C1TM_SCHPO
ID C1TM_SCHPO Reviewed; 972 AA.
AC O43007;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 3.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=C-1-tetrahydrofolate synthase, mitochondrial;
DE Short=C1-THF synthase;
DE Includes:
DE RecName: Full=Methylenetetrahydrofolate dehydrogenase;
DE EC=1.5.1.5;
DE Includes:
DE RecName: Full=Methenyltetrahydrofolate cyclohydrolase;
DE EC=3.5.4.9;
DE Includes:
DE RecName: Full=Formyltetrahydrofolate synthetase;
DE EC=6.3.4.3;
DE Flags: Precursor;
GN Name=ade9; ORFNames=SPBC2G2.08;
OS Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Taphrinomycotina;
OC Schizosaccharomycetes; Schizosaccharomycetales; Schizosaccharomycetaceae;
OC Schizosaccharomyces.
OX NCBI_TaxID=284812;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=972 / ATCC 24843;
RX PubMed=11859360; DOI=10.1038/nature724;
RA Wood V., Gwilliam R., Rajandream M.A., Lyne M.H., Lyne R., Stewart A.,
RA Sgouros J.G., Peat N., Hayles J., Baker S.G., Basham D., Bowman S.,
RA Brooks K., Brown D., Brown S., Chillingworth T., Churcher C.M., Collins M.,
RA Connor R., Cronin A., Davis P., Feltwell T., Fraser A., Gentles S.,
RA Goble A., Hamlin N., Harris D.E., Hidalgo J., Hodgson G., Holroyd S.,
RA Hornsby T., Howarth S., Huckle E.J., Hunt S., Jagels K., James K.D.,
RA Jones L., Jones M., Leather S., McDonald S., McLean J., Mooney P.,
RA Moule S., Mungall K.L., Murphy L.D., Niblett D., Odell C., Oliver K.,
RA O'Neil S., Pearson D., Quail M.A., Rabbinowitsch E., Rutherford K.M.,
RA Rutter S., Saunders D., Seeger K., Sharp S., Skelton J., Simmonds M.N.,
RA Squares R., Squares S., Stevens K., Taylor K., Taylor R.G., Tivey A.,
RA Walsh S.V., Warren T., Whitehead S., Woodward J.R., Volckaert G., Aert R.,
RA Robben J., Grymonprez B., Weltjens I., Vanstreels E., Rieger M.,
RA Schaefer M., Mueller-Auer S., Gabel C., Fuchs M., Duesterhoeft A.,
RA Fritzc C., Holzer E., Moestl D., Hilbert H., Borzym K., Langer I., Beck A.,
RA Lehrach H., Reinhardt R., Pohl T.M., Eger P., Zimmermann W., Wedler H.,
RA Wambutt R., Purnelle B., Goffeau A., Cadieu E., Dreano S., Gloux S.,
RA Lelaure V., Mottier S., Galibert F., Aves S.J., Xiang Z., Hunt C.,
RA Moore K., Hurst S.M., Lucas M., Rochet M., Gaillardin C., Tallada V.A.,
RA Garzon A., Thode G., Daga R.R., Cruzado L., Jimenez J., Sanchez M.,
RA del Rey F., Benito J., Dominguez A., Revuelta J.L., Moreno S.,
RA Armstrong J., Forsburg S.L., Cerutti L., Lowe T., McCombie W.R.,
RA Paulsen I., Potashkin J., Shpakovski G.V., Ussery D., Barrell B.G.,
RA Nurse P.;
RT "The genome sequence of Schizosaccharomyces pombe.";
RL Nature 415:871-880(2002).
RN [2]
RP REVISION OF GENE MODEL.
RX PubMed=21511999; DOI=10.1126/science.1203357;
RA Rhind N., Chen Z., Yassour M., Thompson D.A., Haas B.J., Habib N.,
RA Wapinski I., Roy S., Lin M.F., Heiman D.I., Young S.K., Furuya K., Guo Y.,
RA Pidoux A., Chen H.M., Robbertse B., Goldberg J.M., Aoki K., Bayne E.H.,
RA Berlin A.M., Desjardins C.A., Dobbs E., Dukaj L., Fan L., FitzGerald M.G.,
RA French C., Gujja S., Hansen K., Keifenheim D., Levin J.Z., Mosher R.A.,
RA Mueller C.A., Pfiffner J., Priest M., Russ C., Smialowska A., Swoboda P.,
RA Sykes S.M., Vaughn M., Vengrova S., Yoder R., Zeng Q., Allshire R.,
RA Baulcombe D., Birren B.W., Brown W., Ekwall K., Kellis M., Leatherwood J.,
RA Levin H., Margalit H., Martienssen R., Nieduszynski C.A., Spatafora J.W.,
RA Friedman N., Dalgaard J.Z., Baumann P., Niki H., Regev A., Nusbaum C.;
RT "Comparative functional genomics of the fission yeasts.";
RL Science 332:930-936(2011).
RN [3]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=16823372; DOI=10.1038/nbt1222;
RA Matsuyama A., Arai R., Yashiroda Y., Shirai A., Kamata A., Sekido S.,
RA Kobayashi Y., Hashimoto A., Hamamoto M., Hiraoka Y., Horinouchi S.,
RA Yoshida M.;
RT "ORFeome cloning and global analysis of protein localization in the fission
RT yeast Schizosaccharomyces pombe.";
RL Nat. Biotechnol. 24:841-847(2006).
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;
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;
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 -!- PATHWAY: One-carbon metabolism; tetrahydrofolate interconversion.
CC -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:16823372}.
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.
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; CU329671; CAA17888.3; -; Genomic_DNA.
DR PIR; T40147; T40147.
DR RefSeq; NP_596437.2; NM_001022356.2.
DR AlphaFoldDB; O43007; -.
DR SMR; O43007; -.
DR BioGRID; 276831; 4.
DR STRING; 4896.SPBC2G2.08.1; -.
DR MaxQB; O43007; -.
DR PaxDb; O43007; -.
DR PRIDE; O43007; -.
DR EnsemblFungi; SPBC2G2.08.1; SPBC2G2.08.1:pep; SPBC2G2.08.
DR GeneID; 2540300; -.
DR KEGG; spo:SPBC2G2.08; -.
DR PomBase; SPBC2G2.08; ade9.
DR VEuPathDB; FungiDB:SPBC2G2.08; -.
DR eggNOG; KOG4230; Eukaryota.
DR HOGENOM; CLU_003601_2_0_1; -.
DR InParanoid; O43007; -.
DR OMA; IKRVVDC; -.
DR Reactome; R-SPO-196757; Metabolism of folate and pterines.
DR UniPathway; UPA00193; -.
DR PRO; PR:O43007; -.
DR Proteomes; UP000002485; Chromosome II.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; HDA:PomBase.
DR GO; GO:0005524; F:ATP binding; ISM:PomBase.
DR GO; GO:0004329; F:formate-tetrahydrofolate ligase activity; ISS:PomBase.
DR GO; GO:0004477; F:methenyltetrahydrofolate cyclohydrolase activity; ISS:PomBase.
DR GO; GO:0004488; F:methylenetetrahydrofolate dehydrogenase (NADP+) activity; ISS:PomBase.
DR GO; GO:0009257; P:10-formyltetrahydrofolate biosynthetic process; ISS:PomBase.
DR GO; GO:0046656; P:folic acid biosynthetic process; ISO:PomBase.
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:0009113; P:purine nucleobase biosynthetic process; ISO:PomBase.
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; PS00767; THF_DHG_CYH_2; 1.
PE 3: Inferred from homology;
KW Amino-acid biosynthesis; ATP-binding; Histidine biosynthesis; Hydrolase;
KW Ligase; Methionine biosynthesis; Mitochondrion; Multifunctional enzyme;
KW NADP; Nucleotide-binding; One-carbon metabolism; Oxidoreductase;
KW Purine biosynthesis; Reference proteome; Transit peptide.
FT TRANSIT 1..55
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 56..972
FT /note="C-1-tetrahydrofolate synthase, mitochondrial"
FT /id="PRO_0000315627"
FT REGION 56..340
FT /note="Methylenetetrahydrofolate dehydrogenase and
FT cyclohydrolase"
FT REGION 341..972
FT /note="Formyltetrahydrofolate synthetase"
FT BINDING 84..88
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 131..133
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 202..204
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 227
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 299..303
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 405..412
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
SQ SEQUENCE 972 AA; 105757 MW; A14DFE32C0106F20 CRC64;
MNVMVSFNQL RNYFLESNSL RPSKWLFQSY GTSSSANILN GKLLARKLQR SVAEEVQALK
AKDRNFKPAL AIVQVGKRED SNVYVRMKEK AARLVGIDFK YCPFPETIQM PALLHELKKL
NDDHTVHGVL VQLPLPKHLN ERTVTESITP PKDVDGFGAF NIGLLAKNDA TPIHYPCTPK
GIMELLKDNK ISVAGLNAVV LGRSDIVGNP ISYLLRKDNA TVTVCHSKTK DLIQHISNAD
LVIAALGKPE FVRGEWLKPG SVVVDVGINA VQRNGKRVLV GDVHFESASK VASSITPVPG
GVGPMTVAML MENIVNAAKI ARTENIYRKI DLNPLELKKP VPSDIEIANS QEPKLISNLA
KEMGIYDTEL ENYGNYKAKV NLAVYERLKH RKDGNYVVVS GITPTPFGEG KSTVVAGLVQ
AMGHLGKLGI ACVRQPSQGP TFGVKGGAAG GGYAQFIPMD DFNLHMTGDI HAVTAANNLL
VAALETRMFH ENTQSDAALI KRLIPVKNGR RVIPRGLIGR WNRICASHNM DPEDVNNASP
ELLKEFVRLN VDPDTIECNR VLDVNDRFLR SIEVGKASTE KGHVRKTSFD ISVASECMSI
LALSCDLNDM HSRLSRMVIA NDKYGNAITA GDLGVSGALT VLLKDAIKPN LMQTLEGTPA
FVHAGPFANI SIGASSIIAD KIALKLAGTE SFDRPEDAGY VVTEAGFASD MGMEKFFNIK
CRYSKLVPNT VVLVTTVKAL KLHGGGPKLK PGAPIPEEYL VENLDLVKNG CSNMVKHIQN
CHKFNIPVVV AINSYKTDSS KEHEIIREAA LQAGAVDAVP SDHWAQGGKG AIELAKSVMT
ACDQSSNSKF RLLYDSETSI EDKVNVIAKE MYGANGVEFS SLAKERINTF IKQGFGNLPI
CMAKTQYSLS HNPEFRNVPK NFTVPIRDMR LNAGAGFIYP LAAEIQTIPG LPTAPAYLNI
DICENGEIVG LS
