ID FOLKE_LACLM Reviewed; 349 AA. AC Q8GJP4; A2RKW2; DT 16-JAN-2004, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2003, sequence version 1. DT 27-MAR-2024, entry version 114. DE RecName: Full=Bifunctional protein FolKE; DE Includes: DE RecName: Full=2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase; DE EC=2.7.6.3; DE AltName: Full=6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase; DE Short=PPPK; DE AltName: Full=7,8 dihydro-6-hydroxymethylpterin-pyrophosphokinase; DE Short=HPPK; DE Includes: DE RecName: Full=GTP cyclohydrolase 1; DE EC=3.5.4.16; DE AltName: Full=GTP cyclohydrolase I; DE Short=GTP-CH-I; GN Name=folKE; Synonyms=folE; OrderedLocusNames=llmg_1337; OS Lactococcus lactis subsp. cremoris (strain MG1363). OC Bacteria; Bacillota; Bacilli; Lactobacillales; Streptococcaceae; OC Lactococcus; Lactococcus cremoris subsp. cremoris. OX NCBI_TaxID=416870; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=12788700; DOI=10.1128/aem.69.6.3069-3076.2003; RA Sybesma W., Starrenburg M., Kleerebezem M., Mierau I., de Vos W.M., RA Hugenholtz J.; RT "Increased production of folate by metabolic engineering of Lactococcus RT lactis."; RL Appl. Environ. Microbiol. 69:3069-3076(2003). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=MG1363; RX PubMed=17307855; DOI=10.1128/jb.01768-06; RA Wegmann U., O'Connell-Motherway M., Zomer A., Buist G., Shearman C., RA Canchaya C., Ventura M., Goesmann A., Gasson M.J., Kuipers O.P., RA van Sinderen D., Kok J.; RT "The complete genome sequence of the lactic acid bacterial paradigm RT Lactococcus lactis subsp. cremoris MG1363."; RL J. Bacteriol. 189:3256-3270(2007). CC -!- CATALYTIC ACTIVITY: CC Reaction=6-hydroxymethyl-7,8-dihydropterin + ATP = (7,8-dihydropterin- CC 6-yl)methyl diphosphate + AMP + H(+); Xref=Rhea:RHEA:11412, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:44841, CC ChEBI:CHEBI:72950, ChEBI:CHEBI:456215; EC=2.7.6.3; CC -!- CATALYTIC ACTIVITY: CC Reaction=GTP + H2O = 7,8-dihydroneopterin 3'-triphosphate + formate + CC H(+); Xref=Rhea:RHEA:17473, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:15740, ChEBI:CHEBI:37565, ChEBI:CHEBI:58462; EC=3.5.4.16; CC -!- PATHWAY: Cofactor biosynthesis; 7,8-dihydroneopterin triphosphate CC biosynthesis; 7,8-dihydroneopterin triphosphate from GTP: step 1/1. CC -!- PATHWAY: Cofactor biosynthesis; tetrahydrofolate biosynthesis; 2-amino- CC 4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine diphosphate from 7,8- CC dihydroneopterin triphosphate: step 4/4. CC -!- SUBUNIT: Homomer. {ECO:0000250}. CC -!- SIMILARITY: In the N-terminal section; belongs to the HPPK family. CC {ECO:0000305}. CC -!- SIMILARITY: In the C-terminal section; belongs to the GTP CC cyclohydrolase I 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; AY156932; AAN64306.1; -; Genomic_DNA. DR EMBL; AM406671; CAL97928.1; -; Genomic_DNA. DR RefSeq; WP_011835210.1; NZ_WJVF01000034.1. DR AlphaFoldDB; Q8GJP4; -. DR SMR; Q8GJP4; -. DR STRING; 416870.llmg_1337; -. DR KEGG; llm:llmg_1337; -. DR eggNOG; COG0302; Bacteria. DR eggNOG; COG0801; Bacteria. DR HOGENOM; CLU_775655_0_0_9; -. DR OrthoDB; 9801207at2; -. DR PhylomeDB; Q8GJP4; -. DR UniPathway; UPA00077; UER00155. DR UniPathway; UPA00848; UER00151. DR Proteomes; UP000000364; Chromosome. DR GO; GO:0003848; F:2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase activity; IEA:UniProtKB-EC. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW. DR GO; GO:0003934; F:GTP cyclohydrolase I activity; IEA:UniProtKB-UniRule. DR GO; GO:0016301; F:kinase activity; IEA:UniProtKB-KW. DR GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-UniRule. DR GO; GO:0035998; P:7,8-dihydroneopterin 3'-triphosphate biosynthetic process; IEA:UniProtKB-UniPathway. DR GO; GO:0046656; P:folic acid biosynthetic process; IEA:UniProtKB-KW. DR GO; GO:0006730; P:one-carbon metabolic process; IEA:UniProtKB-UniRule. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:0046654; P:tetrahydrofolate biosynthetic process; IEA:UniProtKB-UniRule. DR CDD; cd00483; HPPK; 1. DR Gene3D; 1.10.286.10; -; 1. DR Gene3D; 3.30.1130.10; -; 1. DR Gene3D; 3.30.70.560; 7,8-Dihydro-6-hydroxymethylpterin-pyrophosphokinase HPPK; 1. DR HAMAP; MF_00223; FolE; 1. DR InterPro; IPR043133; GTP-CH-I_C/QueF. DR InterPro; IPR043134; GTP-CH-I_N. DR InterPro; IPR001474; GTP_CycHdrlase_I. DR InterPro; IPR018234; GTP_CycHdrlase_I_CS. DR InterPro; IPR020602; GTP_CycHdrlase_I_dom. DR InterPro; IPR000550; Hppk. DR InterPro; IPR035907; Hppk_sf. DR NCBIfam; TIGR00063; folE; 1. DR NCBIfam; TIGR01498; folK; 1. DR PANTHER; PTHR11109:SF7; GTP CYCLOHYDROLASE 1; 1. DR PANTHER; PTHR11109; GTP CYCLOHYDROLASE I; 1. DR Pfam; PF01227; GTP_cyclohydroI; 1. DR Pfam; PF01288; HPPK; 1. DR SUPFAM; SSF55083; 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase, HPPK; 1. DR SUPFAM; SSF55620; Tetrahydrobiopterin biosynthesis enzymes-like; 1. DR PROSITE; PS00859; GTP_CYCLOHYDROL_1_1; 1. DR PROSITE; PS00794; HPPK; 1. PE 3: Inferred from homology; KW ATP-binding; Folate biosynthesis; GTP-binding; Hydrolase; Kinase; KW Multifunctional enzyme; Nucleotide-binding; One-carbon metabolism; KW Transferase. FT CHAIN 1..349 FT /note="Bifunctional protein FolKE" FT /id="PRO_0000119472" FT REGION 1..226 FT /note="2-amino-4-hydroxy-6-hydroxymethyldihydropteridine FT pyrophosphokinase" FT REGION 226..349 FT /note="GTP cyclohydrolase 1" SQ SEQUENCE 349 AA; 40261 MW; 105B058C80E3A8B4 CRC64; MQTTYLSMGS NIGDRQYYLH EAIRLLGKHP KIMIEKVSNF YESSPVGGVK QDDFTNLALK VATLLEPLEL LDFIHEVELS LNRERKIHWG PRTIDIDIIF YGNSEIQEEN LIVPHKEAFN RLFVLKPIFE LLSNDFKYYE PIREAIAKLS ESEQELHVIE EEKSPKNRIE EAVKEILFAV GENPNREGLL ETPARVAKMY EEILSSQRLT NFNEYKLFEI DSSKNDSIVL IKDIPFYSMC EHHMLPFFGK AHVAYIPDGG RIIGLSKIPR LVNYVSRKLS VQENITHDIA DILTDILKPK GVAVLVEGRH MCVEMRGVKK VNSLTKTSYF LGEFKENGEK RMEFLESLL //