CRY2
entrez
1408
canonical
uniprot
Q49AN0
canonical
ensembl
ENSG00000121671
resolver
ensp
ENSP00000397419
resolver
ensp
ENSP00000406751
resolver
ensp
ENSP00000478187
resolver
ensp
ENSP00000484684
resolver
enst
ENST00000443527
resolver
enst
ENST00000616623
resolver
genesymbol
CRY2
resolver
genesymbol_syn
KIAA0658
resolver
hgnc
HGNC:2385
resolver
uniprot
A0A0D2X7Z3
resolver
uniprot
A2I2P1
resolver
uniprot
B4DH32
resolver
uniprot
B4DZD6
resolver
uniprot
O75148
resolver
uniprot
Q8IV71
resolver
uniprot_entry
A0A0D2X7Z3_HUMAN
resolver
uniprot_entry
A2I2P1_HUMAN
resolver
uniprot_entry
CRY2_HUMAN
resolver
uniprot_sec
B4DH32
resolver
uniprot_sec
B4DZD6
resolver
uniprot_sec
O75148
resolver
uniprot_sec
Q8IV71
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. {ECO:0000269|PubMed:22798407}.
uniprot
proteins
amino_acid_sequence
MAATVATAAAVAPAPAPGTDSASSVHWFRKGLRLHDNPALLAAVRGARCVRCVYILDPWFAASSSVGINRWRFLLQSLEDLDTSLRKLNSRLFVVRGQPADVFPRLFKEWGVTRLTFEYDSEPFGKERDAAIMKMAKEAGVEVVTENSHTLYDLDRIIELNGQKPPLTYKRFQAIISRMELPKKPVGLVTSQQMESCRAEIQENHDETYGVPSLEELGFPTEGLGPAVWQGGETEALARLDKHLERKAWVANYERPRMNANSLLASPTGLSPYLRFGCLSCRLFYYRLWDLYKKVKRNSTPPLSLFGQLLWREFFYTAATNNPRFDRMEGNPICIQIPWDRNPEALAKWAEGKTGFPWIDAIMTQLRQEGWIHHLARHAVACFLTRGDLWVSWESGVRVFDELLLDADFSVNAGSWMWLSCSAFFQQFFHCYCPVGFGRRTDPSGDYIRRYLPKLKAFPSRYIYEPWNAPESIQKAAKCIIGVDYPRPIVNHAETSRLNIERMKQIYQQLSRYRGLCLLASVPSCVEDLSHPVAEPSSSQAGSMSSAGPRPLPSGPASPKRKLEAAEEPPGEELSKRARVAELPTPELPSKDA
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. Represses the CLOCK-BMAL1 induced transcription of NAMPT (By similarity). Represses PPARD and its target genes in the skeletal muscle and limits exercise capacity (By similarity). Represses the transcriptional activity of NR1I2 (By similarity). {ECO:0000250|UniProtKB:Q9R194, ECO:0000269|PubMed:10531061, ECO:0000269|PubMed:14672706, ECO:0000269|PubMed:16790549}.
uniprot
proteins
mass_dalton
66947
uniprot
proteins
post_translational_modification
PTM: Phosphorylation on Ser-266 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-554 and Ser-558 in the suprachiasmatic nucleus (SCN) and liver. Phosphorylation at Ser-558 by DYRK1A promotes subsequent phosphorylation at Ser-554 by GSK3-beta: the two-step phosphorylation at the neighboring Ser residues leads to its proteasomal degradation. {ECO:0000250|UniProtKB:Q9R194}.; 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-554 and Ser-558. Ubiquitination may be inhibited by PER2. Deubiquitinated by USP7 (By similarity). {ECO:0000250|UniProtKB:Q9R194, ECO:0000269|PubMed:11889036, ECO:0000269|PubMed:17463251, ECO:0000269|PubMed:22798407}.
uniprot
proteins
protein_family
DNA photolyase class-1 family
uniprot
proteins
pubmed
10531061
uniprot
proteins
pubmed
11889036
uniprot
proteins
pubmed
14672706
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16554811
uniprot
proteins
pubmed
16790549
uniprot
proteins
pubmed
17463251
uniprot
proteins
pubmed
22798407
uniprot
proteins
pubmed
23303907
uniprot
proteins
pubmed
23916625
uniprot
proteins
pubmed
26569474
uniprot
proteins
pubmed
30530698
uniprot
proteins
pubmed
31138685
uniprot
proteins
pubmed
8909283
uniprot
proteins
pubmed
9734811
uniprot
proteins
pubmed
9801304
uniprot
proteins
sequence_length
593
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:9801304}. Nucleus {ECO:0000269|PubMed:22798407, ECO:0000269|PubMed:9801304}. Note=Translocated to the nucleus through interaction with other Clock proteins such as PER2 or BMAL1.
uniprot
proteins