ID DYR_THEMA Reviewed; 169 AA. AC Q60034; P96109; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1997, sequence version 1. DT 27-MAR-2024, entry version 160. DE RecName: Full=Dihydrofolate reductase; DE Short=DHFR; DE EC=1.5.1.3; GN Name=folA; Synonyms=dyrA; OrderedLocusNames=TM_1641; OS Thermotoga maritima (strain ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 OS / MSB8). OC Bacteria; Thermotogota; Thermotogae; Thermotogales; Thermotogaceae; OC Thermotoga. OX NCBI_TaxID=243274; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=7789791; DOI=10.1016/0378-1119(95)00090-s; RA van de Casteele M., Legrain C., Wilquet V., Glansdorff N.; RT "The dihydrofolate reductase-encoding gene dyrA of the hyperthermophilic RT bacterium Thermotoga maritima."; RL Gene 158:101-105(1995). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8; RX PubMed=9563834; RA Dams T., Schurig H., Jaenicke R.; RT "Homo-dimeric recombinant dihydrofolate reductase from Thermotoga maritima RT shows extreme intrinsic stability."; RL Biol. Chem. 379:367-371(1998). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8; RX PubMed=10360571; DOI=10.1038/20601; RA Nelson K.E., Clayton R.A., Gill S.R., Gwinn M.L., Dodson R.J., Haft D.H., RA Hickey E.K., Peterson J.D., Nelson W.C., Ketchum K.A., McDonald L.A., RA Utterback T.R., Malek J.A., Linher K.D., Garrett M.M., Stewart A.M., RA Cotton M.D., Pratt M.S., Phillips C.A., Richardson D.L., Heidelberg J.F., RA Sutton G.G., Fleischmann R.D., Eisen J.A., White O., Salzberg S.L., RA Smith H.O., Venter J.C., Fraser C.M.; RT "Evidence for lateral gene transfer between Archaea and Bacteria from RT genome sequence of Thermotoga maritima."; RL Nature 399:323-329(1999). RN [4] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH METHOTREXATE AND RP NADPH. RX PubMed=10731419; DOI=10.1006/jmbi.2000.3570; RA Dams T., Auerbach G., Bader G., Jacob U., Ploom T., Huber R., Jaenicke R.; RT "The crystal structure of dihydrofolate reductase from Thermotoga maritima: RT molecular features of thermostability."; RL J. Mol. Biol. 297:659-672(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 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 -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Temperature dependence: CC Highly thermostable.; CC -!- PATHWAY: Cofactor biosynthesis; tetrahydrofolate biosynthesis; 5,6,7,8- CC tetrahydrofolate from 7,8-dihydrofolate: step 1/1. CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:10731419}. CC -!- INTERACTION: CC Q60034; Q60034: folA; NbExp=2; IntAct=EBI-25642550, EBI-25642550; CC -!- SIMILARITY: Belongs to the dihydrofolate reductase family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAD36708.1; Type=Erroneous initiation; Evidence={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; X81845; CAA57437.1; -; Genomic_DNA. DR EMBL; Y11021; CAA71903.1; -; Genomic_DNA. DR EMBL; AE000512; AAD36708.1; ALT_INIT; Genomic_DNA. DR PIR; A72231; A72231. DR RefSeq; NP_229441.1; NC_000853.1. DR RefSeq; WP_004082129.1; NZ_CP011107.1. DR PDB; 1CZ3; X-ray; 2.10 A; A/B=2-169. DR PDB; 1D1G; X-ray; 2.10 A; A/B=2-169. DR PDBsum; 1CZ3; -. DR PDBsum; 1D1G; -. DR AlphaFoldDB; Q60034; -. DR SMR; Q60034; -. DR STRING; 243274.TM_1641; -. DR PaxDb; 243274-THEMA_06040; -. DR EnsemblBacteria; AAD36708; AAD36708; TM_1641. DR KEGG; tma:TM1641; -. DR PATRIC; fig|243274.5.peg.1660; -. DR eggNOG; COG0262; Bacteria. DR InParanoid; Q60034; -. DR OrthoDB; 9804315at2; -. DR BioCyc; MetaCyc:MONOMER-461; -. DR BRENDA; 1.5.1.3; 6331. DR UniPathway; UPA00077; UER00158. DR EvolutionaryTrace; Q60034; -. DR Proteomes; UP000008183; Chromosome. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0004146; F:dihydrofolate reductase activity; IBA:GO_Central. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. 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: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; 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; PS51330; DHFR_2; 1. PE 1: Evidence at protein level; KW 3D-structure; NADP; One-carbon metabolism; Oxidoreductase; KW Reference proteome. FT CHAIN 1..169 FT /note="Dihydrofolate reductase" FT /id="PRO_0000186418" FT DOMAIN 3..169 FT /note="DHFR" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00660" FT BINDING 7..8 FT /ligand="substrate" FT /evidence="ECO:0000305|PubMed:10731419" FT BINDING 9 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000269|PubMed:10731419" FT BINDING 16 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000269|PubMed:10731419" FT BINDING 28..30 FT /ligand="substrate" FT /evidence="ECO:0000305|PubMed:10731419" FT BINDING 46..51 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000269|PubMed:10731419" FT BINDING 54 FT /ligand="substrate" FT /evidence="ECO:0000305|PubMed:10731419" FT BINDING 59 FT /ligand="substrate" FT /evidence="ECO:0000305|PubMed:10731419" FT BINDING 65..67 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000269|PubMed:10731419" FT BINDING 81 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000269|PubMed:10731419" FT BINDING 101 FT /ligand="substrate" FT /evidence="ECO:0000305|PubMed:10731419" FT BINDING 103..105 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000269|PubMed:10731419" FT CONFLICT 68..81 FT /note="PKTSNNPSLVFFNG -> TQNFQQSFTRFFQR (in Ref. 1)" FT /evidence="ECO:0000305" FT CONFLICT 108 FT /note="T -> S (in Ref. 1)" FT /evidence="ECO:0000305" FT CONFLICT 138..139 FT /note="FE -> LQ (in Ref. 1)" FT /evidence="ECO:0000305" FT STRAND 3..10 FT /evidence="ECO:0007829|PDB:1CZ3" FT STRAND 15..17 FT /evidence="ECO:0007829|PDB:1CZ3" FT HELIX 26..39 FT /evidence="ECO:0007829|PDB:1CZ3" FT STRAND 41..45 FT /evidence="ECO:0007829|PDB:1CZ3" FT HELIX 46..52 FT /evidence="ECO:0007829|PDB:1CZ3" FT STRAND 59..64 FT /evidence="ECO:0007829|PDB:1CZ3" FT STRAND 76..79 FT /evidence="ECO:0007829|PDB:1CZ3" FT HELIX 83..92 FT /evidence="ECO:0007829|PDB:1CZ3" FT STRAND 96..102 FT /evidence="ECO:0007829|PDB:1CZ3" FT HELIX 104..112 FT /evidence="ECO:0007829|PDB:1CZ3" FT STRAND 117..123 FT /evidence="ECO:0007829|PDB:1CZ3" FT STRAND 125..130 FT /evidence="ECO:0007829|PDB:1CZ3" FT STRAND 132..135 FT /evidence="ECO:0007829|PDB:1CZ3" FT STRAND 141..151 FT /evidence="ECO:0007829|PDB:1CZ3" FT STRAND 153..155 FT /evidence="ECO:0007829|PDB:1CZ3" FT STRAND 158..164 FT /evidence="ECO:0007829|PDB:1CZ3" SQ SEQUENCE 169 AA; 19367 MW; F5DA22C978E2C39D CRC64; MAKVIFVLAM DVSGKIASSV ESWSSFEDRK NFRKITTEIG NVVMGRITFE EIGRPLPERL NVVLTRRPKT SNNPSLVFFN GSPADVVKFL EGKGYERVAV IGGKTVFTEF LREKLVDELF VTVEPYVFGK GIPFFDEFEG YFPLKLLEMR RLNERGTLFL KYSVEKSHR //