DYR_RAT
ID DYR_RAT Reviewed; 187 AA.
AC Q920D2;
DT 20-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Dihydrofolate reductase;
DE EC=1.5.1.3;
GN Name=Dhfr;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=11502523; DOI=10.1128/aac.45.9.2517-2523.2001;
RA Wang Y., Bruenn J.A., Queener S.F., Cody V.;
RT "Isolation of rat dihydrofolate reductase gene and characterization of
RT recombinant enzyme.";
RL Antimicrob. Agents Chemother. 45:2517-2523(2001).
RN [2]
RP SUBCELLULAR LOCATION, AND CATALYTIC ACTIVITY.
RX PubMed=25980602; DOI=10.1016/j.febslet.2015.05.017;
RA Hughes L., Carton R., Minguzzi S., McEntee G., Deinum E.E., O'Connell M.J.,
RA Parle-McDermott A.;
RT "An active second dihydrofolate reductase enzyme is not a feature of rat
RT and mouse, but they do have activity in their mitochondria.";
RL FEBS Lett. 589:1855-1862(2015).
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 (By similarity).
CC {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; Evidence={ECO:0000255|PROSITE-
CC ProRule:PRU00660, ECO:0000269|PubMed:25980602};
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:0000269|PubMed:25980602}.
CC Cytoplasm {ECO:0000269|PubMed:25980602}.
CC -!- SIMILARITY: Belongs to the dihydrofolate reductase family.
CC {ECO:0000305}.
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DR EMBL; AF318150; AAL11500.1; -; mRNA.
DR RefSeq; NP_569084.1; NM_130400.2.
DR AlphaFoldDB; Q920D2; -.
DR SMR; Q920D2; -.
DR STRING; 10116.ENSRNOP00000018259; -.
DR BindingDB; Q920D2; -.
DR ChEMBL; CHEMBL2363; -.
DR DrugCentral; Q920D2; -.
DR iPTMnet; Q920D2; -.
DR PhosphoSitePlus; Q920D2; -.
DR jPOST; Q920D2; -.
DR PaxDb; Q920D2; -.
DR PRIDE; Q920D2; -.
DR Ensembl; ENSRNOT00000018259; ENSRNOP00000018259; ENSRNOG00000013521.
DR GeneID; 24312; -.
DR KEGG; rno:24312; -.
DR UCSC; RGD:2500; rat.
DR CTD; 1719; -.
DR RGD; 2500; Dhfr.
DR eggNOG; KOG1324; Eukaryota.
DR GeneTree; ENSGT00390000010283; -.
DR HOGENOM; CLU_043966_2_3_1; -.
DR InParanoid; Q920D2; -.
DR OMA; RDNQLPW; -.
DR OrthoDB; 1489621at2759; -.
DR PhylomeDB; Q920D2; -.
DR TreeFam; TF317636; -.
DR BRENDA; 1.5.1.3; 5301.
DR Reactome; R-RNO-196757; Metabolism of folate and pterines.
DR SABIO-RK; Q920D2; -.
DR UniPathway; UPA00077; UER00158.
DR PRO; PR:Q920D2; -.
DR Proteomes; UP000002494; Chromosome 2.
DR Bgee; ENSRNOG00000013521; Expressed in duodenum and 19 other tissues.
DR ExpressionAtlas; Q920D2; baseline and differential.
DR Genevisible; Q920D2; RN.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0004146; F:dihydrofolate reductase activity; IDA:UniProtKB.
DR GO; GO:0051871; F:dihydrofolic acid binding; IDA:RGD.
DR GO; GO:0005542; F:folic acid binding; ISO:RGD.
DR GO; GO:0003729; F:mRNA binding; ISS:UniProtKB.
DR GO; GO:0000900; F:mRNA regulatory element binding translation repressor activity; ISO:RGD.
DR GO; GO:0050661; F:NADP binding; IDA:RGD.
DR GO; GO:0070402; F:NADPH binding; ISO:RGD.
DR GO; GO:1990825; F:sequence-specific mRNA binding; ISO:RGD.
DR GO; GO:0031103; P:axon regeneration; IMP:BHF-UCL.
DR GO; GO:0046452; P:dihydrofolate metabolic process; IDA:RGD.
DR GO; GO:0046655; P:folic acid metabolic process; IDA:BHF-UCL.
DR GO; GO:0006545; P:glycine biosynthetic process; IEA:InterPro.
DR GO; GO:0017148; P:negative regulation of translation; ISO:RGD.
DR GO; GO:0051000; P:positive regulation of nitric-oxide synthase activity; ISO:RGD.
DR GO; GO:2000121; P:regulation of removal of superoxide radicals; ISO:RGD.
DR GO; GO:0031427; P:response to methotrexate; IEA:UniProtKB-KW.
DR GO; GO:0035094; P:response to nicotine; IEP:RGD.
DR GO; GO:0006729; P:tetrahydrobiopterin biosynthetic process; ISO:RGD.
DR GO; GO:0046654; P:tetrahydrofolate biosynthetic process; IDA:RGD.
DR GO; GO:0035999; P:tetrahydrofolate interconversion; ISO:RGD.
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; Methotrexate resistance; Mitochondrion; NADP;
KW One-carbon metabolism; Oxidoreductase; Reference proteome; RNA-binding.
FT CHAIN 1..187
FT /note="Dihydrofolate reductase"
FT /id="PRO_0000186366"
FT DOMAIN 4..185
FT /note="DHFR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00660"
FT BINDING 10
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P00374"
FT BINDING 16..22
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P00374"
FT BINDING 31..36
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P00374"
FT BINDING 55..57
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P00374"
FT BINDING 71
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P00374"
FT BINDING 77..79
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P00374"
FT BINDING 117..124
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P00374"
FT MOD_RES 33
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00375"
FT MOD_RES 33
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00375"
SQ SEQUENCE 187 AA; 21638 MW; FE1DB4F3515F8B26 CRC64;
MVRPLNCIVA VSQNMGIGKN GDLPWPLLRN EFKYFQRMTT TSSVEGKQNL VIMGRKTWFS
IPEKNRPLKD RINIVLSREL KEPPQGAHFL AKSLDDALKL IEQPELASKV DMVWVVGGSS
VYQEAMNQPG HLRLFVTRIM QEFESDTFFP EIDLEKYKLL PEYPGVLSEI QEEKGIKYKF
EVYEKKD
