Human Gene CRY2 (ENST00000417225.6) from GENCODE V38
  Description: Homo sapiens cryptochrome circadian regulator 2 (CRY2), transcript variant 2, mRNA. (from RefSeq NM_001127457)
RefSeq Summary (NM_001127457): This gene encodes a flavin adenine dinucleotide-binding protein that is a key component of the circadian core oscillator complex, which regulates the circadian clock. This gene is upregulated by CLOCK/ARNTL heterodimers but then represses this upregulation in a feedback loop using PER/CRY heterodimers to interact with CLOCK/ARNTL. Polymorphisms in this gene have been associated with altered sleep patterns. The encoded protein is widely conserved across plants and animals. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2014].
Gencode Transcript: ENST00000417225.6
Gencode Gene: ENSG00000121671.12
Transcript (Including UTRs)
   Position: hg38 chr11:45,847,118-45,881,233 Size: 34,116 Total Exon Count: 12 Strand: +
Coding Region
   Position: hg38 chr11:45,847,250-45,872,231 Size: 24,982 Coding Exon Count: 11 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated at UCSC: 2021-09-27 09:51:20

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr11:45,847,118-45,881,233)mRNA (may differ from genome)Protein (532 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsHGNC

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Cryptochrome-2;
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.
COFACTOR: Binds 1 FAD per subunit (By similarity).
COFACTOR: Binds 1 5,10-methenyltetrahydrofolate non-covalently per subunit (By similarity).
SUBUNIT: 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. Interacts with FBXL3.
SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Translocated to the nucleus through interaction with other Clock proteins such as PER2 or ARNTL.
TISSUE SPECIFICITY: Expressed in all tissues examined including fetal brain, fibroblasts, heart, brain, placenta, lung, liver, skeletal muscle, kidney, pancreas, spleen, thymus, prostate, testis, ovary, small intestine, colon and leukocytes. Highest levels in heart and skeletal muscle.
PTM: 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.
PTM: Ubiquitinated by the SCF(FBXL3) and SCF(FBXL21) complex, leading to its degradation.
SIMILARITY: Belongs to the DNA photolyase class-1 family.
SIMILARITY: Contains 1 photolyase/cryptochrome alpha/beta domain.
SEQUENCE CAUTION: Sequence=AAH35161.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact. Aberrant splice sites; Sequence=BAG57993.1; Type=Erroneous termination; Positions=110; Note=Translated as Trp; Sequence=BAG57993.1; Type=Erroneous translation; Note=Wrong choice of CDS;
WEB RESOURCE: Name=Wikipedia; Note=Cryptochrome entry; URL="";

-  MalaCards Disease Associations
  MalaCards Gene Search: CRY2
Diseases sorted by gene-association score: western equine encephalitis (6), dysthymic disorder (5), major depressive disorder and accelerated response to antidepressant drug treatment (4)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 41.81 RPKM in Brain - Cerebellum
Total median expression: 1043.61 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -46.20132-0.350 Picture PostScript Text
3' UTR -114.40322-0.355 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR006050 - DNA_photolyase_N
IPR005101 - Photolyase_FAD-bd/Cryptochr_C
IPR014729 - Rossmann-like_a/b/a_fold

Pfam Domains:
PF00875 - DNA photolyase
PF03441 - FAD binding domain of DNA photolyase

ModBase Predicted Comparative 3D Structure on Q49AN0
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
Protein SequenceProtein Sequence    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0000976 transcription regulatory region sequence-specific DNA binding
GO:0000989 transcription factor activity, transcription factor binding
GO:0003677 DNA binding
GO:0003684 damaged DNA binding
GO:0003697 single-stranded DNA binding
GO:0005515 protein binding
GO:0009881 photoreceptor activity
GO:0009882 blue light photoreceptor activity
GO:0019902 phosphatase binding
GO:0071949 FAD binding
GO:0003904 deoxyribodipyrimidine photo-lyase activity
GO:0003914 DNA (6-4) photolyase activity

Biological Process:
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0007623 circadian rhythm
GO:0009416 response to light stimulus
GO:0009785 blue light signaling pathway
GO:0018298 protein-chromophore linkage
GO:0032515 negative regulation of phosphoprotein phosphatase activity
GO:0032922 circadian regulation of gene expression
GO:0042593 glucose homeostasis
GO:0042752 regulation of circadian rhythm
GO:0042754 negative regulation of circadian rhythm
GO:0043153 entrainment of circadian clock by photoperiod
GO:0045892 negative regulation of transcription, DNA-templated
GO:0048511 rhythmic process
GO:0050896 response to stimulus
GO:2000118 regulation of sodium-dependent phosphate transport
GO:2000323 negative regulation of glucocorticoid receptor signaling pathway
GO:0000719 photoreactive repair

Cellular Component:
GO:0005576 extracellular region
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0016607 nuclear speck

-  Descriptions from all associated GenBank mRNAs
  BC035161 - Homo sapiens cryptochrome 2 (photolyase-like), mRNA (cDNA clone MGC:43304 IMAGE:5265444), complete cds.
AK294904 - Homo sapiens cDNA FLJ53787 complete cds, highly similar to Homo sapiens cryptochrome 2 (photolyase-like) (CRY2), mRNA.
AK302865 - Homo sapiens cDNA FLJ54895 complete cds, highly similar to Homo sapiens cryptochrome 2 (photolyase-like) (CRY2), mRNA.
LF205782 - JP 2014500723-A/13285: Polycomb-Associated Non-Coding RNAs.
MA441359 - JP 2018138019-A/13285: Polycomb-Associated Non-Coding RNAs.
AK291260 - Homo sapiens cDNA FLJ75050 complete cds, highly similar to Homo sapiens cryptochrome 2 (photolyase-like) (CRY2), mRNA.
BC041814 - Homo sapiens cryptochrome 2 (photolyase-like), mRNA (cDNA clone MGC:43402 IMAGE:5266781), complete cds.
EU219622 - Homo sapiens growth-inhibiting protein 37 mRNA, complete cds.
AB014558 - Homo sapiens mRNA for KIAA0658 protein, partial cds.
LF205783 - JP 2014500723-A/13286: Polycomb-Associated Non-Coding RNAs.
MA441360 - JP 2018138019-A/13286: Polycomb-Associated Non-Coding RNAs.
AK295627 - Homo sapiens cDNA FLJ52645 complete cds, highly similar to Homo sapiens cryptochrome 2 (photolyase-like) (CRY2), mRNA.
AK001194 - Homo sapiens cDNA FLJ10332 fis, clone NT2RM2000636, highly similar to Homo sapiens mRNA for KIAA0658 protein.
CU692042 - Synthetic construct Homo sapiens gateway clone IMAGE:100021000 5' read CRY2 mRNA.
AB383943 - Synthetic construct DNA, clone: pF1KSDA0658, Homo sapiens CRY2 gene for cryptochrome-2, complete cds, without stop codon, in Flexi system.
JF432374 - Synthetic construct Homo sapiens clone IMAGE:100073571 cryptochrome 2 (photolyase-like) (CRY2) gene, encodes complete protein.
KJ901358 - Synthetic construct Homo sapiens clone ccsbBroadEn_10752 CRY2 gene, encodes complete protein.
LF348115 - JP 2014500723-A/155618: Polycomb-Associated Non-Coding RNAs.
MA583692 - JP 2018138019-A/155618: Polycomb-Associated Non-Coding RNAs.
JD100446 - Sequence 81470 from Patent EP1572962.
JD139187 - Sequence 120211 from Patent EP1572962.
JD025873 - Sequence 6897 from Patent EP1572962.
JD323320 - Sequence 304344 from Patent EP1572962.
JD361368 - Sequence 342392 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04710 - Circadian rhythm - mammal

BioCarta from NCI Cancer Genome Anatomy Project
h_circadianPathway - Circadian Rhythms

Reactome (by CSHL, EBI, and GO)

Protein Q49AN0 (Reactome details) participates in the following event(s):

R-HSA-549355 CRY proteins stabilize unphosphorylated BMAL1:CLOCK,NPAS2
R-HSA-400272 FBXL3 binds phosphorylated CRY proteins
R-HSA-400382 CSNK1E,CSNK1D phosphorylate CRY and PER proteins
R-HSA-400256 CRY:PER heterodimer binds the BMAL1:CLOCK/NPAS2 heterodimer
R-HSA-400253 Circadian Clock

-  Other Names for This Gene
  Alternate Gene Symbols: B4DH32, CRY2_HUMAN, ENST00000417225.1, ENST00000417225.2, ENST00000417225.3, ENST00000417225.4, ENST00000417225.5, KIAA0658, NM_001127457, O75148, Q49AN0, Q8IV71, uc009ykw.1, uc009ykw.2, uc009ykw.3, uc009ykw.4
UCSC ID: ENST00000417225.6
RefSeq Accession: NM_001127457
Protein: Q49AN0 (aka CRY2_HUMAN)
CCDS: CCDS44576.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.