ID   FRQ_NEUCR               Reviewed;         989 AA.
AC   P19970; Q01276; Q7RVB1;
DT   01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT   07-JUN-2005, sequence version 3.
DT   22-SEP-2009, entry version 70.
DE   RecName: Full=Frequency clock protein;
GN   Name=frq; ORFNames=B13D24.170, NCU02265;
OS   Neurospora crassa.
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina;
OC   Sordariomycetes; Sordariomycetidae; Sordariales; Sordariaceae;
OC   Neurospora.
OX   NCBI_TaxID=5141;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND MUTAGENESIS OF GLU-364; GLY-459;
RP   GLY-482 AND ALA-895.
RC   STRAIN=ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987;
RX   MEDLINE=94329580; PubMed=8052643; DOI=10.1073/pnas.91.16.7683;
RA   Aronson B.D., Johnson K.A., Dunlap J.C.;
RT   "Circadian clock locus frequency: protein encoded by a single open
RT   reading frame defines period length and temperature compensation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 91:7683-7687(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987;
RX   MEDLINE=22542210; PubMed=12655011; DOI=10.1093/nar/gkg293;
RA   Mannhaupt G., Montrone C., Haase D., Mewes H.-W., Aign V.,
RA   Hoheisel J.D., Fartmann B., Nyakatura G., Kempken F., Maier J.,
RA   Schulte U.;
RT   "What's in the genome of a filamentous fungus? Analysis of the
RT   Neurospora genome sequence.";
RL   Nucleic Acids Res. 31:1944-1954(2003).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987;
RX   MEDLINE=22598136; PubMed=12712197; DOI=10.1038/nature01554;
RA   Galagan J.E., Calvo S.E., Borkovich K.A., Selker E.U., Read N.D.,
RA   Jaffe D.B., FitzHugh W., Ma L.-J., Smirnov S., Purcell S., Rehman B.,
RA   Elkins T., Engels R., Wang S., Nielsen C.B., Butler J., Endrizzi M.,
RA   Qui D., Ianakiev P., Bell-Pedersen D., Nelson M.A.,
RA   Werner-Washburne M., Selitrennikoff C.P., Kinsey J.A., Braun E.L.,
RA   Zelter A., Schulte U., Kothe G.O., Jedd G., Mewes H.-W., Staben C.,
RA   Marcotte E., Greenberg D., Roy A., Foley K., Naylor J.,
RA   Stange-Thomann N., Barrett R., Gnerre S., Kamal M., Kamvysselis M.,
RA   Mauceli E.W., Bielke C., Rudd S., Frishman D., Krystofova S.,
RA   Rasmussen C., Metzenberg R.L., Perkins D.D., Kroken S., Cogoni C.,
RA   Macino G., Catcheside D.E.A., Li W., Pratt R.J., Osmani S.A.,
RA   DeSouza C.P.C., Glass N.L., Orbach M.J., Berglund J.A., Voelker R.,
RA   Yarden O., Plamann M., Seiler S., Dunlap J.C., Radford A., Aramayo R.,
RA   Natvig D.O., Alex L.A., Mannhaupt G., Ebbole D.J., Freitag M.,
RA   Paulsen I., Sachs M.S., Lander E.S., Nusbaum C., Birren B.W.;
RT   "The genome sequence of the filamentous fungus Neurospora crassa.";
RL   Nature 422:859-868(2003).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 202-989.
RX   MEDLINE=89281721; PubMed=2525233; DOI=10.1038/339558a0;
RA   McClung C.R., Fox B.A., Dunlap J.C.;
RT   "The Neurospora clock gene frequency shares a sequence element with
RT   the Drosophila clock gene period.";
RL   Nature 339:558-562(1989).
RN   [5]
RP   PHOSPHORYLATION AT THR-501; SER-513 AND SER-519, AND MUTAGENESIS OF
RP   501-THR--SER-503; 513-SER-THR-514 AND SER-519.
RX   MEDLINE=20087232; PubMed=10618401; DOI=10.1073/pnas.97.1.234;
RA   Liu Y., Loros J., Dunlap J.C.;
RT   "Phosphorylation of the Neurospora clock protein frequency determines
RT   its degradation rate and strongly influences the period length of the
RT   circadian clock.";
RL   Proc. Natl. Acad. Sci. U.S.A. 97:234-239(2000).
RN   [6]
RP   PHOSPHORYLATION BY CK2.
RX   MEDLINE=21956574; PubMed=11959847; DOI=10.1101/gad.965102;
RA   Yang Y., Cheng P., Liu Y.;
RT   "Regulation of the Neurospora circadian clock by casein kinase II.";
RL   Genes Dev. 16:994-1006(2002).
CC   -!- FUNCTION: Circadian clock component involved in the generation of
CC       biological rhythms, in particular in rhythm stability, period
CC       length, and temperature compensation. Oscillates in abundance with
CC       a daily peak early in the morning. Behaves as a negative element
CC       in circadian transcriptional loop. May bind to wc2 protein. The
CC       complex frq-wc2 may turn off the expression of frq.
CC   -!- SUBCELLULAR LOCATION: Nucleus (Potential).
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative initiation; Named isoforms=2;
CC       Name=Long;
CC         IsoId=P19970-1; Sequence=Displayed;
CC         Note=Maintains rhythms at high temperature (30 degrees Celsius);
CC       Name=Short;
CC         IsoId=P19970-2; Sequence=VSP_018781;
CC         Note=Maintains rhythms at lower temperature (18 degrees
CC         Celsius);
CC   -!- INDUCTION: By light; perhaps through white collar-1 (wc1) and
CC       white collar-2 (wc2). Also activated directly by wc1 and wc2.
CC   -!- PTM: Progressive phosphorylation during the late circadian day and
CC       early night. Phosphorylation is also involved in regulating frq
CC       degradation. Phosphorylation by CKII may have at least three
CC       functions; it decreases the stability of frq, reduces the protein
CC       complex formation between frq and the white collar proteins, and
CC       is important for the closing of the Neurospora circadian negative
CC       feedback loop.
CC   -!- SIMILARITY: Belongs to the FRQ family.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=Ref.4; Type=Erroneous gene model prediction;
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DR   EMBL; U17073; AAA57121.1; -; mRNA.
DR   EMBL; BX908789; CAF05882.1; -; Genomic_DNA.
DR   EMBL; AABX02000010; EAA30673.2; ALT_INIT; Genomic_DNA.
DR   PIR; T46659; T46659.
DR   STRING; P19970; -.
DR   NMPDR; fig|5141.1.peg.8974; -.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0045449; P:regulation of transcription; IEA:UniProtKB-KW.
DR   GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR   GO; GO:0006350; P:transcription; IEA:UniProtKB-KW.
DR   InterPro; IPR018554; Frequency_clock_protein.
DR   Pfam; PF09421; FRQ; 1.
PE   1: Evidence at protein level;
KW   Alternative initiation; Biological rhythms; Complete proteome;
KW   Nucleus; Phosphoprotein; Transcription; Transcription regulation.
FT   CHAIN         1    989       Frequency clock protein.
FT                                /FTId=PRO_0000021288.
FT   MOTIF       564    568       Nuclear localization signal (Potential).
FT   COMPBIAS    244    250       Poly-Ser.
FT   COMPBIAS    862    888       Asp/Glu-rich (acidic).
FT   MOD_RES     501    501       Phosphothreonine.
FT   MOD_RES     513    513       Phosphoserine.
FT   MOD_RES     519    519       Phosphoserine.
FT   VAR_SEQ       1     99       Missing (in isoform Short).
FT                                /FTId=VSP_018781.
FT   MUTAGEN     364    364       E->K: In FRQ3; lengthened period.
FT   MUTAGEN     459    459       G->D: In FRQ7; lengthened period.
FT   MUTAGEN     482    482       G->S: In FRQ1; shortened period.
FT   MUTAGEN     501    503       TPS->APG: In FRQ10; no effect.
FT   MUTAGEN     513    514       ST->RA: In FRQ10; strong reduction in the
FT                                degradation rate; lengthened period.
FT   MUTAGEN     513    513       S->D: In FRQ10; reduces phosphorylation;
FT                                slight reduction in the degradation rate;
FT                                loss of rhythmicity.
FT   MUTAGEN     513    513       S->I: In FRQ10; reduces phosphorylation;
FT                                strong reduction in the degradation rate;
FT                                lengthened period.
FT   MUTAGEN     519    519       S->A: In FRQ10; no effect.
FT   MUTAGEN     663    989       Missing: In FRQ9; loss of rhythmicity.
FT   MUTAGEN     895    895       A->T: In FRQ2; shortened period.
FT   CONFLICT    146    146       S -> T (in Ref. 1; AAA57121).
FT   CONFLICT    202    207       EATLRD -> MGGNRP (in Ref. 4).
FT   CONFLICT    207    207       D -> H (in Ref. 1; AAA57121).
FT   CONFLICT    233    233       H -> Y (in Ref. 1; AAA57121).
FT   CONFLICT    962    963       ML -> IV (in Ref. 1; AAA57121 and 4).
SQ   SEQUENCE   989 AA;  108200 MW;  EC4E984FAD39F095 CRC64;
     MADSGDKSQG MRPPPFDSRG HPLPRRASPD KSITLENHRL ARDTSSRVTS SSALGVTESQ
     PQLKSSPTRR NSSGESEPTN WFNQSNRNPA AAFHDESHIM EVDPPFYQKE TDSSNEESRY
     PPGRNPVHPP GGVQLPGFRP VAAHSSAADD YRSVIDDLTV ENKRLKEELK RYKQFGSDVM
     RKEKLFEIKV HGLPRRKKRE LEATLRDFAA SLGDSSESTS QRRKTGRHGT AVHSSGVSLS
     KHDSSSSSRS RPVDSAYNSM STGRSSHAPH SSGPSLGRPS LTRAKSVGTQ KVENYLRDTP
     DGLLPHHIVM TDKEKKKLVV RRLEQLFTGK ISGRNMQRNQ SMPSMDAPLA PEGTNMAPPR
     PPPEGLREAC IQLQDGDNPR KNRSSKDNGS ASNSGGDQTE LGGTGTGSGD GSGSGGRTGN
     NTSPPGAIAP DQRPTRPRDL DPDRVQIPSE NMDYIRHLGL VSPEFLQGSR TSYQDVAPDA
     EGWVYLNLLC NLAQLHMVNV TPSFIRQAVS EKSTKFQLSA DGRKIRWRGG TDGTKFSSDS
     SEDKSQQSPM TEDTEDGSDK NGRRKKRKTQ QASSEIGRFG PSRSPSDTFH YKPMFVHRNS
     SSIETSLEES MSQGSEDAVD ESNMGNSKWD FSGSGTTQQR RKRRYDGAIV YYTGAPFCTD
     LSGDPGDMSP TAQMTAGREV EGSGSGDEVE HVLQRTLSGS SLPIRPLSDD RARVAEVLDF
     DPGNPPELVA DDGSSPNDED FVFPWCEDPA KVRIQPIAKE VMEPSGLGGV LPDDHFVMLV
     TTRRVVRPIL QRQLSRSTTS EDTAEFIAER LAAIRTSSPL PPRSHRLTVA PLQVEYVSGQ
     FRRLNPAPLP PPAIFYPPFS TDSSWDDGDD LASDDEEVEE VEEDSYSEGQ ISRRANPHFS
     DNNTYMRKDD LAFDTETDVR MDSDDNRLSD SGHNMRAMMP RAEAVDGDDS PLAAVTGKEV
     DMLHTGSSVA TAGGAESGYS SSMEDVSSS
//