Cry2
entrez
12953
canonical
uniprot
Q9R194
canonical
ensembl
ENSMUSG00000068742
resolver
ensp
ENSMUSP00000088047
resolver
ensp
ENSMUSP00000106909
resolver
enst
ENSMUST00000090559
resolver
enst
ENSMUST00000111278
resolver
genesymbol
Cry2
resolver
genesymbol_syn
Kiaa0658
resolver
uniprot
O08706
resolver
uniprot
Q6A024
resolver
uniprot_entry
CRY2_MOUSE
resolver
uniprot_sec
O08706
resolver
uniprot_sec
Q6A024
resolver
activity_regulation
ACTIVITY REGULATION: KL001 (N-[3-(9H-carbazol-9-yl)-2-hydroxypropyl]-N-(2-furanylmethyl)-methanesulfonamide) binds to CRY1 and stabilizes it by inhibiting FBXL3- and ubiquitin-dependent degradation of CRY1 resulting in lengthening of the circadian periods. KL001-mediated CRY1 stabilization can inhibit glucagon-induced gluconeogenesis in primary hepatocytes. {ECO:0000269|PubMed:22798407}.
uniprot
proteins
amino_acid_sequence
MAAAAVVAATVPAQSMGADGASSVHWFRKGLRLHDNPALLAAVRGARCVRCVYILDPWFAASSSVGINRWRFLLQSLEDLDTSLRKLNSRLFVVRGQPADVFPRLFKEWGVTRLTFEYDSEPFGKERDAAIMKMAKEAGVEVVTENSHTLYDLDRIIELNGQKPPLTYKRFQALISRMELPKKPAVAVSSQQMESCRAEIQENHDDTYGVPSLEELGFPTEGLGPAVWQGGETEALARLDKHLERKAWVANYERPRMNANSLLASPTGLSPYLRFGCLSCRLFYYRLWDLYKKVKRNSTPPLSLFGQLLWREFFYTAATNNPRFDRMEGNPICIQIPWDRNPEALAKWAEGKTGFPWIDAIMTQLRQEGWIHHLARHAVACFLTRGDLWVSWESGVRVFDELLLDADFSVNAGSWMWLSCSAFFQQFFHCYCPVGFGRRTDPSGDYIRRYLPKLKGFPSRYIYEPWNAPESVQKAAKCIIGVDYPRPIVNHAETSRLNIERMKQIYQQLSRYRGLCLLASVPSCVEDLSHPVAEPGSSQAGSISNTGPRALSSGPASPKRKLEAAEEPPGEELTKRARVTEMPTQEPASKDS
uniprot
proteins
function
FUNCTION: Transcriptional 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, BMAL1, 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 BMAL1 or 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-BMAL1|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 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. Less potent transcriptional repressor in cerebellum and liver than CRY1, though less effective in lengthening the period of the SCN oscillator. Seems to play a critical role in tuning SCN circadian period by opposing the action of CRY1. With CRY1, dispensable for circadian rhythm generation but necessary for the development of intercellular networks for rhythm synchrony. May mediate circadian regulation of cAMP signaling and gluconeogenesis by blocking glucagon-mediated increases in intracellular cAMP concentrations and in CREB1 phosphorylation. Besides its role in the maintenance of the circadian clock, is also involved in the regulation of other processes. 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. Represses glucocorticoid receptor NR3C1/GR-induced transcriptional activity by binding to glucocorticoid response elements (GREs). Represses the CLOCK-BMAL1 induced transcription of BHLHE40/DEC1 and NAMPT. Represses PPARD and its target genes in the skeletal muscle and limits exercise capacity (PubMed:28683290). Represses the transcriptional activity of NR1I2 (PubMed:28751364). {ECO:0000269|PubMed:10428031, ECO:0000269|PubMed:16628007, ECO:0000269|PubMed:17310242, ECO:0000269|PubMed:19299583, ECO:0000269|PubMed:20852621, ECO:0000269|PubMed:22170608, ECO:0000269|PubMed:23531614, ECO:0000269|PubMed:23575670, ECO:0000269|PubMed:23616524, ECO:0000269|PubMed:24154698, ECO:0000269|PubMed:28683290, ECO:0000269|PubMed:28751364}.
uniprot
proteins
mass_dalton
66850
uniprot
proteins
mutagenesis
MUTAGEN 265; /note="S->A: Reduced in vitro MAPK-catalyzed phosphorylation. No effect on inhibition of CLOCK-BMAL1-mediated transcriptional activity. Very little in vitro MAPK-catalyzed phosphorylation; when associated with A-557."; /evidence="ECO:0000269|PubMed:15298678"; MUTAGEN 265; /note="S->D: Reduced inhibition of CLOCK-BMAL1-mediated transcriptional activity. No effect on nuclear localization nor on protein stability."; /evidence="ECO:0000269|PubMed:15298678"; MUTAGEN 310; /note="W->A: Decreases FBXL3 binding. Strongly decreases CRY2 degradation."; /evidence="ECO:0000269|PubMed:23503662"; MUTAGEN 339; /note="D->R: Strongly reduces PER1 binding."; /evidence="ECO:0000269|PubMed:23503662"; MUTAGEN 351; /note="G->D: Loss of ability to inhibit CLOCK-BMAL1-mediated transcriptional activity. No loss of ability to inhibit NR1I2 transcriptional activity."; /evidence="ECO:0000269|PubMed:28751364"; MUTAGEN 354; /note="G->D: Loss of ability to inhibit CLOCK-BMAL1-mediated transcriptional activity. No loss of ability to inhibit NR1I2 transcriptional activity."; /evidence="ECO:0000269|PubMed:28751364"; MUTAGEN 376; /note="R->A: Impairs protein folding. Abolishes binding of BMAL1, PER1 and FBXL3. Strongly reduces SKP1 binding."; /evidence="ECO:0000269|PubMed:23503662"; MUTAGEN 394; /note="S->E: Reduced interaction with NR1I2 and NR1I3. Significant decrease in interaction with NR1I2 and NR1I3; when associated with M-396 and K-397."; /evidence="ECO:0000269|PubMed:28751364"; MUTAGEN 396; /note="V->M: Reduced interaction with NR1I2 and NR1I3. Significant decrease in interaction with NR1I2 and NR1I3; when associated with E-394 and K-397."; /evidence="ECO:0000269|PubMed:28751364"; MUTAGEN 397; /note="R->K: Reduced interaction with NR1I2 and NR1I3. Significant decrease in interaction with NR1I2 and NR1I3; when associated with E-394 and M-396."; /evidence="ECO:0000269|PubMed:28751364"; MUTAGEN 428; /note="F->D: Abolishes binding of FBXL3 and SKP1. Strongly decreases CRY2 degradation."; /evidence="ECO:0000269|PubMed:23503662"; MUTAGEN 499; /note="I->D: Abolishes binding of FBXL3 and SKP1. Strongly decreases CRY2 degradation."; /evidence="ECO:0000269|PubMed:23503662"; MUTAGEN 501; /note="R->Q: Inhibits interaction with PER2. Does not suppress its nuclear localization. Inhibits its repression activity on CLOCK|NPAS2-BMAL1-driven transcription."; /evidence="ECO:0000269|PubMed:20840750"; MUTAGEN 503; /note="K->R: Inhibits interaction with PER2. Does not suppress its nuclear localization. Inhibits its repression activity on CLOCK|NPAS2-BMAL1-driven transcription."; /evidence="ECO:0000269|PubMed:20840750"; MUTAGEN 517; /note="L->D: Decreases FBXL3 binding. Strongly decreases CRY2 degradation."; /evidence="ECO:0000269|PubMed:23503662"; MUTAGEN 553; /note="S->A: Shorter circadian rhythm; when associated with A-557."; /evidence="ECO:0000269|PubMed:20123978"; MUTAGEN 557; /note="S->A: Reduced in vitro MAPK-catalyzed phosphorylation. No effect on inhibition of CLOCK-BMAL1-mediated transcriptional activity. Very little in vitro MAPK-catalyzed phosphorylation; when associated with A-265. Shorter circadian rhythm; when associated with A-553."; /evidence="ECO:0000269|PubMed:15298678, ECO:0000269|PubMed:20123978"; MUTAGEN 557; /note="S->D: Reduced inhibition of CLOCK-BMAL1-mediated transcriptional activity. No effect on nuclear localization nor on protein stability."; /evidence="ECO:0000269|PubMed:15298678, ECO:0000269|PubMed:20123978
uniprot
proteins
post_translational_modification
PTM: Phosphorylation on Ser-265 by MAPK is important for the inhibition of CLOCK-BMAL1-mediated transcriptional activity. Phosphorylation by CSKNE requires interaction with PER1 or PER2. Phosphorylated in a circadian manner at Ser-553 and Ser-557 in the suprachiasmatic nucleus (SCN) and liver. Phosphorylation at Ser-557 by DYRK1A promotes subsequent phosphorylation at Ser-553 by GSK3-beta: the two-step phosphorylation at the neighboring Ser residues leads to its proteasomal degradation. {ECO:0000269|PubMed:11875063, ECO:0000269|PubMed:15298678, ECO:0000269|PubMed:15980066, ECO:0000269|PubMed:20123978}.; PTM: Ubiquitinated by the SCF(FBXL3) and SCF(FBXL21) complexes, regulating the balance between degradation and stabilization. The SCF(FBXL3) complex is mainly nuclear and mediates ubiquitination and subsequent degradation of CRY2. In contrast, cytoplasmic SCF(FBXL21) complex-mediated ubiquitination leads to stabilize CRY2 and counteract the activity of the SCF(FBXL3) complex. The SCF(FBXL3) and SCF(FBXL21) complexes probably mediate ubiquitination at different Lys residues. The SCF(FBXL3) complex recognizes and binds CRY2 phosphorylated at Ser-553 and Ser-557. Ubiquitination may be inhibited by PER2. Deubiquitinated by USP7 (PubMed:27123980). {ECO:0000269|PubMed:15298678, ECO:0000269|PubMed:15980066, ECO:0000269|PubMed:17462724, ECO:0000269|PubMed:20123978, ECO:0000269|PubMed:23452855, ECO:0000269|PubMed:23452856, ECO:0000269|PubMed:26776516, ECO:0000269|PubMed:27123980}.
uniprot
proteins
protein_family
DNA photolyase class-1 family
uniprot
proteins
pubmed
10428031
uniprot
proteins
pubmed
10521578
uniprot
proteins
pubmed
11779462
uniprot
proteins
pubmed
11875063
uniprot
proteins
pubmed
14701732
uniprot
proteins
pubmed
15298678
uniprot
proteins
pubmed
15368895
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15980066
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
16628007
uniprot
proteins
pubmed
16717091
uniprot
proteins
pubmed
17274955
uniprot
proteins
pubmed
17310242
uniprot
proteins
pubmed
17462724
uniprot
proteins
pubmed
19299583
uniprot
proteins
pubmed
19917250
uniprot
proteins
pubmed
20123978
uniprot
proteins
pubmed
20840750
uniprot
proteins
pubmed
20852621
uniprot
proteins
pubmed
22170608
uniprot
proteins
pubmed
22798407
uniprot
proteins
pubmed
23303907
uniprot
proteins
pubmed
23452855
uniprot
proteins
pubmed
23452856
uniprot
proteins
pubmed
23503662
uniprot
proteins
pubmed
23531614
uniprot
proteins
pubmed
23575670
uniprot
proteins
pubmed
23616524
uniprot
proteins
pubmed
23916625
uniprot
proteins
pubmed
24080726
uniprot
proteins
pubmed
24154698
uniprot
proteins
pubmed
24158435
uniprot
proteins
pubmed
24736997
uniprot
proteins
pubmed
26776516
uniprot
proteins
pubmed
27123980
uniprot
proteins
pubmed
28683290
uniprot
proteins
pubmed
28751364
uniprot
proteins
pubmed
29561690
uniprot
proteins
pubmed
9801304
uniprot
proteins
sequence_length
592
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11779462}. Nucleus {ECO:0000269|PubMed:11779462}. Note=Translocated to the nucleus through interaction with other Clock proteins such as PER2 or BMAL1. {ECO:0000269|PubMed:11779462}.
uniprot
proteins