Reviewed, UniProtKB/Swiss-Prot Q49AN0 (CRY2_HUMAN)

Names and origin

Protein names

Recommended name:
    Cryptochrome-2

Gene names

Name:	CRY2
Synonyms:	KIAA0658

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	593 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.5
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 PER1 and PER2 C-terminal domains. Interaction with PER2 inhibits its ubiquitination and vice versa. Interacts with NFIL3 By similarity.
Subcellular location	Cytoplasm. Nucleus. Note: Translocated to the nucleus through interaction with other Clock proteins such as PER2 or ARNTL. Ref.4
Tissue specificity	Expressed in all tissues examined including fetal brain, fibroblasts, heart, brain, placenta, lung, liver, sketal muscle, kidney, pancreas, spleen, thymus, prostate, testis, ovary, small intestine, colon and leukocytes. Highest levels in heart and skeletal muscle. Ref.4 Ref.1
Post-translational modification	Phosphorylation on Ser-266 by MAPK is important for the inhibition of CLOCK-ARNTL-mediated transcriptional activity. Phosphorylation by CSKNE 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 protein-chromophore linkage Inferred from electronic annotation. Source: UniProtKB-KW regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
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
TIMELESS	Q9UNS1	1	EBI-2212355,EBI-2212315

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 593	593	Cryptochrome-2		PRO_0000261148
Regions
	Domain	22 – 189	168	DNA photolyase
	Region	230 – 507	278	FAD-binding
	Region	390 – 489	100	Required for inhibition of CLOCK-ARNTL-mediated transcription By similarity
Amino acid modifications
	Modified residue	266	1	Phosphoserine; by MAPK By similarity
	Modified residue	558	1	Phosphoserine; by MAPK By similarity
Experimental info
	Sequence conflict	422	1	S → G in AAH35161. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q49AN0-1 [UniParc]. Last modified November 28, 2006. Version 2. Checksum: BF380424092BEBFB	FASTA	593	66,947
	10 20 30 40 50 60 MAATVATAAA VAPAPAPGTD SASSVHWFRK GLRLHDNPAL LAAVRGARCV RCVYILDPWF 70 80 90 100 110 120 AASSSVGINR WRFLLQSLED LDTSLRKLNS RLFVVRGQPA DVFPRLFKEW GVTRLTFEYD 130 140 150 160 170 180 SEPFGKERDA AIMKMAKEAG VEVVTENSHT LYDLDRIIEL NGQKPPLTYK RFQAIISRME 190 200 210 220 230 240 LPKKPVGLVT SQQMESCRAE IQENHDETYG VPSLEELGFP TEGLGPAVWQ GGETEALARL 250 260 270 280 290 300 DKHLERKAWV ANYERPRMNA NSLLASPTGL SPYLRFGCLS CRLFYYRLWD LYKKVKRNST 310 320 330 340 350 360 PPLSLFGQLL WREFFYTAAT NNPRFDRMEG NPICIQIPWD RNPEALAKWA EGKTGFPWID 370 380 390 400 410 420 AIMTQLRQEG WIHHLARHAV ACFLTRGDLW VSWESGVRVF DELLLDADFS VNAGSWMWLS 430 440 450 460 470 480 CSAFFQQFFH CYCPVGFGRR TDPSGDYIRR YLPKLKAFPS RYIYEPWNAP ESIQKAAKCI 490 500 510 520 530 540 IGVDYPRPIV NHAETSRLNI ERMKQIYQQL SRYRGLCLLA SVPSCVEDLS HPVAEPSSSQ 550 560 570 580 590 AGSMSSAGPR PLPSGPASPK RKLEAAEEPP GEELSKRARV AELPTPELPS KDA

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 SPECIFICITY. Tissue: Fetal brain.
[2]	"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: Testis.
[3]	"Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro." Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 5:169-176(1998) [PubMed: 9734811] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 5-593. Tissue: Brain.
[4]	"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: TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[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.
+	Additional computationally mapped references.

Web resources

Wikipedia

Cryptochrome entry

Cross-references

Sequence databases
EMBLGenBankDDBJ	BC035161 mRNA. Translation: AAH35161.1. Different initiation. BC041814 mRNA. Translation: AAH41814.1. AB014558 mRNA. Translation: BAA31633.1.
IPI	IPI00216898.
RefSeq	NP_001120929.1. NP_066940.2.
UniGene	Hs.532491
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q49AN0. 1 interaction.
Proteomic databases
PRIDE	Q49AN0.
Genome annotation databases
Ensembl	ENSG00000121671. Homo sapiens. [Contig view]
GeneID	1408.
KEGG	hsa:1408.
NMPDR	fig|9606.3.peg.5504.
Organism-specific databases
GeneCards	GC11P045825.
HGNC	HGNC:2385. CRY2.
MIM	603732. gene.
PharmGKB	PA26905.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q49AN0.
OMA	Q49AN0. AKWAEGK.
Gene expression databases
ArrayExpress	Q49AN0.
Bgee	Q49AN0.
CleanEx	HS_CRY2.
GermOnline	ENSG00000121671. Homo sapiens.
Family and domain databases
InterPro	IPR018394. DNA_photolyase_1_CS_C. IPR006050. DNA_photolyase_N. IPR005101. Photolyase_FAD-bd/Cryptochr_C. [Graphical view]
Pfam	PF00875. DNA_photolyase. 1 hit. PF03441. FAD_binding_7. 1 hit. [Graphical view]
ProDom	PD004390. FAD_binding_N. 1 hit. [Graphical view] [Entries sharing at least one domain]
PROSITE	PS00394. DNA_PHOTOLYASES_1_1. False negative. [Graphical view]
ProtoNet	Search...
Other Resources
SOURCE	Search...

Entry information

Entry name

CRY2_HUMAN

Accession

Primary (citable) accession number: Q49AN0
Secondary accession number(s): O75148, Q8IV71

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 28, 2006
Last sequence update:	November 28, 2006
Last modified:	June 16, 2009
This is version 34 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)