ID   CRY2_HUMAN              Reviewed;         593 AA.
AC   Q49AN0; B4DH32; O75148; Q8IV71;
DT   28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT   28-NOV-2006, sequence version 2.
DT   25-JAN-2012, entry version 63.
DE   RecName: Full=Cryptochrome-2;
GN   Name=CRY2; Synonyms=KIAA0658;
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] (ISOFORM 1), CHARACTERIZATION, AND TISSUE
RP   SPECIFICITY.
RC   TISSUE=Fetal brain;
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 [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Brain;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16554811; DOI=10.1038/nature04632;
RA   Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA   Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F.,
RA   Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E.,
RA   FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S.,
RA   Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W.,
RA   Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S.,
RA   Sakaki Y.;
RT   "Human chromosome 11 DNA sequence and analysis including novel gene
RT   identification.";
RL   Nature 440:497-500(2006).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Testis;
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   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 5-593 (ISOFORM 1).
RC   TISSUE=Brain;
RX   MEDLINE=98403880; PubMed=9734811; DOI=10.1093/dnares/5.3.169;
RA   Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H.,
RA   Nomura N., Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes. X.
RT   The complete sequences of 100 new cDNA clones from brain which can
RT   code for large proteins in vitro.";
RL   DNA Res. 5:169-176(1998).
RN   [6]
RP   TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX   MEDLINE=99030511; PubMed=9801304; DOI=10.1093/nar/26.22.5086;
RA   Kobayashi K., Kanno S., Smit B., van der Horst G.T.J., Takao M.,
RA   Yasui A.;
RT   "Characterization of photolyase/blue-light receptor homologs in mouse
RT   and human cells.";
RL   Nucleic Acids Res. 26:5086-5092(1998).
RN   [7]
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   [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.,
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   -!- COFACTOR: Binds 1 FAD per subunit (By similarity).
CC   -!- COFACTOR: Binds 1 5,10-methenyltetrahydrofolate non-covalently per
CC       subunit (By similarity).
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 PER1 and PER2 C-terminal domains. Interaction with PER2
CC       inhibits its ubiquitination and vice versa. Interacts with NFIL3.
CC       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.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q49AN0-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q49AN0-2; Sequence=VSP_038970;
CC         Note=No experimental confirmation available. Ref.2 (BAG57993)
CC         sequence is in conflict in position: 9:H->L;
CC   -!- TISSUE SPECIFICITY: Expressed in all tissues examined including
CC       fetal brain, fibroblasts, heart, brain, placenta, lung, liver,
CC       skeletal muscle, kidney, pancreas, spleen, thymus, prostate,
CC       testis, ovary, small intestine, colon and leukocytes. Highest
CC       levels in heart and skeletal muscle.
CC   -!- PTM: Phosphorylation on Ser-266 by MAPK is important for the
CC       inhibition of CLOCK-ARNTL-mediated transcriptional activity.
CC       Phosphorylation by CSKNE requires interaction with PER1 or PER2.
CC   -!- PTM: Ubiquitinated by the SCF(FBXL3) and SCF(FBXL21) complex,
CC       leading to its degradation.
CC   -!- SIMILARITY: Belongs to the DNA photolyase class-1 family.
CC   -!- SIMILARITY: Contains 1 DNA photolyase domain.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAH35161.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact. Aberrant splice sites;
CC       Sequence=BAG57993.1; Type=Erroneous termination; Positions=110; Note=Translated as Trp;
CC       Sequence=BAG57993.1; Type=Erroneous translation; Note=Wrong choice of CDS;
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Cryptochrome entry;
CC       URL="http://en.wikipedia.org/wiki/Cryptochrome";
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DR   EMBL; AK294904; BAG57993.1; ALT_SEQ; mRNA.
DR   EMBL; AC068385; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC035161; AAH35161.1; ALT_SEQ; mRNA.
DR   EMBL; BC041814; AAH41814.1; -; mRNA.
DR   EMBL; AB014558; BAA31633.1; -; mRNA.
DR   IPI; IPI00216898; -.
DR   IPI; IPI00895886; -.
DR   RefSeq; NP_001120929.1; NM_001127457.1.
DR   RefSeq; NP_066940.2; NM_021117.3.
DR   UniGene; Hs.532491; -.
DR   ProteinModelPortal; Q49AN0; -.
DR   SMR; Q49AN0; 6-513.
DR   IntAct; Q49AN0; 2.
DR   STRING; Q49AN0; -.
DR   DMDM; 118572252; -.
DR   PRIDE; Q49AN0; -.
DR   Ensembl; ENST00000263762; ENSP00000263762; ENSG00000121671.
DR   Ensembl; ENST00000417225; ENSP00000397419; ENSG00000121671.
DR   Ensembl; ENST00000443527; ENSP00000406751; ENSG00000121671.
DR   GeneID; 1408; -.
DR   KEGG; hsa:1408; -.
DR   NMPDR; fig|9606.3.peg.5504; -.
DR   CTD; 1408; -.
DR   GeneCards; GC11P045868; -.
DR   H-InvDB; HIX0201587; -.
DR   HGNC; HGNC:2385; CRY2.
DR   HPA; HPA037577; -.
DR   MIM; 603732; gene.
DR   neXtProt; NX_Q49AN0; -.
DR   GeneTree; ENSGT00500000044813; -.
DR   HOVERGEN; HBG053470; -.
DR   InParanoid; Q49AN0; -.
DR   OrthoDB; EOG4VT5WZ; -.
DR   PhylomeDB; Q49AN0; -.
DR   Reactome; REACT_24941; Circadian Clock.
DR   ArrayExpress; Q49AN0; -.
DR   Bgee; Q49AN0; -.
DR   CleanEx; HS_CRY2; -.
DR   Genevestigator; Q49AN0; -.
DR   GermOnline; ENSG00000121671; Homo sapiens.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0009882; F:blue light photoreceptor activity; NAS:UniProtKB.
DR   GO; GO:0003684; F:damaged DNA binding; IDA:UniProtKB.
DR   GO; GO:0003913; F:DNA photolyase activity; IEA:InterPro.
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:0003697; F:single-stranded DNA binding; IDA:UniProtKB.
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: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   Alternative splicing; Biological rhythms; Chromophore;
KW   Complete proteome; Cytoplasm; FAD; Flavoprotein; Nucleotide-binding;
KW   Nucleus; Phosphoprotein; Photoreceptor protein; Receptor;
KW   Reference proteome; Repressor; Sensory transduction; Transcription;
KW   Transcription regulation; Ubl conjugation.
FT   CHAIN         1    593       Cryptochrome-2.
FT                                /FTId=PRO_0000261148.
FT   DOMAIN       22    189       DNA photolyase.
FT   REGION      230    507       FAD-binding.
FT   REGION      390    489       Required for inhibition of CLOCK-ARNTL-
FT                                mediated transcription (By similarity).
FT   MOD_RES     266    266       Phosphoserine; by MAPK (By similarity).
FT   MOD_RES     558    558       Phosphoserine; by MAPK (By similarity).
FT   VAR_SEQ       1     72       MAATVATAAAVAPAPAPGTDSASSVHWFRKGLRLHDNPALL
FT                                AAVRGARCVRCVYILDPWFAASSSVGINRWR -> MPAPPG
FT                                RTHTW (in isoform 2).
FT                                /FTId=VSP_038970.
FT   CONFLICT    422    422       S -> G (in Ref. 4; AAH35161).
SQ   SEQUENCE   593 AA;  66947 MW;  BF380424092BEBFB CRC64;
     MAATVATAAA VAPAPAPGTD SASSVHWFRK GLRLHDNPAL LAAVRGARCV RCVYILDPWF
     AASSSVGINR WRFLLQSLED LDTSLRKLNS RLFVVRGQPA DVFPRLFKEW GVTRLTFEYD
     SEPFGKERDA AIMKMAKEAG VEVVTENSHT LYDLDRIIEL NGQKPPLTYK RFQAIISRME
     LPKKPVGLVT SQQMESCRAE IQENHDETYG VPSLEELGFP TEGLGPAVWQ GGETEALARL
     DKHLERKAWV ANYERPRMNA NSLLASPTGL SPYLRFGCLS CRLFYYRLWD LYKKVKRNST
     PPLSLFGQLL WREFFYTAAT NNPRFDRMEG NPICIQIPWD RNPEALAKWA EGKTGFPWID
     AIMTQLRQEG WIHHLARHAV ACFLTRGDLW VSWESGVRVF DELLLDADFS VNAGSWMWLS
     CSAFFQQFFH CYCPVGFGRR TDPSGDYIRR YLPKLKAFPS RYIYEPWNAP ESIQKAAKCI
     IGVDYPRPIV NHAETSRLNI ERMKQIYQQL SRYRGLCLLA SVPSCVEDLS HPVAEPSSSQ
     AGSMSSAGPR PLPSGPASPK RKLEAAEEPP GEELSKRARV AELPTPELPS KDA
//