C1TM_YEAST
ID C1TM_YEAST Reviewed; 975 AA.
AC P09440; D6VQ83;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 203.
DE RecName: Full=C-1-tetrahydrofolate synthase, mitochondrial {ECO:0000305};
DE Short=C1-THF synthase;
DE Includes:
DE RecName: Full=Methylenetetrahydrofolate dehydrogenase;
DE EC=1.5.1.5 {ECO:0000269|PubMed:3528153};
DE Includes:
DE RecName: Full=Methenyltetrahydrofolate cyclohydrolase;
DE EC=3.5.4.9 {ECO:0000269|PubMed:3528153};
DE Includes:
DE RecName: Full=Formyltetrahydrofolate synthetase;
DE EC=6.3.4.3 {ECO:0000269|PubMed:3528153};
DE Flags: Precursor;
GN Name=MIS1 {ECO:0000303|PubMed:2836393}; OrderedLocusNames=YBR084W;
GN ORFNames=YBR0751;
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].
RX PubMed=2836393; DOI=10.1016/s0021-9258(18)68558-8;
RA Shannon K.W., Rabinowitz J.C.;
RT "Isolation and characterization of the Saccharomyces cerevisiae MIS1 gene
RT encoding mitochondrial C1-tetrahydrofolate synthase.";
RL J. Biol. Chem. 263:7717-7725(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=7813418; DOI=10.1002/j.1460-2075.1994.tb06923.x;
RA Feldmann H., Aigle M., Aljinovic G., Andre B., Baclet M.C., Barthe C.,
RA Baur A., Becam A.-M., Biteau N., Boles E., Brandt T., Brendel M.,
RA Brueckner M., Bussereau F., Christiansen C., Contreras R., Crouzet M.,
RA Cziepluch C., Demolis N., Delaveau T., Doignon F., Domdey H.,
RA Duesterhus S., Dubois E., Dujon B., El Bakkoury M., Entian K.-D.,
RA Feuermann M., Fiers W., Fobo G.M., Fritz C., Gassenhuber J., Glansdorff N.,
RA Goffeau A., Grivell L.A., de Haan M., Hein C., Herbert C.J.,
RA Hollenberg C.P., Holmstroem K., Jacq C., Jacquet M., Jauniaux J.-C.,
RA Jonniaux J.-L., Kallesoee T., Kiesau P., Kirchrath L., Koetter P.,
RA Korol S., Liebl S., Logghe M., Lohan A.J.E., Louis E.J., Li Z.Y.,
RA Maat M.J., Mallet L., Mannhaupt G., Messenguy F., Miosga T., Molemans F.,
RA Mueller S., Nasr F., Obermaier B., Perea J., Pierard A., Piravandi E.,
RA Pohl F.M., Pohl T.M., Potier S., Proft M., Purnelle B., Ramezani Rad M.,
RA Rieger M., Rose M., Schaaff-Gerstenschlaeger I., Scherens B.,
RA Schwarzlose C., Skala J., Slonimski P.P., Smits P.H.M., Souciet J.-L.,
RA Steensma H.Y., Stucka R., Urrestarazu L.A., van der Aart Q.J.M.,
RA Van Dyck L., Vassarotti A., Vetter I., Vierendeels F., Vissers S.,
RA Wagner G., de Wergifosse P., Wolfe K.H., Zagulski M., Zimmermann F.K.,
RA Mewes H.-W., Kleine K.;
RT "Complete DNA sequence of yeast chromosome II.";
RL EMBO J. 13:5795-5809(1994).
RN [3]
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 [4]
RP PROTEIN SEQUENCE OF 35-74, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION,
RP SUBUNIT, AND PATHWAY.
RX PubMed=3528153; DOI=10.1016/s0021-9258(18)67234-5;
RA Shannon K.W., Rabinowitz J.C.;
RT "Purification and characterization of a mitochondrial isozyme of C1-
RT tetrahydrofolate synthase from Saccharomyces cerevisiae.";
RL J. Biol. Chem. 261:12266-12271(1986).
RN [5]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=14562095; DOI=10.1038/nature02026;
RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA Weissman J.S., O'Shea E.K.;
RT "Global analysis of protein localization in budding yeast.";
RL Nature 425:686-691(2003).
RN [6]
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 [7]
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).
CC -!- FUNCTION: Mitochondrial isozyme of C-1-tetrahydrofolate synthase. The
CC trifunctional enzyme catalyzes the interconversion of the one-carbon
CC derivatives of tetrahydrofolate (THF) between different oxidation
CC states by the enzymatic activities 10-formyltetrahydrofolate
CC synthetase, 5,lO-methenyltetrahydrofolate cyclohydrolase, and 5,lO-
CC methylenetetrahydrofolate dehydrogenase. {ECO:0000269|PubMed:3528153}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + NADP(+) = 5,10-
CC methenyltetrahydrofolate + NADPH; Xref=Rhea:RHEA:22812,
CC ChEBI:CHEBI:15636, ChEBI:CHEBI:57455, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; EC=1.5.1.5; Evidence={ECO:0000269|PubMed:3528153};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22813;
CC Evidence={ECO:0000305|PubMed:3528153};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:22814;
CC Evidence={ECO:0000305|PubMed:3528153};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5,10-methenyltetrahydrofolate + H2O = (6S)-10-
CC formyltetrahydrofolate + H(+); Xref=Rhea:RHEA:23700,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57454,
CC ChEBI:CHEBI:57455; EC=3.5.4.9; Evidence={ECO:0000269|PubMed:3528153};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23701;
CC Evidence={ECO:0000305|PubMed:3528153};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:23702;
CC Evidence={ECO:0000305|PubMed:3528153};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6S)-5,6,7,8-tetrahydrofolate + ATP + formate = (6S)-10-
CC formyltetrahydrofolate + ADP + phosphate; Xref=Rhea:RHEA:20221,
CC ChEBI:CHEBI:15740, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57453, ChEBI:CHEBI:57454, ChEBI:CHEBI:456216; EC=6.3.4.3;
CC Evidence={ECO:0000269|PubMed:3528153};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20222;
CC Evidence={ECO:0000305|PubMed:3528153};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:20223;
CC Evidence={ECO:0000305|PubMed:3528153};
CC -!- PATHWAY: One-carbon metabolism; tetrahydrofolate interconversion.
CC {ECO:0000305|PubMed:3528153}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:3528153}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:14562095,
CC ECO:0000269|PubMed:14576278, ECO:0000269|PubMed:3528153}.
CC -!- DOMAIN: This trifunctional enzyme consists of two major domains: an N-
CC terminal part containing the methylene-THF dehydrogenase and
CC cyclohydrolase activities and a larger C-terminal part containing
CC formyl-THF synthetase activity. {ECO:0000250|UniProtKB:P07245}.
CC -!- MISCELLANEOUS: Present with 11400 molecules/cell in log phase SD
CC medium. {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the tetrahydrofolate
CC dehydrogenase/cyclohydrolase family. {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the formate--
CC tetrahydrofolate ligase family. {ECO:0000305}.
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DR EMBL; Z35953; CAA85029.1; -; Genomic_DNA.
DR EMBL; J03724; AAA34781.1; -; Genomic_DNA.
DR EMBL; BK006936; DAA07203.1; -; Genomic_DNA.
DR PIR; A28174; A28174.
DR RefSeq; NP_009640.1; NM_001178432.1.
DR AlphaFoldDB; P09440; -.
DR SMR; P09440; -.
DR BioGRID; 32788; 243.
DR DIP; DIP-6724N; -.
DR IntAct; P09440; 51.
DR MINT; P09440; -.
DR STRING; 4932.YBR084W; -.
DR iPTMnet; P09440; -.
DR MaxQB; P09440; -.
DR PaxDb; P09440; -.
DR PRIDE; P09440; -.
DR EnsemblFungi; YBR084W_mRNA; YBR084W; YBR084W.
DR GeneID; 852378; -.
DR KEGG; sce:YBR084W; -.
DR SGD; S000000288; MIS1.
DR VEuPathDB; FungiDB:YBR084W; -.
DR eggNOG; KOG4230; Eukaryota.
DR GeneTree; ENSGT01000000220033; -.
DR HOGENOM; CLU_003601_2_0_1; -.
DR InParanoid; P09440; -.
DR OMA; IKRVVDC; -.
DR BioCyc; YEAST:YBR084W-MON; -.
DR BRENDA; 3.5.4.9; 984.
DR BRENDA; 6.3.4.3; 984.
DR Reactome; R-SCE-196757; Metabolism of folate and pterines.
DR UniPathway; UPA00193; -.
DR PRO; PR:P09440; -.
DR Proteomes; UP000002311; Chromosome II.
DR RNAct; P09440; protein.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IDA:SGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004329; F:formate-tetrahydrofolate ligase activity; IDA:SGD.
DR GO; GO:0004477; F:methenyltetrahydrofolate cyclohydrolase activity; IDA:SGD.
DR GO; GO:0004488; F:methylenetetrahydrofolate dehydrogenase (NADP+) activity; IDA:SGD.
DR GO; GO:0046656; P:folic acid biosynthetic process; IDA:SGD.
DR GO; GO:0000105; P:histidine biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0009086; P:methionine biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0006139; P:nucleobase-containing compound metabolic process; IMP:SGD.
DR GO; GO:0006164; P:purine nucleotide biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0035999; P:tetrahydrofolate interconversion; IBA:GO_Central.
DR CDD; cd00477; FTHFS; 1.
DR CDD; cd01080; NAD_bind_m-THF_DH_Cyclohyd; 1.
DR Gene3D; 3.40.50.300; -; 2.
DR HAMAP; MF_01543; FTHFS; 1.
DR HAMAP; MF_01576; THF_DHG_CYH; 1.
DR InterPro; IPR046346; Aminiacid_DH-like_N_sf.
DR InterPro; IPR000559; Formate_THF_ligase.
DR InterPro; IPR020628; Formate_THF_ligase_CS.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR000672; THF_DH/CycHdrlase.
DR InterPro; IPR020630; THF_DH/CycHdrlase_cat_dom.
DR InterPro; IPR020867; THF_DH/CycHdrlase_CS.
DR InterPro; IPR020631; THF_DH/CycHdrlase_NAD-bd_dom.
DR Pfam; PF01268; FTHFS; 1.
DR Pfam; PF00763; THF_DHG_CYH; 1.
DR Pfam; PF02882; THF_DHG_CYH_C; 1.
DR PRINTS; PR00085; THFDHDRGNASE.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF53223; SSF53223; 1.
DR PROSITE; PS00721; FTHFS_1; 1.
DR PROSITE; PS00722; FTHFS_2; 1.
DR PROSITE; PS00766; THF_DHG_CYH_1; 1.
DR PROSITE; PS00767; THF_DHG_CYH_2; 1.
PE 1: Evidence at protein level;
KW Amino-acid biosynthesis; ATP-binding; Direct protein sequencing;
KW Histidine biosynthesis; Hydrolase; Ligase; Methionine biosynthesis;
KW Mitochondrion; Multifunctional enzyme; NADP; Nucleotide-binding;
KW One-carbon metabolism; Oxidoreductase; Purine biosynthesis;
KW Reference proteome; Transit peptide.
FT TRANSIT 1..34
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:3528153"
FT CHAIN 35..975
FT /note="C-1-tetrahydrofolate synthase, mitochondrial"
FT /id="PRO_0000034052"
FT REGION 35..343
FT /note="Methylenetetrahydrofolate dehydrogenase and
FT cyclohydrolase"
FT /evidence="ECO:0000250|UniProtKB:P07245"
FT REGION 344..975
FT /note="Formyltetrahydrofolate synthetase"
FT /evidence="ECO:0000250|UniProtKB:P07245"
FT BINDING 83..87
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 130..132
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 201..203
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 226
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 301..305
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 408..415
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
SQ SEQUENCE 975 AA; 106217 MW; B9421D4F8981531F CRC64;
MLSRLSLLSN SRAFQQARWR IYRLKVSPTV HASQYHILSG RKLAQSIREK ANDEIQAIKL
KHPNFKPTLK IIQVGARPDS STYVRMKLKA SKDSNVDCII EKLPAEITEV ELLKKISDIN
DDDSIHGLLI QLPLPRHLDE TTITNAVDFK KDVDGFHRYN AGELAKKGGK PYFIPCTPYG
CMKLLEEAHV KLDGKNAVVL GRSSIVGNPI ASLLKNANAT VTVCHSHTRN IAEVVSQADI
VIAACGIPQY VKSDWIKEGA VVIDVGINYV PDISKKSGQK LVGDVDFDSV KEKTSYITPV
PGGVGPMTVA MLVSNVLLAA KRQFVESEKL PVIKPLPLHL ESPVPSDIDI SRAQSPKHIK
QVAEELGIHS HELELYGHYK AKISPNIFKR LESRENGKYV LVAGITPTPL GEGKSTTTMG
LVQALSAHLG KPSIANVRQP SLGPTLGVKG GAAGGGYAQV IPMDEFNLHL TGDIHAISAA
NNLLAAAIDT RMFHEATQKN DSTFYKRLVP RKKGIRKFTP SMQRRLKRLD IEKEDPDALT
PEEVKRFARL NINPDTITIR RVVDINDRML RQITIGEAAT EKGFTRTTGF DITVASELMA
ILALSKSLHE MKERIGRMVI GADYDNKPVT VEDIGCTGAL TALLRDAIKP NLMQTLEGTP
VMVHAGPFAN ISIGASSVIA DLMALKLVGS EKNPLNDKNI HEPGYVVTEA GFDFAMGGER
FFDIKCRSSG LVPDAVVLVA TVRALKSHGG APNVKPGQSL PKEYTEENID FVAKGVSNLV
KQIENIKTFG IPVVVAINRF ETDSQAEIEV IKKAALNAGA SHAVTSNHWM EGGKGAVELA
HAVVDATKEP KNFNFLYDVN SSIEDKLTSI VQKMYGGAKI EVSPEAQKKI DTYKKQGFGN
LPICIAKTQY SLSHDPSLKG VPRGFTFPIR DVRASIGAGY LYALAAEIQT IPGLSTYAGY
MAVEVDDDGE IEGLF
