CRY1_MOUSE
ID CRY1_MOUSE Reviewed; 606 AA.
AC P97784;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Cryptochrome-1;
GN Name=Cry1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Brain, Keratinocyte, and Liver;
RX PubMed=9801304; DOI=10.1093/nar/26.22.5086;
RA Kobayashi K., Kanno S., Smit B., van der Horst G.T.J., Takao M., Yasui A.;
RT "Characterization of photolyase/blue-light receptor homologs in mouse and
RT human cells.";
RL Nucleic Acids Res. 26:5086-5092(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J;
RA Kume K., Reppert S.M.;
RT "Analysis of mouse cryptochromes.";
RL Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryo;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and FVB/N;
RC TISSUE=Brain, Embryonic brain, and Mammary tumor;
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 TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=9600923; DOI=10.1073/pnas.95.11.6097;
RA Miyamoto Y., Sancar A.;
RT "Vitamin B2-based blue-light photoreceptors in the retinohypothalamic tract
RT as the photoactive pigments for setting the circadian clock in mammals.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:6097-6102(1998).
RN [6]
RP FUNCTION, INTERACTION WITH PER1; PER2; PER3 AND TIMELESS, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=10428031; DOI=10.1016/s0092-8674(00)81014-4;
RA Kume K., Zylka M.J., Sriram S., Shearman L.P., Weaver D.R., Jin X.,
RA Maywood E.S., Hastings M.H., Reppert S.M.;
RT "mCRY1 and mCRY2 are essential components of the negative limb of the
RT circadian clock feedback loop.";
RL Cell 98:193-205(1999).
RN [7]
RP TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=10521578; DOI=10.1016/s0169-328x(99)00192-8;
RA Miyamoto Y., Sancar A.;
RT "Circadian regulation of cryptochrome genes in the mouse.";
RL Brain Res. Mol. Brain Res. 71:238-243(1999).
RN [8]
RP IDENTIFICATION IN A COMPLEX WITH CLOCK; PER1; PER2; CRY1; CRY2; CSNK1D AND
RP CSNK1E, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=11779462; DOI=10.1016/s0092-8674(01)00610-9;
RA Lee C., Etchegaray J.-P., Cagampang F.R.A., Loudon A.S.I., Reppert S.M.;
RT "Posttranslational mechanisms regulate the mammalian circadian clock.";
RL Cell 107:855-867(2001).
RN [9]
RP INTERACTION WITH PER2, SUBCELLULAR LOCATION, AND UBIQUITINATION.
RX PubMed=11889036; DOI=10.1093/emboj/21.6.1301;
RA Yagita K., Tamanini F., Yasuda M., Hoeijmakers J.H., van der Horst G.T.,
RA Okamura H.;
RT "Nucleocytoplasmic shuttling and mCRY-dependent inhibition of
RT ubiquitylation of the mPER2 clock protein.";
RL EMBO J. 21:1301-1314(2002).
RN [10]
RP INTERACTION WITH PER1 AND PER2, PHOSPHORYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=11875063; DOI=10.1074/jbc.m111466200;
RA Eide E.J., Vielhaber E.L., Hinz W.A., Virshup D.M.;
RT "The circadian regulatory proteins BMAL1 and cryptochromes are substrates
RT of casein kinase Iepsilon.";
RL J. Biol. Chem. 277:17248-17254(2002).
RN [11]
RP PHOSPHORYLATION AT SER-247, AND MUTAGENESIS OF SER-247.
RX PubMed=15298678; DOI=10.1111/j.1356-9597.2004.00758.x;
RA Sanada K., Harada Y., Sakai M., Todo T., Fukada Y.;
RT "Serine phosphorylation of mCRY1 and mCRY2 by mitogen-activated protein
RT kinase.";
RL Genes Cells 9:697-708(2004).
RN [12]
RP INTERACTION WITH PER1; PER2 AND PER3.
RX PubMed=14701732; DOI=10.1128/mcb.24.2.584-594.2004;
RA Lee C., Weaver D.R., Reppert S.M.;
RT "Direct association between mouse PERIOD and CKIepsilon is critical for a
RT functioning circadian clock.";
RL Mol. Cell. Biol. 24:584-594(2004).
RN [13]
RP FUNCTION AS TRANSCRIPTION REPRESSOR, AND INTERACTION WITH HDAC1; HDAC2 AND
RP SIN3B.
RX PubMed=15226430; DOI=10.1128/mcb.24.14.6278-6287.2004;
RA Naruse Y., Oh-hashi K., Iijima N., Naruse M., Yoshioka H., Tanaka M.;
RT "Circadian and light-induced transcription of clock gene Per1 depends on
RT histone acetylation and deacetylation.";
RL Mol. Cell. Biol. 24:6278-6287(2004).
RN [14]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=16628007; DOI=10.4161/cc.5.8.2684;
RA Kondratov R.V., Kondratova A.A., Lee C., Gorbacheva V.Y., Chernov M.V.,
RA Antoch M.P.;
RT "Post-translational regulation of circadian transcriptional
RT CLOCK(NPAS2)/BMAL1 complex by CRYPTOCHROMES.";
RL Cell Cycle 5:890-895(2006).
RN [15]
RP INTERACTION WITH EZH2; CLOCK AND ARNTL.
RX PubMed=16717091; DOI=10.1074/jbc.m603722200;
RA Etchegaray J.P., Yang X., DeBruyne J.P., Peters A.H., Weaver D.R.,
RA Jenuwein T., Reppert S.M.;
RT "The polycomb group protein EZH2 is required for mammalian circadian clock
RT function.";
RL J. Biol. Chem. 281:21209-21215(2006).
RN [16]
RP FUNCTION, INTERACTION WITH PER1 AND PER2, AND SUBCELLULAR LOCATION.
RX PubMed=16478995; DOI=10.1128/mcb.26.5.1743-1753.2006;
RA Chaves I., Yagita K., Barnhoorn S., Okamura H., van der Horst G.T.J.,
RA Tamanini F.;
RT "Functional evolution of the photolyase/cryptochrome protein family:
RT importance of the C terminus of mammalian CRY1 for circadian core
RT oscillator performance.";
RL Mol. Cell. Biol. 26:1743-1753(2006).
RN [17]
RP TISSUE SPECIFICITY, AND INDUCTION.
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 [18]
RP INTERACTION WITH FBXL3, AND UBIQUITINATION.
RX PubMed=17462724; DOI=10.1016/j.cell.2007.04.030;
RA Siepka S.M., Yoo S.H., Park J., Song W., Kumar V., Hu Y., Lee C.,
RA Takahashi J.S.;
RT "Circadian mutant Overtime reveals F-box protein FBXL3 regulation of
RT cryptochrome and period gene expression.";
RL Cell 129:1011-1023(2007).
RN [19]
RP FUNCTION.
RX PubMed=17310242; DOI=10.1038/ncb1539;
RA Zhao W.N., Malinin N., Yang F.C., Staknis D., Gekakis N., Maier B.,
RA Reischl S., Kramer A., Weitz C.J.;
RT "CIPC is a mammalian circadian clock protein without invertebrate
RT homologues.";
RL Nat. Cell Biol. 9:268-275(2007).
RN [20]
RP INTERACTION WITH FBXL21, AND UBIQUITINATION.
RX PubMed=18953409; DOI=10.1371/journal.pone.0003530;
RA Dardente H., Mendoza J., Fustin J.M., Challet E., Hazlerigg D.G.;
RT "Implication of the F-Box Protein FBXL21 in circadian pacemaker function in
RT mammals.";
RL PLoS ONE 3:E3530-E3530(2008).
RN [21]
RP INTERACTION WITH ARNTL AND CLOCK, AND INDUCTION.
RX PubMed=19917250; DOI=10.1016/j.molcel.2009.10.012;
RA Chen R., Schirmer A., Lee Y., Lee H., Kumar V., Yoo S.H., Takahashi J.S.,
RA Lee C.;
RT "Rhythmic PER abundance defines a critical nodal point for negative
RT feedback within the circadian clock mechanism.";
RL Mol. Cell 36:417-430(2009).
RN [22]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH MYBBP1A; DOCK7;
RP HNRNPU; RPL7A; RPL8 AND RPS3.
RX PubMed=19129230; DOI=10.1093/nar/gkn1013;
RA Hara Y., Onishi Y., Oishi K., Miyazaki K., Fukamizu A., Ishida N.;
RT "Molecular characterization of Mybbp1a as a co-repressor on the Period2
RT promoter.";
RL Nucleic Acids Res. 37:1115-1126(2009).
RN [23]
RP PHOSPHORYLATION AT SER-71 AND SER-280, AND MUTAGENESIS OF SER-71 AND
RP SER-280.
RX PubMed=19833968; DOI=10.1126/science.1172156;
RA Lamia K.A., Sachdeva U.M., DiTacchio L., Williams E.C., Alvarez J.G.,
RA Egan D.F., Vasquez D.S., Juguilon H., Panda S., Shaw R.J., Thompson C.B.,
RA Evans R.M.;
RT "AMPK regulates the circadian clock by cryptochrome phosphorylation and
RT degradation.";
RL Science 326:437-440(2009).
RN [24]
RP FUNCTION.
RX PubMed=19299583; DOI=10.1126/science.1171641;
RA Ramsey K.M., Yoshino J., Brace C.S., Abrassart D., Kobayashi Y.,
RA Marcheva B., Hong H.K., Chong J.L., Buhr E.D., Lee C., Takahashi J.S.,
RA Imai S., Bass J.;
RT "Circadian clock feedback cycle through NAMPT-mediated NAD+ biosynthesis.";
RL Science 324:651-654(2009).
RN [25]
RP INTERACTION WITH PER2.
RX PubMed=20159955; DOI=10.1101/gad.564110;
RA Schmutz I., Ripperger J.A., Baeriswyl-Aebischer S., Albrecht U.;
RT "The mammalian clock component PERIOD2 coordinates circadian output by
RT interaction with nuclear receptors.";
RL Genes Dev. 24:345-357(2010).
RN [26]
RP FUNCTION, AND INDUCTION.
RX PubMed=20385766; DOI=10.1128/mcb.01141-09;
RA Guillaumond F., Grechez-Cassiau A., Subramaniam M., Brangolo S.,
RA Peteri-Brunback B., Staels B., Fievet C., Spelsberg T.C., Delaunay F.,
RA Teboul M.;
RT "Kruppel-like factor KLF10 is a link between the circadian clock and
RT metabolism in liver.";
RL Mol. Cell. Biol. 30:3059-3070(2010).
RN [27]
RP FUNCTION IN GLUCONEOGENESIS, AND DISRUPTION PHENOTYPE.
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 [28]
RP FUNCTION IN CIRCADIAN RHYTHMS REGULATION, AND INDUCTION.
RX PubMed=21236481; DOI=10.1016/j.cell.2010.12.019;
RA Ukai-Tadenuma M., Yamada R.G., Xu H., Ripperger J.A., Liu A.C., Ueda H.R.;
RT "Delay in feedback repression by cryptochrome 1 is required for circadian
RT clock function.";
RL Cell 144:268-281(2011).
RN [29]
RP INTERACTION WITH CLOCK-ARNTL AND 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 [30]
RP FUNCTION.
RX PubMed=21768648; DOI=10.1074/jbc.m111.258970;
RA Koyanagi S., Hamdan A.M., Horiguchi M., Kusunose N., Okamoto A.,
RA Matsunaga N., Ohdo S.;
RT "cAMP-response element (CRE)-mediated transcription by activating
RT transcription factor-4 (ATF4) is essential for circadian expression of the
RT Period2 gene.";
RL J. Biol. Chem. 286:32416-32423(2011).
RN [31]
RP FUNCTION AS NR3C1 REPRESSOR, INTERACTION WITH AR; NR1D1; NR3C1; RORA AND
RP RORC, AND DISRUPTION PHENOTYPE.
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 [32]
RP FUNCTION, INDUCTION, 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 [33]
RP ACTIVITY REGULATION.
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 [34]
RP FUNCTION IN METABOLISM, AND DISRUPTION PHENOTYPE.
RX PubMed=23531614; DOI=10.1152/ajpendo.00512.2012;
RA Barclay J.L., Shostak A., Leliavski A., Tsang A.H., Johren O.,
RA Muller-Fielitz H., Landgraf D., Naujokat N., van der Horst G.T., Oster H.;
RT "High-fat diet-induced hyperinsulinemia and tissue-specific insulin
RT resistance in Cry-deficient mice.";
RL Am. J. Physiol. 304:E1053-E1063(2013).
RN [35]
RP UBIQUITINATION BY THE SCF(FBXL3) AND SCF(FBXL21) COMPLEXES, INTERACTION
RP WITH FBXL3 AND FBXL21, AND UBIQUITINATION AT LYS-11.
RX PubMed=23452855; DOI=10.1016/j.cell.2013.01.055;
RA Yoo S.H., Mohawk J.A., Siepka S.M., Shan Y., Huh S.K., Hong H.K.,
RA Kornblum I., Kumar V., Koike N., Xu M., Nussbaum J., Liu X., Chen Z.,
RA Chen Z.J., Green C.B., Takahashi J.S.;
RT "Competing E3 ubiquitin ligases govern circadian periodicity by degradation
RT of CRY in nucleus and cytoplasm.";
RL Cell 152:1091-1105(2013).
RN [36]
RP UBIQUITINATION BY THE SCF(FBXL3) AND SCF(FBXL21) COMPLEXES, UBIQUITINATION
RP AT LYS-107; LYS-159; LYS-329 AND LYS-485, INTERACTION WITH FBXL3 AND
RP FBXL21, AND MUTAGENESIS OF LYS-107.
RX PubMed=23452856; DOI=10.1016/j.cell.2013.01.054;
RA Hirano A., Yumimoto K., Tsunematsu R., Matsumoto M., Oyama M.,
RA Kozuka-Hata H., Nakagawa T., Lanjakornsiripan D., Nakayama K.I., Fukada Y.;
RT "FBXL21 regulates oscillation of the circadian clock through ubiquitination
RT and stabilization of cryptochromes.";
RL Cell 152:1106-1118(2013).
RN [37]
RP FUNCTION IN CIRCADIAN CLOCK, INTERACTION WITH PRKDC, PHOSPHORYLATION AT
RP SER-588, AND MUTAGENESIS OF SER-551; SER-564 AND SER-588.
RX PubMed=24158435; DOI=10.1074/jbc.m113.509604;
RA Gao P., Yoo S.H., Lee K.J., Rosensweig C., Takahashi J.S., Chen B.P.,
RA Green C.B.;
RT "Phosphorylation of the cryptochrome 1 C-terminal tail regulates circadian
RT period length.";
RL J. Biol. Chem. 288:35277-35286(2013).
RN [38]
RP FUNCTION IN CIRCADIAN CLOCK, AND DISRUPTION PHENOTYPE.
RX PubMed=23616524; DOI=10.1523/jneurosci.4950-12.2013;
RA Anand S.N., Maywood E.S., Chesham J.E., Joynson G., Banks G.T.,
RA Hastings M.H., Nolan P.M.;
RT "Distinct and separable roles for endogenous CRY1 and CRY2 within the
RT circadian molecular clockwork of the suprachiasmatic nucleus, as revealed
RT by the Fbxl3(Afh) mutation.";
RL J. Neurosci. 33:7145-7153(2013).
RN [39]
RP FUNCTION IN CIRCADIAN CLOCK.
RX PubMed=23575670; DOI=10.1038/ncomms2670;
RA Ono D., Honma S., Honma K.;
RT "Cryptochromes are critical for the development of coherent circadian
RT rhythms in the mouse suprachiasmatic nucleus.";
RL Nat. Commun. 4:1666-1666(2013).
RN [40]
RP FUNCTION.
RX PubMed=24089055; DOI=10.1038/ncomms3545;
RA Li D.Q., Pakala S.B., Reddy S.D., Peng S., Balasenthil S., Deng C.X.,
RA Lee C.C., Rea M.A., Kumar R.;
RT "Metastasis-associated protein 1 is an integral component of the circadian
RT molecular machinery.";
RL Nat. Commun. 4:2545-2545(2013).
RN [41]
RP INTERACTION WITH TIMELESS AND PER2, AND SUBCELLULAR LOCATION.
RX PubMed=23418588; DOI=10.1371/journal.pone.0056623;
RA Engelen E., Janssens R.C., Yagita K., Smits V.A., van der Horst G.T.,
RA Tamanini F.;
RT "Mammalian TIMELESS is involved in period determination and DNA damage-
RT dependent phase advancing of the circadian clock.";
RL PLoS ONE 8:E56623-E56623(2013).
RN [42]
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 [43]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24385426; DOI=10.1074/jbc.m113.534651;
RA Annayev Y., Adar S., Chiou Y.Y., Lieb J., Sancar A., Ye R.;
RT "Gene model 129 (Gm129) encodes a novel transcriptional repressor that
RT modulates circadian gene expression.";
RL J. Biol. Chem. 289:5013-5024(2014).
RN [44]
RP FUNCTION IN GR REPRESSION.
RX PubMed=24378737; DOI=10.1016/j.mce.2013.12.013;
RA Han D.H., Lee Y.J., Kim K., Kim C.J., Cho S.;
RT "Modulation of glucocorticoid receptor induction properties by core
RT circadian clock proteins.";
RL Mol. Cell. Endocrinol. 383:170-180(2014).
RN [45]
RP FUNCTION IN DNA DAMAGE CHECKPOINT, INTERACTION WITH TIMELESS, AND
RP SUBCELLULAR LOCATION.
RX PubMed=24489120; DOI=10.1093/nar/gku094;
RA Kang T.H., Leem S.H.;
RT "Modulation of ATR-mediated DNA damage checkpoint response by cryptochrome
RT 1.";
RL Nucleic Acids Res. 42:4427-4434(2014).
RN [46]
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 [47]
RP FUNCTION, INTERACTION WITH DDB1-CUL4A COMPLEX, UBIQUITINATION AT LYS-585,
RP AND MUTAGENESIS OF LYS-585.
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 [48]
RP UBIQUITINATION AND PROTEASOMAL DEGRADATION, AND INTERACTION WITH HDAC3 AND
RP ARNTL.
RX PubMed=26776516; DOI=10.1016/j.celrep.2015.12.076;
RA Shi G., Xie P., Qu Z., Zhang Z., Dong Z., An Y., Xing L., Liu Z., Dong Y.,
RA Xu G., Yang L., Liu Y., Xu Y.;
RT "Distinct roles of HDAC3 in the core circadian negative feedback loop are
RT critical for clock function.";
RL Cell Rep. 14:823-834(2016).
RN [49]
RP DEUBIQUITINATION BY USP7, AND INTERACTION WITH TRIM28; KCTD5 AND DDB1.
RX PubMed=27123980; DOI=10.1371/journal.pone.0154263;
RA Hirano A., Nakagawa T., Yoshitane H., Oyama M., Kozuka-Hata H.,
RA Lanjakornsiripan D., Fukada Y.;
RT "USP7 and TDP-43: pleiotropic regulation of cryptochrome protein stability
RT paces the oscillation of the mammalian circadian clock.";
RL PLoS ONE 11:E0154263-E0154263(2016).
RN [50]
RP FUNCTION, DISRUPTION PHENOTYPE, AND INTERACTION WITH PPARA; PPARD AND
RP PPARG.
RX PubMed=28683290; DOI=10.1016/j.cmet.2017.06.002;
RA Jordan S.D., Kriebs A., Vaughan M., Duglan D., Fan W., Henriksson E.,
RA Huber A.L., Papp S.J., Nguyen M., Afetian M., Downes M., Yu R.T.,
RA Kralli A., Evans R.M., Lamia K.A.;
RT "CRY1/2 selectively repress PPARdelta and limit exercise capacity.";
RL Cell Metab. 26:243-255(2017).
RN [51]
RP FUNCTION, AND INTERACTION WITH FOXO1.
RX PubMed=28790135; DOI=10.2337/db16-1600;
RA Tong X., Zhang D., Charney N., Jin E., VanDommelen K., Stamper K.,
RA Gupta N., Saldate J., Yin L.;
RT "DDB1-mediated CRY1 degradation promotes FOXO1-driven gluconeogenesis in
RT liver.";
RL Diabetes 66:2571-2582(2017).
RN [52]
RP FUNCTION, AND INTERACTION WITH NR1I2; NR1I3; NR3C1; PPARD; VDR; AR AND
RP HNF4A.
RX PubMed=28751364; DOI=10.1073/pnas.1704955114;
RA Kriebs A., Jordan S.D., Soto E., Henriksson E., Sandate C.R., Vaughan M.E.,
RA Chan A.B., Duglan D., Papp S.J., Huber A.L., Afetian M.E., Yu R.T.,
RA Zhao X., Downes M., Evans R.M., Lamia K.A.;
RT "Circadian repressors CRY1 and CRY2 broadly interact with nuclear receptors
RT and modulate transcriptional activity.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:8776-8781(2017).
RN [53]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=29561690; DOI=10.1096/fj.201701165rr;
RA Wong J.C.Y., Smyllie N.J., Banks G.T., Pothecary C.A., Barnard A.R.,
RA Maywood E.S., Jagannath A., Hughes S., van der Horst G.T.J., MacLaren R.E.,
RA Hankins M.W., Hastings M.H., Nolan P.M., Foster R.G., Peirson S.N.;
RT "Differential roles for cryptochromes in the mammalian retinal clock.";
RL FASEB J. 32:4302-4314(2018).
RN [54]
RP INTERACTION WITH KDM8; FBXL3 AND PSMD2.
RX PubMed=30500822; DOI=10.1371/journal.pbio.2006145;
RA Saran A.R., Kalinowska D., Oh S., Janknecht R., DiTacchio L.;
RT "JMJD5 links CRY1 function and proteasomal degradation.";
RL PLoS Biol. 16:E2006145-E2006145(2018).
RN [55]
RP FUNCTION, INTERACTION WITH MAP1LC3B, LIR MOTIFS, DEGRADATION VIA AUTOPHAGY,
RP AND MUTAGENESIS OF TYR-273; VAL-276; TYR-287; LEU-290; TYR-488; LEU-491;
RP TYR-494 AND LEU-497.
RX PubMed=29937374; DOI=10.1016/j.cmet.2018.05.023;
RA Toledo M., Batista-Gonzalez A., Merheb E., Aoun M.L., Tarabra E., Feng D.,
RA Sarparanta J., Merlo P., Botre F., Schwartz G.J., Pessin J.E., Singh R.;
RT "Autophagy regulates the liver clock and glucose metabolism by degrading
RT CRY1.";
RL Cell Metab. 28:268-281(2018).
RN [56]
RP X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF APOPROTEIN, INTERACTION WITH
RP ARNTL; PER2 AND FBXL3, FUNCTION, FAD-BINDING SITES, AND MUTAGENESIS OF
RP HIS-224; SER-247; 382-GLU-GLU-383; PHE-405 AND LYS-485.
RX PubMed=23746849; DOI=10.1016/j.cell.2013.05.011;
RA Czarna A., Berndt A., Singh H.R., Grudziecki A., Ladurner A.G.,
RA Timinszky G., Kramer A., Wolf E.;
RT "Structures of Drosophila cryptochrome and mouse cryptochrome1 provide
RT insight into circadian function.";
RL Cell 153:1394-1405(2013).
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, ATF4, MTA1, KLF10
CC and NAMPT. 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. Besides its role in the maintenance of
CC the circadian clock, is also involved in the regulation of other
CC 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. Represses PPARD and its target genes in
CC the skeletal muscle and limits exercise capacity (PubMed:28683290).
CC Plays an essential role in the generation of circadian rhythms in the
CC retina (PubMed:29561690). Represses the transcriptional activity of
CC NR1I2 (PubMed:28751364). {ECO:0000269|PubMed:10428031,
CC ECO:0000269|PubMed:15226430, ECO:0000269|PubMed:16478995,
CC ECO:0000269|PubMed:16628007, ECO:0000269|PubMed:17310242,
CC ECO:0000269|PubMed:19129230, ECO:0000269|PubMed:19299583,
CC ECO:0000269|PubMed:20385766, ECO:0000269|PubMed:20852621,
CC ECO:0000269|PubMed:21236481, ECO:0000269|PubMed:21768648,
CC ECO:0000269|PubMed:22170608, ECO:0000269|PubMed:23133559,
CC ECO:0000269|PubMed:23531614, ECO:0000269|PubMed:23575670,
CC ECO:0000269|PubMed:23616524, ECO:0000269|PubMed:23746849,
CC ECO:0000269|PubMed:24089055, ECO:0000269|PubMed:24158435,
CC ECO:0000269|PubMed:24378737, ECO:0000269|PubMed:24385426,
CC ECO:0000269|PubMed:24489120, ECO:0000269|PubMed:26431207,
CC ECO:0000269|PubMed:28683290, ECO:0000269|PubMed:28751364,
CC ECO:0000269|PubMed:28790135, ECO:0000269|PubMed:29561690,
CC ECO:0000269|PubMed:29937374}.
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:23746849};
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:0000269|PubMed:23746849};
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 -!- 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. KL001-mediated CRY1
CC stabilization can inhibit glucagon-induced gluconeogenesis in primary
CC hepatocytes. {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 (PubMed:11779462).
CC Interacts directly with TIMELESS (PubMed:10428031, PubMed:24489120,
CC PubMed:23418588). Interacts directly with PER1 and PER2; interaction
CC with PER2 inhibits its ubiquitination and vice versa (PubMed:10428031,
CC PubMed:11889036, PubMed:11875063, PubMed:14701732, PubMed:16478995,
CC PubMed:23746849, PubMed:23418588, PubMed:21613214, PubMed:20159955).
CC Interacts with PER3 (PubMed:10428031, PubMed:14701732). Interacts with
CC FBXL21 (PubMed:18953409, PubMed:23452855, PubMed:23452856). Interacts
CC with FBXL3 (PubMed:17462724, PubMed:23746849, PubMed:23452855,
CC PubMed:23452856, PubMed:30500822). Interacts with PPP5C (via TPR
CC repeats) (By similarity). Interacts with CLOCK-ARNTL/BMAL1
CC independently of PER2 and DNA (PubMed:21613214). Interacts with HDAC1,
CC HDAC2 and SIN3B (PubMed:15226430). Interacts with nuclear receptors AR,
CC NR1D1, NR3C1/GR, RORA and RORC; the interaction with at least NR3C1/GR
CC is ligand dependent (PubMed:22170608, PubMed:28751364). Interacts with
CC PRKDC (PubMed:24158435). Interacts with the G protein subunit alpha
CC GNAS; the interaction may block GPCR-mediated regulation of cAMP
CC concentrations (By similarity). Interacts with PRMT5 (PubMed:23133559).
CC Interacts with EZH2 (PubMed:16717091). Interacts with MYBBP1A, DOCK7,
CC HNRNPU, RPL7A, RPL8 and RPS3 (PubMed:19129230). Interacts with MAP1LC3B
CC (PubMed:29937374). Interacts with CLOCK (PubMed:16717091,
CC PubMed:19917250). Interacts with ARNTL/BMAL1 (PubMed:26776516,
CC PubMed:16717091, PubMed:19917250, PubMed:23746849). Interacts weakly
CC with HDAC3; this interaction is enhanced in the presence of FBXL3
CC (PubMed:26776516). Interacts with TRIM28, KCTD5 and DDB1
CC (PubMed:27123980). Interacts with DTL (By similarity). Interacts with
CC DDB1-CUL4A complex (PubMed:26431207). Interacts with FOXO1
CC (PubMed:28790135). Interacts with PSMD2 in a KDM8-dependent manner
CC (PubMed:30500822). Interacts with KDM8 in a FBXL3-dependent manner
CC (PubMed:30500822). Interacts with PPARA (PubMed:28683290). Interacts
CC with PPARG in a ligand-dependent manner (PubMed:28683290). Interacts
CC with PPARD (via domain NR LBD) in a ligand-dependent manner
CC (PubMed:28683290, PubMed:28751364). Interacts with NR1I2 (via domain NR
CC LBD) in a ligand-dependent manner (PubMed:28751364). Interacts with
CC NR1I3, VDR and HNF4A (PubMed:28751364). {ECO:0000250|UniProtKB:Q16526,
CC ECO:0000269|PubMed:10428031, ECO:0000269|PubMed:11779462,
CC ECO:0000269|PubMed:11875063, ECO:0000269|PubMed:11889036,
CC ECO:0000269|PubMed:14701732, ECO:0000269|PubMed:15226430,
CC ECO:0000269|PubMed:16478995, ECO:0000269|PubMed:16717091,
CC ECO:0000269|PubMed:17462724, ECO:0000269|PubMed:18953409,
CC ECO:0000269|PubMed:19129230, ECO:0000269|PubMed:19917250,
CC ECO:0000269|PubMed:20159955, ECO:0000269|PubMed:21613214,
CC ECO:0000269|PubMed:22170608, ECO:0000269|PubMed:23133559,
CC ECO:0000269|PubMed:23418588, ECO:0000269|PubMed:23452855,
CC ECO:0000269|PubMed:23452856, ECO:0000269|PubMed:23746849,
CC ECO:0000269|PubMed:24158435, ECO:0000269|PubMed:24489120,
CC ECO:0000269|PubMed:26431207, ECO:0000269|PubMed:26776516,
CC ECO:0000269|PubMed:27123980, ECO:0000269|PubMed:28683290,
CC ECO:0000269|PubMed:28751364, ECO:0000269|PubMed:28790135,
CC ECO:0000269|PubMed:29937374, ECO:0000269|PubMed:30500822}.
CC -!- INTERACTION:
CC P97784; Q9WTL8: Arntl; NbExp=23; IntAct=EBI-1266607, EBI-644534;
CC P97784; Q9WTL8-2: Arntl; NbExp=4; IntAct=EBI-1266607, EBI-644559;
CC P97784; Q9WTL8-4: Arntl; NbExp=4; IntAct=EBI-1266607, EBI-644568;
CC P97784; Q2VPD4: Arntl2; NbExp=3; IntAct=EBI-1266607, EBI-9696862;
CC P97784; O08785: Clock; NbExp=10; IntAct=EBI-1266607, EBI-79859;
CC P97784; P67871: Csnk2b; NbExp=4; IntAct=EBI-1266607, EBI-348179;
CC P97784; Q8BFZ4: Fbxl21; NbExp=10; IntAct=EBI-1266607, EBI-6898235;
CC P97784; Q8C4V4: Fbxl3; NbExp=12; IntAct=EBI-1266607, EBI-1266589;
CC P97784; P06537-1: Nr3c1; NbExp=3; IntAct=EBI-1266607, EBI-15959147;
CC P97784; O35973: Per1; NbExp=3; IntAct=EBI-1266607, EBI-1266764;
CC P97784; O54943: Per2; NbExp=22; IntAct=EBI-1266607, EBI-1266779;
CC P97784; Q8CIG8: Prmt5; NbExp=2; IntAct=EBI-1266607, EBI-2527009;
CC P97784; P67870: CSNK2B; Xeno; NbExp=2; IntAct=EBI-1266607, EBI-348169;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11779462}. Nucleus
CC {ECO:0000269|PubMed:11779462, ECO:0000269|PubMed:19129230}.
CC Note=Transloctaed to the nucleus through interaction with other clock
CC proteins such as PER2 or ARNTL/BMAL1.
CC -!- TISSUE SPECIFICITY: Expressed in cones, amacrine cells, and retinal
CC ganglion cells of the retina (at protein level) (PubMed:29561690).
CC Expressed in all tissues examined including heart, brain, spleen, lung,
CC liver, skeletal muscle, kidney and testis. Higher levels in brain,
CC liver and testis. In the retina, highly expressed in the ganglion cell
CC layer (GCL) and in the inner nuclear layer (INL). Evenly distributed in
CC central and peripheral retina. In the brain, highly expressed in the
CC suprachiasmatic nucleus (SCN). High levels in cerebral cortical layers
CC particularly in the pyramidial cell layer of the hippocampus, the
CC granular cell layer of the dentate gyrus (DG) and the pyramidal cell
CC layer of the piriform cortex (PFC). {ECO:0000269|PubMed:10428031,
CC ECO:0000269|PubMed:10521578, ECO:0000269|PubMed:11779462,
CC ECO:0000269|PubMed:16790549, ECO:0000269|PubMed:29561690,
CC ECO:0000269|PubMed:9600923, ECO:0000269|PubMed:9801304}.
CC -!- INDUCTION: Oscillates diurnally, rhythmic expression in the early night
CC is critical for clock function (at protein level). In SCN, exhibits
CC circadian rhythm expression with highest levels during the light phase
CC at CT10. No detectable expression after 8 hours in the dark. Circadian
CC oscillations also observed in liver, skeletal muscle and cerebellum,
CC but not in testis. {ECO:0000269|PubMed:10428031,
CC ECO:0000269|PubMed:10521578, ECO:0000269|PubMed:16790549,
CC ECO:0000269|PubMed:19917250, ECO:0000269|PubMed:20385766,
CC ECO:0000269|PubMed:21236481, ECO:0000269|PubMed:23133559,
CC ECO:0000269|PubMed:9600923}.
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:0000269|PubMed:29937374}.
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-588 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:0000269|PubMed:11875063, ECO:0000269|PubMed:15298678,
CC ECO:0000269|PubMed:19833968, ECO:0000269|PubMed:24158435}.
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. Deubiquitinated by USP7
CC (PubMed:27123980). {ECO:0000269|PubMed:11889036,
CC ECO:0000269|PubMed:17462724, ECO:0000269|PubMed:18953409,
CC ECO:0000269|PubMed:23452855, ECO:0000269|PubMed:23452856,
CC ECO:0000269|PubMed:26776516, ECO:0000269|PubMed:27123980}.
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:0000269|PubMed:29937374}.
CC -!- DISRUPTION PHENOTYPE: Mice show an advanced phase shift (around 4
CC hours) in the expression of DBP, NR1D1 and PER1 genes in the liver.
CC Double knockouts of CRY1 and CRY2 show slightly decrease body weight
CC and lose the cycling rhythmicity of feeding behavior, energy
CC expenditure and glucocorticoids expression. Glucose homeostasis is
CC severely disrupted and animals exhibit elevated blood glucose in
CC response to acute feeding after an overnight fast as well as severely
CC impaired glucose clearance in a glucose tolerance test. When challenged
CC with high-fat diet, animals rapidly gain weight and surpass that of
CC wild-type mice, despite displaying hypophagia. They exhibit
CC hyperinsulinemia and selective insulin resistance in the liver and
CC muscle but show high insulin sensitivity in adipose tissue and
CC consequent increased lipid uptake. Mice display enlarged gonadal,
CC subcutaneous and perirenal fat deposits with adipocyte hypertrophy and
CC increased lipied accumulation in liver. Mice show loss of circadian
CC rhythms in photopic ERG b-wave amplitudes, visual contrast sensitivity
CC and pupillary light responses, with reduced robustness and stability of
CC bioluminescent rhythms (PubMed:29561690). Both single CRY1 knockout and
CC double CRY1 and CRY2 knockout mice show increased exercise performance
CC and increased mitochondrial reserve capacity in primary myotubes
CC (PubMed:28683290). {ECO:0000269|PubMed:20852621,
CC ECO:0000269|PubMed:22170608, ECO:0000269|PubMed:23531614,
CC ECO:0000269|PubMed:23616524, ECO:0000269|PubMed:24385426,
CC ECO:0000269|PubMed:28683290, ECO:0000269|PubMed:29561690}.
CC -!- SIMILARITY: Belongs to the DNA photolyase class-1 family.
CC {ECO:0000305}.
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DR EMBL; AB000777; BAA19175.1; -; mRNA.
DR EMBL; AF156986; AAD39548.1; -; mRNA.
DR EMBL; AK162460; BAE36931.1; -; mRNA.
DR EMBL; BC022174; AAH22174.1; -; mRNA.
DR EMBL; BC085499; AAH85499.1; -; mRNA.
DR CCDS; CCDS24089.1; -.
DR RefSeq; NP_031797.1; NM_007771.3.
DR PDB; 4CT0; X-ray; 2.45 A; A=1-496.
DR PDB; 4K0R; X-ray; 2.65 A; A=1-606.
DR PDB; 5T5X; X-ray; 1.84 A; A=1-491.
DR PDB; 6KX4; X-ray; 2.00 A; A=1-496.
DR PDB; 6KX5; X-ray; 2.00 A; A=1-496.
DR PDB; 6KX6; X-ray; 2.00 A; A/B=1-496.
DR PDB; 6KX7; X-ray; 2.10 A; A=1-496.
DR PDB; 6LUE; X-ray; 2.10 A; A/B=1-496.
DR PDB; 6OF7; X-ray; 3.11 A; A=1-491.
DR PDB; 7D0M; X-ray; 1.95 A; A=1-496.
DR PDB; 7D19; X-ray; 2.35 A; A/B=1-496.
DR PDB; 7D1C; X-ray; 1.91 A; A=1-496.
DR PDB; 7DLI; X-ray; 2.20 A; A/B/C=1-496.
DR PDBsum; 4CT0; -.
DR PDBsum; 4K0R; -.
DR PDBsum; 5T5X; -.
DR PDBsum; 6KX4; -.
DR PDBsum; 6KX5; -.
DR PDBsum; 6KX6; -.
DR PDBsum; 6KX7; -.
DR PDBsum; 6LUE; -.
DR PDBsum; 6OF7; -.
DR PDBsum; 7D0M; -.
DR PDBsum; 7D19; -.
DR PDBsum; 7D1C; -.
DR PDBsum; 7DLI; -.
DR AlphaFoldDB; P97784; -.
DR SMR; P97784; -.
DR BioGRID; 198906; 35.
DR ComplexPortal; CPX-3209; Cry1-Per2 complex.
DR ComplexPortal; CPX-3216; Cry1-Per1 complex.
DR ComplexPortal; CPX-3217; Cry1-Per3 complex.
DR CORUM; P97784; -.
DR DIP; DIP-38515N; -.
DR IntAct; P97784; 49.
DR MINT; P97784; -.
DR STRING; 10090.ENSMUSP00000020227; -.
DR iPTMnet; P97784; -.
DR PhosphoSitePlus; P97784; -.
DR EPD; P97784; -.
DR MaxQB; P97784; -.
DR PaxDb; P97784; -.
DR PeptideAtlas; P97784; -.
DR PRIDE; P97784; -.
DR ProteomicsDB; 284026; -.
DR Antibodypedia; 3122; 297 antibodies from 35 providers.
DR DNASU; 12952; -.
DR Ensembl; ENSMUST00000020227; ENSMUSP00000020227; ENSMUSG00000020038.
DR GeneID; 12952; -.
DR KEGG; mmu:12952; -.
DR UCSC; uc007gle.1; mouse.
DR CTD; 1407; -.
DR MGI; MGI:1270841; Cry1.
DR VEuPathDB; HostDB:ENSMUSG00000020038; -.
DR eggNOG; KOG0133; Eukaryota.
DR GeneTree; ENSGT00940000155455; -.
DR HOGENOM; CLU_010348_3_4_1; -.
DR InParanoid; P97784; -.
DR OMA; WQWSASS; -.
DR OrthoDB; 378952at2759; -.
DR PhylomeDB; P97784; -.
DR TreeFam; TF323191; -.
DR BioGRID-ORCS; 12952; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Cry1; mouse.
DR PRO; PR:P97784; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; P97784; protein.
DR Bgee; ENSMUSG00000020038; Expressed in secondary oocyte and 266 other tissues.
DR ExpressionAtlas; P97784; baseline and differential.
DR Genevisible; P97784; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IBA:GO_Central.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:0003690; F:double-stranded DNA binding; IDA:UniProtKB.
DR GO; GO:0070888; F:E-box binding; IDA:UniProtKB.
DR GO; GO:0071949; F:FAD binding; IBA:GO_Central.
DR GO; GO:0042826; F:histone deacetylase binding; IPI:UniProtKB.
DR GO; GO:0019900; F:kinase binding; IPI:UniProtKB.
DR GO; GO:0016922; F:nuclear receptor binding; IPI:UniProtKB.
DR GO; GO:0019902; F:phosphatase binding; ISO:MGI.
DR GO; GO:0009881; F:photoreceptor activity; IEA:UniProtKB-KW.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0032922; P:circadian regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0007623; P:circadian rhythm; IDA:MGI.
DR GO; GO:0006975; P:DNA damage induced protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0043153; P:entrainment of circadian clock by photoperiod; IMP:UniProtKB.
DR GO; GO:0006094; P:gluconeogenesis; IMP:UniProtKB.
DR GO; GO:0042593; P:glucose homeostasis; IGI:UniProtKB.
DR GO; GO:0019915; P:lipid storage; IGI:UniProtKB.
DR GO; GO:0042754; P:negative regulation of circadian rhythm; IDA:UniProtKB.
DR GO; GO:0045744; P:negative regulation of G protein-coupled receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:2000323; P:negative regulation of glucocorticoid receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:2000850; P:negative regulation of glucocorticoid secretion; IGI:UniProtKB.
DR GO; GO:0045721; P:negative regulation of gluconeogenesis; IMP:UniProtKB.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IMP:UniProtKB.
DR GO; GO:0042752; P:regulation of circadian rhythm; IMP:UniProtKB.
DR GO; GO:2000001; P:regulation of DNA damage checkpoint; IDA:UniProtKB.
DR GO; GO:0014823; P:response to activity; IMP:UniProtKB.
DR GO; GO:0033762; P:response to glucagon; IMP:UniProtKB.
DR GO; GO:0032868; P:response to insulin; IGI:UniProtKB.
DR GO; GO:0009416; P:response to light stimulus; IMP:UniProtKB.
DR DisProt; DP03007; -.
DR Gene3D; 3.40.50.620; -; 1.
DR IDEAL; IID50287; -.
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 3D-structure; Biological rhythms; Chromophore; Cytoplasm; FAD;
KW Flavoprotein; 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..606
FT /note="Cryptochrome-1"
FT /id="PRO_0000261142"
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:0000269|PubMed:16478995"
FT REGION 471..493
FT /note="Interaction with TIMELESS"
FT /evidence="ECO:0000269|PubMed:23418588"
FT REGION 559..606
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 50..54
FT /note="LIR 1"
FT /evidence="ECO:0000305|PubMed:29937374"
FT MOTIF 82..87
FT /note="LIR 2"
FT /evidence="ECO:0000305|PubMed:29937374"
FT MOTIF 151..156
FT /note="LIR 3"
FT /evidence="ECO:0000305|PubMed:29937374"
FT MOTIF 255..260
FT /note="LIR 4"
FT /evidence="ECO:0000305|PubMed:29937374"
FT MOTIF 271..276
FT /note="LIR 5"
FT /evidence="ECO:0000305|PubMed:29937374"
FT MOTIF 285..290
FT /note="LIR 6"
FT /evidence="ECO:0000305|PubMed:29937374"
FT MOTIF 335..339
FT /note="LIR 7"
FT /evidence="ECO:0000305|PubMed:29937374"
FT MOTIF 379..384
FT /note="LIR 8"
FT /evidence="ECO:0000305|PubMed:29937374"
FT MOTIF 395..400
FT /note="LIR 9"
FT /evidence="ECO:0000305|PubMed:29937374"
FT MOTIF 411..416
FT /note="LIR 10"
FT /evidence="ECO:0000305|PubMed:29937374"
FT MOTIF 430..435
FT /note="LIR 11"
FT /evidence="ECO:0000305|PubMed:29937374"
FT MOTIF 486..491
FT /note="LIR 12"
FT /evidence="ECO:0000305|PubMed:29937374"
FT MOTIF 492..497
FT /note="LIR 13"
FT /evidence="ECO:0000305|PubMed:29937374"
FT BINDING 252
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:23746849"
FT BINDING 289
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:23746849"
FT BINDING 355
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:23746849"
FT BINDING 387..389
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:23746849"
FT MOD_RES 71
FT /note="Phosphoserine; by AMPK"
FT /evidence="ECO:0000269|PubMed:19833968"
FT MOD_RES 247
FT /note="Phosphoserine; by MAPK"
FT /evidence="ECO:0000269|PubMed:15298678"
FT MOD_RES 280
FT /note="Phosphoserine; by AMPK"
FT /evidence="ECO:0000269|PubMed:19833968"
FT MOD_RES 588
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:24158435"
FT CROSSLNK 11
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000305|PubMed:23452855"
FT CROSSLNK 107
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:23452856"
FT CROSSLNK 159
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:23452856"
FT CROSSLNK 329
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:23452856"
FT CROSSLNK 485
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:23452856"
FT CROSSLNK 585
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:26431207"
FT MUTAGEN 71
FT /note="S->A: Phosphomimetic mutant that leads to
FT stabilization of the protein; when associated with A-280."
FT /evidence="ECO:0000269|PubMed:19833968"
FT MUTAGEN 71
FT /note="S->D: Phosphomimetic mutant that leads to
FT destabilization of the protein and abolishes ability to
FT bind PER2; when associated with D-280."
FT /evidence="ECO:0000269|PubMed:19833968"
FT MUTAGEN 107
FT /note="K->R: Sensitive to FBXL3-ediated degradation but noz
FT affected by expression of FBXL21."
FT /evidence="ECO:0000269|PubMed:23452856"
FT MUTAGEN 224
FT /note="H->E: Reduces affinity for FBXL3."
FT /evidence="ECO:0000269|PubMed:23746849"
FT MUTAGEN 247
FT /note="S->A: Reduced MAPK-catalyzed in vitro
FT phosphorylation. No effect on inhibition of CLOCK-
FT ARNTL/BMAL1-mediated transcriptional activity."
FT /evidence="ECO:0000269|PubMed:15298678,
FT ECO:0000269|PubMed:23746849"
FT MUTAGEN 247
FT /note="S->D: Reduced inhibition of CLOCK-ARNTL/BMAL1-
FT mediated transcriptional activity."
FT /evidence="ECO:0000269|PubMed:15298678,
FT ECO:0000269|PubMed:23746849"
FT MUTAGEN 273
FT /note="Y->A: Reduced interaction with MAP1LC3B and
FT significant decrease in its autophagy-mediated degradation;
FT when associated with A-276."
FT /evidence="ECO:0000269|PubMed:29937374"
FT MUTAGEN 276
FT /note="V->A: Reduced interaction with MAP1LC3B and
FT significant decrease in its autophagy-mediated degradation;
FT when associated with A-273."
FT /evidence="ECO:0000269|PubMed:29937374"
FT MUTAGEN 280
FT /note="S->A: Phosphomimetic mutant that leads to
FT stabilization of the protein; when associated with A-71."
FT /evidence="ECO:0000269|PubMed:19833968"
FT MUTAGEN 280
FT /note="S->D: Phosphomimetic mutant that leads to
FT destabilization of the protein and abolishes ability to
FT bind PER2; when associated with D-71."
FT /evidence="ECO:0000269|PubMed:19833968"
FT MUTAGEN 287
FT /note="Y->A: No effect on its interaction with MAP1LC3B and
FT moderate decrease in its autophagy-mediated degradation;
FT when associated with A-290."
FT /evidence="ECO:0000269|PubMed:29937374"
FT MUTAGEN 290
FT /note="L->A: No effect on its interaction with MAP1LC3B and
FT moderate decrease in its autophagy-mediated degradation;
FT when associated with A-287."
FT /evidence="ECO:0000269|PubMed:29937374"
FT MUTAGEN 336
FT /note="G->D: Abolishes transcriptional repression of target
FT genes. Abolishes interaction with PER2."
FT MUTAGEN 382..383
FT /note="EE->RR: Decreases transcriptional repression of
FT target genes. Decreases FBXL3 binding. Increases PER2
FT binding."
FT /evidence="ECO:0000269|PubMed:23746849"
FT MUTAGEN 405
FT /note="F->A: Decreases affinity for FBXL3. Slightly
FT increases affinity for PER2."
FT /evidence="ECO:0000269|PubMed:23746849"
FT MUTAGEN 485
FT /note="K->D,E: Strongly reduces FBXL3 binding. Reduces PER2
FT binding."
FT /evidence="ECO:0000269|PubMed:23746849"
FT MUTAGEN 488
FT /note="Y->A: No effect on its interaction with MAP1LC3B and
FT moderate decrease in its autophagy-mediated degradation;
FT when associated with A-491."
FT /evidence="ECO:0000269|PubMed:29937374"
FT MUTAGEN 491
FT /note="L->A: No effect on its interaction with MAP1LC3B and
FT moderate decrease in its autophagy-mediated degradation;
FT when associated with A-488."
FT /evidence="ECO:0000269|PubMed:29937374"
FT MUTAGEN 494
FT /note="Y->A: Loss of interaction with MAP1LC3B and
FT significant decrease in its autophagy-mediated degradation;
FT when associated with A-497."
FT /evidence="ECO:0000269|PubMed:29937374"
FT MUTAGEN 497
FT /note="L->A: Loss of interaction with MAP1LC3B and
FT significant decrease in its autophagy-mediated degradation;
FT when associated with A-494."
FT /evidence="ECO:0000269|PubMed:29937374"
FT MUTAGEN 551
FT /note="S->A: No effect on circadian period length and
FT protein stability."
FT /evidence="ECO:0000269|PubMed:24158435"
FT MUTAGEN 551
FT /note="S->D: No effect on circadian period length and
FT protein stability."
FT /evidence="ECO:0000269|PubMed:24158435"
FT MUTAGEN 564
FT /note="S->A: No effect on circadian period length and
FT protein stability."
FT /evidence="ECO:0000269|PubMed:24158435"
FT MUTAGEN 564
FT /note="S->D: No effect on circadian period length and
FT protein stability."
FT /evidence="ECO:0000269|PubMed:24158435"
FT MUTAGEN 585
FT /note="K->A: Loss of ubiquitination. No loss of interaction
FT with DDB1-CUL4A complex."
FT /evidence="ECO:0000269|PubMed:26431207"
FT MUTAGEN 588
FT /note="S->A: No effect on circadian period length and
FT protein stability."
FT /evidence="ECO:0000269|PubMed:24158435"
FT MUTAGEN 588
FT /note="S->D: Lengthen circadian period. No effect on
FT repressive activity. Increases protein stability."
FT /evidence="ECO:0000269|PubMed:24158435"
FT STRAND 4..11
FT /evidence="ECO:0007829|PDB:5T5X"
FT STRAND 14..17
FT /evidence="ECO:0007829|PDB:5T5X"
FT HELIX 19..25
FT /evidence="ECO:0007829|PDB:5T5X"
FT STRAND 29..37
FT /evidence="ECO:0007829|PDB:5T5X"
FT HELIX 39..41
FT /evidence="ECO:0007829|PDB:6KX7"
FT HELIX 42..44
FT /evidence="ECO:0007829|PDB:7D1C"
FT HELIX 46..48
FT /evidence="ECO:0007829|PDB:7D19"
FT HELIX 49..67
FT /evidence="ECO:0007829|PDB:5T5X"
FT TURN 68..70
FT /evidence="ECO:0007829|PDB:5T5X"
FT STRAND 73..78
FT /evidence="ECO:0007829|PDB:5T5X"
FT HELIX 80..91
FT /evidence="ECO:0007829|PDB:5T5X"
FT STRAND 93..99
FT /evidence="ECO:0007829|PDB:5T5X"
FT HELIX 104..119
FT /evidence="ECO:0007829|PDB:5T5X"
FT STRAND 123..127
FT /evidence="ECO:0007829|PDB:5T5X"
FT STRAND 130..133
FT /evidence="ECO:0007829|PDB:5T5X"
FT HELIX 135..141
FT /evidence="ECO:0007829|PDB:5T5X"
FT HELIX 150..158
FT /evidence="ECO:0007829|PDB:5T5X"
FT TURN 174..177
FT /evidence="ECO:0007829|PDB:5T5X"
FT HELIX 186..190
FT /evidence="ECO:0007829|PDB:5T5X"
FT TURN 195..199
FT /evidence="ECO:0007829|PDB:5T5X"
FT HELIX 214..229
FT /evidence="ECO:0007829|PDB:5T5X"
FT TURN 231..234
FT /evidence="ECO:0007829|PDB:7DLI"
FT HELIX 241..244
FT /evidence="ECO:0007829|PDB:5T5X"
FT HELIX 252..256
FT /evidence="ECO:0007829|PDB:5T5X"
FT HELIX 262..277
FT /evidence="ECO:0007829|PDB:5T5X"
FT HELIX 284..287
FT /evidence="ECO:0007829|PDB:5T5X"
FT HELIX 288..300
FT /evidence="ECO:0007829|PDB:5T5X"
FT TURN 304..307
FT /evidence="ECO:0007829|PDB:5T5X"
FT HELIX 324..332
FT /evidence="ECO:0007829|PDB:5T5X"
FT HELIX 338..350
FT /evidence="ECO:0007829|PDB:5T5X"
FT HELIX 355..365
FT /evidence="ECO:0007829|PDB:5T5X"
FT TURN 366..370
FT /evidence="ECO:0007829|PDB:5T5X"
FT HELIX 374..384
FT /evidence="ECO:0007829|PDB:5T5X"
FT HELIX 390..400
FT /evidence="ECO:0007829|PDB:5T5X"
FT STRAND 403..405
FT /evidence="ECO:0007829|PDB:6KX7"
FT HELIX 417..422
FT /evidence="ECO:0007829|PDB:5T5X"
FT HELIX 427..432
FT /evidence="ECO:0007829|PDB:5T5X"
FT HELIX 434..436
FT /evidence="ECO:0007829|PDB:5T5X"
FT TURN 441..445
FT /evidence="ECO:0007829|PDB:5T5X"
FT HELIX 447..449
FT /evidence="ECO:0007829|PDB:5T5X"
FT HELIX 452..457
FT /evidence="ECO:0007829|PDB:5T5X"
FT TURN 462..464
FT /evidence="ECO:0007829|PDB:5T5X"
FT HELIX 473..487
FT /evidence="ECO:0007829|PDB:5T5X"
FT HELIX 490..494
FT /evidence="ECO:0007829|PDB:7D1C"
SQ SEQUENCE 606 AA; 68001 MW; 2F2B8DD53F0A9AF9 CRC64;
MGVNAVHWFR KGLRLHDNPA LKECIQGADT IRCVYILDPW FAGSSNVGIN RWRFLLQCLE
DLDANLRKLN SRLFVIRGQP ADVFPRLFKE WNITKLSIEY DSEPFGKERD AAIKKLATEA
GVEVIVRISH TLYDLDKIIE LNGGQPPLTY KRFQTLVSKM EPLEMPADTI TSDVIGKCMT
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 ASVPSNSNGN GGLMGYAPGE NVPSCSSSGN GGLMGYAPGE
NVPSCSGGNC SQGSGILHYA HGDSQQTHSL KQGRSSAGTG LSSGKRPSQE EDAQSVGPKV
QRQSSN
