ID DYR_BPT4 Reviewed; 193 AA. AC P04382; DT 20-MAR-1987, integrated into UniProtKB/Swiss-Prot. DT 20-MAR-1987, sequence version 1. DT 04-NOV-2026, entry version 130. DE RecName: Full=Dihydrofolate reductase; DE Short=DHFR; DE EC=1.5.1.3; GN Name=frd; OS Enterobacteria phage T4 (Bacteriophage T4). OC Viruses; Duplodnaviria; Heunggongvirae; Uroviricota; Caudoviricetes; OC Pantevenvirales; Straboviridae; Tevenvirinae; Tequatrovirus. OX NCBI_TaxID=10665; OH NCBI_TaxID=562; Escherichia coli. RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=6327673; DOI=10.1016/s0021-9258(20)82135-8; RA Purohit S., Mathews C.K.; RT "Nucleotide sequence reveals overlap between T4 phage genes encoding RT dihydrofolate reductase and thymidylate synthase."; RL J. Biol. Chem. 259:6261-6266(1984). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12626685; DOI=10.1128/mmbr.67.1.86-156.2003; RA Miller E.S., Kutter E., Mosig G., Arisaka F., Kunisawa T., Ruger W.; RT "Bacteriophage T4 genome."; RL Microbiol. Mol. Biol. Rev. 67:86-156(2003). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 123-193. RC STRAIN=ALC4; RX PubMed=3698096; DOI=10.1016/0092-8674(86)90379-x; RA Chu F.K., Maley G.F., West D.K., Belfort M., Maley F.; RT "Characterization of the intron in the phage T4 thymidylate synthase gene RT and evidence for its self-excision from the primary transcript."; RL Cell 45:157-166(1986). RN [4] RP INTERACTION WITH DEOXYCYTIDYLATE 5-HYDROXYMETHYLTRANSFERASE. RX PubMed=1560001; DOI=10.1016/s0021-9258(18)42566-5; RA Wheeler L., Wang Y., Mathews C.K.; RT "Specific associations of T4 bacteriophage proteins with immobilized RT deoxycytidylate hydroxymethylase."; RL J. Biol. Chem. 267:7664-7670(1992). RN [5] {ECO:0007744|PDB:1JUV} RP X-RAY CRYSTALLOGRAPHY IN COMPLEX WITH NADPH, AND SUBUNIT. RX PubMed=10818362; DOI=10.1107/s0907444900005266; RA Oh Y.K., Moon J., Lee J.Y., Cho S.W., Shin W., Suh S.W.; RT "Overexpression, crystallization and preliminary X-ray crystallographic RT analysis of dihydrofolate reductase from bacteriophage T4."; RL Acta Crystallogr. D 56:775-777(2000). 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 NADPH + H(+); 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 -!- SUBUNIT: homodimer (PubMed:10818362). Interacts with deoxycytidylate 5- CC hydroxymethyltransferase; this interaction is probably involved in the CC building of an instable dNTP synthetase complex (PubMed:1560001). CC {ECO:0000269|PubMed:10818362, ECO:0000269|PubMed:1560001}. 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; AH001329; AAA32491.1; -; Genomic_DNA. DR EMBL; AF158101; AAD42577.1; -; Genomic_DNA. DR EMBL; M12742; AAC12815.1; -; Genomic_DNA. DR PIR; A00396; RDBPT4. DR RefSeq; NP_049850.1; NC_000866.4. DR PDB; 1JUV; X-ray; 1.70 A; A=1-193. DR MDposit; P04382; -. DR SMR; P04382; -. DR GeneID; 1258671; -. DR KEGG; vg:1258671; -. DR OrthoDB; 9577at10239; -. DR UniPathway; UPA00077; UER00158. DR EvolutionaryTrace; P04382; -. DR Proteomes; UP000009087; Segment. DR GO; GO:0004146; F:dihydrofolate reductase activity; IDA:CACAO. 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:0031427; P:response to methotrexate; IEA:UniProtKB-KW. DR GO; GO:0046654; P:tetrahydrofolate biosynthetic process; IEA:UniProtKB-UniPathway. 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 PRINTS; PR00070; DHFR. DR SUPFAM; SSF53597; Dihydrofolate reductase-like; 1. DR PROSITE; PS00075; DHFR_1; 1. DR PROSITE; PS51330; DHFR_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Antibiotic resistance; Methotrexate resistance; NADP; KW One-carbon metabolism; Oxidoreductase; Reference proteome; KW Trimethoprim resistance. FT CHAIN 1..193 FT /note="Dihydrofolate reductase" FT /id="PRO_0000186434" FT DOMAIN 1..193 FT /note="DHFR" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00660" FT BINDING 7 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT BINDING 22..27 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT BINDING 52..55 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT BINDING 73..77 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT STRAND 2..12 FT /evidence="ECO:0007829|PDB:1JUV" FT STRAND 18..24 FT /evidence="ECO:0007829|PDB:1JUV" FT HELIX 34..44 FT /evidence="ECO:0007829|PDB:1JUV" FT STRAND 47..52 FT /evidence="ECO:0007829|PDB:1JUV" FT HELIX 53..57 FT /evidence="ECO:0007829|PDB:1JUV" FT STRAND 68..71 FT /evidence="ECO:0007829|PDB:1JUV" FT STRAND 88..91 FT /evidence="ECO:0007829|PDB:1JUV" FT HELIX 93..100 FT /evidence="ECO:0007829|PDB:1JUV" FT STRAND 105..108 FT /evidence="ECO:0007829|PDB:1JUV" FT STRAND 115..118 FT /evidence="ECO:0007829|PDB:1JUV" FT STRAND 124..128 FT /evidence="ECO:0007829|PDB:1JUV" FT HELIX 130..136 FT /evidence="ECO:0007829|PDB:1JUV" FT HELIX 137..139 FT /evidence="ECO:0007829|PDB:1JUV" FT STRAND 141..152 FT /evidence="ECO:0007829|PDB:1JUV" FT STRAND 157..160 FT /evidence="ECO:0007829|PDB:1JUV" FT HELIX 162..169 FT /evidence="ECO:0007829|PDB:1JUV" FT STRAND 173..182 FT /evidence="ECO:0007829|PDB:1JUV" FT STRAND 185..192 FT /evidence="ECO:0007829|PDB:1JUV" SQ SEQUENCE 193 AA; 21713 MW; 64E033916E628178 CRC64; MIKLVFRYSP TKTVDGFNEL AFGLGDGLPW GRVKKDLQNF KARTEGTIMI MGAKTFQSLP TLLPGRSHIV VCDLARDYPV TKDGDLAHFY ITWEQYITYI SGGEIQVSSP NAPFETMLDQ NSKVSVIGGP ALLYAALPYA DEVVVSRIVK RHRVNSTVQL DASFLDDISK REMVETHWYK IDEVTTLTES VYK //