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 24-JAN-2024, entry version 113. 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}. 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 PIR; A00389; RDPGD. DR AlphaFoldDB; P00377; -. DR SMR; P00377; -. DR STRING; 9823.ENSSSCP00000041285; -. DR PaxDb; 9823-ENSSSCP00000015020; -. DR PeptideAtlas; P00377; -. DR eggNOG; KOG1324; Eukaryota. DR InParanoid; P00377; -. DR UniPathway; UPA00077; UER00158. DR Proteomes; UP000008227; Unplaced. DR Proteomes; UP000314985; Unplaced. DR Proteomes; UP000694570; Unplaced. DR Proteomes; UP000694571; Unplaced. DR Proteomes; UP000694720; Unplaced. DR Proteomes; UP000694722; Unplaced. DR Proteomes; UP000694723; Unplaced. DR Proteomes; UP000694724; Unplaced. DR Proteomes; UP000694725; Unplaced. DR Proteomes; UP000694726; Unplaced. DR Proteomes; UP000694727; Unplaced. DR Proteomes; UP000694728; 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; 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:0031427; P:response to methotrexate; IEA:UniProtKB-KW. DR GO; GO:0046654; P:tetrahydrofolate biosynthetic process; IBA:GO_Central. DR GO; GO:0046653; P:tetrahydrofolate metabolic process; ISS:UniProtKB. 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; IPR017925; DHFR_CS. DR InterPro; IPR001796; DHFR_dom. DR PANTHER; PTHR48069; DIHYDROFOLATE REDUCTASE; 1. DR PANTHER; PTHR48069:SF6; 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 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 //