CRY1 cryptochrome circadian regulator 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CRY1provided by HGNC
Official Full Name: cryptochrome circadian regulator 1provided by HGNC
Primary source: HGNC:HGNC:2384
See related: Ensembl:ENSG00000008405 MIM:601933
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: DSPD; PHLL1
Summary: 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. Loss of the related gene in mouse results in a shortened circadian cycle in complete darkness. [provided by RefSeq, Jan 2014]
Expression: Broad expression in testis (RPKM 23.5), thyroid (RPKM 10.6) and 25 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 12q23.3

Exon count:: 14

Annotation release	Status	Assembly	Chr	Location
109.20190905	current	GRCh38.p13 (GCF_000001405.39)	12	NC_000012.12 (106991364..107093872, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (107385142..107487635, complement)

Chromosome 12 - NC_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Bibliography

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

this study identified two distinct light chain 3 (LC3)-interacting region (LIR) motifs on CRY1 that exert circadian glycemic control by regulating CRY1 degradation, revealing LIRs as potential targets for controlling hyperglycemia.
Title: Autophagy Regulates the Liver Clock and Glucose Metabolism by Degrading CRY1.
In colorectal cancer, higher expression of cry1 in the right-sided colon tumor tissue was associated with worse survival in women and the expression of cry1 in the left-sided colorectum was significantly higher in the adjacent tissue compared to tumor in men but not in women
Title: The expression of clock genes cry1 and cry2 in human colorectal cancer and tumor adjacent tissues correlates differently dependent on tumor location.
Neuroglobin correlates with cryptochrome-1 in obstructive sleep apnea with primary aldosteronism
Title: Neuroglobin correlates with cryptochrome-1 in obstructive sleep apnea with primary aldosteronism.
CRY-1 was expressed in 94% of the CLL patients at diagnosis. The median CRY-1 relative gene expression level (0.006) stratified patients into high and low expression groups. Forty of 100 (40%) CLL patients showed high CRY-1, 54/100 (54%) showed low CRY-1, and 6/100 (6%) had undetectable CRY-1 gene expression.
Title: <i>Cryptochrome</i>-1 Gene Expression is a Reliable Prognostic Indicator in Egyptian Patients with Chronic Lymphocytic Leukemia: A Prospective Cohort Study
Independent silencing of CRY1 and CRY2 genes in HAC15 cells resulted in a mild upregulation of HSD3B2 without affecting HSD3B1 expression. In conclusion, our results support the hypothesis that CRY1 and CRY2, being AngII-regulated genes, and showing a differential expression in APAs when compared with the adjacent adrenal cortex, might be involved in adrenal cell function, and in the regulation of aldosterone production
Title: Role of Cryptochrome-1 and Cryptochrome-2 in Aldosterone-Producing Adenomas and Adrenocortical Cells.
The studies in this review reported contrasting results about the association of different single nucleotide polymorphisms (SNPs) in clock genes and Major Depressive Disorder. The most consistent result reported the association between SNP rs2287161 of CRY1 and MDD development.
Title: The role of clock genes in the etiology of Major Depressive Disorder: Special Section on "Translational and Neuroscience Studies in Affective Disorders". Section Editor, Maria Nobile MD, PhD. This Section of JAD focuses on the relevance of translational and neuroscience studies in providing a better understanding of the neural basis of affective disorders. The main aim is to briefly summaries relevant research findings in clinical neuroscience with particular regards to specific innovative topics in mood and anxiety disorders.
CRY1/2 serve as corepressors for many NRs.
Title: Circadian repressors CRY1 and CRY2 broadly interact with nuclear receptors and modulate transcriptional activity.
Study confirms the prognostic role of CRY1 in chronic lymphocytic leukemia, as its aberrant methylation and expression is associated with high risk of treatment initiation and survival.
Title: Genome-wide DNA methylation profiling integrated with gene expression profiling identifies <i>PAX9</i> as a novel prognostic marker in chronic lymphocytic leukemia.
CRY1 SNP rs714359 showed nominally significant association with the problematicity of seasonal variations (problematic vs. no variation) of mood disorder. The set-based analysis did not support these associations. However, the CRY1 haplotype TAG including rs714359 showed nominally significant association with the problematicity of seasonal variations in mood disorder.
Title: CRY1 and CRY2 genetic variants in seasonality: A longitudinal and cross-sectional study.
CRY1 variants were not associated with major depressive disorder.
Title: PRKCDBP (CAVIN3) and CRY2 associate with major depressive disorder.

Submit: New GeneRIF Correction See all GeneRIFs (51)

Phenotypes

Go to the top of the page Help

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Sleep-wake schedule disorder, delayed phase type MedGen: C3279991 OMIM: 614163 GeneReviews: Not available	Compare labs

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from BioSystems

Go to the top of the page Help

BMAL1:CLOCK,NPAS2 activates circadian gene expression, organism-specific biosystem (from REACTOME)
BMAL1:CLOCK,NPAS2 activates circadian gene expression, organism-specific biosystemAs inferred from mouse, BMAL1:CLOCK (ARNTL:CLOCK) and BMAL1:NPAS2 (ARNTL:NPAS2) heterodimers bind to sequence elements (E boxes) in the promoters of target genes and enhance transcription (Gekakis et...
Circadian Clock, organism-specific biosystem (from REACTOME)
Circadian Clock, organism-specific biosystemAt the center of the mammalian circadian clock is a negative transcription/translation-based feedback loop: The BMAL1:CLOCK/NPAS2 (ARNTL:CLOCK/NPAS2) heterodimer transactivates CRY and PER genes by b...
Circadian rhythm, organism-specific biosystem (from KEGG)
Circadian rhythm, organism-specific biosystemCircadian rhythm is an internal biological clock, which enables to sustain an approximately 24-hour rhythm in the absence of environmental cues. In mammals, the circadian clock mechanism consists of ...
Circadian rhythm, conserved biosystem (from KEGG)
Circadian rhythm, conserved biosystemCircadian rhythm is an internal biological clock, which enables to sustain an approximately 24-hour rhythm in the absence of environmental cues. In mammals, the circadian clock mechanism consists of ...
Circadian rythm related genes, organism-specific biosystem (from WikiPathways)
Circadian rythm related genes, organism-specific biosystemThis is currently not a pathway but a list of circadian rhythm related genes and proteins. The source for this information is the gene ontology. The genes and proteins were filtered for "circadian rh...
Diurnally Regulated Genes with Circadian Orthologs, organism-specific biosystem (from WikiPathways)
Diurnally Regulated Genes with Circadian Orthologs, organism-specific biosystemHuman genes regulated in the diurnal comparison with orthologues that display circadian regulation in mouse heart and liver (Panda 2002, Storch 2002), and SCN (Panda 2002). The 608 significantly regu...
Melatonin metabolism and effects, organism-specific biosystem (from WikiPathways)
Melatonin metabolism and effects, organism-specific biosystemMelatonin is an important regulator of circadian rythmus and influences also insulin secretion, immune function, retinal function and neuroprotection. The synthesis starts with the amino acid tryptop...

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

RH79737 (e-PCR)
- UniSTS:87879

RH93858 (e-PCR)
- UniSTS:85601

AB074458 (e-PCR)
- UniSTS:480113

CRY1_1267 (e-PCR)
- UniSTS:277130

G54218 (e-PCR)
- UniSTS:109485

Homology

Homologs of the CRY1 gene: The CRY1 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, mosquito, and frog.
Orthologs from Annotation Pipeline: 254 organisms have orthologs with human gene CRY1
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
NOT DNA (6-4) photolyase activity	IDA Inferred from Direct Assay more info	PubMed
DNA binding	TAS Traceable Author Statement more info	PubMed
E-box binding	IEA Inferred from Electronic Annotation more info
blue light photoreceptor activity	NAS Non-traceable Author Statement more info	PubMed
NOT deoxyribodipyrimidine photo-lyase activity	IDA Inferred from Direct Assay more info	PubMed
double-stranded DNA binding	IDA Inferred from Direct Assay more info	PubMed
histone deacetylase binding	IEA Inferred from Electronic Annotation more info
nuclear hormone receptor binding	IPI Inferred from Physical Interaction more info	PubMed
nucleotide binding	IEA Inferred from Electronic Annotation more info
phosphatase binding	IPI Inferred from Physical Interaction more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein kinase binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
DNA damage induced protein phosphorylation	ISS Inferred from Sequence or Structural Similarity more info
blue light signaling pathway	NAS Non-traceable Author Statement more info	PubMed
circadian regulation of gene expression	ISS Inferred from Sequence or Structural Similarity more info
circadian rhythm	ISS Inferred from Sequence or Structural Similarity more info
entrainment of circadian clock by photoperiod	ISS Inferred from Sequence or Structural Similarity more info
gluconeogenesis	ISS Inferred from Sequence or Structural Similarity more info
glucose homeostasis	ISS Inferred from Sequence or Structural Similarity more info
lipid storage	IEA Inferred from Electronic Annotation more info
negative regulation of G protein-coupled receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of circadian rhythm	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of glucocorticoid receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of glucocorticoid secretion	IEA Inferred from Electronic Annotation more info
negative regulation of gluconeogenesis	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of protein ubiquitination	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
negative regulation of transcription, DNA-templated	IDA Inferred from Direct Assay more info	PubMed
negative regulation of transcription, DNA-templated	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of protein ubiquitination	ISS Inferred from Sequence or Structural Similarity more info
protein-chromophore linkage	IEA Inferred from Electronic Annotation more info
regulation of DNA damage checkpoint	ISS Inferred from Sequence or Structural Similarity more info
regulation of circadian rhythm	ISS Inferred from Sequence or Structural Similarity more info
response to activity	ISS Inferred from Sequence or Structural Similarity more info
response to glucagon	ISS Inferred from Sequence or Structural Similarity more info
response to insulin	IEA Inferred from Electronic Annotation more info
response to light stimulus	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
mitochondrion	IEA Inferred from Electronic Annotation more info
nucleus	IDA Inferred from Direct Assay more info	PubMed
nucleus	ISS Inferred from Sequence or Structural Similarity more info

General protein information

Go to the top of the page Help

Preferred Names: cryptochrome-1

Names: cryptochrome 1 (photolyase-like); cryptochrome circadian clock 1

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_004075.5 → NP_004066.1 cryptochrome-1

See identical proteins and their annotated locations for NP_004066.1

Status: REVIEWED

Source sequence(s)

AK290552, BC017466, BJ993835, DB454192

Consensus CDS

CCDS9112.1

UniProtKB/Swiss-Prot

Q16526

UniProtKB/TrEMBL

A2I2P0

Related

ENSP00000008527.5, ENST00000008527.10

Conserved Domains (2) summary

COG0415
Location:6 → 491

PhrB; Deoxyribodipyrimidine photolyase [Replication, recombination and repair]

pfam03441
Location:288 → 486

FAD_binding_7; FAD binding domain of DNA photolyase

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109.20190905

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000012.12 Reference GRCh38.p13 Primary Assembly

Range

106991364..107093872 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_024448845.1 → XP_024304613.1 cryptochrome-1 isoform X2

Conserved Domains (2) summary

pfam03441
Location:260 → 458

FAD_binding_7; FAD binding domain of DNA photolyase

cl27275
Location:24 → 463

DNA_photolyase; DNA photolyase
XM_024448844.1 → XP_024304612.1 cryptochrome-1 isoform X1

Conserved Domains (2) summary

COG0415
Location:6 → 491

PhrB; Deoxyribodipyrimidine photolyase [Replication, recombination and repair]

pfam03441
Location:288 → 486

FAD_binding_7; FAD binding domain of DNA photolyase
XM_017018832.2 → XP_016874321.1 cryptochrome-1 isoform X3

Conserved Domains (2) summary

pfam00875
Location:21 → 125

DNA_photolyase; DNA photolyase

pfam03441
Location:185 → 458

FAD_binding_7; FAD binding domain of DNA photolyase