKB
    13. transcription factor binding transcription factor activity Source: Ensembl
    14. ubiquitin binding Source: UniProtKB

    GO - Biological processi

    1. circadian regulation of gene expression Source: UniProtKB
    2. circadian rhythm Source: UniProtKB
    3. DNA damage induced protein phosphorylation Source: UniProtKB
    4. DNA repair Source: InterPro
    5. entrainment of circadian clock by photoperiod Source: UniProtKB
    6. gluconeogenesis Source: UniProtKB
    7. glucose homeostasis Source: UniProtKB
    8. lipid storage Source: UniProtKB
    9. negative regulation of circadian rhythm Source: UniProtKB
    10. negative regulation of glucocorticoid receptor signaling pathway Source: UniProtKB
    11. negative regulation of glucocorticoid secretion Source: UniProtKB
    12. negative regulation of G-protein coupled receptor protein signaling pathway Source: UniProtKB
    13. negative regulation of protein ubiquitination Source: UniProtKB
    14. negative regulation of transcription, DNA-templated Source: UniProtKB
    15. negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
    16. protein-chromophore linkage Source: UniProtKB-KW
    17. regulation of circadian rhythm Source: UniProtKB
    18. regulation of DNA damage checkpoint Source: UniProtKB
    19. response to glucagon Source: UniProtKB
    20. response to insulin Source: UniProtKB
    21. 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-1
    Gene namesi
    Name:Cry1
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 10

    Organism-specific databases

    MGIiMGI:1270841. Cry1.

    Subcellular locationi

    Cytoplasm. Nucleus
    Note: Transloctaed to the nucleus through interaction with other Clock proteins such as PER2 or ARNTL/BMAL1.

    GO - Cellular componenti

    1. cytosol Source: Reactome
    2. mitochondrion Source: UniProtKB
    3. nucleoplasm Source: Reactome
    4. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Disruption phenotypei

    Mice show an advanced phase shift (around 4 hours) in the expression of DBP, NR1D1 and PER1 genes in the liver. Double knockouts of CRY1 and CRY2 show slightly decrease body weight and lose the cycling rhythmicity of feeding behavior, energy expenditure and glucocorticoids 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.5 Publications

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi71 – 711S → A: Phosphomimetic mutant that leads to stabilization of the protein; when associated with A-280. 1 Publication
    Mutagenesisi71 – 711S → D: Phosphomimetic mutant that leads to destabilization of the protein and abolishes ability to bind PER2; when associated with D-280. 1 Publication
    Mutagenesisi107 – 1071K → R: Sensitive to FBXL3-ediated degradation but noz affected by expression of FBXL21. 1 Publication
    Mutagenesisi224 – 2241H → E: Reduces affinity for FBXL3. 1 Publication
    Mutagenesisi247 – 2471S → A: Reduced MAPK-catalyzed in vitro phosphorylation. No effect on inhibition of CLOCK-ARNTL/BMAL1-mediated transcriptional activity. 2 Publications
    Mutagenesisi247 – 2471S → D: Reduced inhibition of CLOCK-ARNTL/BMAL1-mediated transcriptional activity. 2 Publications
    Mutagenesisi280 – 2801S → A: Phosphomimetic mutant that leads to stabilization of the protein; when associated with A-71. 1 Publication
    Mutagenesisi280 – 2801S → D: Phosphomimetic mutant that leads to destabilization of the protein and abolishes ability to bind PER2; when associated with D-71. 1 Publication
    Mutagenesisi336 – 3361G → D: Abolishes transcriptional repression of target genes. Abolishes interaction with PER2.
    Mutagenesisi382 – 3832EE → RR: Decreases transcriptional repression of target genes. Decreases FBXL3 binding. Increases PER2 binding.
    Mutagenesisi405 – 4051F → A: Decreases affinity for FBXL3. Slightly increases affinity for PER2. 1 Publication
    Mutagenesisi485 – 4851K → D or E: Strongly reduces FBXL3 binding. Reduces PER2 binding. 1 Publication
    Mutagenesisi551 – 5511S → A: No effect on circadian period length and protein stability. 1 Publication
    Mutagenesisi551 – 5511S → D: No effect on circadian period length and protein stability. 1 Publication
    Mutagenesisi564 – 5641S → A: No effect on circadian period length and protein stability. 1 Publication
    Mutagenesisi564 – 5641S → D: No effect on circadian period length and protein stability. 1 Publication
    Mutagenesisi588 – 5881S → A: No effect on circadian period length and protein stability. 1 Publication
    Mutagenesisi588 – 5881S → D: Lengthen circadian period. No effect on repressive activity. Increases protein stability. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 606606Cryptochrome-1PRO_0000261142Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Cross-linki11 – 11Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
    Modified residuei71 – 711Phosphoserine; by AMPK2 Publications
    Cross-linki107 – 107Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
    Cross-linki159 – 159Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
    Modified residuei247 – 2471Phosphoserine; by MAPK2 Publications
    Modified residuei280 – 2801Phosphoserine; by AMPK2 Publications
    Cross-linki329 – 329Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
    Cross-linki485 – 485Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
    Modified residuei588 – 5881Phosphoserine2 Publications

    Post-translational modificationi

    Phosphorylation on Ser-247 by MAPK is important for the inhibition of CLOCK-ARNTL/BMAL1-mediated transcriptional activity. Phosphorylation by CSNK1E requires interaction with PER1 or PER2. Phosphorylation at Ser-71 and Ser-280 by AMPK decreases protein stability. Phosphorylation at Ser-588 exhibits a robust circadian rhythm with a peak at CT8, increases protein stability, prevents SCF(FBXL3)-mediated degradation and is antagonized by interaction with PRKDC.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 CRY1. In contrast, cytoplasmic SCF(FBXL21) complex-mediated ubiquitination leads to stabilize CRY1 and counteract the activity of the SCF(FBXL3) complex. The SCF(FBXL3) and SCF(FBXL21) complexes probably mediate ubiquitination at different Lys residues. Ubiquitination at Lys-11 and Lys-107 are specifically ubiquitinated by the SCF(FBXL21) complex but not by the SCF(FBXL3) complex. Ubiquitination may be inhibit by PER2.5 Publications

    Keywords - PTMi

    Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    PaxDbiP97784.
    PRIDEiP97784.

    PTM databases

    PhosphoSiteiP97784.

    Expressioni

    Tissue specificityi

    Expressed in all tissues examined including heart, brain, spleen, lung, liver, skeletal muscle, kidney and testis. Higher levels in brain, liver and testis. In the retina, highly expressed in the ganglion cell layer (GCL) and in the inner nuclear layer (INL). Evenly distributed in central and peripheral retina. In the brain, highly expressed in the suprachiasmatic nucleus (SCN). High levels in cerebral cortical layers particularly in the pyramidial cell layer of the hippocampus, the granular cell layer of the dentate gyrus (DG) and the pyramidal cell layer of the piriform cortex (PFC).5 Publications

    Inductioni

    Oscillates diurnally, rhythmic expression in the early night is critical for clock function (at ptrotein level). In SCN, exhibits circadian rhythm expression with highest levels during the light phase at CT10. No detectable expression after 8 hours in the dark. Circadian oscillations also observed in liver, skeletal muscle and cerebellum, but not in testis.7 Publications

    Gene expression databases

    BgeeiP97784.
    CleanExiMM_CRY1.
    GenevestigatoriP97784.

    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 TIMELESS. Interacts directly with PER1 and PER2 C-terminal domains. Interaction with PER2 inhibits its ubiquitination and vice versa. Interacts with FBXL21. Interacts with FBXL3. Interacts with PPP5C (via TPR repeats). Interacts with of the CLOCK-ARNTL/BMAL1 independently of PER2 and DNA. Interacts with HDAC1, HDAC2 and SIN3B. Interacts with nuclear receptors AR, NR1D1, NR3C1/GR, RORA and RORC; the interaction with at least NR3C1/GR is ligand dependent. Interacts with PRKDC. Interacts with the G protein subunit alpha GNAS; the interaction may block GPCR-mediated regulation of cAMP concentrations. Interacts with PRMT5.19 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    ArntlQ9WTL812EBI-1266607,EBI-644534
    ClockO087857EBI-1266607,EBI-79859
    Fbxl21Q8BFZ410EBI-1266607,EBI-6898235
    Fbxl3Q8C4V412EBI-1266607,EBI-1266589
    Per2O549433EBI-1266607,EBI-1266779

    Protein-protein interaction databases

    BioGridi198906. 19 interactions.
    DIPiDIP-38515N.
    IntActiP97784. 18 interactions.
    MINTiMINT-4084985.
    STRINGi10090.ENSMUSP00000020227.

    Structurei

    Secondary structure

    1
    606
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi4 – 118
    Beta strandi15 – 173
    Helixi19 – 257
    Beta strandi29 – 379
    Helixi49 – 6820
    Beta strandi74 – 785
    Helixi80 – 9011
    Beta strandi95 – 995
    Helixi104 – 11916
    Beta strandi123 – 1275
    Beta strandi130 – 1334
    Helixi135 – 1417
    Helixi150 – 1578
    Beta strandi188 – 1914
    Helixi196 – 1983
    Helixi214 – 23219
    Helixi252 – 2576
    Helixi262 – 27615
    Helixi284 – 2874
    Helixi288 – 30013
    Turni304 – 3074
    Helixi324 – 3318
    Helixi338 – 35013
    Helixi355 – 36511
    Turni366 – 3705
    Helixi374 – 38411
    Helixi390 – 40011
    Helixi417 – 4226
    Helixi427 – 4326
    Helixi434 – 4363
    Turni441 – 4433
    Helixi447 – 4493
    Helixi452 – 4587
    Turni462 – 4643
    Helixi473 – 48513
    Helixi486 – 4883

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    4CT0X-ray2.45A1-496[»]
    4K0RX-ray2.65A1-606[»]
    ProteinModelPortaliP97784.
    SMRiP97784. Positions 3-489.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini3 – 132130Photolyase/cryptochrome alpha/betaAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni371 – 470100Required for inhibition of CLOCK-ARNTL/BMAL1-mediated transcriptionAdd
    BLAST
    Regioni471 – 49323Interaction with TIMELESSAdd
    BLAST

    Sequence similaritiesi

    Belongs to the DNA photolyase class-1 family.Curated

    Phylogenomic databases

    eggNOGiCOG0415.
    GeneTreeiENSGT00500000044813.
    HOGENOMiHOG000245622.
    HOVERGENiHBG053470.
    InParanoidiP97784.
    KOiK02295.
    OMAiFDTDGLP.
    OrthoDBiEOG7QG43M.
    PhylomeDBiP97784.
    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.

    P97784-1 [UniParc]FASTAAdd to Basket

    « Hide

    MGVNAVHWFR KGLRLHDNPA LKECIQGADT IRCVYILDPW FAGSSNVGIN    50
    RWRFLLQCLE DLDANLRKLN SRLFVIRGQP ADVFPRLFKE WNITKLSIEY 100
    DSEPFGKERD AAIKKLATEA GVEVIVRISH TLYDLDKIIE LNGGQPPLTY 150
    KRFQTLVSKM EPLEMPADTI TSDVIGKCMT PLSDDHDEKY GVPSLEELGF 200
    DTDGLSSAVW PGGETEALTR LERHLERKAW VANFERPRMN ANSLLASPTG 250
    LSPYLRFGCL SCRLFYFKLT DLYKKVKKNS SPPLSLYGQL LWREFFYTAA 300
    TNNPRFDKME GNPICVQIPW DKNPEALAKW AEGRTGFPWI DAIMTQLRQE 350
    GWIHHLARHA VACFLTRGDL WISWEEGMKV FEELLLDADW SINAGSWMWL 400
    SCSSFFQQFF HCYCPVGFGR RTDPNGDYIR RYLPVLRGFP AKYIYDPWNA 450
    PEGIQKVAKC LIGVNYPKPM VNHAEASRLN IERMKQIYQQ LSRYRGLGLL 500
    ASVPSNSNGN GGLMGYAPGE NVPSCSSSGN GGLMGYAPGE NVPSCSGGNC 550
    SQGSGILHYA HGDSQQTHSL KQGRSSAGTG LSSGKRPSQE EDAQSVGPKV 600
    QRQSSN 606
    Length:606
    Mass (Da):68,001
    Last modified:May 1, 1997 - v1
    Checksum:i2F2B8DD53F0A9AF9
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB000777 mRNA. Translation: BAA19175.1.
    AF156986 mRNA. Translation: AAD39548.1.
    AK162460 mRNA. Translation: BAE36931.1.
    BC022174 mRNA. Translation: AAH22174.1.
    BC085499 mRNA. Translation: AAH85499.1.
    CCDSiCCDS24089.1.
    RefSeqiNP_031797.1. NM_007771.3.
    UniGeneiMm.26237.

    Genome annotation databases

    EnsembliENSMUST00000020227; ENSMUSP00000020227; ENSMUSG00000020038.
    GeneIDi12952.
    KEGGimmu:12952.
    UCSCiuc007gle.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB000777 mRNA. Translation: BAA19175.1 .
    AF156986 mRNA. Translation: AAD39548.1 .
    AK162460 mRNA. Translation: BAE36931.1 .
    BC022174 mRNA. Translation: AAH22174.1 .
    BC085499 mRNA. Translation: AAH85499.1 .
    CCDSi CCDS24089.1.
    RefSeqi NP_031797.1. NM_007771.3.
    UniGenei Mm.26237.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    4CT0 X-ray 2.45 A 1-496 [» ]
    4K0R X-ray 2.65 A 1-606 [» ]
    ProteinModelPortali P97784.
    SMRi P97784. Positions 3-489.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 198906. 19 interactions.
    DIPi DIP-38515N.
    IntActi P97784. 18 interactions.
    MINTi MINT-4084985.
    STRINGi 10090.ENSMUSP00000020227.

    PTM databases

    PhosphoSitei P97784.

    Proteomic databases

    PaxDbi P97784.
    PRIDEi P97784.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000020227 ; ENSMUSP00000020227 ; ENSMUSG00000020038 .
    GeneIDi 12952.
    KEGGi mmu:12952.
    UCSCi uc007gle.1. mouse.

    Organism-specific databases

    CTDi 1407.
    MGIi MGI:1270841. Cry1.

    Phylogenomic databases

    eggNOGi COG0415.
    GeneTreei ENSGT00500000044813.
    HOGENOMi HOG000245622.
    HOVERGENi HBG053470.
    InParanoidi P97784.
    KOi K02295.
    OMAi FDTDGLP.
    OrthoDBi EOG7QG43M.
    PhylomeDBi P97784.
    TreeFami TF323191.

    Enzyme and pathway databases

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

    Miscellaneous databases

    NextBioi 282662.
    PROi P97784.
    SOURCEi Search...

    Gene expression databases

    Bgeei P97784.
    CleanExi MM_CRY1.
    Genevestigatori P97784.

    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. "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], SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
      Tissue: Brain, Keratinocyte and Liver.
    2. "Analysis of mouse cryptochromes."
      Kume K., Reppert S.M.
      Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: C57BL/6.
    3. "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.
    4. "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 FVB/N.
      Tissue: Brain, Embryonic brain and Mammary tumor.
    5. "Vitamin B2-based blue-light photoreceptors in the retinohypothalamic tract as the photoactive pigments for setting the circadian clock in mammals."
      Miyamoto Y., Sancar A.
      Proc. Natl. Acad. Sci. U.S.A. 95:6097-6102(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY, INDUCTION.
    6. "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: FUNCTION, INTERACTION WITH PER1; PER2; PER3 AND TIMELESS, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION.
    7. "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.
    8. "Nucleocytoplasmic shuttling and mCRY-dependent inhibition of ubiquitylation of the mPER2 clock protein."
      Yagita K., Tamanini F., Yasuda M., Hoeijmakers J.H., van der Horst G.T., Okamura H.
      EMBO J. 21:1301-1314(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PER2, SUBCELLULAR LOCATION, UBIQUITINATION.
    9. "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.
    10. "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-247, MUTAGENESIS OF SER-247.
    11. "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.
    12. "Circadian and light-induced transcription of clock gene Per1 depends on histone acetylation and deacetylation."
      Naruse Y., Oh-hashi K., Iijima N., Naruse M., Yoshioka H., Tanaka M.
      Mol. Cell. Biol. 24:6278-6287(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION AS TRANSCRIPTION REPRESSOR, INTERACTION WITH HDAC1; HDAC2 AND SIN3B.
    13. "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: FUNCTION, SUBCELLULAR LOCATION.
    14. "Functional evolution of the photolyase/cryptochrome protein family: importance of the C terminus of mammalian CRY1 for circadian core oscillator performance."
      Chaves I., Yagita K., Barnhoorn S., Okamura H., van der Horst G.T.J., Tamanini F.
      Mol. Cell. Biol. 26:1743-1753(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH PER1 AND PER2, SUBCELLULAR LOCATION.
    15. "Posttranslational regulation of the mammalian circadian clock by cryptochrome and protein phosphatase 5."
      Partch C.L., Shields K.F., Thompson C.L., Selby C.P., Sancar A.
      Proc. Natl. Acad. Sci. U.S.A. 103:10467-10472(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY, INDUCTION.
    16. "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.
    17. "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.
    18. "Implication of the F-Box Protein FBXL21 in circadian pacemaker function in mammals."
      Dardente H., Mendoza J., Fustin J.M., Challet E., Hazlerigg D.G.
      PLoS ONE 3:E3530-E3530(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH FBXL21, UBIQUITINATION.
    19. "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.
    20. Cited for: PHOSPHORYLATION AT SER-71 AND SER-280, MUTAGENESIS OF SER-71 AND SER-280.
    21. "The mammalian clock component PERIOD2 coordinates circadian output by interaction with nuclear receptors."
      Schmutz I., Ripperger J.A., Baeriswyl-Aebischer S., Albrecht U.
      Genes Dev. 24:345-357(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PER2.
    22. "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.
    23. "Delay in feedback repression by cryptochrome 1 is required for circadian clock function."
      Ukai-Tadenuma M., Yamada R.G., Xu H., Ripperger J.A., Liu A.C., Ueda H.R.
      Cell 144:268-281(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN CIRCADIAN RHYTHMS REGULATION, INDUCTION.
    24. "Biochemical analysis of the canonical model for the mammalian circadian clock."
      Ye R., Selby C.P., Ozturk N., Annayev Y., Sancar A.
      J. Biol. Chem. 286:25891-25902(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ARNTL; CLOCK AND PER2.
    25. "cAMP-response element (CRE)-mediated transcription by activating transcription factor-4 (ATF4) is essential for circadian expression of the Period2 gene."
      Koyanagi S., Hamdan A.M., Horiguchi M., Kusunose N., Okamoto A., Matsunaga N., Ohdo S.
      J. Biol. Chem. 286:32416-32423(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    26. "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; NR1D1; NR3C1; RORA AND RORC, DISRUPTION PHENOTYPE.
    27. "Role of type II protein arginine methyltransferase 5 in the regulation of Circadian Per1 gene."
      Na J., Lee K., Kim H.G., Shin J.Y., Na W., Jeong H., Lee J.W., Cho S., Kim W.S., Ju B.G.
      PLoS ONE 7:E48152-E48152(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INDUCTION, INTERACTION WITH PRMT5.
    28. "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.
    29. "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, UBIQUITINATION AT LYS-11.
    30. "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-107; LYS-159; LYS-329 AND LYS-485, INTERACTION WITH FBXL3 AND FBXL21, MUTAGENESIS OF LYS-107.
    31. "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: FUNCTION IN CIRCADIAN CLOCK, INTERACTION WITH PRKDC, PHOSPHORYLATION AT SER-588, MUTAGENESIS OF SER-551; SER-564 AND SER-588.
    32. "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.
    33. "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 CLOCK.
    34. "Metastasis-associated protein 1 is an integral component of the circadian molecular machinery."
      Li D.Q., Pakala S.B., Reddy S.D., Peng S., Balasenthil S., Deng C.X., Lee C.C., Rea M.A., Kumar R.
      Nat. Commun. 4:2545-2545(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    35. "Mammalian TIMELESS is involved in period determination and DNA damage-dependent phase advancing of the circadian clock."
      Engelen E., Janssens R.C., Yagita K., Smits V.A., van der Horst G.T., Tamanini F.
      PLoS ONE 8:E56623-E56623(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH TIMELESS AND PER2, SUBCELLULAR LOCATION.
    36. "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.
    37. "Gene model 129 (Gm129) encodes a novel transcriptional repressor that modulates circadian gene expression."
      Annayev Y., Adar S., Chiou Y.Y., Lieb J., Sancar A., Ye R.
      J. Biol. Chem. 289:5013-5024(2014) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, DISRUPTION PHENOTYPE.
    38. "Modulation of glucocorticoid receptor induction properties by core circadian clock proteins."
      Han D.H., Lee Y.J., Kim K., Kim C.J., Cho S.
      Mol. Cell. Endocrinol. 383:170-180(2014) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN GR REPRESSION.
    39. "Modulation of ATR-mediated DNA damage checkpoint response by cryptochrome 1."
      Kang T.H., Leem S.H.
      Nucleic Acids Res. 42:4427-4434(2014) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN DNA DAMAGE CHECKPOINT, INTERACTION WITH TIMELESS, SUBCELLULAR LOCATION.
    40. "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.
    41. "Structures of Drosophila cryptochrome and mouse cryptochrome1 provide insight into circadian function."
      Czarna A., Berndt A., Singh H.R., Grudziecki A., Ladurner A.G., Timinszky G., Kramer A., Wolf E.
      Cell 153:1394-1405(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF APOPROTEIN, INTERACTION WITH ARNTL; PER2 AND FBXL3, FUNCTION, MUTAGENESIS OF HIS-224; SER-247; 382-GLU-GLU-383; PHE-405 AND LYS-485.

    Entry informationi

    Entry nameiCRY1_MOUSE
    AccessioniPrimary (citable) accession number: P97784
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 28, 2006
    Last sequence update: May 1, 1997
    Last modified: October 1, 2014
    This is version 118 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