ID   DYR_PIG                 Reviewed;         186 AA.
AC   P00377;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   21-JUL-1986, sequence version 1.
DT   03-AUG-2022, entry version 106.
DE   RecName: Full=Dihydrofolate reductase;
DE            EC=1.5.1.3;
GN   Name=DHFR;
OS   Sus scrofa (Pig).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX   NCBI_TaxID=9823;
RN   [1]
RP   PROTEIN SEQUENCE.
RC   TISSUE=Liver;
RX   PubMed=500653; DOI=10.1016/s0021-9258(19)86510-9;
RA   Smith S.L., Patrick P., Stone D., Phillips A.W., Burchall J.J.;
RT   "Porcine liver dihydrofolate reductase. Purification, properties, and amino
RT   acid sequence.";
RL   J. Biol. Chem. 254:11475-11484(1979).
CC   -!- FUNCTION: Key enzyme in folate metabolism. Contributes to the de novo
CC       mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential
CC       reaction for de novo glycine and purine synthesis, and for DNA
CC       precursor synthesis. Binds its own mRNA and that of DHFR2 (By
CC       similarity). {ECO:0000250|UniProtKB:P00374}.
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;
CC         Evidence={ECO:0000250|UniProtKB:P00375, 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. {ECO:0000250|UniProtKB:P00374}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:P00375}.
CC       Cytoplasm {ECO:0000250|UniProtKB:P00375}.
CC   -!- SIMILARITY: Belongs to the dihydrofolate reductase family.
CC       {ECO:0000305}.
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DR   PIR; A00389; RDPGD.
DR   AlphaFoldDB; P00377; -.
DR   SMR; P00377; -.
DR   STRING; 9823.ENSSSCP00000015020; -.
DR   PaxDb; P00377; -.
DR   PeptideAtlas; P00377; -.
DR   PRIDE; P00377; -.
DR   eggNOG; KOG1324; Eukaryota.
DR   InParanoid; P00377; -.
DR   UniPathway; UPA00077; UER00158.
DR   Proteomes; UP000008227; Unplaced.
DR   Proteomes; UP000314985; Unplaced.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR   GO; GO:0004146; F:dihydrofolate reductase activity; ISS:UniProtKB.
DR   GO; GO:0003729; F:mRNA binding; ISS:UniProtKB.
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:0031427; P:response to methotrexate; IEA:UniProtKB-KW.
DR   GO; GO:0046654; P:tetrahydrofolate biosynthetic process; IEA:UniProtKB-UniPathway.
DR   GO; GO:0046653; P:tetrahydrofolate metabolic process; ISS:UniProtKB.
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   SUPFAM; SSF53597; SSF53597; 1.
DR   PROSITE; PS00075; DHFR_1; 1.
DR   PROSITE; PS51330; DHFR_2; 1.
PE   1: Evidence at protein level;
KW   Acetylation; Cytoplasm; Direct protein sequencing; Methotrexate resistance;
KW   Mitochondrion; NADP; One-carbon metabolism; Oxidoreductase;
KW   Reference proteome; RNA-binding.
FT   CHAIN           1..186
FT                   /note="Dihydrofolate reductase"
FT                   /id="PRO_0000186365"
FT   DOMAIN          3..184
FT                   /note="DHFR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00660"
FT   BINDING         9
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:P00374"
FT   BINDING         15..21
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:P00374"
FT   BINDING         30..35
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P00374"
FT   BINDING         54..56
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:P00374"
FT   BINDING         70
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P00374"
FT   BINDING         76..78
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:P00374"
FT   BINDING         116..123
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:P00374"
FT   MOD_RES         32
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P00375"
FT   MOD_RES         32
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P00375"
FT   MOD_RES         162
FT                   /note="Cysteine derivative; partial"
SQ   SEQUENCE   186 AA;  21455 MW;  D05DB526FE5C12CE CRC64;
     VRPLNCIVAV SQNMGIGKNG DLPWPPLRNE YKYFQRMTTT SSVEGKQNLV IMGRKTWFSI
     PEKNRPLKDR INIVLSRELK EPPQGAHFLA KSLDDALKLT EQPELKDKVD MVWIVGGSSV
     YKEAMNKPGH IRLFVTRIMK EFESDTFFPE IDLEKYKLLS ECSGVPSDVQ EEKGIKYKFE
     VYEKNN