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Q9R194

- CRY2_MOUSE

UniProt

Q9R194 - CRY2_MOUSE

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Protein

Cryptochrome-2

Gene

Cry2

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

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 NR1D1/2 and RORA/B/G, 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 and NAMPT.10 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 kinase binding Source: UniProtKB
  8. single-stranded DNA binding Source: Ensembl
  9. transcription factor binding transcription factor activity Source: Ensembl
  10. transcription regulatory region sequence-specific DNA binding Source: UniProtKB
  11. 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
Complete GO annotation...

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
Complete GO annotation...

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

MaxQBiQ9R194.
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

BgeeiQ9R194.
CleanExiMM_CRY2.
ExpressionAtlasiQ9R194. baseline and differential.
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.17 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 – 265Combined sources
Beta strandi32 – 354Combined sources
Helixi37 – 437Combined sources
Beta strandi47 – 559Combined sources
Helixi59 – 613Combined sources
Helixi67 – 8519Combined sources
Turni86 – 883Combined sources
Beta strandi91 – 966Combined sources
Helixi98 – 10912Combined sources
Beta strandi113 – 1175Combined sources
Helixi122 – 13716Combined sources
Beta strandi141 – 1455Combined sources
Beta strandi148 – 1514Combined sources
Helixi153 – 1597Combined sources
Turni160 – 1623Combined sources
Helixi168 – 1769Combined sources
Helixi190 – 1945Combined sources
Helixi204 – 2085Combined sources
Turni213 – 2175Combined sources
Helixi232 – 24211Combined sources
Helixi245 – 2517Combined sources
Helixi259 – 2624Combined sources
Helixi270 – 2745Combined sources
Helixi280 – 29415Combined sources
Beta strandi295 – 2973Combined sources
Helixi302 – 3054Combined sources
Helixi306 – 31813Combined sources
Turni322 – 3254Combined sources
Helixi342 – 3509Combined sources
Helixi356 – 36813Combined sources
Helixi373 – 38311Combined sources
Turni384 – 3885Combined sources
Helixi392 – 40211Combined sources
Helixi408 – 41811Combined sources
Beta strandi421 – 4233Combined sources
Helixi435 – 4406Combined sources
Helixi445 – 4506Combined sources
Helixi452 – 4543Combined sources
Helixi459 – 4624Combined sources
Helixi465 – 4673Combined sources
Helixi470 – 4756Combined sources
Turni480 – 4823Combined sources
Helixi491 – 50717Combined sources
Beta strandi517 – 5215Combined sources

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

        10         20         30         40         50
MAAAAVVAAT VPAQSMGADG ASSVHWFRKG LRLHDNPALL AAVRGARCVR
60 70 80 90 100
CVYILDPWFA ASSSVGINRW RFLLQSLEDL DTSLRKLNSR LFVVRGQPAD
110 120 130 140 150
VFPRLFKEWG VTRLTFEYDS EPFGKERDAA IMKMAKEAGV EVVTENSHTL
160 170 180 190 200
YDLDRIIELN GQKPPLTYKR FQALISRMEL PKKPAVAVSS QQMESCRAEI
210 220 230 240 250
QENHDDTYGV PSLEELGFPT EGLGPAVWQG GETEALARLD KHLERKAWVA
260 270 280 290 300
NYERPRMNAN SLLASPTGLS PYLRFGCLSC RLFYYRLWDL YKKVKRNSTP
310 320 330 340 350
PLSLFGQLLW REFFYTAATN NPRFDRMEGN PICIQIPWDR NPEALAKWAE
360 370 380 390 400
GKTGFPWIDA IMTQLRQEGW IHHLARHAVA CFLTRGDLWV SWESGVRVFD
410 420 430 440 450
ELLLDADFSV NAGSWMWLSC SAFFQQFFHC YCPVGFGRRT DPSGDYIRRY
460 470 480 490 500
LPKLKGFPSR YIYEPWNAPE SVQKAAKCII GVDYPRPIVN HAETSRLNIE
510 520 530 540 550
RMKQIYQQLS RYRGLCLLAS VPSCVEDLSH PVAEPGSSQA GSISNTGPRA
560 570 580 590
LSSGPASPKR KLEAAEEPPG EELTKRARVT EMPTQEPASK DS
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

MaxQBi Q9R194.
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

Bgeei Q9R194.
CleanExi MM_CRY2.
ExpressionAtlasi Q9R194. baseline and differential.
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

« Hide 'large scale' publications
  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 polycomb group protein EZH2 is required for mammalian circadian clock function."
    Etchegaray J.P., Yang X., DeBruyne J.P., Peters A.H., Weaver D.R., Jenuwein T., Reppert S.M.
    J. Biol. Chem. 281:21209-21215(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH CLOCK AND ARNTL.
  13. "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.
  14. "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.
  15. "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.
  16. "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.
  17. Cited for: FUNCTION.
  18. "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.
  19. "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.
  20. "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.
  21. "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.
  22. "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.
  23. "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.
  24. "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.
  25. "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.
  26. "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.
  27. "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.
  28. "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.
  29. "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.
  30. Cited for: INTERACTION WITH CIART.
  31. "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.
  32. "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.
  33. "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 29, 2014
This is version 111 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