DYR_BOVIN
ID DYR_BOVIN Reviewed; 187 AA.
AC P00376; Q29RI1;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Dihydrofolate reductase;
DE EC=1.5.1.3;
GN Name=DHFR;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Heart ventricle;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (FEB-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP PROTEIN SEQUENCE OF 2-187.
RC TISSUE=Liver;
RX PubMed=7115669; DOI=10.1021/bi00257a006;
RA Lai P.-H., Pan Y.-C.E., Gleisner J.M., Peterson D.L., Williams K.R.,
RA Blakley R.L.;
RT "Structure of dihydrofolate reductase: primary sequence of the bovine liver
RT enzyme.";
RL Biochemistry 21:3284-3294(1982).
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 EMBL; BC114162; AAI14163.1; -; mRNA.
DR PIR; A00388; RDBOD.
DR RefSeq; NP_001071351.1; NM_001077883.1.
DR AlphaFoldDB; P00376; -.
DR SMR; P00376; -.
DR STRING; 9913.ENSBTAP00000010103; -.
DR BindingDB; P00376; -.
DR ChEMBL; CHEMBL1075051; -.
DR DrugCentral; P00376; -.
DR PaxDb; P00376; -.
DR PeptideAtlas; P00376; -.
DR PRIDE; P00376; -.
DR GeneID; 508809; -.
DR KEGG; bta:508809; -.
DR CTD; 1719; -.
DR eggNOG; KOG1324; Eukaryota.
DR HOGENOM; CLU_043966_2_3_1; -.
DR InParanoid; P00376; -.
DR OrthoDB; 1489621at2759; -.
DR TreeFam; TF317636; -.
DR SABIO-RK; P00376; -.
DR UniPathway; UPA00077; UER00158.
DR PRO; PR:P00376; -.
DR Proteomes; UP000009136; 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; -; 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 Cytoplasm; Direct protein sequencing; Methotrexate resistance;
KW Mitochondrion; NADP; One-carbon metabolism; Oxidoreductase;
KW Reference proteome; RNA-binding.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:7115669"
FT CHAIN 2..187
FT /note="Dihydrofolate reductase"
FT /id="PRO_0000186361"
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 CONFLICT 22
FT /note="D -> N (in Ref. 1; AAI14163)"
FT /evidence="ECO:0000305"
FT CONFLICT 102
FT /note="E -> Q (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 187 AA; 21604 MW; 0727DD855C8A7CD8 CRC64;
MVRPLNCIVA VSQNMGIGKN GDLPWPPLRN EFQYFQRMTT VSSVEGKQNL VIMGRKTWFS
IPEKNRPLKD RINIVLSREL KEPPKGAHFL AKSLDDALEL IEDPELTNKV DVVWIVGGSS
VYKEAMNKPG HVRLFVTRIM QEFESDAFFP EIDFEKYKLL PEYPGVPLDV QEEKGIKYKF
EVYEKNN
