ID FOLD_RICPR Reviewed; 286 AA. AC Q9ZD32; DT 11-JUL-2001, integrated into UniProtKB/Swiss-Prot. DT 11-OCT-2004, sequence version 2. DT 24-JAN-2024, entry version 118. DE RecName: Full=Bifunctional protein FolD {ECO:0000255|HAMAP-Rule:MF_01576}; DE Includes: DE RecName: Full=Methylenetetrahydrofolate dehydrogenase {ECO:0000255|HAMAP-Rule:MF_01576}; DE EC=1.5.1.5 {ECO:0000255|HAMAP-Rule:MF_01576}; DE Includes: DE RecName: Full=Methenyltetrahydrofolate cyclohydrolase {ECO:0000255|HAMAP-Rule:MF_01576}; DE EC=3.5.4.9 {ECO:0000255|HAMAP-Rule:MF_01576}; GN Name=folD {ECO:0000255|HAMAP-Rule:MF_01576}; OrderedLocusNames=RP515; OS Rickettsia prowazekii (strain Madrid E). OC Bacteria; Pseudomonadota; Alphaproteobacteria; Rickettsiales; OC Rickettsiaceae; Rickettsieae; Rickettsia; typhus group. OX NCBI_TaxID=272947; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Madrid E; RX PubMed=9823893; DOI=10.1038/24094; RA Andersson S.G.E., Zomorodipour A., Andersson J.O., Sicheritz-Ponten T., RA Alsmark U.C.M., Podowski R.M., Naeslund A.K., Eriksson A.-S., Winkler H.H., RA Kurland C.G.; RT "The genome sequence of Rickettsia prowazekii and the origin of RT mitochondria."; RL Nature 396:133-140(1998). CC -!- FUNCTION: Catalyzes the oxidation of 5,10-methylenetetrahydrofolate to CC 5,10-methenyltetrahydrofolate and then the hydrolysis of 5,10- CC methenyltetrahydrofolate to 10-formyltetrahydrofolate. CC {ECO:0000255|HAMAP-Rule:MF_01576}. 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; Evidence={ECO:0000255|HAMAP- CC Rule:MF_01576}; 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; Evidence={ECO:0000255|HAMAP- CC Rule:MF_01576}; CC -!- PATHWAY: One-carbon metabolism; tetrahydrofolate interconversion. CC {ECO:0000255|HAMAP-Rule:MF_01576}. CC -!- SUBUNIT: Homodimer. {ECO:0000255|HAMAP-Rule:MF_01576}. CC -!- SIMILARITY: Belongs to the tetrahydrofolate CC dehydrogenase/cyclohydrolase family. {ECO:0000255|HAMAP-Rule:MF_01576}. CC -!- SEQUENCE CAUTION: CC Sequence=CAA14967.1; Type=Erroneous initiation; Evidence={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; AJ235272; CAA14967.1; ALT_INIT; Genomic_DNA. DR PIR; E71655; E71655. DR RefSeq; NP_220891.1; NC_000963.1. DR AlphaFoldDB; Q9ZD32; -. DR SMR; Q9ZD32; -. DR STRING; 272947.gene:17555595; -. DR EnsemblBacteria; CAA14967; CAA14967; CAA14967. DR KEGG; rpr:RP515; -. DR PATRIC; fig|272947.5.peg.526; -. DR eggNOG; COG0190; Bacteria. DR HOGENOM; CLU_034045_2_0_5; -. DR OrthoDB; 9803580at2; -. DR UniPathway; UPA00193; -. DR Proteomes; UP000002480; Chromosome. DR GO; GO:0004477; F:methenyltetrahydrofolate cyclohydrolase activity; IEA:UniProtKB-UniRule. DR GO; GO:0004488; F:methylenetetrahydrofolate dehydrogenase (NADP+) activity; IEA:UniProtKB-UniRule. 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; cd01080; NAD_bind_m-THF_DH_Cyclohyd; 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 HAMAP; MF_01576; THF_DHG_CYH; 1. DR InterPro; IPR046346; Aminoacid_DH-like_N_sf. DR InterPro; IPR036291; NAD(P)-bd_dom_sf. 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; 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 PROSITE; PS00766; THF_DHG_CYH_1; 1. DR PROSITE; PS00767; THF_DHG_CYH_2; 1. PE 3: Inferred from homology; KW Amino-acid biosynthesis; Histidine biosynthesis; Hydrolase; KW Methionine biosynthesis; Multifunctional enzyme; NADP; KW One-carbon metabolism; Oxidoreductase; Purine biosynthesis; KW Reference proteome. FT CHAIN 1..286 FT /note="Bifunctional protein FolD" FT /id="PRO_0000199314" FT BINDING 167..169 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01576" FT BINDING 192 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01576" FT BINDING 233 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01576" SQ SEQUENCE 286 AA; 30560 MW; 118DE987C14D857B CRC64; MVNNIIDGKA LANEILADLK LEIQGFKEKT KTSPKLAIVL VGDNPASMIY VKNKIKNAHQ VGIDTLLVNL STNIYTDDLI LKINELNLDK GISGIIVQLP LPSSIDENKI LSAVLPSKDS DGFHPLNVGY LHSGINQGFI PCTALGCLAV IKKYAPNLNG KDAVIVGRSN IVGKPLSALL LQENCSVTIC HSKTCNLSSI TSKADIVVVA IGSPLKLTAE YFNPEAIVID VGINRISHNK IAGDVDFENV KSKVKYITPV PGGIGPMTIA FLLKNTVKAF KNAIAL //