CRY2_CHICK
ID CRY2_CHICK Reviewed; 582 AA.
AC Q8QG60; Q8QG52; Q8QGQ5;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2006, sequence version 2.
DT 03-AUG-2022, entry version 100.
DE RecName: Full=Cryptochrome-2;
GN Name=CRY2;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
RC TISSUE=Pineal gland;
RX PubMed=11684328; DOI=10.1016/s0304-3940(01)02227-3;
RA Yamamoto K., Okano T., Fukada Y.;
RT "Chicken pineal Cry genes: light-dependent up-regulation of cCry1 and cCry2
RT transcripts.";
RL Neurosci. Lett. 313:13-16(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 52-582, AND NUCLEOTIDE SEQUENCE [MRNA]
RP OF 317-582.
RX PubMed=11904144; DOI=10.1016/s0014-5793(02)02276-7;
RA Bailey M.J., Chong N.W., Xiong J., Cassone V.M.;
RT "Chickens' Cry2: molecular analysis of an avian cryptochrome in retinal and
RT pineal photoreceptors.";
RL FEBS Lett. 513:169-174(2002).
CC -!- FUNCTION: Transcriptional repressor which forms a core component of the
CC circadian clock. The circadian clock, an internal time-keeping system,
CC regulates various physiological processes through the generation of
CC approximately 24 hour circadian rhythms in gene expression, which are
CC translated into rhythms in metabolism and behavior. It is derived from
CC the Latin roots 'circa' (about) and 'diem' (day) and acts as an
CC important regulator of a wide array of physiological functions
CC including metabolism, sleep, body temperature, blood pressure,
CC endocrine, immune, cardiovascular, and renal function. Consists of two
CC major components: the central clock, residing in the suprachiasmatic
CC nucleus (SCN) of the brain, and the peripheral clocks that are present
CC in nearly every tissue and organ system. Both the central and
CC peripheral clocks can be reset by environmental cues, also known as
CC Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the
CC central clock is light, which is sensed by retina and signals directly
CC to the SCN. The central clock entrains the peripheral clocks through
CC neuronal and hormonal signals, body temperature and feeding-related
CC cues, aligning all clocks with the external light/dark cycle. Circadian
CC rhythms allow an organism to achieve temporal homeostasis with its
CC environment at the molecular level by regulating gene expression to
CC create a peak of protein expression once every 24 hours to control when
CC a particular physiological process is most active with respect to the
CC solar day. Transcription and translation of core clock components
CC (CLOCK, NPAS2, ARNTL/BMAL1, ARNTL2/BMAL2, PER1, PER2, PER3, CRY1 and
CC CRY2) plays a critical role in rhythm generation, whereas delays
CC imposed by post-translational modifications (PTMs) are important for
CC determining the period (tau) of the rhythms (tau refers to the period
CC of a rhythm and is the length, in time, of one complete cycle). A
CC diurnal rhythm is synchronized with the day/night cycle, while the
CC ultradian and infradian rhythms have a period shorter and longer than
CC 24 hours, respectively. Disruptions in the circadian rhythms contribute
CC to the pathology of cardiovascular diseases, cancer, metabolic
CC syndromes and aging. A transcription/translation feedback loop (TTFL)
CC forms the core of the molecular circadian clock mechanism.
CC Transcription factors, CLOCK or NPAS2 and ARNTL/BMAL1 or ARNTL2/BMAL2,
CC form the positive limb of the feedback loop, act in the form of a
CC heterodimer and activate the transcription of core clock genes and
CC clock-controlled genes (involved in key metabolic processes), harboring
CC E-box elements (5'-CACGTG-3') within their promoters. The core clock
CC genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form
CC the negative limb of the feedback loop and interact with the
CC CLOCK|NPAS2-ARNTL/BMAL1|ARNTL2/BMAL2 heterodimer inhibiting its
CC activity and thereby negatively regulating their own expression. This
CC heterodimer also activates nuclear receptors NR1D1/2, RORA/B/G, which
CC form a second feedback loop and which activate and repress ARNTL/BMAL1
CC transcription, respectively. CRY1 and CRY2 have redundant functions but
CC also differential and selective contributions at least in defining the
CC pace of the SCN circadian clock and its circadian transcriptional
CC outputs. Less potent transcriptional repressor in cerebellum and liver
CC than CRY1, though less effective in lengthening the period of the SCN
CC oscillator. Seems to play a critical role in tuning SCN circadian
CC period by opposing the action of CRY1. With CRY1, dispensable for
CC circadian rhythm generation but necessary for the development of
CC intercellular networks for rhythm synchrony (By similarity). Represses
CC CLOCK-ARNTL/BMAL1-mediated transcriptional activation
CC (PubMed:11684328). {ECO:0000250|UniProtKB:Q9R194,
CC ECO:0000269|PubMed:11684328}.
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:Q9R194};
CC Note=Binds 1 FAD per subunit. {ECO:0000250|UniProtKB:Q9R194};
CC -!- COFACTOR:
CC Name=(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate;
CC Xref=ChEBI:CHEBI:15636; Evidence={ECO:0000250};
CC Note=Binds 1 5,10-methenyltetrahydrofolate (MTHF) non-covalently per
CC subunit. {ECO:0000250};
CC -!- SUBUNIT: Component of the circadian core oscillator, which includes the
CC CRY proteins, CLOCK or NPAS2, ARNTL/BMAL1 or ARNTL2/BMAL2, CSNK1E, and
CC the PER proteins. {ECO:0000250|UniProtKB:Q9R194}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9R194}. Nucleus
CC {ECO:0000250|UniProtKB:Q9R194}.
CC -!- TISSUE SPECIFICITY: Expressed in the pineal gland.
CC {ECO:0000269|PubMed:11684328}.
CC -!- INDUCTION: Exhibits some circadian rhythm expression. Levels increase
CC slightly during subjective day peaking at 10 hours. Levels decrease
CC between 14 hours and 18 hours to peak again at 20 hours-22 hours.
CC {ECO:0000269|PubMed:11684328}.
CC -!- SIMILARITY: Belongs to the DNA photolyase class-1 family.
CC {ECO:0000305}.
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DR EMBL; AY034433; AAK61386.1; -; mRNA.
DR EMBL; AY046568; AAL46564.1; -; Genomic_DNA.
DR EMBL; AF251344; AAM19303.1; -; mRNA.
DR RefSeq; NP_989575.1; NM_204244.1.
DR AlphaFoldDB; Q8QG60; -.
DR SMR; Q8QG60; -.
DR STRING; 9031.ENSGALP00000013730; -.
DR PaxDb; Q8QG60; -.
DR GeneID; 374092; -.
DR KEGG; gga:374092; -.
DR CTD; 1408; -.
DR VEuPathDB; HostDB:geneid_374092; -.
DR eggNOG; KOG0133; Eukaryota.
DR InParanoid; Q8QG60; -.
DR OrthoDB; 378952at2759; -.
DR PhylomeDB; Q8QG60; -.
DR PRO; PR:Q8QG60; -.
DR Proteomes; UP000000539; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IBA:GO_Central.
DR GO; GO:0071949; F:FAD binding; ISS:UniProtKB.
DR GO; GO:0009881; F:photoreceptor activity; IEA:UniProtKB-KW.
DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0007623; P:circadian rhythm; ISS:UniProtKB.
DR GO; GO:0043153; P:entrainment of circadian clock by photoperiod; ISS:UniProtKB.
DR GO; GO:0042754; P:negative regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:0009416; P:response to light stimulus; ISS:UniProtKB.
DR Gene3D; 3.40.50.620; -; 1.
DR InterPro; IPR036134; Crypto/Photolyase_FAD-like_sf.
DR InterPro; IPR036155; Crypto/Photolyase_N_sf.
DR InterPro; IPR005101; Cryptochr/Photolyase_FAD-bd.
DR InterPro; IPR002081; Cryptochrome/DNA_photolyase_1.
DR InterPro; IPR006050; DNA_photolyase_N.
DR InterPro; IPR014729; Rossmann-like_a/b/a_fold.
DR PANTHER; PTHR11455; PTHR11455; 1.
DR Pfam; PF00875; DNA_photolyase; 1.
DR Pfam; PF03441; FAD_binding_7; 1.
DR SUPFAM; SSF48173; SSF48173; 1.
DR SUPFAM; SSF52425; SSF52425; 1.
DR PROSITE; PS51645; PHR_CRY_ALPHA_BETA; 1.
PE 2: Evidence at transcript level;
KW Biological rhythms; Chromophore; Cytoplasm; FAD; Flavoprotein;
KW Nucleotide-binding; Nucleus; Photoreceptor protein; Receptor;
KW Reference proteome; Repressor; Sensory transduction; Transcription;
KW Transcription regulation.
FT CHAIN 1..582
FT /note="Cryptochrome-2"
FT /id="PRO_0000261151"
FT DOMAIN 12..141
FT /note="Photolyase/cryptochrome alpha/beta"
FT REGION 521..559
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 525..543
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 545..559
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 261
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q9R194"
FT BINDING 298
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P97784"
FT BINDING 364
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q9R194"
FT BINDING 396..398
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q9R194"
FT CONFLICT 106
FT /note="A -> T (in Ref. 1; AAK61386)"
FT /evidence="ECO:0000305"
FT CONFLICT 143
FT /note="N -> D (in Ref. 1; AAK61386)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 582 AA; 66097 MW; EB209D18E15822BB CRC64;
MAAAASPPRG FCRSVHWFRR GLRLHDNPAL QAALRGAASL RCIYILDPWF AASSAVGINR
WRFLLQSLED LDNSLRKLNS RLFVVRGQPT DVFPRLFKEW GVTRLAFEYD SEPFGKERDA
AIIKLAKEAG VEVVIENSHT LYNLDRIIEL NGNKPPLTYK RFQAIISRME LPKKPVSSIV
SQQMETCKVD IQENHDDVYG VPSLEELGFP TDGLAPAVWQ GGETEALARL DKHLERKAWV
ANYERPRMNA NSLLASPTGL SPYLRFGCLS CRLFYYRLWE LYKKVKRNST PPLSLYGQLL
WREFFYTAAT NNPKFDRMEG NPICIQIPWD KNPEALAKWA EGKTGFPWID AIMTQLRQEG
WIHHLARHAV ACFLTRGDLW ISWESGVRVF DELLLDADFS VNAGSWMWLS CSAFFQQFFH
CYCPVGFGRR TDPSGDYVKR YLPKLKGFPS RYIYEPWNAP ESVQKAAKCI IGVDYPKPMV
NHAETSRLNI ERMKQIYQQL SRYRGLCLLA SVPSCVEDLS GPVTDSAPGQ GSSTSTAVRL
PQSDQASPKR KHEGAEELCT EELYKRAKVT GLPAPEIPGK SS
