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   25-JAN-2012, entry version 86.
DE   RecName: Full=Cryptochrome-1;
GN   Name=CRY1; Synonyms=PHLL1;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; 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.,
RA   Wei Y.-F., 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   MEDLINE=97079678; 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
RT   with 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   MEDLINE=96178677; 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
RT   project: 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   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-432, AND MASS
RP   SPECTROMETRY.
RC   TISSUE=Lung carcinoma;
RX   PubMed=18083107; DOI=10.1016/j.cell.2007.11.025;
RA   Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J.,
RA   Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L.,
RA   Mitchell J., Wetzel R., Macneill J., Ren J.M., Yuan J.,
RA   Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X.,
RA   Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.;
RT   "Global survey of phosphotyrosine signaling identifies oncogenic
RT   kinases in lung cancer.";
RL   Cell 131:1190-1203(2007).
RN   [7]
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.,
RA   Godinho S.I., Draetta G.F., Pagano M.;
RT   "SCFFbxl3 controls the oscillation of the circadian clock by directing
RT   the degradation of cryptochrome proteins.";
RL   Science 316:900-904(2007).
CC   -!- FUNCTION: Blue light-dependent regulator of the circadian feedback
CC       loop. Inhibits CLOCK|NPAS2-ARNTL E box-mediated transcription.
CC       Acts, in conjunction with CRY2, in maintaining period length and
CC       circadian rhythmicity. Has no photolyase activity. Capable of
CC       translocating circadian clock core proteins such as PER proteins
CC       to the nucleus. May inhibit CLOCK|NPAS2-ARNTL transcriptional
CC       activity through stabilizing the unphosphorylated form of ARNTL
CC       (By similarity).
CC   -!- COFACTOR: Binds 1 FAD per subunit.
CC   -!- COFACTOR: Binds 1 5,10-methenyltetrahydrofolate non-covalently per
CC       subunit.
CC   -!- SUBUNIT: Component of the circadian core oscillator, which
CC       includes the CRY proteins, CLOCK or NPAS2, ARNTL or ARNTL2, CSNK1D
CC       and/or CSNK1E, TIMELESS, and the PER proteins. Interacts directly
CC       with TIMELESS and the PER proteins. Interacts directly with PER1
CC       and PER2 C-terminal domains. Interaction with PER2 inhibits its
CC       ubiquitination and vice versa. Binds MAPK. Interacts with FBXL21
CC       (By similarity). Interacts with FBXL3.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Translocated to the
CC       nucleus through interaction with other Clock proteins such as PER2
CC       or ARNTL (By similarity).
CC   -!- INDUCTION: Expression is regulated by light and circadian rhythms.
CC       Peak expression in the suprachiasma nucleus (SCN) and eye at the
CC       day/night transition (CT12). Levels decrease with ARNTL-CLOCK
CC       inhibition as part of the autoregulatory feedback loop.
CC   -!- PTM: Phosphorylation on Ser-247 by MAPK is important for the
CC       inhibition of CLOCK-ARNTL-mediated transcriptional activity.
CC       Phosphorylation by CSNK1E requires interaction with PER1 or PER2.
CC       Phosphorylation at Ser-71 and Ser-280 by AMPK destabilizes it (By
CC       similarity).
CC   -!- PTM: Ubiquitinated by the SCF(FBXL3) and SCF(FBXL21) complex
CC       leading to degradation.
CC   -!- SIMILARITY: Belongs to the DNA photolyase class-1 family.
CC   -!- SIMILARITY: Contains 1 DNA photolyase domain.
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Cryptochrome entry;
CC       URL="http://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   IPI; IPI00002540; -.
DR   RefSeq; NP_004066.1; NM_004075.3.
DR   UniGene; Hs.151573; -.
DR   ProteinModelPortal; Q16526; -.
DR   SMR; Q16526; 2-494.
DR   IntAct; Q16526; 11.
DR   MINT; MINT-1437226; -.
DR   STRING; Q16526; -.
DR   PhosphoSite; Q16526; -.
DR   DMDM; 74735764; -.
DR   PRIDE; Q16526; -.
DR   Ensembl; ENST00000008527; ENSP00000008527; ENSG00000008405.
DR   GeneID; 1407; -.
DR   KEGG; hsa:1407; -.
DR   UCSC; uc001tmi.2; human.
DR   CTD; 1407; -.
DR   GeneCards; GC12M107385; -.
DR   H-InvDB; HIX0010959; -.
DR   HGNC; HGNC:2384; CRY1.
DR   HPA; CAB018762; -.
DR   MIM; 601933; gene.
DR   neXtProt; NX_Q16526; -.
DR   GeneTree; ENSGT00500000044813; -.
DR   HOGENOM; HBG693486; -.
DR   HOVERGEN; HBG053470; -.
DR   InParanoid; Q16526; -.
DR   OMA; FDTDGLP; -.
DR   OrthoDB; EOG4DBTDC; -.
DR   PhylomeDB; Q16526; -.
DR   Reactome; REACT_24941; Circadian Clock.
DR   NextBio; 5753; -.
DR   ArrayExpress; Q16526; -.
DR   Bgee; Q16526; -.
DR   CleanEx; HS_CRY1; -.
DR   Genevestigator; Q16526; -.
DR   GermOnline; ENSG00000008405; Homo sapiens.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0009882; F:blue light photoreceptor activity; NAS:UniProtKB.
DR   GO; GO:0003913; F:DNA photolyase activity; IEA:InterPro.
DR   GO; GO:0003690; F:double-stranded DNA binding; IDA:UniProtKB.
DR   GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR   GO; GO:0005515; F:protein binding; IPI:UniProtKB.
DR   GO; GO:0000988; F:protein binding transcription factor activity; IDA:BHF-UCL.
DR   GO; GO:0006281; P:DNA repair; IEA:InterPro.
DR   GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL.
DR   GO; GO:0018298; P:protein-chromophore linkage; IEA:UniProtKB-KW.
DR   GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR   GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR   InterPro; IPR006050; DNA_photolyase_N.
DR   InterPro; IPR005101; Photolyase_FAD-bd/Cryptochr_C.
DR   InterPro; IPR014729; Rossmann-like_a/b/a_fold.
DR   Gene3D; G3DSA:3.40.50.620; Rossmann-like_a/b/a_fold; 1.
DR   KO; K02295; -.
DR   Pfam; PF00875; DNA_photolyase; 1.
DR   Pfam; PF03441; FAD_binding_7; 1.
DR   SUPFAM; SSF52425; DNA_photolyase_N; 1.
DR   SUPFAM; SSF48173; Photolyase_FAD-bd/Cryptochr_C; 1.
DR   PROSITE; PS00394; DNA_PHOTOLYASES_1_1; FALSE_NEG.
PE   1: Evidence at protein level;
KW   Biological rhythms; Chromophore; Complete proteome; Cytoplasm; FAD;
KW   Flavoprotein; Nucleotide-binding; Nucleus; Phosphoprotein;
KW   Photoreceptor protein; Receptor; Reference proteome; Repressor;
KW   Sensory transduction; Transcription; Transcription regulation;
KW   Ubl conjugation.
FT   CHAIN         1    586       Cryptochrome-1.
FT                                /FTId=PRO_0000261140.
FT   DOMAIN        3    178       DNA photolyase.
FT   REGION      211    488       FAD-binding.
FT   REGION      371    470       Required for inhibition of CLOCK-ARNTL-
FT                                mediated transcription (By similarity).
FT   MOD_RES      71     71       Phosphoserine; by AMPK (By similarity).
FT   MOD_RES     247    247       Phosphoserine; by MAPK (By similarity).
FT   MOD_RES     280    280       Phosphoserine; by AMPK (By similarity).
FT   MOD_RES     432    432       Phosphotyrosine.
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
//