CRY1_HUMAN
ID CRY1_HUMAN Reviewed; 586 AA.
AC Q16526;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Cryptochrome-1;
GN Name=CRY1; Synonyms=PHLL1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND CHARACTERIZATION.
RC TISSUE=Fibroblast;
RX PubMed=8909283; DOI=10.1021/bi962209o;
RA Hsu D.S., Zhao X., Zhao S., Kazantsev A., Wang R.-P., Todo T., Wei Y.-F.,
RA Sancar A.;
RT "Putative human blue-light photoreceptors hCRY1 and hCRY2 are
RT flavoproteins.";
RL Biochemistry 35:13871-13877(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=8921389; DOI=10.1006/geno.1996.0539;
RA van der Spek P.J., Kobayashi K., Bootsma D., Takao M., Eker A.P.M.,
RA Yasui A.;
RT "Cloning, tissue expression, and mapping of a human photolyase homolog with
RT similarity to plant blue-light receptors.";
RL Genomics 37:177-182(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=8600518; DOI=10.1126/science.272.5258.109;
RA Todo T., Ryo H., Yamamoto K., Toh H., Inui T., Ayaki H., Nomura T.,
RA Ikenaga M.;
RT "Similarity among the Drosophila (6-4)photolyase, a human photolyase
RT homolog, and the DNA photolyase-blue-light photoreceptor family.";
RL Science 272:109-112(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION.
RX PubMed=10531061; DOI=10.1126/science.286.5440.768;
RA Griffin E.A. Jr., Staknis D., Weitz C.J.;
RT "Light-independent role of CRY1 and CRY2 in the mammalian circadian
RT clock.";
RL Science 286:768-771(1999).
RN [6]
RP FUNCTION.
RX PubMed=14672706; DOI=10.1016/j.bbrc.2003.11.099;
RA Kawamoto T., Noshiro M., Sato F., Maemura K., Takeda N., Nagai R.,
RA Iwata T., Fujimoto K., Furukawa M., Miyazaki K., Honma S., Honma K.I.,
RA Kato Y.;
RT "A novel autofeedback loop of Dec1 transcription involved in circadian
RT rhythm regulation.";
RL Biochem. Biophys. Res. Commun. 313:117-124(2004).
RN [7]
RP INTERACTION WITH PPP5C.
RX PubMed=16790549; DOI=10.1073/pnas.0604138103;
RA Partch C.L., Shields K.F., Thompson C.L., Selby C.P., Sancar A.;
RT "Posttranslational regulation of the mammalian circadian clock by
RT cryptochrome and protein phosphatase 5.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:10467-10472(2006).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY, UBIQUITINATION BY FBXL3, AND
RP INTERACTION WITH FBXL3.
RX PubMed=17463251; DOI=10.1126/science.1141194;
RA Busino L., Bassermann F., Maiolica A., Lee C., Nolan P.M., Godinho S.I.,
RA Draetta G.F., Pagano M.;
RT "SCFFbxl3 controls the oscillation of the circadian clock by directing the
RT degradation of cryptochrome proteins.";
RL Science 316:900-904(2007).
RN [9]
RP INTERACTION WITH GNAS.
RX PubMed=20852621; DOI=10.1038/nm.2214;
RA Zhang E.E., Liu Y., Dentin R., Pongsawakul P.Y., Liu A.C., Hirota T.,
RA Nusinow D.A., Sun X., Landais S., Kodama Y., Brenner D.A., Montminy M.,
RA Kay S.A.;
RT "Cryptochrome mediates circadian regulation of cAMP signaling and hepatic
RT gluconeogenesis.";
RL Nat. Med. 16:1152-1156(2010).
RN [10]
RP INTERACTION WITH PER2.
RX PubMed=21613214; DOI=10.1074/jbc.m111.254680;
RA Ye R., Selby C.P., Ozturk N., Annayev Y., Sancar A.;
RT "Biochemical analysis of the canonical model for the mammalian circadian
RT clock.";
RL J. Biol. Chem. 286:25891-25902(2011).
RN [11]
RP FUNCTION AS NR3C1 REPRESSOR, AND INTERACTION WITH AR; NR1D1; NR3C1; RORA
RP AND RORC.
RX PubMed=22170608; DOI=10.1038/nature10700;
RA Lamia K.A., Papp S.J., Yu R.T., Barish G.D., Uhlenhaut N.H., Jonker J.W.,
RA Downes M., Evans R.M.;
RT "Cryptochromes mediate rhythmic repression of the glucocorticoid
RT receptor.";
RL Nature 480:552-556(2011).
RN [12]
RP FUNCTION, AND INTERACTION WITH PRMT5.
RX PubMed=23133559; DOI=10.1371/journal.pone.0048152;
RA Na J., Lee K., Kim H.G., Shin J.Y., Na W., Jeong H., Lee J.W., Cho S.,
RA Kim W.S., Ju B.G.;
RT "Role of type II protein arginine methyltransferase 5 in the regulation of
RT Circadian Per1 gene.";
RL PLoS ONE 7:E48152-E48152(2012).
RN [13]
RP ACTIVITY REGULATION, SUBCELLULAR LOCATION, UBIQUITINATION, AND MUTAGENESIS
RP OF ASP-387 AND ASN-393.
RX PubMed=22798407; DOI=10.1126/science.1223710;
RA Hirota T., Lee J.W., St John P.C., Sawa M., Iwaisako K., Noguchi T.,
RA Pongsawakul P.Y., Sonntag T., Welsh D.K., Brenner D.A., Doyle F.J. III,
RA Schultz P.G., Kay S.A.;
RT "Identification of small molecule activators of cryptochrome.";
RL Science 337:1094-1097(2012).
RN [14]
RP REVIEW.
RX PubMed=23303907; DOI=10.1152/physrev.00016.2012;
RA Eckel-Mahan K., Sassone-Corsi P.;
RT "Metabolism and the circadian clock converge.";
RL Physiol. Rev. 93:107-135(2013).
RN [15]
RP REVIEW.
RX PubMed=23916625; DOI=10.1016/j.tcb.2013.07.002;
RA Partch C.L., Green C.B., Takahashi J.S.;
RT "Molecular architecture of the mammalian circadian clock.";
RL Trends Cell Biol. 24:90-99(2014).
RN [16]
RP INTERACTION WITH DDB1-CUE4A COMPLEX AND DTL, AND SUBCELLULAR LOCATION.
RX PubMed=26431207; DOI=10.1371/journal.pone.0139725;
RA Tong X., Zhang D., Guha A., Arthurs B., Cazares V., Gupta N., Yin L.;
RT "CUL4-DDB1-CDT2 E3 ligase regulates the molecular clock activity by
RT promoting ubiquitination-dependent degradation of the mammalian CRY1.";
RL PLoS ONE 10:E0139725-E0139725(2015).
RN [17]
RP UBIQUITINATION.
RX PubMed=27565346; DOI=10.1016/j.cell.2016.07.027;
RA Scott D.C., Rhee D.Y., Duda D.M., Kelsall I.R., Olszewski J.L., Paulo J.A.,
RA de Jong A., Ovaa H., Alpi A.F., Harper J.W., Schulman B.A.;
RT "Two distinct types of E3 ligases work in unison to regulate substrate
RT ubiquitylation.";
RL Cell 166:1198-1214(2016).
RN [18]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CLOCK-ARNTL, AND
RP INVOLVEMENT IN DSPS.
RX PubMed=28388406; DOI=10.1016/j.cell.2017.03.027;
RA Patke A., Murphy P.J., Onat O.E., Krieger A.C., Oezcelik T., Campbell S.S.,
RA Young M.W.;
RT "Mutation of the human circadian clock gene CRY1 in familial delayed sleep
RT phase disorder.";
RL Cell 169:203-215(2017).
RN [19]
RP INTERACTION WITH HNF4A.
RX PubMed=30530698; DOI=10.1073/pnas.1816411115;
RA Qu M., Duffy T., Hirota T., Kay S.A.;
RT "Nuclear receptor HNF4A transrepresses CLOCK:BMAL1 and modulates tissue-
RT specific circadian networks.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:E12305-E12312(2018).
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 and RORA/B/G,
CC which form a second feedback loop and which activate and repress
CC ARNTL/BMAL1 transcription, respectively. CRY1 and CRY2 have redundant
CC functions but also differential and selective contributions at least in
CC defining the pace of the SCN circadian clock and its circadian
CC transcriptional outputs. More potent transcriptional repressor in
CC cerebellum and liver than CRY2, though more effective in lengthening
CC the period of the SCN oscillator. On its side, CRY2 seems to play a
CC critical role in tuning SCN circadian period by opposing the action of
CC CRY1. With CRY2, is dispensable for circadian rhythm generation but
CC necessary for the development of intercellular networks for rhythm
CC synchrony. Capable of translocating circadian clock core proteins such
CC as PER proteins to the nucleus. Interacts with CLOCK-ARNTL/BMAL1
CC independently of PER proteins and is found at CLOCK-ARNTL/BMAL1-bound
CC sites, suggesting that CRY may act as a molecular gatekeeper to
CC maintain CLOCK-ARNTL/BMAL1 in a poised and repressed state until the
CC proper time for transcriptional activation. Represses the CLOCK-
CC ARNTL/BMAL1 induced transcription of BHLHE40/DEC1. Represses the CLOCK-
CC ARNTL/BMAL1 induced transcription of ATF4, MTA1, KLF10 and NAMPT (By
CC similarity). May repress circadian target genes expression in
CC collaboration with HDAC1 and HDAC2 through histone deacetylation.
CC Mediates the clock-control activation of ATR and modulates ATR-mediated
CC DNA damage checkpoint. In liver, mediates circadian regulation of cAMP
CC signaling and gluconeogenesis by binding to membrane-coupled G proteins
CC and blocking glucagon-mediated increases in intracellular cAMP
CC concentrations and CREB1 phosphorylation. Inhibits hepatic
CC gluconeogenesis by decreasing nuclear FOXO1 levels that down-regulates
CC gluconeogenic gene expression (By similarity). Besides its role in the
CC maintenance of the circadian clock, is also involved in the regulation
CC of other processes. Represses glucocorticoid receptor NR3C1/GR-induced
CC transcriptional activity by binding to glucocorticoid response elements
CC (GREs). Plays a key role in glucose and lipid metabolism modulation, in
CC part, through the transcriptional regulation of genes involved in these
CC pathways, such as LEP or ACSL4 (By similarity). Represses PPARD and its
CC target genes in the skeletal muscle and limits exercise capacity (By
CC similarity). Plays an essential role in the generation of circadian
CC rhythms in the retina (By similarity). Represses the transcriptional
CC activity of NR1I2 (By similarity). {ECO:0000250|UniProtKB:P97784,
CC ECO:0000269|PubMed:10531061, ECO:0000269|PubMed:14672706,
CC ECO:0000269|PubMed:22170608, ECO:0000269|PubMed:23133559,
CC ECO:0000269|PubMed:28388406}.
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:P97784};
CC Note=Binds 1 FAD per subunit. Only a minority of the protein molecules
CC contain bound FAD. Contrary to the situation in photolyases, the FAD is
CC bound in a shallow, surface-exposed pocket.
CC {ECO:0000250|UniProtKB:P97784};
CC -!- COFACTOR:
CC Name=(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate;
CC Xref=ChEBI:CHEBI:15636;
CC Note=Binds 1 5,10-methenyltetrahydrofolate (MTHF) non-covalently per
CC subunit.;
CC -!- ACTIVITY REGULATION: KL001 (N-[3-(9H-carbazol-9-yl)-2-hydroxypropyl]-N-
CC (2-furanylmethyl)-methanesulfonamide) binds to CRY1 and stabilizes it
CC by inhibiting FBXL3- and ubiquitin-dependent degradation of CRY1
CC resulting in lengthening of the circadian periods.
CC {ECO:0000269|PubMed:22798407}.
CC -!- SUBUNIT: Component of the circadian core oscillator, which includes the
CC CRY proteins, CLOCK or NPAS2, ARNTL/BMAL1 or ARNTL2/BMAL2, CSNK1D
CC and/or CSNK1E, TIMELESS, and the PER proteins (By similarity).
CC Interacts directly with TIMELESS (By similarity). Interacts directly
CC with PER1 and PER3 (By similarity). Interacts directly with PER2;
CC interaction with PER2 inhibits its ubiquitination and vice versa
CC (PubMed:21613214). Interacts with FBXL21 (By similarity). Interacts
CC with FBXL3 (PubMed:17463251). Interacts with PPP5C (via TPR repeats)
CC (PubMed:16790549). Interacts with CLOCK-ARNTL/BMAL1 independently of
CC PER2 and DNA (PubMed:28388406). Interacts with HDAC1, HDAC2 and SIN3B.
CC Interacts with nuclear receptors AR, NR1D1, NR3C1/GR, RORA and RORC;
CC the interaction with at least NR3C1/GR is ligand dependent
CC (PubMed:22170608). Interacts with PRKDC (By similarity). Interacts with
CC the G protein subunit alpha GNAS; the interaction may block GPCR-
CC mediated regulation of cAMP concentrations (PubMed:20852621). Interacts
CC with PRMT5 (PubMed:23133559). Interacts with EZH2 (By similarity).
CC Interacts with MYBBP1A, DOCK7, HNRNPU, RPL7A, RPL8 and RPS3 (By
CC similarity). Interacts with MAP1LC3B (By similarity). Interacts with
CC CLOCK (By similarity). Interacts with ARNTL/BMAL1 (By similarity).
CC Interacts weakly with HDAC3; this interaction is enhanced in the
CC presence of FBXL3 (By similarity). Interacts with TRIM28, KCTD5 and
CC DDB1 (By similarity). Interacts with FOXO1 (By similarity). Interacts
CC with DTL and DDB1-CUL4A complex (PubMed:26431207). Interacts with HNF4A
CC (PubMed:30530698). Interacts with PSMD2 in a KDM8-dependent manner (By
CC similarity). Interacts with KDM8 in a FBXL3-dependent manner (By
CC similarity). Interacts with PPARG in a ligand-dependent manner (By
CC similarity). Interacts with PPARD (via domain NR LBD) and NR1I2 (via
CC domain NR LBD) in a ligand-dependent manner (By similarity). Interacts
CC with PPARA, NR1I3 and VDR (By similarity).
CC {ECO:0000250|UniProtKB:P97784, ECO:0000269|PubMed:16790549,
CC ECO:0000269|PubMed:17463251, ECO:0000269|PubMed:20852621,
CC ECO:0000269|PubMed:21613214, ECO:0000269|PubMed:22170608,
CC ECO:0000269|PubMed:23133559, ECO:0000269|PubMed:26431207,
CC ECO:0000269|PubMed:28388406, ECO:0000269|PubMed:30530698}.
CC -!- INTERACTION:
CC Q16526; O14744: PRMT5; NbExp=3; IntAct=EBI-741297, EBI-351098;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus {ECO:0000269|PubMed:22798407,
CC ECO:0000269|PubMed:26431207, ECO:0000269|PubMed:28388406}.
CC Note=Translocated to the nucleus through interaction with other clock
CC proteins such as PER2 or ARNTL/BMAL1. {ECO:0000250|UniProtKB:P97784}.
CC -!- INDUCTION: Expression is regulated by light and circadian rhythms and
CC osicllates diurnally. Peak expression in the suprachiasma nucleus (SCN)
CC and eye at the day/night transition (CT12). Levels decrease with
CC ARNTL/BMAL1-CLOCK inhibition as part of the autoregulatory feedback
CC loop.
CC -!- DOMAIN: The LIR motifs (LC3-interacting region) 3 and 5 are required
CC for its interaction with MAP1LC3B and for its autophagy-mediated
CC degradation. {ECO:0000250|UniProtKB:P97784}.
CC -!- PTM: Phosphorylation on Ser-247 by MAPK is important for the inhibition
CC of CLOCK-ARNTL/BMAL1-mediated transcriptional activity. Phosphorylation
CC by CSNK1E requires interaction with PER1 or PER2. Phosphorylation at
CC Ser-71 and Ser-280 by AMPK decreases protein stability. Phosphorylation
CC at Ser-568 exhibits a robust circadian rhythm with a peak at CT8,
CC increases protein stability, prevents SCF(FBXL3)-mediated degradation
CC and is antagonized by interaction with PRKDC.
CC {ECO:0000250|UniProtKB:P97784}.
CC -!- PTM: Ubiquitinated by the SCF(FBXL3) and SCF(FBXL21) complexes,
CC regulating the balance between degradation and stabilization. The
CC SCF(FBXL3) complex is mainly nuclear and mediates ubiquitination and
CC subsequent degradation of CRY1. In contrast, cytoplasmic SCF(FBXL21)
CC complex-mediated ubiquitination leads to stabilize CRY1 and counteract
CC the activity of the SCF(FBXL3) complex. The SCF(FBXL3) and SCF(FBXL21)
CC complexes probably mediate ubiquitination at different Lys residues.
CC Ubiquitination at Lys-11 and Lys-107 are specifically ubiquitinated by
CC the SCF(FBXL21) complex but not by the SCF(FBXL3) complex.
CC Ubiquitination may be inhibited by PER2 (PubMed:17463251,
CC PubMed:22798407, PubMed:27565346). Deubiquitinated by USP7 (By
CC similarity). {ECO:0000250|UniProtKB:P97784,
CC ECO:0000269|PubMed:17463251, ECO:0000269|PubMed:22798407,
CC ECO:0000269|PubMed:27565346}.
CC -!- PTM: Undergoes autophagy-mediated degradation in the liver in a time-
CC dependent manner. Autophagic degradation of CRY1 (an inhibitor of
CC gluconeogenesis) occurs during periods of reduced feeding allowing
CC induction of gluconeogenesis and maintenance of blood glucose levels.
CC {ECO:0000250|UniProtKB:P97784}.
CC -!- DISEASE: Delayed sleep phase syndrome (DSPS) [MIM:614163]: A circadian
CC rhythm sleep disorder characterized by sleep-onset insomnia and
CC difficulty in awakening at the desired time. Patients with DSPS have
CC chronic difficulty in adjusting their sleep-onset and wake-up times to
CC occupational, school, and social activities.
CC {ECO:0000269|PubMed:28388406}. Note=Disease susceptibility is
CC associated with variants affecting the gene represented in this entry.
CC An adenine-to-cytosine transversion within the 5'splice site following
CC exon 11 has been found in multiple members of a DSPD family and
CC segregates with the disorder with autosomal dominant inheritance
CC pattern. This variant is predicted to cause exon 11 skipping and in-
CC frame deletion of 24 residues in the C-terminal region of CRY1.
CC Functional studies show that the mutated protein acts as a more potent
CC transcriptional repressor than wild-type, causes reduced expression of
CC key transcriptional targets and lengthens the period of circadian
CC molecular rhythms. {ECO:0000269|PubMed:28388406}.
CC -!- SIMILARITY: Belongs to the DNA photolyase class-1 family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Cryptochrome entry;
CC URL="https://en.wikipedia.org/wiki/Cryptochrome";
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DR EMBL; D84657; BAA12710.1; -; mRNA.
DR EMBL; D83702; BAA12068.1; -; mRNA.
DR EMBL; BC030519; AAH30519.1; -; mRNA.
DR CCDS; CCDS9112.1; -.
DR RefSeq; NP_004066.1; NM_004075.4.
DR AlphaFoldDB; Q16526; -.
DR SMR; Q16526; -.
DR BioGRID; 107797; 156.
DR ComplexPortal; CPX-3219; Cry1-Per2 complex.
DR ComplexPortal; CPX-3222; Cry1-Per1 complex.
DR ComplexPortal; CPX-3223; Cry1-Per3 complex.
DR CORUM; Q16526; -.
DR DIP; DIP-56602N; -.
DR IntAct; Q16526; 127.
DR MINT; Q16526; -.
DR STRING; 9606.ENSP00000008527; -.
DR GuidetoPHARMACOLOGY; 2876; -.
DR iPTMnet; Q16526; -.
DR PhosphoSitePlus; Q16526; -.
DR BioMuta; CRY1; -.
DR DMDM; 74735764; -.
DR EPD; Q16526; -.
DR jPOST; Q16526; -.
DR MassIVE; Q16526; -.
DR MaxQB; Q16526; -.
DR PaxDb; Q16526; -.
DR PeptideAtlas; Q16526; -.
DR PRIDE; Q16526; -.
DR ProteomicsDB; 60893; -.
DR Antibodypedia; 3122; 297 antibodies from 35 providers.
DR DNASU; 1407; -.
DR Ensembl; ENST00000008527.10; ENSP00000008527.5; ENSG00000008405.12.
DR GeneID; 1407; -.
DR KEGG; hsa:1407; -.
DR MANE-Select; ENST00000008527.10; ENSP00000008527.5; NM_004075.5; NP_004066.1.
DR UCSC; uc001tmi.5; human.
DR CTD; 1407; -.
DR DisGeNET; 1407; -.
DR GeneCards; CRY1; -.
DR HGNC; HGNC:2384; CRY1.
DR HPA; ENSG00000008405; Low tissue specificity.
DR MIM; 601933; gene.
DR MIM; 614163; phenotype.
DR neXtProt; NX_Q16526; -.
DR OpenTargets; ENSG00000008405; -.
DR PharmGKB; PA26904; -.
DR VEuPathDB; HostDB:ENSG00000008405; -.
DR eggNOG; KOG0133; Eukaryota.
DR GeneTree; ENSGT00940000155455; -.
DR HOGENOM; CLU_010348_3_4_1; -.
DR InParanoid; Q16526; -.
DR OMA; WQWSASS; -.
DR OrthoDB; 378952at2759; -.
DR PhylomeDB; Q16526; -.
DR TreeFam; TF323191; -.
DR PathwayCommons; Q16526; -.
DR Reactome; R-HSA-400253; Circadian Clock.
DR SignaLink; Q16526; -.
DR SIGNOR; Q16526; -.
DR BioGRID-ORCS; 1407; 7 hits in 1084 CRISPR screens.
DR ChiTaRS; CRY1; human.
DR GenomeRNAi; 1407; -.
DR Pharos; Q16526; Tchem.
DR PRO; PR:Q16526; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q16526; protein.
DR Bgee; ENSG00000008405; Expressed in oocyte and 206 other tissues.
DR ExpressionAtlas; Q16526; baseline and differential.
DR Genevisible; Q16526; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0009882; F:blue light photoreceptor activity; NAS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IBA:GO_Central.
DR GO; GO:0003690; F:double-stranded DNA binding; IDA:UniProtKB.
DR GO; GO:0070888; F:E-box binding; IEA:Ensembl.
DR GO; GO:0071949; F:FAD binding; IBA:GO_Central.
DR GO; GO:0042826; F:histone deacetylase binding; IEA:Ensembl.
DR GO; GO:0016922; F:nuclear receptor binding; IPI:UniProtKB.
DR GO; GO:0019902; F:phosphatase binding; IPI:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
DR GO; GO:0009785; P:blue light signaling pathway; NAS:UniProtKB.
DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0007623; P:circadian rhythm; ISS:UniProtKB.
DR GO; GO:0006975; P:DNA damage induced protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0043153; P:entrainment of circadian clock by photoperiod; ISS:UniProtKB.
DR GO; GO:0006094; P:gluconeogenesis; ISS:UniProtKB.
DR GO; GO:0042593; P:glucose homeostasis; ISS:UniProtKB.
DR GO; GO:0019915; P:lipid storage; IEA:Ensembl.
DR GO; GO:0042754; P:negative regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:0045744; P:negative regulation of G protein-coupled receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:2000323; P:negative regulation of glucocorticoid receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:2000850; P:negative regulation of glucocorticoid secretion; IEA:Ensembl.
DR GO; GO:0045721; P:negative regulation of gluconeogenesis; ISS:UniProtKB.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:2000001; P:regulation of DNA damage checkpoint; ISS:UniProtKB.
DR GO; GO:0014823; P:response to activity; ISS:UniProtKB.
DR GO; GO:0033762; P:response to glucagon; ISS:UniProtKB.
DR GO; GO:0032868; P:response to insulin; IEA:Ensembl.
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 1: Evidence at protein level;
KW Biological rhythms; Chromophore; Cytoplasm; FAD; Flavoprotein;
KW Isopeptide bond; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Photoreceptor protein; Receptor; Reference proteome; Repressor;
KW Sensory transduction; Transcription; Transcription regulation;
KW Ubl conjugation.
FT CHAIN 1..586
FT /note="Cryptochrome-1"
FT /id="PRO_0000261140"
FT DOMAIN 3..132
FT /note="Photolyase/cryptochrome alpha/beta"
FT REGION 371..470
FT /note="Required for inhibition of CLOCK-ARNTL/BMAL1-
FT mediated transcription"
FT /evidence="ECO:0000250|UniProtKB:P97784"
FT REGION 471..493
FT /note="Interaction with TIMELESS"
FT /evidence="ECO:0000250|UniProtKB:P97784"
FT REGION 552..586
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 50..54
FT /note="LIR 1"
FT /evidence="ECO:0000250|UniProtKB:P97784"
FT MOTIF 82..87
FT /note="LIR 2"
FT /evidence="ECO:0000250|UniProtKB:P97784"
FT MOTIF 151..156
FT /note="LIR 3"
FT /evidence="ECO:0000250|UniProtKB:P97784"
FT MOTIF 255..260
FT /note="LIR 4"
FT /evidence="ECO:0000250|UniProtKB:P97784"
FT MOTIF 271..276
FT /note="LIR 5"
FT /evidence="ECO:0000250|UniProtKB:P97784"
FT MOTIF 285..290
FT /note="LIR 6"
FT /evidence="ECO:0000250|UniProtKB:P97784"
FT MOTIF 335..339
FT /note="LIR 7"
FT /evidence="ECO:0000250|UniProtKB:P97784"
FT MOTIF 379..384
FT /note="LIR 8"
FT /evidence="ECO:0000250|UniProtKB:P97784"
FT MOTIF 395..400
FT /note="LIR 9"
FT /evidence="ECO:0000250|UniProtKB:P97784"
FT MOTIF 411..416
FT /note="LIR 10"
FT /evidence="ECO:0000250|UniProtKB:P97784"
FT MOTIF 430..435
FT /note="LIR 11"
FT /evidence="ECO:0000250|UniProtKB:P97784"
FT MOTIF 486..491
FT /note="LIR 12"
FT /evidence="ECO:0000250|UniProtKB:P97784"
FT MOTIF 492..497
FT /note="LIR 13"
FT /evidence="ECO:0000250|UniProtKB:P97784"
FT BINDING 252
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P97784"
FT BINDING 289
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P97784"
FT BINDING 355
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P97784"
FT BINDING 387..389
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P97784"
FT MOD_RES 71
FT /note="Phosphoserine; by AMPK"
FT /evidence="ECO:0000250|UniProtKB:P97784"
FT MOD_RES 247
FT /note="Phosphoserine; by MAPK"
FT /evidence="ECO:0000250|UniProtKB:P97784"
FT MOD_RES 280
FT /note="Phosphoserine; by AMPK"
FT /evidence="ECO:0000250|UniProtKB:P97784"
FT MOD_RES 568
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P97784"
FT CROSSLNK 11
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P97784"
FT CROSSLNK 107
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P97784"
FT CROSSLNK 159
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P97784"
FT CROSSLNK 329
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P97784"
FT CROSSLNK 485
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P97784"
FT CROSSLNK 565
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P97784"
FT MUTAGEN 387
FT /note="D->N: Loss of binding to KL001."
FT /evidence="ECO:0000269|PubMed:22798407"
FT MUTAGEN 393
FT /note="N->D: Loss of binding to KL001."
FT /evidence="ECO:0000269|PubMed:22798407"
SQ SEQUENCE 586 AA; 66395 MW; 96A5B09A6364D3B9 CRC64;
MGVNAVHWFR KGLRLHDNPA LKECIQGADT IRCVYILDPW FAGSSNVGIN RWRFLLQCLE
DLDANLRKLN SRLFVIRGQP ADVFPRLFKE WNITKLSIEY DSEPFGKERD AAIKKLATEA
GVEVIVRISH TLYDLDKIIE LNGGQPPLTY KRFQTLISKM EPLEIPVETI TSEVIEKCTT
PLSDDHDEKY GVPSLEELGF DTDGLSSAVW PGGETEALTR LERHLERKAW VANFERPRMN
ANSLLASPTG LSPYLRFGCL SCRLFYFKLT DLYKKVKKNS SPPLSLYGQL LWREFFYTAA
TNNPRFDKME GNPICVQIPW DKNPEALAKW AEGRTGFPWI DAIMTQLRQE GWIHHLARHA
VACFLTRGDL WISWEEGMKV FEELLLDADW SINAGSWMWL SCSSFFQQFF HCYCPVGFGR
RTDPNGDYIR RYLPVLRGFP AKYIYDPWNA PEGIQKVAKC LIGVNYPKPM VNHAEASRLN
IERMKQIYQQ LSRYRGLGLL ASVPSNPNGN GGFMGYSAEN IPGCSSSGSC SQGSGILHYA
HGDSQQTHLL KQGRSSMGTG LSGGKRPSQE EDTQSIGPKV QRQSTN
