Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000695
UniProt IDQ16526
Primary gene name(s)CRY1
Synonym gene name(s)PHLL1
Protein nameCryptochrome-1
Protein functionTranscriptional repressor which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa', about and 'diem', day and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus, SCN of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers, German for 'timegivers'. The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components, CLOCK, NPAS2, ARNTL/BMAL1, ARNTL2/BMAL2, PER1, PER2, PER3, CRY1 and CRY2 plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications, PTMs are important for determining the period, tau of the rhythms, tau refers to the period of a rhythm and is the length, in time, of one complete cycle. A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop, TTFL forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and ARNTL/BMAL1 or ARNTL2/BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes, involved in key metabolic processes, harboring E-box elements, 5'-CACGTG-3' within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-ARNTL/BMAL1|ARNTL2/BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress ARNTL/BMAL1 transcription, respectively. CRY1 and CRY2 have redundant functions but also differential and selective contributions at least in defining the pace of the SCN circadian clock and its circadian transcriptional outputs. More potent transcriptional repressor in cerebellum and liver than CRY2, though more effective in lengthening the period of the SCN oscillator. On its side, CRY2 seems to play a critical role in tuning SCN circadian period by opposing the action of CRY1. With CRY2, is dispensable for circadian rhythm generation but necessary for the development of intercellular networks for rhythm synchrony. Capable of translocating circadian clock core proteins such as PER proteins to the nucleus. Interacts with CLOCK-ARNTL/BMAL1 independently of PER proteins and is found at CLOCK-ARNTL/BMAL1-bound sites, suggesting that CRY may act as a molecular gatekeeper to maintain CLOCK-ARNTL/BMAL1 in a poised and repressed state until the proper time for transcriptional activation. Represses the CLOCK-ARNTL/BMAL1 induced transcription of BHLHE40/DEC1. Represses the CLOCK-ARNTL/BMAL1 induced transcription of ATF4, MTA1, KLF10 and NAMPT, By similarity. May repress circadian target genes expression in collaboration with HDAC1 and HDAC2 through histone deacetylation. Mediates the clock-control activation of ATR and modulates ATR-mediated DNA damage checkpoint. In liver, mediates circadian regulation of cAMP signaling and gluconeogenesis by binding to membrane-coupled G proteins and blocking glucagon-mediated increases in intracellular cAMP concentrations and CREB1 phosphorylation. Besides its role in the maintenance of the circadian clock, is also involved in the regulation of other processes. Represses glucocorticoid receptor NR3C1/GR-induced transcriptional activity by binding to glucocorticoid response elements, GREs. Plays a key role in glucose and lipid metabolism modulation, in part, through the transcriptional regulation of genes involved in these pathways, such as LEP or ACSL4. {ECO:0000250|UniProtKB:P97784, ECO:0000269|PubMed:10531061, ECO:0000269|PubMed:14672706, ECO:0000269|PubMed:22170608, ECO:0000269|PubMed:23133559}.
Subcellular locationCytoplasm. Nucleus {ECO:0000269|PubMed:22798407}. Note=Translocated to the nucleus through interaction with other clock proteins such as PER2 or ARNTL/BMAL1. {ECO:0000250}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q16526
Gene Ontology
(Biological Process)
Complete annatation
blue light signaling pathway [GO:0009785];
circadian regulation of gene expression [GO:0032922];
DNA damage induced protein phosphorylation [GO:0006975];
entrainment of circadian clock by photoperiod [GO:0043153];
gluconeogenesis [GO:0006094];
glucose homeostasis [GO:0042593];
lipid storage [GO:0019915];
negative regulation of circadian rhythm [GO:0042754];
negative regulation of glucocorticoid receptor signaling pathway [GO:2000323];
negative regulation of glucocorticoid secretion [GO:2000850];
negative regulation of G-protein coupled receptor protein signaling pathway [GO:0045744];
negative regulation of protein ubiquitination [GO:0031397];
negative regulation of transcription, DNA-templated [GO:0045892];
negative regulation of transcription from RNA polymerase II promoter [GO:0000122];
protein-chromophore linkage [GO:0018298];
regulation of circadian rhythm [GO:0042752];
regulation of DNA damage checkpoint [GO:2000001];
response to glucagon [GO:0033762];
response to insulin [GO:0032868];
transcription, DNA-templated [GO:0006351]
Gene Ontology
(Molecular Function)
Complete annatation
blue light photoreceptor activity [GO:0009882];
core promoter binding [GO:0001047];
core promoter sequence-specific DNA binding [GO:0001046];
DNA binding [GO:0003677];
double-stranded DNA binding [GO:0003690];
nuclear hormone receptor binding [GO:0035257];
nucleotide binding [GO:0000166];
phosphatase binding [GO:0019902];
transcription factor activity, transcription factor binding [GO:0000989];
ubiquitin binding [GO:0043130]
Gene Ontology
(Cellular Component)
Complete annatation
mitochondrion [GO:0005739];
nucleus [GO:0005634]
Protein-protein interaction107797
Phylogenetic treeQ16526
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD31.446230143951091.54940499859091e-059.15071792271245e-05
AZA vs. DISU0.8582797906421120.004592908004524940.174594010686945
AZA vs. IL7-0.03299122663068780.9014977952113910.999311006273513
AZA vs. SAHA1.065752174882020.003047355441498370.0446462832221364
DISU vs. CD3-0.6020265230353180.1000186266810390.186524901470987
DISU vs. IL7-0.8987705625859820.002126243757868850.0443221875946854
DISU vs. SAHA0.2077053276504050.5884544082842840.868538144966454
DMSO vs. AZA-0.01811482941887770.9450722735117251
DMSO vs. CD3-1.482171928326735.82515474345513e-063.54283230561774e-05
DMSO vs. DISU-0.8799035980893290.002342505509617450.10352363058632
DMSO vs. IL7-0.006860654912387160.9782824922907760.996015724298726
DMSO vs. SAHA1.077443093482160.002067498360970750.0297889749504687
HIV vs. Mock in Activation-0.5411711660648540.3857727161790940.999983755607037
HIV vs. Mock in Latency-0.4572116857027160.007308683382185490.264834358901596
IL7 vs. CD3-1.468334594988487.82717214753426e-066.24557786023207e-05
SAHA vs. CD3-0.4068875109886840.2547046673728950.364693523734872
SAHA vs. IL71.093369288799290.00215406996297240.0207877404749334
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) TRUE
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK 0.0190665 0.938411
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
unknown unknown unknown unknown unknown
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
209674_at 1.79 No downregulated in CD8+ cells

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

not found

Protein Secondary Structure       (annotations from PDB)      top

not found

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

not found

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04710 Circadian rhythm - Homo sapiens (human)