C1TC_SCHPO
ID C1TC_SCHPO Reviewed; 937 AA.
AC Q8WZJ7;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 119.
DE RecName: Full=C-1-tetrahydrofolate synthase, cytoplasmic;
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;
GN ORFNames=SPBC839.16;
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 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: Cytoplasm {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}.
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DR EMBL; CU329671; CAB46709.1; -; Genomic_DNA.
DR PIR; T40723; T40723.
DR RefSeq; NP_595256.1; NM_001021162.2.
DR AlphaFoldDB; Q8WZJ7; -.
DR SMR; Q8WZJ7; -.
DR BioGRID; 277731; 4.
DR STRING; 4896.SPBC839.16.1; -.
DR iPTMnet; Q8WZJ7; -.
DR MaxQB; Q8WZJ7; -.
DR PaxDb; Q8WZJ7; -.
DR PRIDE; Q8WZJ7; -.
DR EnsemblFungi; SPBC839.16.1; SPBC839.16.1:pep; SPBC839.16.
DR GeneID; 2541217; -.
DR KEGG; spo:SPBC839.16; -.
DR PomBase; SPBC839.16; -.
DR VEuPathDB; FungiDB:SPBC839.16; -.
DR eggNOG; KOG4230; Eukaryota.
DR HOGENOM; CLU_003601_2_0_1; -.
DR InParanoid; Q8WZJ7; -.
DR OMA; KVDTYTK; -.
DR PhylomeDB; Q8WZJ7; -.
DR Reactome; R-SPO-196757; Metabolism of folate and pterines.
DR UniPathway; UPA00193; -.
DR PRO; PR:Q8WZJ7; -.
DR Proteomes; UP000002485; Chromosome II.
DR GO; GO:0005829; C:cytosol; HDA:PomBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004329; F:formate-tetrahydrofolate ligase activity; IDA:PomBase.
DR GO; GO:0004477; F:methenyltetrahydrofolate cyclohydrolase activity; IDA:PomBase.
DR GO; GO:0004488; F:methylenetetrahydrofolate dehydrogenase (NADP+) activity; IDA:PomBase.
DR GO; GO:0003697; F:single-stranded DNA binding; IDA:PomBase.
DR GO; GO:0009257; P:10-formyltetrahydrofolate biosynthetic process; IDA:PomBase.
DR GO; GO:0046656; P:folic acid biosynthetic process; IDA: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:0006730; P:one-carbon metabolic process; IDA:PomBase.
DR GO; GO:0009113; P:purine nucleobase biosynthetic process; IDA: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; 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.
PE 3: Inferred from homology;
KW Amino-acid biosynthesis; ATP-binding; Cytoplasm; Histidine biosynthesis;
KW Hydrolase; Ligase; Methionine biosynthesis; Multifunctional enzyme; NADP;
KW Nucleotide-binding; One-carbon metabolism; Oxidoreductase;
KW Purine biosynthesis; Reference proteome.
FT CHAIN 1..937
FT /note="C-1-tetrahydrofolate synthase, cytoplasmic"
FT /id="PRO_0000315626"
FT REGION 1..309
FT /note="Methylenetetrahydrofolate dehydrogenase and
FT cyclohydrolase"
FT REGION 310..937
FT /note="Formyltetrahydrofolate synthetase"
FT BINDING 50..54
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 97..99
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 168..170
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 193
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 268..272
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 374..381
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
SQ SEQUENCE 937 AA; 101203 MW; 70FF8700FD023C90 CRC64;
MALLLEGTSL ARKVREELRE QISSIKSVDP YFNVSLKIIQ VGGREDSNVY VRMKTRAANE
AGISCEHVNF PEDITEYDLL LAIKGFNEDP TVHGIIVQLP LPAHINEQII TEAVAPEKDV
DGFCETNLGK LTKREGQPLF TACTPKGIMC ILKHYGINVQ GKHAVVIGRS NIVGRPMSIL
LEKANATVTL CHSKTESIAD IVRTADIVVA AIGIPHFVKA DWLKKGVVAI DVGINSIPDA
TKKSGYRLTG DIDFENAKEV ASAITPVPGS VGPMTVAMLL QNVVESAVRF RKMSRKRKPT
LLPLKLQTPV PSDIEIARSQ TPKNIGDLAS EIGIAKSELE FYGSHKAKVN LEILQRLAHR
RDGHYVVVTG ITPTPFGEGK STLTAGLVQA LSNLDKLAIA CVRQPSQGPT FGIKGGAAGG
GYSQFIPMEE FNLHLTGDIH AITAATNLLA AAIDTRMFHE NTQSDAALYK RLTLVKGNKR
EFAPVMFRRL KKLGIDKTNP EELTEEEQRK FARLDIEPST ISWNRTLDVN DRFLRKITIG
ENPTEKGFTR QTGFDLSVAS ECMSVLALAT DLKDMRERLG RMVVASNKSG EPVTADDLGV
GGALTVLLKD AIKPTLMQTL EGTPALVHAG PFANISIGAS SILADRIALK LAGTEVDEDA
KKEAGYVVTE AGFASDIGME KFFNIKCRTS GLKPDAIVIV ATVQALKLHG GGPPVGPGKP
IPEVYKREDV DLVRKGCANL AKHISNARKY GLPVVVAINK FSSDSPNEIS AIREEALAAG
ATDAVDSNHW AEGGKGALGV ARALINACEN VDSEFRLLYD VHEPIEKKIE IIAKEMYGAD
GIELSPLAKE RLETFTKQGY NNLPICIAKT QYSLSHDPDL KGAPTNFTVP IRDMRLSAGA
GFIYPLAAAI STIPGLPTKP AYYNIDIAEN GDIVGLS
