Reviewed, UniProtKB/Swiss-Prot P97784 (CRY1_MOUSE)

Names and origin

Protein names

Recommended name:
    Cryptochrome-1

Gene names

Name:

Cry1

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	606 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Blue light-dependent regulator of the circadian feedback loop. Inhibits CLOCK|NPAS2-ARNTL E box-mediated transcription. Acts, in conjunction with CRY2, in maintaining period length and circadian rhythmicity. Has no photolyase activity. Capable of translocating circadian clock core proteins such as PER proteins to the nucleus. May inhibit CLOCK|NPAS2-ARNTL transcriptional activity through stabilizing the unphosphorylated form of ARNTL. Ref.6 Ref.10 Ref.11
Cofactor	Binds 1 FAD per subunit 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 and the PER proteins. Interacts directly with PER1 and PER2 C-terminal domains. Interaction with PER2 inhibits its ubiquitination and vice versa. Binds MAPK. Ref.6 Ref.11 Ref.8 Ref.9
Subcellular location	Cytoplasm. Nucleus. Note: Transloctaed to the nucleus through interaction with other Clock proteins such as PER2 or ARNTL. Ref.6 Ref.10 Ref.11 Ref.8 Ref.1
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.6 Ref.1 Ref.5 Ref.7
Induction	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.6 Ref.5 Ref.7
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.
Sequence similarities	Belongs to the DNA photolyase class-1 family. Contains 1 DNA photolyase domain.

Ontologies

Keywords
Biological process	Biological rhythms Sensory transduction Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Ligand	Chromophore FAD Flavoprotein Nucleotide-binding
Molecular function	Photoreceptor protein Receptor Repressor
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	DNA repair Inferred from electronic annotation. Source: InterPro circadian rhythm Inferred from direct assay. Source: MGI protein-chromophore linkage Inferred from electronic annotation. Source: UniProtKB-KW regulation of transcription Inferred from electronic annotation. Source: UniProtKB-KW transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	mitochondrion Inferred from direct assay. Source: MGI nucleus Inferred from direct assay. Source: MGI
Molecular function	DNA photolyase activity Inferred from electronic annotation. Source: InterPro nucleotide binding Inferred from electronic annotation. Source: UniProtKB-KW photoreceptor activity Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Arntl	Q9WTL8	3	EBI-1266607,EBI-644534
Fbxl3	Q8C4V4	1	EBI-1266607,EBI-1266589

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 606	606	Cryptochrome-1		PRO_0000261142
Regions
	Domain	3 – 178	176	DNA photolyase
	Region	211 – 488	278	FAD-binding
	Region	371 – 470	100	Required for inhibition of CLOCK-ARNTL-mediated transcription
Amino acid modifications
	Modified residue	247	1	Phosphoserine; by MAPK Ref.9
	Modified residue	432	1	Phosphotyrosine By similarity
Experimental info
	Mutagenesis	247	1	S → A: Reduced MAPK-catalyzed in vitro phosphorylation. No effect on inhibition of CLOCK-ARNTL-mediated transcriptional activity. Ref.9
	Mutagenesis	247	1	S → D: Reduced inhibition of CLOCK-ARNTL-mediated transcriptional activity. Ref.9

Sequences

	Sequence		Length	Mass (Da)
	P97784-1 [UniParc]. Last modified May 1, 1997. Version 1. Checksum: 2F2B8DD53F0A9AF9	FASTA	606	68,001
	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

References

	« Hide 'large scale' referencesShow '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: 9801304] [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: 16141072] [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: 15489334] [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: 9600923] [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: 10428031] [Abstract] Cited for: INTERACTION WITH PER1; PER2; PER3 AND TIMELESS, FUNCTION, 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: 10521578] [Abstract] Cited for: TISSUE SPECIFICITY, INDUCTION.
[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: 11875063] [Abstract] Cited for: INTERACTION WITH PER1 AND PER2, PHOSPHORYLATION, SUBCELLULAR LOCATION.
[9]	"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: 15298678] [Abstract] Cited for: INTERACTION WITH MAPK, PHOSPHORYLATION AT SER-247, MUTAGENESIS OF SER-247.
[10]	"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: 16628007] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[11]	"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: 16478995] [Abstract] Cited for: FUNCTION, INTERACTION WITH PER1 AND PER2, SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	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.
IPI	IPI00129123.
RefSeq	NP_031797.1.
UniGene	Mm.26237
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	P97784. 4 interactions.
STRING	P97784.
PTM databases
PhosphoSite	P97784.
Proteomic databases
PRIDE	P97784.
Genome annotation databases
Ensembl	ENSMUST00000020227; ENSMUSP00000020227; ENSMUSG00000020038; Mus musculus. [Genome view]
GeneID	12952.
KEGG	mmu:12952.
UCSC	uc007gle.1. mouse.
Organism-specific databases
CTD	12952.
MGI	MGI:1270841. Cry1.
Phylogenomic databases
HOGENOM	HBG693486.
HOVERGEN	P97784.
InParanoid	P97784.
OMA	QSVGPKV.
OrthoDB	EOG94J53P.
Gene expression databases
ArrayExpress	P97784.
Bgee	P97784.
CleanEx	MM_CRY1.
Genevestigator	P97784.
GermOnline	ENSMUSG00000020038. Mus musculus.
Family and domain databases
InterPro	IPR006050. DNA_photolyase_N. IPR005101. Photolyase_FAD-bd/Cryptochr_C. IPR014729. Rossmann-like_a/b/a_fold. [Graphical view]
Gene3D	G3DSA:3.40.50.620. Rossmann-like_a/b/a_fold. 1 hit.
Pfam	PF00875. DNA_photolyase. 1 hit. PF03441. FAD_binding_7. 1 hit. [Graphical view]
PROSITE	PS00394. DNA_PHOTOLYASES_1_1. False negative. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	282662.
SOURCE	Search...

Entry information

Entry name

CRY1_MOUSE

Accession

Primary (citable) accession number: P97784

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 28, 2006
Last sequence update:	May 1, 1997
Last modified:	December 15, 2009
This is version 77 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)