ID   DYRB_HALVO              Reviewed;         194 AA.
AC   Q9UWQ4;
DT   14-MAY-2014, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   03-AUG-2022, entry version 67.
DE   RecName: Full=Dihydrofolate reductase HdrB;
DE            Short=DHFR B;
DE            Short=hDHFR-2;
DE            EC=1.5.1.3;
GN   Name=hdrB;
OS   Haloferax volcanii (Halobacterium volcanii).
OC   Archaea; Euryarchaeota; Stenosarchaea group; Halobacteria; Haloferacales;
OC   Haloferacaceae; Haloferax.
OX   NCBI_TaxID=2246;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, ACTIVITY
RP   REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, AND DISRUPTION PHENOTYPE.
RC   STRAIN=WR341;
RX   PubMed=10760149; DOI=10.1046/j.1365-2958.2000.01815.x;
RA   Ortenberg R., Rozenblatt-Rosen O., Mevarech M.;
RT   "The extremely halophilic archaeon Haloferax volcanii has two very
RT   different dihydrofolate reductases.";
RL   Mol. Microbiol. 35:1493-1505(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. {ECO:0000269|PubMed:10760149}.
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, ECO:0000269|PubMed:10760149};
CC   -!- ACTIVITY REGULATION: Maximum activity at KCl concentration of 0.5 M and
CC       activity decreases with increasing concentration of KCl.
CC       {ECO:0000269|PubMed:10760149}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       pH dependence:
CC         Optimum pH is 6.0. {ECO:0000269|PubMed:10760149};
CC   -!- PATHWAY: Cofactor biosynthesis; tetrahydrofolate biosynthesis; 5,6,7,8-
CC       tetrahydrofolate from 7,8-dihydrofolate: step 1/1.
CC   -!- DISRUPTION PHENOTYPE: Thymidine auxotrophy.
CC       {ECO:0000269|PubMed:10760149}.
CC   -!- SIMILARITY: Belongs to the dihydrofolate reductase family.
CC       {ECO:0000305}.
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DR   EMBL; AF124982; AAF23265.1; -; Genomic_DNA.
DR   AlphaFoldDB; Q9UWQ4; -.
DR   SMR; Q9UWQ4; -.
DR   UniPathway; UPA00077; UER00158.
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   1: Evidence at protein level;
KW   NADP; One-carbon metabolism; Oxidoreductase.
FT   CHAIN           1..194
FT                   /note="Dihydrofolate reductase HdrB"
FT                   /id="PRO_0000428867"
FT   DOMAIN          18..194
FT                   /note="DHFR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00660"
FT   REGION          173..194
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         24
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         30..36
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         44
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         62..63
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         69
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         78
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         84..85
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         123..130
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         141
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   194 AA;  21111 MW;  ECD8B15A962C5E4B CRC64;
     MSGEELSGSE TEGDAAVRFV LVAAVADNRV IGRDGTMPWH LPEDLKQFKR TTTGHPVVMG
     RKTYESIARQ LGGPLPERHS VLLTTRDLDL PEGAEAVESV ESAVAAAEDA ADEMGVETVY
     VVGGATVYEQ FLGRAAGLVL TELDAAHEGD TRFPEWDRGK WVETDRDDRD GFSFVTYERK
     QPAAADRGAE ESDE