DYR_LACLA
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 03-AUG-2022, entry version 123.
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; Firmicutes; 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}.
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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 STRING; 272623.L162872; -.
DR ChEMBL; CHEMBL4012; -.
DR DrugCentral; Q59487; -.
DR PaxDb; Q59487; -.
DR EnsemblBacteria; AAK05248; AAK05248; L162872.
DR GeneID; 66442061; -.
DR KEGG; lla:L162872; -.
DR PATRIC; fig|272623.7.peg.1229; -.
DR eggNOG; COG0262; Bacteria.
DR HOGENOM; CLU_043966_5_2_9; -.
DR OMA; RDNQLPW; -.
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; -; 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; PTHR48069; 1.
DR Pfam; PF00186; DHFR_1; 1.
DR PIRSF; PIRSF000194; DHFR; 1.
DR SUPFAM; SSF53597; SSF53597; 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
