Reviewed, UniProtKB/Swiss-Prot P19970 (FRQ_NEUCR)

Names and origin

Protein names

Recommended name:
    Frequency clock protein

Gene names

Name:	frq
ORF Names:	B13D24.170, NCU02265

Organism

Neurospora crassa [Complete proteome]

Taxonomic identifier

5141 [NCBI]

Taxonomic lineage

Eukaryota › Fungi › Dikarya › Ascomycota › Pezizomycotina › Sordariomycetes › Sordariomycetidae › Sordariales › Sordariaceae › Neurospora

Protein attributes

Sequence length	989 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Circadian clock component involved in the generation of biological rhythms, in particular in rhythm stability, period length, and temperature compensation. Oscillates in abundance with a daily peak early in the morning. Behaves as a negative element in circadian transcriptional loop. May bind to wc2 protein. The complex frq-wc2 may turn off the expression of frq.
Subcellular location	Nucleus Potential.
Induction	By light; perhaps through white collar-1 (wc1) and white collar-2 (wc2). Also activated directly by wc1 and wc2.
Post-translational modification	Progressive phosphorylation during the late circadian day and early night. Phosphorylation is also involved in regulating frq degradation. Phosphorylation by CKII may have at least three functions; it decreases the stability of frq, reduces the protein complex formation between frq and the white collar proteins, and is important for the closing of the Neurospora circadian negative feedback loop.
Sequence similarities	Belongs to the FRQ family.
Sequence caution	The sequence described in Ref.4 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Biological rhythms Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative initiation
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW rhythmic process Inferred from electronic annotation. Source: UniProtKB-KW transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative initiation. [Align] [Select]

Isoform Long (identifier: P19970-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Note: Maintains rhythms at high temperature (30 degrees Celsius).

Isoform Short (identifier: P19970-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-99: Missing.

Note: Maintains rhythms at lower temperature (18 degrees Celsius).

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 989	989	Frequency clock protein		PRO_0000021288
Regions
	Motif	564 – 568	5	Nuclear localization signal Potential
	Compositional bias	244 – 250	7	Poly-Ser
	Compositional bias	862 – 888	27	Asp/Glu-rich (acidic)
Amino acid modifications
	Modified residue	501	1	Phosphothreonine Ref.5
	Modified residue	513	1	Phosphoserine Ref.5
	Modified residue	519	1	Phosphoserine Ref.5
Natural variations
	Alternative sequence	1 – 99	99	Missing in isoform Short.		VSP_018781
Experimental info
	Mutagenesis	364	1	E → K in FRQ3; lengthened period. Ref.1
	Mutagenesis	459	1	G → D in FRQ7; lengthened period. Ref.1
	Mutagenesis	482	1	G → S in FRQ1; shortened period. Ref.1
	Mutagenesis	501 – 503	3	TPS → APG in FRQ10; no effect.
	Mutagenesis	513 – 514	2	ST → RA in FRQ10; strong reduction in the degradation rate; lengthened period.
	Mutagenesis	513	1	S → D in FRQ10; reduces phosphorylation; slight reduction in the degradation rate; loss of rhythmicity.
	Mutagenesis	513	1	S → I in FRQ10; reduces phosphorylation; strong reduction in the degradation rate; lengthened period.
	Mutagenesis	519	1	S → A in FRQ10; no effect. Ref.5
	Mutagenesis	663 – 989	327	Missing in FRQ9; loss of rhythmicity.
	Mutagenesis	895	1	A → T in FRQ2; shortened period. Ref.1
	Sequence conflict	146	1	S → T in AAA57121. Ref.1
	Sequence conflict	202 – 207	6	EATLRD → MGGNRP Ref.4
	Sequence conflict	207	1	D → H in AAA57121. Ref.1
	Sequence conflict	233	1	H → Y in AAA57121. Ref.1
	Sequence conflict	962 – 963	2	ML → IV in AAA57121. Ref.1
	Sequence conflict	962 – 963	2	ML → IV Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified June 7, 2005. Version 3. Checksum: EC4E984FAD39F095	FASTA	989	108,200
	10 20 30 40 50 60 MADSGDKSQG MRPPPFDSRG HPLPRRASPD KSITLENHRL ARDTSSRVTS SSALGVTESQ 70 80 90 100 110 120 PQLKSSPTRR NSSGESEPTN WFNQSNRNPA AAFHDESHIM EVDPPFYQKE TDSSNEESRY 130 140 150 160 170 180 PPGRNPVHPP GGVQLPGFRP VAAHSSAADD YRSVIDDLTV ENKRLKEELK RYKQFGSDVM 190 200 210 220 230 240 RKEKLFEIKV HGLPRRKKRE LEATLRDFAA SLGDSSESTS QRRKTGRHGT AVHSSGVSLS 250 260 270 280 290 300 KHDSSSSSRS RPVDSAYNSM STGRSSHAPH SSGPSLGRPS LTRAKSVGTQ KVENYLRDTP 310 320 330 340 350 360 DGLLPHHIVM TDKEKKKLVV RRLEQLFTGK ISGRNMQRNQ SMPSMDAPLA PEGTNMAPPR 370 380 390 400 410 420 PPPEGLREAC IQLQDGDNPR KNRSSKDNGS ASNSGGDQTE LGGTGTGSGD GSGSGGRTGN 430 440 450 460 470 480 NTSPPGAIAP DQRPTRPRDL DPDRVQIPSE NMDYIRHLGL VSPEFLQGSR TSYQDVAPDA 490 500 510 520 530 540 EGWVYLNLLC NLAQLHMVNV TPSFIRQAVS EKSTKFQLSA DGRKIRWRGG TDGTKFSSDS 550 560 570 580 590 600 SEDKSQQSPM TEDTEDGSDK NGRRKKRKTQ QASSEIGRFG PSRSPSDTFH YKPMFVHRNS 610 620 630 640 650 660 SSIETSLEES MSQGSEDAVD ESNMGNSKWD FSGSGTTQQR RKRRYDGAIV YYTGAPFCTD 670 680 690 700 710 720 LSGDPGDMSP TAQMTAGREV EGSGSGDEVE HVLQRTLSGS SLPIRPLSDD RARVAEVLDF 730 740 750 760 770 780 DPGNPPELVA DDGSSPNDED FVFPWCEDPA KVRIQPIAKE VMEPSGLGGV LPDDHFVMLV 790 800 810 820 830 840 TTRRVVRPIL QRQLSRSTTS EDTAEFIAER LAAIRTSSPL PPRSHRLTVA PLQVEYVSGQ 850 860 870 880 890 900 FRRLNPAPLP PPAIFYPPFS TDSSWDDGDD LASDDEEVEE VEEDSYSEGQ ISRRANPHFS 910 920 930 940 950 960 DNNTYMRKDD LAFDTETDVR MDSDDNRLSD SGHNMRAMMP RAEAVDGDDS PLAAVTGKEV 970 980 DMLHTGSSVA TAGGAESGYS SSMEDVSSS
	Isoform Short. Checksum: 833EDBB126628E24	FASTA	890	97,363
	10 20 30 40 50 60 MEVDPPFYQK ETDSSNEESR YPPGRNPVHP PGGVQLPGFR PVAAHSSAAD DYRSVIDDLT 70 80 90 100 110 120 VENKRLKEEL KRYKQFGSDV MRKEKLFEIK VHGLPRRKKR ELEATLRDFA ASLGDSSEST 130 140 150 160 170 180 SQRRKTGRHG TAVHSSGVSL SKHDSSSSSR SRPVDSAYNS MSTGRSSHAP HSSGPSLGRP 190 200 210 220 230 240 SLTRAKSVGT QKVENYLRDT PDGLLPHHIV MTDKEKKKLV VRRLEQLFTG KISGRNMQRN 250 260 270 280 290 300 QSMPSMDAPL APEGTNMAPP RPPPEGLREA CIQLQDGDNP RKNRSSKDNG SASNSGGDQT 310 320 330 340 350 360 ELGGTGTGSG DGSGSGGRTG NNTSPPGAIA PDQRPTRPRD LDPDRVQIPS ENMDYIRHLG 370 380 390 400 410 420 LVSPEFLQGS RTSYQDVAPD AEGWVYLNLL CNLAQLHMVN VTPSFIRQAV SEKSTKFQLS 430 440 450 460 470 480 ADGRKIRWRG GTDGTKFSSD SSEDKSQQSP MTEDTEDGSD KNGRRKKRKT QQASSEIGRF 490 500 510 520 530 540 GPSRSPSDTF HYKPMFVHRN SSSIETSLEE SMSQGSEDAV DESNMGNSKW DFSGSGTTQQ 550 560 570 580 590 600 RRKRRYDGAI VYYTGAPFCT DLSGDPGDMS PTAQMTAGRE VEGSGSGDEV EHVLQRTLSG 610 620 630 640 650 660 SSLPIRPLSD DRARVAEVLD FDPGNPPELV ADDGSSPNDE DFVFPWCEDP AKVRIQPIAK 670 680 690 700 710 720 EVMEPSGLGG VLPDDHFVML VTTRRVVRPI LQRQLSRSTT SEDTAEFIAE RLAAIRTSSP 730 740 750 760 770 780 LPPRSHRLTV APLQVEYVSG QFRRLNPAPL PPPAIFYPPF STDSSWDDGD DLASDDEEVE 790 800 810 820 830 840 EVEEDSYSEG QISRRANPHF SDNNTYMRKD DLAFDTETDV RMDSDDNRLS DSGHNMRAMM 850 860 870 880 890 PRAEAVDGDD SPLAAVTGKE VDMLHTGSSV ATAGGAESGY SSSMEDVSSS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Circadian clock locus frequency: protein encoded by a single open reading frame defines period length and temperature compensation." Aronson B.D., Johnson K.A., Dunlap J.C. Proc. Natl. Acad. Sci. U.S.A. 91:7683-7687(1994) [PubMed: 8052643] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS OF GLU-364; GLY-459; GLY-482 AND ALA-895. Strain: ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987.
[2]	"What's in the genome of a filamentous fungus? Analysis of the Neurospora genome sequence." Mannhaupt G., Montrone C., Haase D., Mewes H.-W., Aign V., Hoheisel J.D., Fartmann B., Nyakatura G., Kempken F., Maier J., Schulte U. Nucleic Acids Res. 31:1944-1954(2003) [PubMed: 12655011] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987.
[3]	"The genome sequence of the filamentous fungus Neurospora crassa." Galagan J.E., Calvo S.E., Borkovich K.A., Selker E.U., Read N.D., Jaffe D.B., FitzHugh W., Ma L.-J., Smirnov S., Purcell S., Rehman B., Elkins T., Engels R., Wang S., Nielsen C.B., Butler J., Endrizzi M., Qui D. , Ianakiev P., Bell-Pedersen D., Nelson M.A., Werner-Washburne M., Selitrennikoff C.P., Kinsey J.A., Braun E.L., Zelter A., Schulte U., Kothe G.O., Jedd G., Mewes H.-W., Staben C., Marcotte E., Greenberg D., Roy A., Foley K., Naylor J., Stange-Thomann N., Barrett R., Gnerre S., Kamal M., Kamvysselis M., Mauceli E.W., Bielke C., Rudd S., Frishman D., Krystofova S., Rasmussen C., Metzenberg R.L., Perkins D.D., Kroken S., Cogoni C., Macino G., Catcheside D.E.A., Li W., Pratt R.J., Osmani S.A., DeSouza C.P.C., Glass N.L., Orbach M.J., Berglund J.A., Voelker R., Yarden O., Plamann M., Seiler S., Dunlap J.C., Radford A., Aramayo R., Natvig D.O., Alex L.A., Mannhaupt G., Ebbole D.J., Freitag M., Paulsen I., Sachs M.S., Lander E.S., Nusbaum C., Birren B.W. Nature 422:859-868(2003) [PubMed: 12712197] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987.
[4]	"The Neurospora clock gene frequency shares a sequence element with the Drosophila clock gene period." McClung C.R., Fox B.A., Dunlap J.C. Nature 339:558-562(1989) [PubMed: 2525233] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 202-989.
[5]	"Phosphorylation of the Neurospora clock protein frequency determines its degradation rate and strongly influences the period length of the circadian clock." Liu Y., Loros J., Dunlap J.C. Proc. Natl. Acad. Sci. U.S.A. 97:234-239(2000) [PubMed: 10618401] [Abstract] Cited for: PHOSPHORYLATION AT THR-501; SER-513 AND SER-519, MUTAGENESIS OF 501-THR--SER-503; 513-SER-THR-514 AND SER-519.
[6]	"Regulation of the Neurospora circadian clock by casein kinase II." Yang Y., Cheng P., Liu Y. Genes Dev. 16:994-1006(2002) [PubMed: 11959847] [Abstract] Cited for: PHOSPHORYLATION BY CK2.

Cross-references

Sequence databases
EMBLGenBankDDBJ	U17073 mRNA. Translation: AAA57121.1. BX908789 Genomic DNA. Translation: CAF05882.1. AABX02000010 Genomic DNA. Translation: EAA30673.2. Different initiation.
PIR	T46659.
3D structure databases
ModBase	Search...
Genome annotation databases
NMPDR	fig|5141.1.peg.8974.
Family and domain databases
InterPro	IPR018554. Frequency_clock_protein. [Graphical view]
Pfam	PF09421. FRQ. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

FRQ_NEUCR

Accession

Primary (citable) accession number: P19970
Secondary accession number(s): Q01276, Q7RVB1

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	June 7, 2005
Last modified:	June 16, 2009
This is version 68 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

FPAP (Fungal Proteome Annotation Project)