ID C1TC_SPOFR Reviewed; 933 AA. AC Q27772; DT 16-JAN-2004, integrated into UniProtKB/Swiss-Prot. DT 16-JAN-2004, sequence version 3. DT 27-MAR-2024, entry version 112. 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; OS Spodoptera frugiperda (Fall armyworm). OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota; OC Neoptera; Endopterygota; Lepidoptera; Glossata; Ditrysia; Noctuoidea; OC Noctuidae; Amphipyrinae; Spodoptera. OX NCBI_TaxID=7108; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Ovary; RX PubMed=7893749; DOI=10.1016/0167-4781(95)00004-z; RA Tremblay G.B., MacKenzie R.E.; RT "Primary structure of a folate-dependent trifunctional enzyme from RT Spodoptera frugiperda."; RL Biochim. Biophys. Acta 1261:129-133(1995). CC -!- CATALYTIC ACTIVITY: CC Reaction=(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + NADP(+) = (6R)- CC 5,10-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=(6R)-5,10-methenyltetrahydrofolate + H2O = (6R)-10- CC formyltetrahydrofolate + H(+); Xref=Rhea:RHEA:23700, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57455, CC ChEBI:CHEBI:195366; EC=3.5.4.9; CC -!- CATALYTIC ACTIVITY: CC Reaction=(6S)-5,6,7,8-tetrahydrofolate + ATP + formate = (6R)-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:195366, ChEBI:CHEBI:456216; CC EC=6.3.4.3; CC -!- PATHWAY: One-carbon metabolism; tetrahydrofolate interconversion. CC -!- SUBUNIT: Homodimer. {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. 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 CC formate--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; L36189; AAA74302.1; -; mRNA. DR PIR; S53523; S53523. DR AlphaFoldDB; Q27772; -. DR SMR; Q27772; -. DR UniPathway; UPA00193; -. DR Proteomes; UP000829999; Genome assembly. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004329; F:formate-tetrahydrofolate ligase activity; IEA:UniProtKB-EC. DR GO; GO:0004477; F:methenyltetrahydrofolate cyclohydrolase activity; IEA:UniProtKB-EC. DR GO; GO:0004488; F:methylenetetrahydrofolate dehydrogenase (NADP+) activity; IEA:UniProtKB-EC. 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:0006164; P:purine nucleotide biosynthetic process; IEA:UniProtKB-KW. DR GO; GO:0035999; P:tetrahydrofolate interconversion; IEA:UniProtKB-UniPathway. DR CDD; cd00477; FTHFS; 1. DR CDD; cd01080; NAD_bind_m-THF_DH_Cyclohyd; 1. DR Gene3D; 1.10.8.770; -; 1. DR Gene3D; 3.10.410.10; Formyltetrahydrofolate synthetase, domain 3; 1. DR Gene3D; 3.40.50.10860; Leucine Dehydrogenase, chain A, domain 1; 1. DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 2. DR HAMAP; MF_01543; FTHFS; 1. DR HAMAP; MF_01576; THF_DHG_CYH; 1. DR InterPro; IPR046346; Aminoacid_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 PANTHER; PTHR48099:SF5; C-1-TETRAHYDROFOLATE SYNTHASE, CYTOPLASMIC; 1. DR PANTHER; PTHR48099; C-1-TETRAHYDROFOLATE SYNTHASE, CYTOPLASMIC-RELATED; 1. 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; SSF53223; Aminoacid dehydrogenase-like, N-terminal domain; 1. DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 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 2: Evidence at transcript level; 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. FT CHAIN 1..933 FT /note="C-1-tetrahydrofolate synthase, cytoplasmic" FT /id="PRO_0000199325" FT REGION 1..303 FT /note="Methylenetetrahydrofolate dehydrogenase and FT cyclohydrolase" FT REGION 304..933 FT /note="Formyltetrahydrofolate synthetase" FT BINDING 51..55 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 98..100 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 170..172 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250" FT BINDING 195 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250" FT BINDING 270..274 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 378..385 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250" SQ SEQUENCE 933 AA; 100618 MW; 55C3FA820C1A55CB CRC64; MWEPQGSLDP VLESIENELR DQVAEARSRW AGFDARLAIV QVGGREDSNV YIRMKLRAAE NIGITAEHIQ LPRDITETEL LANITSLNES PYVHGIIVQM PLDSVHPIDS HAITDAVSPD KDVDGLNTIN EGRVRVGDLS GFIPCTPAGC VELIKRTGVT IAGKNVVVLG RSRIVGTPVS ELLKWEHATV TVCHSKTKNL SEITKTADIL VVAIGRGEMV RGSWIKPGAV VIDCGINPIS DPTKKSGQRL VGDVAYEEAV QVASHVTPVP GGVGPMTVAM LMRNTVQAAR RQLDRLLAPT WPLRPLRITP LSPPPSDIVI ARSQKPKDIS ELAHEIGLFS NEVSQYGRTK AKISLSVLDR MRNQQGAKYI VVAGITPTPL GEGKSTTLLG LVQALSAHRG RNSFAVMRQP SQGPTFGVKG GAAGGGYSQV IPMEEFNLHL TGDIHAGTAA NNLLAAQMDA RIFHELTQKD GPLFDRLVPK IKGVRKFSPI QLRRLKRLGI TKTDPDTLTE GEKSKFARLN IDTSKIMWNR VVDLNDRYLR KITVGQSPTE KGFTRETAFD ISVASEIMAI LALGRDVEDI KERLANMVVA LDKSGNPVTA DDLGMTGALL VLLRDAFEPT LMQSLEGTPV LVHTGPFANI RHGCSSILAD KIAMKLAGEN GYVATEAGFG SDIGMEKFFD IKCRASGDTP HCAVIVSTVR ALKMHGGGPP VSAGMPLNDV YVQENLELLS KGLCNLGKHI SNGNKFGVPV VVAINKHGND TPAELNLVKE FAVKNGAFRA VLCDHWAKGG LGALELADAV IEACDSKSKF DFLYPLQLSI QEKIQIIAKE MYGAGQVEYT DEVLEKIKTF TDMGYDKFPI CMAKTSNSLT GDPAVKGAPT GFTLKINGIF ASVGAGFVVP MVGEISKMPG LPTRPSIYDI DLNTKTGEIE GLF //