FTHC_YEAST
ID FTHC_YEAST Reviewed; 211 AA.
AC P40099; D3DM92;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=5-formyltetrahydrofolate cyclo-ligase;
DE EC=6.3.3.2;
DE AltName: Full=5,10-methenyl-tetrahydrofolate synthetase;
DE Short=MTHFS;
DE Short=Methenyl-THF synthetase;
GN Name=FAU1; OrderedLocusNames=YER183C;
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 [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169868;
RA Dietrich F.S., Mulligan J.T., Hennessy K.M., Yelton M.A., Allen E.,
RA Araujo R., Aviles E., Berno A., Brennan T., Carpenter J., Chen E.,
RA Cherry J.M., Chung E., Duncan M., Guzman E., Hartzell G., Hunicke-Smith S.,
RA Hyman R.W., Kayser A., Komp C., Lashkari D., Lew H., Lin D., Mosedale D.,
RA Nakahara K., Namath A., Norgren R., Oefner P., Oh C., Petel F.X.,
RA Roberts D., Sehl P., Schramm S., Shogren T., Smith V., Taylor P., Wei Y.,
RA Botstein D., Davis R.W.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome V.";
RL Nature 387:78-81(1997).
RN [2]
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 [3]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=11923304; DOI=10.1074/jbc.m201242200;
RA Holmes W.B., Appling D.R.;
RT "Cloning and characterization of methenyltetrahydrofolate synthetase from
RT Saccharomyces cerevisiae.";
RL J. Biol. Chem. 277:20205-20213(2002).
RN [4]
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 [5]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 76625 / YPH499;
RX PubMed=14576278; DOI=10.1073/pnas.2135385100;
RA Sickmann A., Reinders J., Wagner Y., Joppich C., Zahedi R.P., Meyer H.E.,
RA Schoenfisch B., Perschil I., Chacinska A., Guiard B., Rehling P.,
RA Pfanner N., Meisinger C.;
RT "The proteome of Saccharomyces cerevisiae mitochondria.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:13207-13212(2003).
RN [6]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS].
RX PubMed=19756047; DOI=10.1038/msb.2009.64;
RA Kung L.A., Tao S.-C., Qian J., Smith M.G., Snyder M., Zhu H.;
RT "Global analysis of the glycoproteome in Saccharomyces cerevisiae reveals
RT new roles for protein glycosylation in eukaryotes.";
RL Mol. Syst. Biol. 5:308-308(2009).
CC -!- FUNCTION: Only enzyme known to utilize 5-formyltetrahydrofolate
CC (folinic acid) as substrate. Contributes to tetrahydrofolate metabolism
CC in an alternative way of folate biosynthesis. May regulate carbon flow
CC through the folate-dependent one-carbon metabolic network that supplies
CC carbon for the biosynthesis of purines, thymidine and amino acids.
CC {ECO:0000269|PubMed:11923304}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6S)-5-formyl-5,6,7,8-tetrahydrofolate + ATP = 5,10-
CC methenyltetrahydrofolate + ADP + phosphate; Xref=Rhea:RHEA:10488,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57455,
CC ChEBI:CHEBI:57457, ChEBI:CHEBI:456216; EC=6.3.3.2;
CC Evidence={ECO:0000269|PubMed:11923304};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=43 uM for ATP {ECO:0000269|PubMed:11923304};
CC KM=33 uM for 5-formyltetrahydrofolate {ECO:0000269|PubMed:11923304};
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:14576278}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:19756047}.
CC -!- DISRUPTION PHENOTYPE: Abolishes methenyltetrahydrofolate synthase
CC activity and leads to accumulation of folinic acid. Leads to a striking
CC methionine deficiency when combined with ADE16 and ADE17, 2 isoenzymes
CC involved in the purine synthesis. {ECO:0000269|PubMed:11923304}.
CC -!- MISCELLANEOUS: Present with 468 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the 5-formyltetrahydrofolate cyclo-ligase
CC family. {ECO:0000305}.
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DR EMBL; U18922; AAB64710.1; -; Genomic_DNA.
DR EMBL; BK006939; DAA07846.1; -; Genomic_DNA.
DR PIR; S50686; S50686.
DR RefSeq; NP_011110.1; NM_001179073.1.
DR AlphaFoldDB; P40099; -.
DR SMR; P40099; -.
DR BioGRID; 36937; 43.
DR IntAct; P40099; 2.
DR MINT; P40099; -.
DR STRING; 4932.YER183C; -.
DR MaxQB; P40099; -.
DR PaxDb; P40099; -.
DR PRIDE; P40099; -.
DR EnsemblFungi; YER183C_mRNA; YER183C; YER183C.
DR GeneID; 856932; -.
DR KEGG; sce:YER183C; -.
DR SGD; S000000985; FAU1.
DR VEuPathDB; FungiDB:YER183C; -.
DR eggNOG; KOG3093; Eukaryota.
DR GeneTree; ENSGT00390000017791; -.
DR HOGENOM; CLU_066245_2_1_1; -.
DR InParanoid; P40099; -.
DR OMA; DKWGIPT; -.
DR BioCyc; YEAST:YER183C-MON; -.
DR Reactome; R-SCE-196757; Metabolism of folate and pterines.
DR SABIO-RK; P40099; -.
DR PRO; PR:P40099; -.
DR Proteomes; UP000002311; Chromosome V.
DR RNAct; P40099; protein.
DR GO; GO:0005739; C:mitochondrion; HDA:SGD.
DR GO; GO:0030272; F:5-formyltetrahydrofolate cyclo-ligase activity; IDA:SGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0009396; P:folic acid-containing compound biosynthetic process; IDA:SGD.
DR GO; GO:0035999; P:tetrahydrofolate interconversion; IBA:GO_Central.
DR Gene3D; 3.40.50.10420; -; 1.
DR InterPro; IPR002698; FTHF_cligase.
DR InterPro; IPR024185; FTHF_cligase-like_sf.
DR InterPro; IPR037171; NagB/RpiA_transferase-like.
DR PANTHER; PTHR23407:SF1; PTHR23407:SF1; 1.
DR Pfam; PF01812; 5-FTHF_cyc-lig; 1.
DR PIRSF; PIRSF006806; FTHF_cligase; 1.
DR SUPFAM; SSF100950; SSF100950; 1.
DR TIGRFAMs; TIGR02727; MTHFS_bact; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Glycoprotein; Ligase; Mitochondrion; Nucleotide-binding;
KW Reference proteome.
FT CHAIN 1..211
FT /note="5-formyltetrahydrofolate cyclo-ligase"
FT /id="PRO_0000200280"
FT BINDING 4..8
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 56
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 151..158
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 152..156
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 194
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
SQ SEQUENCE 211 AA; 24059 MW; 96F0D84B3B69DD57 CRC64;
MATKQLLRRQ IKRVINALDY DIIAAESHTI SQAVRSLIAS ANSRRVACYM SMDKGEVTTG
EIIKNLFQDG QEVFLPRCTH TSESKHFKLR EDHHPHLIFH RMSSLKMVRD LKPQGPYQLK
EPEPHIEESD ILDVVLVPGV AFDIKTGARM GHGAGYYDDF FQRYKILHEG QKPLLVGLCL
MEQVASPIPL EKHDYSMDCI VCGDGSIHWF Q
