ID DYR_LACLA Reviewed; 168 AA. AC Q59487; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 27-APR-2001, sequence version 2. DT 27-MAR-2024, entry version 130. DE RecName: Full=Dihydrofolate reductase; DE EC=1.5.1.3; GN Name=folA; Synonyms=dhfR; OrderedLocusNames=LL1150; ORFNames=L162872; OS Lactococcus lactis subsp. lactis (strain IL1403) (Streptococcus lactis). OC Bacteria; Bacillota; Bacilli; Lactobacillales; Streptococcaceae; OC Lactococcus. OX NCBI_TaxID=272623; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=51-MG/7; RX PubMed=7574597; DOI=10.1128/aem.61.2.561-566.1995; RA Leszczynska K., Bolhuis A., Leenhouts K., Venema G., Ceglowski P.; RT "Cloning and molecular analysis of the dihydrofolate reductase gene from RT Lactococcus lactis."; RL Appl. Environ. Microbiol. 61:561-566(1995). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=IL1403; RX PubMed=11337471; DOI=10.1101/gr.gr-1697r; RA Bolotin A., Wincker P., Mauger S., Jaillon O., Malarme K., Weissenbach J., RA Ehrlich S.D., Sorokin A.; RT "The complete genome sequence of the lactic acid bacterium Lactococcus RT lactis ssp. lactis IL1403."; RL Genome Res. 11:731-753(2001). CC -!- FUNCTION: Key enzyme in folate metabolism. Catalyzes an essential CC reaction for de novo glycine and purine synthesis, and for DNA CC precursor synthesis (By similarity). {ECO:0000250}. CC -!- CATALYTIC ACTIVITY: CC Reaction=(6S)-5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate + CC H(+) + NADPH; Xref=Rhea:RHEA:15009, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:57451, ChEBI:CHEBI:57453, ChEBI:CHEBI:57783, CC ChEBI:CHEBI:58349; EC=1.5.1.3; Evidence={ECO:0000255|PROSITE- CC ProRule:PRU00660}; CC -!- PATHWAY: Cofactor biosynthesis; tetrahydrofolate biosynthesis; 5,6,7,8- CC tetrahydrofolate from 7,8-dihydrofolate: step 1/1. CC -!- SIMILARITY: Belongs to the dihydrofolate reductase family. CC {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; X60681; CAA43094.1; -; Genomic_DNA. DR EMBL; AE005176; AAK05248.1; -; Genomic_DNA. DR PIR; F86768; F86768. DR PIR; S47467; S47467. DR RefSeq; NP_267306.1; NC_002662.1. DR RefSeq; WP_010905786.1; NC_002662.1. DR AlphaFoldDB; Q59487; -. DR SMR; Q59487; -. DR ChEMBL; CHEMBL4012; -. DR DrugCentral; Q59487; -. DR PaxDb; 272623-L162872; -. DR EnsemblBacteria; AAK05248; AAK05248; L162872. DR KEGG; lla:L162872; -. DR PATRIC; fig|272623.7.peg.1229; -. DR eggNOG; COG0262; Bacteria. DR HOGENOM; CLU_043966_5_2_9; -. DR OrthoDB; 9804315at2; -. DR UniPathway; UPA00077; UER00158. DR Proteomes; UP000002196; Chromosome. DR GO; GO:0004146; F:dihydrofolate reductase activity; IEA:UniProtKB-EC. DR GO; GO:0050661; F:NADP binding; IEA:InterPro. DR GO; GO:0006545; P:glycine biosynthetic process; IEA:InterPro. DR GO; GO:0006730; P:one-carbon metabolic process; IEA:UniProtKB-KW. DR GO; GO:0046654; P:tetrahydrofolate biosynthetic process; IEA:UniProtKB-UniPathway. DR CDD; cd00209; DHFR; 1. DR Gene3D; 3.40.430.10; Dihydrofolate Reductase, subunit A; 1. DR InterPro; IPR012259; DHFR. DR InterPro; IPR024072; DHFR-like_dom_sf. DR InterPro; IPR017925; DHFR_CS. DR InterPro; IPR001796; DHFR_dom. DR PANTHER; PTHR48069; DIHYDROFOLATE REDUCTASE; 1. DR PANTHER; PTHR48069:SF3; DIHYDROFOLATE REDUCTASE; 1. DR Pfam; PF00186; DHFR_1; 1. DR PIRSF; PIRSF000194; DHFR; 1. DR PRINTS; PR00070; DHFR. DR SUPFAM; SSF53597; Dihydrofolate reductase-like; 1. DR PROSITE; PS00075; DHFR_1; 1. DR PROSITE; PS51330; DHFR_2; 1. PE 3: Inferred from homology; KW NADP; One-carbon metabolism; Oxidoreductase; Reference proteome. FT CHAIN 1..168 FT /note="Dihydrofolate reductase" FT /id="PRO_0000186394" FT DOMAIN 1..164 FT /note="DHFR" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00660" FT BINDING 5..7 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 6..7 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250" FT BINDING 14..19 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250" FT BINDING 27 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 43..46 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250" FT BINDING 58 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 63..66 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250" FT BINDING 99..104 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250" FT BINDING 118 FT /ligand="substrate" FT /evidence="ECO:0000250" FT CONFLICT 11 FT /note="A -> Q (in Ref. 1; CAA43094)" FT /evidence="ECO:0000305" FT CONFLICT 29 FT /note="Q -> K (in Ref. 1; CAA43094)" FT /evidence="ECO:0000305" FT CONFLICT 72 FT /note="D -> E (in Ref. 1; CAA43094)" FT /evidence="ECO:0000305" FT CONFLICT 90 FT /note="H -> Y (in Ref. 1; CAA43094)" FT /evidence="ECO:0000305" FT CONFLICT 93 FT /note="N -> D (in Ref. 1; CAA43094)" FT /evidence="ECO:0000305" FT CONFLICT 125 FT /note="K -> Q (in Ref. 1; CAA43094)" FT /evidence="ECO:0000305" FT CONFLICT 132..133 FT /note="ST -> TH (in Ref. 1; CAA43094)" FT /evidence="ECO:0000305" FT CONFLICT 138 FT /note="R -> K (in Ref. 1; CAA43094)" FT /evidence="ECO:0000305" FT CONFLICT 141 FT /note="L -> V (in Ref. 1; CAA43094)" FT /evidence="ECO:0000305" FT CONFLICT 145 FT /note="K -> I (in Ref. 1; CAA43094)" FT /evidence="ECO:0000305" FT CONFLICT 154 FT /note="S -> A (in Ref. 1; CAA43094)" FT /evidence="ECO:0000305" SQ SEQUENCE 168 AA; 19729 MW; 0BB4D97167F247F4 CRC64; MIIGIWAEDE AGLIGEADKM PWSLPAEQQH FKETTMNQVI LMGRKTFEGM NKRVLPGRIS IILTRDETYQ SDNEKVLIMH SPKEVLDWYH KQNKDLFITG GAEILALFES ELELLYRTVV HEKFKGDTYF PSTFDFGRFK LVSEKFHDKD ERNSYTFTIK KYEKVKQP //