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P97784 (CRY1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 116. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cryptochrome-1
Gene names
Name:Cry1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length606 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. 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. Ref.6 Ref.12 Ref.13 Ref.14 Ref.17 Ref.22 Ref.23 Ref.25 Ref.26 Ref.29 Ref.30 Ref.31 Ref.33 Ref.34 Ref.35 Ref.37

Cofactor

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.

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

Subunit structure

Component of the circadian core oscillator, which includes the CRY proteins, CLOCK or NPAS2, ARNTL or ARNTL2, CSNK1D and/or CSNK1E, TIMELESS, and the PER proteins. Interacts directly with 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. Ref.6 Ref.8 Ref.9 Ref.11 Ref.12 Ref.14 Ref.16 Ref.18 Ref.19 Ref.21 Ref.24 Ref.25 Ref.27 Ref.28 Ref.29 Ref.35 Ref.37

Subcellular location

Cytoplasm. Nucleus. Note: Transloctaed to the nucleus through interaction with other Clock proteins such as PER2 or ARNTL. Ref.1 Ref.6 Ref.8 Ref.9 Ref.13 Ref.14 Ref.35

Tissue specificity

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). Ref.1 Ref.5 Ref.6 Ref.7 Ref.15

Induction

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. Ref.5 Ref.6 Ref.7 Ref.15 Ref.19 Ref.23

Post-translational modification

Phosphorylation on Ser-247 by MAPK is important for the inhibition of CLOCK-ARNTL-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.

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. Ref.8 Ref.16 Ref.18 Ref.27 Ref.28

Disruption phenotype

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. Ref.22 Ref.25 Ref.26 Ref.30 Ref.33

Sequence similarities

Belongs to the DNA photolyase class-1 family.

Contains 1 photolyase/cryptochrome alpha/beta domain.

Ontologies

Keywords
   Biological processBiological rhythms
Sensory transduction
Transcription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   LigandChromophore
FAD
Flavoprotein
Nucleotide-binding
   Molecular functionPhotoreceptor protein
Receptor
Repressor
   PTMIsopeptide bond
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA damage induced protein phosphorylation

Inferred from direct assay Ref.35. Source: UniProtKB

DNA repair

Inferred from electronic annotation. Source: InterPro

circadian regulation of gene expression

Inferred from mutant phenotype Ref.30Ref.33. Source: UniProtKB

circadian rhythm

Inferred from direct assay PubMed 12843397. Source: MGI

gluconeogenesis

Inferred from mutant phenotype Ref.22. Source: UniProtKB

glucose homeostasis

Inferred from genetic interaction Ref.25. Source: UniProtKB

lipid storage

Inferred from genetic interaction Ref.26. Source: UniProtKB

negative regulation of G-protein coupled receptor protein signaling pathway

Inferred from mutant phenotype Ref.22. Source: UniProtKB

negative regulation of circadian rhythm

Inferred from direct assay PubMed 19605937. Source: UniProtKB

negative regulation of glucocorticoid receptor signaling pathway

Inferred from direct assay Ref.34. Source: UniProtKB

negative regulation of glucocorticoid secretion

Inferred from genetic interaction Ref.26. Source: UniProtKB

negative regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype Ref.22. Source: UniProtKB

negative regulation of transcription, DNA-templated

Inferred from direct assay PubMed 12738229Ref.17PubMed 18316400PubMed 19605937Ref.33. Source: UniProtKB

positive regulation of transcription, DNA-templated

Inferred from direct assay. Source: UniProtKB

protein-chromophore linkage

Inferred from electronic annotation. Source: UniProtKB-KW

regulation of DNA damage checkpoint

Inferred from direct assay Ref.35. Source: UniProtKB

regulation of circadian rhythm

Inferred from mutant phenotype PubMed 10217146Ref.20Ref.23Ref.31Ref.30. Source: UniProtKB

response to glucagon

Inferred from mutant phenotype Ref.22. Source: UniProtKB

response to insulin

Inferred from genetic interaction Ref.26. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

mitochondrion

Inferred from direct assay Ref.1. Source: UniProtKB

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay Ref.35. Source: UniProtKB

   Molecular_functionDNA photolyase activity

Inferred from electronic annotation. Source: InterPro

core promoter binding

Inferred from direct assay Ref.33. Source: UniProtKB

double-stranded DNA binding

Inferred from direct assay Ref.1. Source: UniProtKB

histone deacetylase binding

Inferred from physical interaction Ref.12. Source: UniProtKB

kinase binding

Inferred from physical interaction Ref.29. Source: UniProtKB

nuclear hormone receptor binding

Inferred from physical interaction Ref.25. Source: UniProtKB

nucleotide binding

Inferred from electronic annotation. Source: UniProtKB-KW

photoreceptor activity

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction Ref.8Ref.11Ref.12Ref.16Ref.21Ref.24Ref.27Ref.28PubMed 24413057Ref.35. Source: UniProtKB

protein kinase binding

Inferred from physical interaction Ref.20. Source: UniProtKB

transcription factor binding

Inferred from physical interaction Ref.24. Source: UniProtKB

transcription factor binding transcription factor activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 606606Cryptochrome-1
PRO_0000261142

Regions

Domain3 – 132130Photolyase/cryptochrome alpha/beta
Nucleotide binding387 – 3893FAD By similarity
Region371 – 470100Required for inhibition of CLOCK-ARNTL-mediated transcription

Sites

Binding site2521FAD; via amide nitrogen By similarity
Binding site2891FAD By similarity
Binding site3551FAD By similarity

Amino acid modifications

Modified residue711Phosphoserine; by AMPK Ref.20
Modified residue2471Phosphoserine; by MAPK Ref.10
Modified residue2801Phosphoserine; by AMPK Ref.20
Modified residue5881Phosphoserine Ref.29
Cross-link11Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Probable
Cross-link107Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.28
Cross-link159Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.28
Cross-link329Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.28
Cross-link485Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.28

Experimental info

Mutagenesis711S → A: Phosphomimetic mutant that leads to stabilization of the protein; when associated with A-280. Ref.20
Mutagenesis711S → D: Phosphomimetic mutant that leads to destabilization of the protein and abolishes ability to bind PER2; when associated with D-280. Ref.20
Mutagenesis1071K → R: Sensitive to FBXL3-ediated degradation but noz affected by expression of FBXL21. Ref.28
Mutagenesis2241H → E: Reduces affinity for FBXL3. Ref.37
Mutagenesis2471S → A: Reduced MAPK-catalyzed in vitro phosphorylation. No effect on inhibition of CLOCK-ARNTL-mediated transcriptional activity. Ref.10 Ref.37
Mutagenesis2471S → D: Reduced inhibition of CLOCK-ARNTL-mediated transcriptional activity. Ref.10 Ref.37
Mutagenesis2801S → A: Phosphomimetic mutant that leads to stabilization of the protein; when associated with A-71. Ref.20
Mutagenesis2801S → D: Phosphomimetic mutant that leads to destabilization of the protein and abolishes ability to bind PER2; when associated with D-71. Ref.20
Mutagenesis3361G → D: Abolishes transcriptional repression of target genes. Abolishes interaction with PER2.
Mutagenesis382 – 3832EE → RR: Decreases transcriptional repression of target genes. Decreases FBXL3 binding. Increases PER2 binding.
Mutagenesis4051F → A: Decreases affinity for FBXL3. Slightly increases affinity for PER2. Ref.37
Mutagenesis4851K → D or E: Strongly reduces FBXL3 binding. Reduces PER2 binding. Ref.37
Mutagenesis5511S → A: No effect on circadian period length and protein stability. Ref.29
Mutagenesis5511S → D: No effect on circadian period length and protein stability. Ref.29
Mutagenesis5641S → A: No effect on circadian period length and protein stability. Ref.29
Mutagenesis5641S → D: No effect on circadian period length and protein stability. Ref.29
Mutagenesis5881S → A: No effect on circadian period length and protein stability. Ref.29
Mutagenesis5881S → D: Lengthen circadian period. No effect on repressive activity. Increases protein stability. Ref.29

Secondary structure

...................................................................... 606
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P97784 [UniParc].

Last modified May 1, 1997. Version 1.
Checksum: 2F2B8DD53F0A9AF9

FASTA60668,001
        10         20         30         40         50         60 
MGVNAVHWFR KGLRLHDNPA LKECIQGADT IRCVYILDPW FAGSSNVGIN RWRFLLQCLE 

        70         80         90        100        110        120 
DLDANLRKLN SRLFVIRGQP ADVFPRLFKE WNITKLSIEY DSEPFGKERD AAIKKLATEA 

       130        140        150        160        170        180 
GVEVIVRISH TLYDLDKIIE LNGGQPPLTY KRFQTLVSKM EPLEMPADTI TSDVIGKCMT 

       190        200        210        220        230        240 
PLSDDHDEKY GVPSLEELGF DTDGLSSAVW PGGETEALTR LERHLERKAW VANFERPRMN 

       250        260        270        280        290        300 
ANSLLASPTG LSPYLRFGCL SCRLFYFKLT DLYKKVKKNS SPPLSLYGQL LWREFFYTAA 

       310        320        330        340        350        360 
TNNPRFDKME GNPICVQIPW DKNPEALAKW AEGRTGFPWI DAIMTQLRQE GWIHHLARHA 

       370        380        390        400        410        420 
VACFLTRGDL WISWEEGMKV FEELLLDADW SINAGSWMWL SCSSFFQQFF HCYCPVGFGR 

       430        440        450        460        470        480 
RTDPNGDYIR RYLPVLRGFP AKYIYDPWNA PEGIQKVAKC LIGVNYPKPM VNHAEASRLN 

       490        500        510        520        530        540 
IERMKQIYQQ LSRYRGLGLL ASVPSNSNGN GGLMGYAPGE NVPSCSSSGN GGLMGYAPGE 

       550        560        570        580        590        600 
NVPSCSGGNC SQGSGILHYA HGDSQQTHSL KQGRSSAGTG LSSGKRPSQE EDAQSVGPKV 


QRQSSN 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"AMPK regulates the circadian clock by cryptochrome phosphorylation and degradation."
Lamia K.A., Sachdeva U.M., DiTacchio L., Williams E.C., Alvarez J.G., Egan D.F., Vasquez D.S., Juguilon H., Panda S., Shaw R.J., Thompson C.B., Evans R.M.
Science 326:437-440(2009) [PubMed] [Europe PMC] [Abstract]
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]"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.
[26]"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.
[27]"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.
[28]"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.
[29]"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 CYRCADIAN CLOCK, INTERACTION WITH PRKDC, PHOSPHORYLATION AT SER-588, MUTAGENESIS OF SER-551; SER-564 AND SER-588.
[30]"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.
[31]"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.
[32]"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.
[33]"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.
[34]"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.
[35]"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.
[36]"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.
[37]"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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS24089.1.
RefSeqNP_031797.1. NM_007771.3.
UniGeneMm.26237.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4K0RX-ray2.65A1-606[»]
ProteinModelPortalP97784.
SMRP97784. Positions 3-489.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid198906. 19 interactions.
DIPDIP-38515N.
IntActP97784. 18 interactions.
MINTMINT-4084985.
STRING10090.ENSMUSP00000020227.

PTM databases

PhosphoSiteP97784.

Proteomic databases

PaxDbP97784.
PRIDEP97784.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000020227; ENSMUSP00000020227; ENSMUSG00000020038.
GeneID12952.
KEGGmmu:12952.
UCSCuc007gle.1. mouse.

Organism-specific databases

CTD1407.
MGIMGI:1270841. Cry1.

Phylogenomic databases

eggNOGCOG0415.
GeneTreeENSGT00500000044813.
HOGENOMHOG000245622.
HOVERGENHBG053470.
InParanoidP97784.
KOK02295.
OMAFDTDGLP.
OrthoDBEOG7QG43M.
PhylomeDBP97784.
TreeFamTF323191.

Enzyme and pathway databases

ReactomeREACT_200794. Mus musculus biological processes.

Gene expression databases

BgeeP97784.
CleanExMM_CRY1.
GenevestigatorP97784.

Family and domain databases

Gene3D3.40.50.620. 1 hit.
InterProIPR006050. DNA_photolyase_N.
IPR005101. Photolyase_FAD-bd/Cryptochr_C.
IPR014729. Rossmann-like_a/b/a_fold.
[Graphical view]
PfamPF00875. DNA_photolyase. 1 hit.
PF03441. FAD_binding_7. 1 hit.
[Graphical view]
SUPFAMSSF48173. SSF48173. 1 hit.
SSF52425. SSF52425. 1 hit.
PROSITEPS51645. PHR_CRY_ALPHA_BETA. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio282662.
PROP97784.
SOURCESearch...

Entry information

Entry nameCRY1_MOUSE
AccessionPrimary (citable) accession number: P97784
Entry history
Integrated into UniProtKB/Swiss-Prot: November 28, 2006
Last sequence update: May 1, 1997
Last modified: July 9, 2014
This is version 116 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot