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Q16526 (CRY1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 106. 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·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cryptochrome-1
Gene names
Name:CRY1
Synonyms:PHLL1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length586 AA.
Sequence statusComplete.
Protein existenceEvidence 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.5

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.

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

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. Interacts with FBXL21 By similarity. Interacts with FBXL3. Interacts with PPP5C (via TPR repeats). Ref.6 Ref.7

Subcellular location

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

Induction

Expression is regulated by light and circadian rhythms. Peak expression in the suprachiasma nucleus (SCN) and eye at the day/night transition (CT12). Levels decrease with ARNTL-CLOCK inhibition as part of the autoregulatory feedback loop.

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 destabilizes it By similarity.

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 Probable. Ref.7

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 termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA repair

Inferred from electronic annotation. Source: InterPro

blue light signaling pathway

Non-traceable author statement Ref.1. Source: UniProtKB

circadian regulation of gene expression

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 12397359PubMed 14672706PubMed 15147242. Source: BHF-UCL

negative regulation of transcription, DNA-templated

Inferred from sequence or structural similarity. Source: UniProtKB

protein-chromophore linkage

Inferred from electronic annotation. Source: UniProtKB-KW

regulation of circadian rhythm

Inferred from sequence or structural similarity. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Inferred from direct assay. Source: HPA

mitochondrion

Inferred from electronic annotation. Source: Ensembl

nucleolus

Inferred from direct assay. Source: HPA

   Molecular_functionDNA binding

Traceable author statement PubMed 9801304. Source: ProtInc

DNA photolyase activity

Inferred from electronic annotation. Source: InterPro

blue light photoreceptor activity

Non-traceable author statement Ref.1. Source: UniProtKB

core promoter binding

Inferred from sequence or structural similarity. Source: UniProtKB

double-stranded DNA binding

Inferred from direct assay PubMed 9801304. Source: UniProtKB

nucleotide binding

Inferred from electronic annotation. Source: UniProtKB-KW

phosphatase binding

Inferred from physical interaction PubMed 9383998. Source: UniProtKB

transcription factor binding transcription factor activity

Inferred from direct assay PubMed 15147242. Source: BHF-UCL

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 586586Cryptochrome-1
PRO_0000261140

Regions

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

Sites

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

Amino acid modifications

Modified residue711Phosphoserine; by AMPK By similarity
Modified residue2471Phosphoserine; by MAPK By similarity
Modified residue2801Phosphoserine; by AMPK By similarity
Cross-link11Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link107Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link159Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link329Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link485Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Sequences

Sequence LengthMass (Da)Tools
Q16526 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 96A5B09A6364D3B9

FASTA58666,395
        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 KRFQTLISKM EPLEIPVETI TSEVIEKCTT 

       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 ASVPSNPNGN GGFMGYSAEN IPGCSSSGSC SQGSGILHYA 

       550        560        570        580 
HGDSQQTHLL KQGRSSMGTG LSGGKRPSQE EDTQSIGPKV QRQSTN 

« Hide

References

« Hide 'large scale' references
[1]"Putative human blue-light photoreceptors hCRY1 and hCRY2 are flavoproteins."
Hsu D.S., Zhao X., Zhao S., Kazantsev A., Wang R.-P., Todo T., Wei Y.-F., Sancar A.
Biochemistry 35:13871-13877(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION.
Tissue: Fibroblast.
[2]"Cloning, tissue expression, and mapping of a human photolyase homolog with similarity to plant blue-light receptors."
van der Spek P.J., Kobayashi K., Bootsma D., Takao M., Eker A.P.M., Yasui A.
Genomics 37:177-182(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
Tissue: Testis.
[3]"Similarity among the Drosophila (6-4)photolyase, a human photolyase homolog, and the DNA photolyase-blue-light photoreceptor family."
Todo T., Ryo H., Yamamoto K., Toh H., Inui T., Ayaki H., Nomura T., Ikenaga M.
Science 272:109-112(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
Tissue: Brain.
[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].
Tissue: Brain.
[5]"Light-independent role of CRY1 and CRY2 in the mammalian circadian clock."
Griffin E.A. Jr., Staknis D., Weitz C.J.
Science 286:768-771(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[6]"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: INTERACTION WITH PPP5C.
[7]"SCFFbxl3 controls the oscillation of the circadian clock by directing the degradation of cryptochrome proteins."
Busino L., Bassermann F., Maiolica A., Lee C., Nolan P.M., Godinho S.I., Draetta G.F., Pagano M.
Science 316:900-904(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY, UBIQUITINATION BY FBXL3, INTERACTION WITH FBXL3.
+Additional computationally mapped references.

Web resources

Wikipedia

Cryptochrome entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D84657 mRNA. Translation: BAA12710.1.
D83702 mRNA. Translation: BAA12068.1.
BC030519 mRNA. Translation: AAH30519.1.
RefSeqNP_004066.1. NM_004075.4.
UniGeneHs.151573.

3D structure databases

ProteinModelPortalQ16526.
SMRQ16526. Positions 3-489.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107797. 25 interactions.
IntActQ16526. 12 interactions.
MINTMINT-1437226.
STRING9606.ENSP00000008527.

PTM databases

PhosphoSiteQ16526.

Polymorphism databases

DMDM74735764.

Proteomic databases

PaxDbQ16526.
PRIDEQ16526.

Protocols and materials databases

DNASU1407.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000008527; ENSP00000008527; ENSG00000008405.
GeneID1407.
KEGGhsa:1407.
UCSCuc001tmi.4. human.

Organism-specific databases

CTD1407.
GeneCardsGC12M107385.
HGNCHGNC:2384. CRY1.
HPACAB018762.
HPA047596.
MIM601933. gene.
neXtProtNX_Q16526.
PharmGKBPA26904.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0415.
HOGENOMHOG000245622.
HOVERGENHBG053470.
InParanoidQ16526.
KOK02295.
OMAFDTDGLP.
OrthoDBEOG7QG43M.
PhylomeDBQ16526.
TreeFamTF323191.

Enzyme and pathway databases

ReactomeREACT_24941. Circadian Clock.

Gene expression databases

ArrayExpressQ16526.
BgeeQ16526.
CleanExHS_CRY1.
GenevestigatorQ16526.

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

ChiTaRSCRY1. human.
GenomeRNAi1407.
NextBio5753.
PROQ16526.
SOURCESearch...

Entry information

Entry nameCRY1_HUMAN
AccessionPrimary (citable) accession number: Q16526
Entry history
Integrated into UniProtKB/Swiss-Prot: November 28, 2006
Last sequence update: November 1, 1996
Last modified: April 16, 2014
This is version 106 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM