DYR_HAEIN
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 03-AUG-2022, entry version 129.
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; Proteobacteria; 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}.
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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 RefSeq; WP_005648125.1; 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 OMA; RDNQLPW; -.
DR PhylomeDB; P43791; -.
DR BioCyc; HINF71421:G1GJ1-939-MON; -.
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; -; 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 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
