ID DYR_HAEIN Reviewed; 160 AA. AC P43791; DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1995, sequence version 1. DT 27-MAR-2024, entry version 135. DE RecName: Full=Dihydrofolate reductase; DE EC=1.5.1.3; GN Name=folA; Synonyms=folH; OrderedLocusNames=HI_0899; OS Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd). OC Bacteria; Pseudomonadota; Gammaproteobacteria; Pasteurellales; OC Pasteurellaceae; Haemophilus. OX NCBI_TaxID=71421; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 51907 / DSM 11121 / KW20 / Rd; RX PubMed=7542800; DOI=10.1126/science.7542800; RA Fleischmann R.D., Adams M.D., White O., Clayton R.A., Kirkness E.F., RA Kerlavage A.R., Bult C.J., Tomb J.-F., Dougherty B.A., Merrick J.M., RA McKenney K., Sutton G.G., FitzHugh W., Fields C.A., Gocayne J.D., RA Scott J.D., Shirley R., Liu L.-I., Glodek A., Kelley J.M., Weidman J.F., RA Phillips C.A., Spriggs T., Hedblom E., Cotton M.D., Utterback T.R., RA Hanna M.C., Nguyen D.T., Saudek D.M., Brandon R.C., Fine L.D., RA Fritchman J.L., Fuhrmann J.L., Geoghagen N.S.M., Gnehm C.L., McDonald L.A., RA Small K.V., Fraser C.M., Smith H.O., Venter J.C.; RT "Whole-genome random sequencing and assembly of Haemophilus influenzae RT Rd."; RL Science 269:496-512(1995). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=Isolate R1042, Isolate R1047, and Isolate R906; RA de Groot R.; RL Submitted (FEB-1995) to the EMBL/GenBank/DDBJ databases. 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 -!- MISCELLANEOUS: Isolates R906, R1042, and R1047 are trimethoprim- CC resistant. 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; L42023; AAC22559.1; -; Genomic_DNA. DR EMBL; X84207; CAA58993.1; -; Genomic_DNA. DR EMBL; X84205; CAA58991.1; -; Genomic_DNA. DR EMBL; X84206; CAA58992.1; -; Genomic_DNA. DR PIR; C64101; C64101. DR PIR; S52336; S52336. DR PIR; S52337; S52337. DR PIR; S52338; S52338. DR RefSeq; NP_439060.1; NC_000907.1. DR AlphaFoldDB; P43791; -. DR SMR; P43791; -. DR STRING; 71421.HI_0899; -. DR EnsemblBacteria; AAC22559; AAC22559; HI_0899. DR KEGG; hin:HI_0899; -. DR PATRIC; fig|71421.8.peg.941; -. DR eggNOG; COG0262; Bacteria. DR HOGENOM; CLU_043966_5_1_6; -. DR OrthoDB; 9804315at2; -. DR PhylomeDB; P43791; -. DR BioCyc; HINF71421:G1GJ1-939-MONOMER; -. DR UniPathway; UPA00077; UER00158. DR Proteomes; UP000000579; Chromosome. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0004146; F:dihydrofolate reductase activity; IBA:GO_Central. DR GO; GO:0050661; F:NADP binding; IBA:GO_Central. DR GO; GO:0046452; P:dihydrofolate metabolic process; IBA:GO_Central. DR GO; GO:0046655; P:folic acid metabolic process; IBA:GO_Central. 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:0046677; P:response to antibiotic; IEA:UniProtKB-KW. DR GO; GO:0046654; P:tetrahydrofolate biosynthetic process; IBA:GO_Central. 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 Antibiotic resistance; NADP; One-carbon metabolism; Oxidoreductase; KW Reference proteome; Trimethoprim resistance. FT CHAIN 1..160 FT /note="Dihydrofolate reductase" FT /id="PRO_0000186391" FT DOMAIN 2..159 FT /note="DHFR" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00660" FT BINDING 6 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 8 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250" FT BINDING 14..20 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250" FT BINDING 28 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 46..47 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250" FT BINDING 53 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 58 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 64..65 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250" FT BINDING 96..103 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250" FT BINDING 114 FT /ligand="substrate" FT /evidence="ECO:0000250" FT VARIANT 13 FT /note="N -> S (in strain: Isolate R1042 and Isolate R1047)" FT VARIANT 21 FT /note="M -> I (in strain: Isolate R1047)" FT VARIANT 54 FT /note="P -> A (in strain: Isolate R1047)" FT VARIANT 56 FT /note="P -> A (in strain: Isolate R906)" FT VARIANT 67 FT /note="L -> P (in strain: Isolate R1042)" FT VARIANT 69 FT /note="E -> K (in strain: Isolate R1042)" FT VARIANT 74 FT /note="I -> V (in strain: Isolate R1042)" FT VARIANT 77 FT /note="D -> N (in strain: Isolate R1042)" FT VARIANT 79 FT /note="F -> L (in strain: Isolate R1042)" FT VARIANT 95 FT /note="I -> L (in strain: Isolate R1047)" FT VARIANT 135 FT /note="E -> K (in strain: Isolate R1042)" FT VARIANT 142 FT /note="R -> H (in strain: Isolate R1042)" FT VARIANT 154 FT /note="F -> S (in strain: Isolate R1042)" SQ SEQUENCE 160 AA; 18913 MW; 384A1D64092B8C4F CRC64; MTFSLIVATT LNNVIGKDNQ MPWHLPADLA WFRQNTTGKP VIMGRKTFES IGRPLPKRTN IVLSRQLFEH EGVIWKDSFE SAVNFVRDFD EIMLIGGGEL FKQYLPKADK LYLTQIQTEL DGDTFFPQLN WEEWEIEFDE YRKADEQNRY DCRFLILTRK //