FKH1_YEAST
ID FKH1_YEAST Reviewed; 484 AA.
AC P40466; D6VVF6; Q45U14;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Fork head protein homolog 1 {ECO:0000303|PubMed:10747051};
GN Name=FKH1 {ECO:0000303|PubMed:10747051}; OrderedLocusNames=YIL131C;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RA Zhu G., Davis T.N.;
RT "Two fork head homologs in S. cerevisiae.";
RL Submitted (JAN-1995) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=SK1;
RX PubMed=16273108; DOI=10.1038/ng1674;
RA Deutschbauer A.M., Davis R.W.;
RT "Quantitative trait loci mapped to single-nucleotide resolution in yeast.";
RL Nat. Genet. 37:1333-1340(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169870;
RA Churcher C.M., Bowman S., Badcock K., Bankier A.T., Brown D.,
RA Chillingworth T., Connor R., Devlin K., Gentles S., Hamlin N., Harris D.E.,
RA Horsnell T., Hunt S., Jagels K., Jones M., Lye G., Moule S., Odell C.,
RA Pearson D., Rajandream M.A., Rice P., Rowley N., Skelton J., Smith V.,
RA Walsh S.V., Whitehead S., Barrell B.G.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome IX.";
RL Nature 387:84-87(1997).
RN [4]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=10959837; DOI=10.1016/s0960-9822(00)00618-7;
RA Kumar R., Reynolds D.M., Shevchenko A., Shevchenko A., Goldstone S.D.,
RA Dalton S.;
RT "Forkhead transcription factors, Fkh1p and Fkh2p, collaborate with Mcm1p to
RT control transcription required for M-phase.";
RL Curr. Biol. 10:896-906(2000).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=10747051; DOI=10.1093/genetics/154.4.1533;
RA Hollenhorst P.C., Bose M.E., Mielke M.R., Mueller U., Fox C.A.;
RT "Forkhead genes in transcriptional silencing, cell morphology and the cell
RT cycle. Overlapping and distinct functions for FKH1 and FKH2 in
RT Saccharomyces cerevisiae.";
RL Genetics 154:1533-1548(2000).
RN [7]
RP FUNCTION.
RX PubMed=10894548; DOI=10.1038/35017581;
RA Zhu G., Spellman P.T., Volpe T., Brown P.O., Botstein D., Davis T.N.,
RA Futcher B.;
RT "Two yeast forkhead genes regulate the cell cycle and pseudohyphal
RT growth.";
RL Nature 406:90-94(2000).
RN [8]
RP FUNCTION.
RX PubMed=10894549; DOI=10.1038/35017589;
RA Koranda M., Schleiffer A., Endler L., Ammerer G.;
RT "Forkhead-like transcription factors recruit Ndd1 to the chromatin of G2/M-
RT specific promoters.";
RL Nature 406:94-98(2000).
RN [9]
RP FUNCTION, AND DNA-BINDING.
RX PubMed=11562353; DOI=10.1101/gad.906201;
RA Hollenhorst P.C., Pietz G., Fox C.A.;
RT "Mechanisms controlling differential promoter-occupancy by the yeast
RT forkhead proteins Fkh1p and Fkh2p: implications for regulating the cell
RT cycle and differentiation.";
RL Genes Dev. 15:2445-2456(2001).
RN [10]
RP FUNCTION.
RX PubMed=12183363; DOI=10.1101/gad.994902;
RA Sun K., Coic E., Zhou Z., Durrens P., Haber J.E.;
RT "Saccharomyces forkhead protein Fkh1 regulates donor preference during
RT mating-type switching through the recombination enhancer.";
RL Genes Dev. 16:2085-2096(2002).
RN [11]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [12]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=12702877; DOI=10.1126/science.1081379;
RA Morillon A., O'Sullivan J., Azad A., Proudfoot N., Mellor J.;
RT "Regulation of elongating RNA polymerase II by forkhead transcription
RT factors in yeast.";
RL Science 300:492-495(2003).
RN [13]
RP FUNCTION.
RX PubMed=16809780; DOI=10.1128/mcb.02443-05;
RA Coic E., Sun K., Wu C., Haber J.E.;
RT "Cell cycle-dependent regulation of Saccharomyces cerevisiae donor
RT preference during mating-type switching by SBF (Swi4/Swi6) and Fkh1.";
RL Mol. Cell. Biol. 26:5470-5480(2006).
RN [14]
RP FUNCTION.
RX PubMed=17283050; DOI=10.1128/mcb.01798-06;
RA Sherriff J.A., Kent N.A., Mellor J.;
RT "The Isw2 chromatin-remodeling ATPase cooperates with the Fkh2
RT transcription factor to repress transcription of the B-type cyclin gene
RT CLB2.";
RL Mol. Cell. Biol. 27:2848-2860(2007).
RN [15]
RP FUNCTION, AND INTERACTION WITH ORC.
RX PubMed=22265405; DOI=10.1016/j.cell.2011.12.012;
RA Knott S.R., Peace J.M., Ostrow A.Z., Gan Y., Rex A.E., Viggiani C.J.,
RA Tavare S., Aparicio O.M.;
RT "Forkhead transcription factors establish origin timing and long-range
RT clustering in S. cerevisiae.";
RL Cell 148:99-111(2012).
RN [16]
RP SUBCELLULAR LOCATION.
RX PubMed=22932476; DOI=10.1186/2045-3701-2-30;
RA Dastidar R.G., Hooda J., Shah A., Cao T.M., Henke R.M., Zhang L.;
RT "The nuclear localization of SWI/SNF proteins is subjected to oxygen
RT regulation.";
RL Cell Biosci. 2:30-30(2012).
RN [17]
RP FUNCTION.
RX PubMed=22438832; DOI=10.1371/journal.pgen.1002583;
RA Postnikoff S.D., Malo M.E., Wong B., Harkness T.A.;
RT "The yeast forkhead transcription factors fkh1 and fkh2 regulate lifespan
RT and stress response together with the anaphase-promoting complex.";
RL PLoS Genet. 8:e1002583-e1002583(2012).
RN [18]
RP FUNCTION, AND DOMAIN.
RX PubMed=22496671; DOI=10.1371/journal.pgen.1002630;
RA Li J., Coic E., Lee K., Lee C.S., Kim J.A., Wu Q., Haber J.E.;
RT "Regulation of budding yeast mating-type switching donor preference by the
RT FHA domain of Fkh1.";
RL PLoS Genet. 8:e1002630-e1002630(2012).
RN [19]
RP FUNCTION, AND DNA-BINDING.
RX PubMed=24504085; DOI=10.1371/journal.pone.0087647;
RA Ostrow A.Z., Nellimoottil T., Knott S.R., Fox C.A., Tavare S.,
RA Aparicio O.M.;
RT "Fkh1 and Fkh2 bind multiple chromosomal elements in the S. cerevisiae
RT genome with distinct specificities and cell cycle dynamics.";
RL PLoS ONE 9:e87647-e87647(2014).
RN [20]
RP FUNCTION.
RX PubMed=26728715; DOI=10.1101/gr.196857.115;
RA Peace J.M., Villwock S.K., Zeytounian J.L., Gan Y., Aparicio O.M.;
RT "Quantitative BrdU immunoprecipitation method demonstrates that Fkh1 and
RT Fkh2 are rate-limiting activators of replication origins that reprogram
RT replication timing in G1 phase.";
RL Genome Res. 26:365-375(2016).
RN [21]
RP FUNCTION, INTERACTION WITH ECM30; GLN3; URE2; MPH1 AND FDO1, AND
RP MUTAGENESIS OF ARG-80; SER-110 AND ARG-111.
RX PubMed=27257873; DOI=10.1371/journal.pgen.1006094;
RA Dummer A.M., Su Z., Cherney R., Choi K., Denu J., Zhao X., Fox C.A.;
RT "Binding of the Fkh1 forkhead associated domain to a phosphopeptide within
RT the Mph1 DNA helicase regulates mating-type switching in budding yeast.";
RL PLoS Genet. 12:e1006094-e1006094(2016).
CC -!- FUNCTION: Transcription factor that regulates the expression of the
CC CLB2 cluster of genes during the G2/M phase of the mitotic cell cycle
CC (PubMed:10959837, PubMed:10894548, PubMed:10894549, PubMed:11562353,
CC PubMed:12702877, PubMed:17283050, PubMed:24504085). The CLB2 cluster of
CC genes includes mitotic regulators such as CLB1, CLB2, CDC5 and CDC20 as
CC well as SWI5 and ACE2, transcription factors required for the
CC subsequent temporal wave of cell cycle regulated gene expression in the
CC M/G1 phase interval (PubMed:10959837, PubMed:10894548,
CC PubMed:11562353). Involved in HMRa silencing (PubMed:10747051). FKH1
CC and FKH2 associate with the coding regions of active genes and
CC influence, in opposing ways, transcriptional elongation and
CC termination, and coordinate early transcription elongation and pre-mRNA
CC processing (PubMed:12702877). Both FKH1 and FKH2 play a role as
CC regulators of lifespan in collaboration with the anaphase-promoting
CC complex (APC), likely through combined regulation of stress response,
CC genomic stability, and cell cycle regulation (PubMed:22438832). FKH1
CC and FKH2 function also in controlling yeast cell morphology by
CC preventing preudohyphal growth (PubMed:10747051, PubMed:10894548). Acts
CC as a rate-limiting replication origin activator via its interactin with
CC the origin recognition complex (ORC) (PubMed:22265405,
CC PubMed:26728715). Plays a transcription-independent role in
CC recombination donor preference during mating-type switching through
CC binding to the recombination enhancer (RE), a 700-bp cis-acting element
CC that controls recombination along the left arm of chromosome III
CC (PubMed:12183363, PubMed:16809780, PubMed:22496671, PubMed:27257873).
CC {ECO:0000269|PubMed:10747051, ECO:0000269|PubMed:10894548,
CC ECO:0000269|PubMed:10894549, ECO:0000269|PubMed:10959837,
CC ECO:0000269|PubMed:11562353, ECO:0000269|PubMed:12183363,
CC ECO:0000269|PubMed:12702877, ECO:0000269|PubMed:16809780,
CC ECO:0000269|PubMed:17283050, ECO:0000269|PubMed:22265405,
CC ECO:0000269|PubMed:22438832, ECO:0000269|PubMed:22496671,
CC ECO:0000269|PubMed:24504085, ECO:0000269|PubMed:26728715,
CC ECO:0000269|PubMed:27257873}.
CC -!- SUBUNIT: Interacts (via FHA domain) with ECM30, GLN3, URE2, MPH1 AND
CC FDO1 (PubMed:27257873). Interacts with the origin recognition complex
CC (ORC) composed of ORC1 to ORC6 (PubMed:22265405).
CC {ECO:0000269|PubMed:22265405, ECO:0000269|PubMed:27257873}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:22932476}. Cytoplasm,
CC cytosol {ECO:0000269|PubMed:12702877}. Note=Relocalizes to the cytosol
CC in response to hypoxia. {ECO:0000269|PubMed:12702877}.
CC -!- DOMAIN: The phosphothreonine-binding FHA domain is required for the
CC interaction with MPH1 and controlling recombination donor preference
CC during mating-type switching. {ECO:0000269|PubMed:22496671}.
CC -!- DISRUPTION PHENOTYPE: Causes only a modest decline in CLB2 cluster
CC genes expression, but this expression is abolished when both FKH1 and
CC FKH2 are deleted (PubMed:10959837). Leads to a defect in silencing HMRa
CC (PubMed:10747051). Causes a form of yeast pseudohyphal growth, when
CC FKH2 is also deleted (PubMed:10747051). Affects cell-cycle progression
CC and CLB2 mRNA expression (PubMed:10747051). Leads to defect in pre-mRNA
CC 3' end formation during transcription of targeted genes
CC (PubMed:12702877). {ECO:0000269|PubMed:10747051,
CC ECO:0000269|PubMed:10959837, ECO:0000269|PubMed:12702877}.
CC -!- MISCELLANEOUS: Present with 1720 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
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DR EMBL; L38848; AAA60938.1; -; Genomic_DNA.
DR EMBL; DQ115392; AAZ22496.1; -; Genomic_DNA.
DR EMBL; Z38059; CAA86147.1; -; Genomic_DNA.
DR EMBL; BK006942; DAA08422.1; -; Genomic_DNA.
DR PIR; S48403; S48403.
DR RefSeq; NP_012135.1; NM_001179479.1.
DR AlphaFoldDB; P40466; -.
DR SMR; P40466; -.
DR BioGRID; 34860; 131.
DR DIP; DIP-5220N; -.
DR IntAct; P40466; 34.
DR STRING; 4932.YIL131C; -.
DR iPTMnet; P40466; -.
DR MaxQB; P40466; -.
DR PaxDb; P40466; -.
DR PRIDE; P40466; -.
DR EnsemblFungi; YIL131C_mRNA; YIL131C; YIL131C.
DR GeneID; 854675; -.
DR KEGG; sce:YIL131C; -.
DR SGD; S000001393; FKH1.
DR VEuPathDB; FungiDB:YIL131C; -.
DR eggNOG; KOG2294; Eukaryota.
DR GeneTree; ENSGT00940000173882; -.
DR HOGENOM; CLU_044386_0_0_1; -.
DR InParanoid; P40466; -.
DR OMA; WIADHYA; -.
DR BioCyc; YEAST:G3O-31382-MON; -.
DR Reactome; R-SCE-3232118; SUMOylation of transcription factors.
DR Reactome; R-SCE-9018519; Estrogen-dependent gene expression.
DR PRO; PR:P40466; -.
DR Proteomes; UP000002311; Chromosome IX.
DR RNAct; P40466; protein.
DR GO; GO:0005829; C:cytosol; IDA:SGD.
DR GO; GO:0005634; C:nucleus; IDA:SGD.
DR GO; GO:0019237; F:centromeric DNA binding; IDA:SGD.
DR GO; GO:0003682; F:chromatin binding; IDA:SGD.
DR GO; GO:0003688; F:DNA replication origin binding; IDA:SGD.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:SGD.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:SGD.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:SGD.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:SGD.
DR GO; GO:0006338; P:chromatin remodeling; IMP:SGD.
DR GO; GO:0007535; P:donor selection; IMP:SGD.
DR GO; GO:0031124; P:mRNA 3'-end processing; IMP:SGD.
DR GO; GO:2000221; P:negative regulation of pseudohyphal growth; IGI:SGD.
DR GO; GO:0034244; P:negative regulation of transcription elongation from RNA polymerase II promoter; IMP:SGD.
DR GO; GO:0071930; P:negative regulation of transcription involved in G1/S transition of mitotic cell cycle; IGI:SGD.
DR GO; GO:0090419; P:negative regulation of transcription involved in G2/M transition of mitotic cell cycle; IMP:SGD.
DR GO; GO:1903468; P:positive regulation of DNA replication initiation; IMP:SGD.
DR GO; GO:0032298; P:positive regulation of DNA-templated DNA replication initiation; IMP:SGD.
DR GO; GO:0090055; P:positive regulation of silent mating-type cassette heterochromatin assembly; IMP:SGD.
DR GO; GO:0090282; P:positive regulation of transcription involved in G2/M transition of mitotic cell cycle; IGI:SGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006369; P:termination of RNA polymerase II transcription; IMP:SGD.
DR CDD; cd00059; FH; 1.
DR CDD; cd00060; FHA; 1.
DR Gene3D; 1.10.10.10; -; 1.
DR InterPro; IPR000253; FHA_dom.
DR InterPro; IPR001766; Fork_head_dom.
DR InterPro; IPR008984; SMAD_FHA_dom_sf.
DR InterPro; IPR018122; TF_fork_head_CS_1.
DR InterPro; IPR030456; TF_fork_head_CS_2.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR Pfam; PF00498; FHA; 1.
DR Pfam; PF00250; Forkhead; 1.
DR PRINTS; PR00053; FORKHEAD.
DR SMART; SM00339; FH; 1.
DR SMART; SM00240; FHA; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR SUPFAM; SSF49879; SSF49879; 1.
DR PROSITE; PS50006; FHA_DOMAIN; 1.
DR PROSITE; PS00657; FORK_HEAD_1; 1.
DR PROSITE; PS00658; FORK_HEAD_2; 1.
DR PROSITE; PS50039; FORK_HEAD_3; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; DNA-binding; Nucleus; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..484
FT /note="Fork head protein homolog 1"
FT /id="PRO_0000091903"
FT DOMAIN 76..142
FT /note="FHA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00086"
FT DNA_BIND 302..393
FT /note="Fork-head"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00089"
FT MUTAGEN 80
FT /note="R->A: Leads to reduced colony size when FKH2 is
FT deleted."
FT /evidence="ECO:0000269|PubMed:27257873"
FT MUTAGEN 110
FT /note="S->A: Leads to reduced colony size when FKH2 is
FT deleted."
FT /evidence="ECO:0000269|PubMed:27257873"
FT MUTAGEN 111
FT /note="R->A: Leads to reduced colony size when FKH2 is
FT deleted."
FT /evidence="ECO:0000269|PubMed:27257873"
SQ SEQUENCE 484 AA; 53490 MW; 7159073EB979C489 CRC64;
MSVTSREQKF SGKYSSYTAQ DRQGLVNAVT CVLSSSSDPV AVSSDYSNSL SIAREVNAYA
KIAGCDWTYY VQKLEVTIGR NTDSLNLNAV PGTVVKKNID IDLGPAKIVS RKHAAIRFNL
ESGSWELQIF GRNGAKVNFR RIPTGPDSPP TVLQSGCIID IGGVQMIFIL PEQETIISDY
CLNHLMPKLL STYGTNGNNN PLLRNIIEGS TYLREQRLQE EARLQQLDHL HTPLSSSSDV
NPIGDPHGDT IMMEEDEEDE NYTRGGIRPN TYTSSSNNAV TNGNVPHIEN PSDLSLDENR
YIKPPQSYAS MITQAILSTP EGSISLADIY KFISDNYAFY RFSQMAWQNS VRHNLSLNKA
FEKVPKRAGQ QGKGMNWKIS DEVRRDFLNK WNAGKLSKIR RGASVTRQLQ LHMSKFGEIP
APESSSIDPR GIKAQKVKKS LQATSSILGE SAPQLQRTQL TGQISTTTSM DVTTNANVNN
SSLS
