Q16526 (CRY1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cryptochrome-1

Gene names

Name:	CRY1
Synonyms:	PHLL1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	586 AA.
Sequence status	Complete.
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 By similarity. Ref.5
Cofactor	Binds 1 FAD per subunit. 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. 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) complex leading to degradation. Ref.7
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 Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	DNA repair Inferred from electronic annotation. Source: InterPro negative regulation of transcription from RNA polymerase II promoter Inferred from direct assay. Source: BHF-UCL protein-chromophore linkage Inferred from electronic annotation. Source: UniProtKB-KW regulation of circadian rhythm Inferred from sequence or structural similarity. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	DNA photolyase activity Inferred from electronic annotation. Source: InterPro blue light photoreceptor activity Non-traceable author statement Ref.1. Source: UniProtKB double-stranded DNA binding Inferred from direct assay. Source: UniProtKB nucleotide binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction Ref.7. Source: UniProtKB protein binding transcription factor activity Inferred from direct assay. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 586	586	Cryptochrome-1		PRO_0000261140
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 By similarity
Amino acid modifications
	Modified residue	71	1	Phosphoserine; by AMPK By similarity
	Modified residue	247	1	Phosphoserine; by MAPK By similarity
	Modified residue	280	1	Phosphoserine; by AMPK By similarity
	Modified residue	432	1	Phosphotyrosine Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Q16526 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 96A5B09A6364D3B9	FASTA	586	66,395
	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

References

	« Hide 'large scale' referencesShow '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: 8909283] [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: 8921389] [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: 8600518] [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: 15489334] [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: 10531061] [Abstract] Cited for: FUNCTION.
[6]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-432, MASS SPECTROMETRY. Tissue: Lung carcinoma.
[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: 17463251] [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.
IPI	IPI00002540.
RefSeq	NP_004066.1. NM_004075.3.
UniGene	Hs.151573.
3D structure databases
ProteinModelPortal	Q16526.
SMR	Q16526. Positions 2-494.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q16526. 11 interactions.
MINT	MINT-1437226.
STRING	Q16526.
PTM databases
PhosphoSite	Q16526.
Polymorphism databases
DMDM	74735764.
Proteomic databases
PRIDE	Q16526.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000008527; ENSP00000008527; ENSG00000008405.
GeneID	1407.
KEGG	hsa:1407.
UCSC	uc001tmi.2. human.
Organism-specific databases
CTD	1407.
GeneCards	GC12M107385.
H-InvDB	HIX0010959.
HGNC	HGNC:2384. CRY1.
HPA	CAB018762.
MIM	601933. gene.
neXtProt	NX_Q16526.
GenAtlas	Search...
Phylogenomic databases
GeneTree	ENSGT00500000044813.
HOGENOM	HBG693486.
HOVERGEN	HBG053470.
InParanoid	Q16526.
OMA	FDTDGLP.
OrthoDB	EOG4DBTDC.
PhylomeDB	Q16526.
Enzyme and pathway databases
Reactome	REACT_24941. Circadian Clock.
Gene expression databases
ArrayExpress	Q16526.
Bgee	Q16526.
CleanEx	HS_CRY1.
Genevestigator	Q16526.
GermOnline	ENSG00000008405. Homo sapiens.
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.
KO	K02295.
Pfam	PF00875. DNA_photolyase. 1 hit. PF03441. FAD_binding_7. 1 hit. [Graphical view]
SUPFAM	SSF52425. DNA_photolyase_N. 1 hit. SSF48173. Photolyase_FAD-bd/Cryptochr_C. 1 hit.
PROSITE	PS00394. DNA_PHOTOLYASES_1_1. False negative. [Graphical view]
ProtoNet	Search...
Other
NextBio	5753.
SOURCE	Search...

Entry information

Entry name

CRY1_HUMAN

Accession

Primary (citable) accession number: Q16526

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 28, 2006
Last sequence update:	November 1, 1996
Last modified:	January 25, 2012
This is version 86 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.