DYR_CHICK
ID DYR_CHICK Reviewed; 189 AA.
AC P00378;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Dihydrofolate reductase;
DE EC=1.5.1.3;
GN Name=DHFR;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP PROTEIN SEQUENCE.
RX PubMed=6766736; DOI=10.1021/bi00545a010;
RA Kumar A.A., Blankenship D.T., Kaufman B.T., Freisheim J.H.;
RT "Primary structure of chicken liver dihydrofolate reductase.";
RL Biochemistry 19:667-678(1980).
RN [2]
RP PROTEIN SEQUENCE OF 19-22; 138-141 AND 158-161.
RX PubMed=8670138; DOI=10.1042/bj3150097;
RA Fan Y.X., Ju M., Zhou J.M., Tsou C.L.;
RT "Activation of chicken liver dihydrofolate reductase by urea and guanidine
RT hydrochloride is accompanied by conformational change at the active site.";
RL Biochem. J. 315:97-102(1996).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEXES WITH NADPH AND
RP DIHYDROBIOPTERIN.
RX PubMed=1510919; DOI=10.1021/bi00147a009;
RA McTigue M.A., Davies J.F. II, Kaufman B.T., Kraut J.;
RT "Crystal structure of chicken liver dihydrofolate reductase complexed with
RT NADP+ and biopterin.";
RL Biochemistry 31:7264-7273(1992).
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. May bind to mRNA.
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};
CC -!- PATHWAY: Cofactor biosynthesis; tetrahydrofolate biosynthesis; 5,6,7,8-
CC tetrahydrofolate from 7,8-dihydrofolate: step 1/1.
CC -!- SIMILARITY: Belongs to the dihydrofolate reductase family.
CC {ECO:0000305}.
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DR PIR; A00390; RDCHD.
DR PDB; 1DR1; X-ray; 2.20 A; A=1-189.
DR PDB; 1DR2; X-ray; 2.30 A; A=1-189.
DR PDB; 1DR3; X-ray; 2.30 A; A=1-189.
DR PDB; 1DR4; X-ray; 2.40 A; A=1-189.
DR PDB; 1DR5; X-ray; 2.40 A; A=1-189.
DR PDB; 1DR6; X-ray; 2.40 A; A=1-189.
DR PDB; 1DR7; X-ray; 2.40 A; A=1-189.
DR PDB; 8DFR; X-ray; 1.70 A; A=1-189.
DR PDBsum; 1DR1; -.
DR PDBsum; 1DR2; -.
DR PDBsum; 1DR3; -.
DR PDBsum; 1DR4; -.
DR PDBsum; 1DR5; -.
DR PDBsum; 1DR6; -.
DR PDBsum; 1DR7; -.
DR PDBsum; 8DFR; -.
DR AlphaFoldDB; P00378; -.
DR SMR; P00378; -.
DR STRING; 9031.ENSGALP00000041459; -.
DR BindingDB; P00378; -.
DR ChEMBL; CHEMBL2575; -.
DR DrugBank; DB03904; Urea.
DR DrugCentral; P00378; -.
DR PaxDb; P00378; -.
DR VEuPathDB; HostDB:geneid_427317; -.
DR eggNOG; KOG1324; Eukaryota.
DR InParanoid; P00378; -.
DR BRENDA; 1.5.1.3; 1306.
DR SABIO-RK; P00378; -.
DR UniPathway; UPA00077; UER00158.
DR EvolutionaryTrace; P00378; -.
DR PRO; PR:P00378; -.
DR Proteomes; UP000000539; Unplaced.
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 3D-structure; Direct protein sequencing; Methotrexate resistance; NADP;
KW One-carbon metabolism; Oxidoreductase; Reference proteome; RNA-binding.
FT CHAIN 1..189
FT /note="Dihydrofolate reductase"
FT /id="PRO_0000186367"
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:0000269|PubMed:1510919,
FT ECO:0007744|PDB:1DR1"
FT BINDING 15..21
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000305|PubMed:1510919"
FT BINDING 30..35
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:1510919"
FT BINDING 54..56
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:1510919,
FT ECO:0007744|PDB:1DR1"
FT BINDING 64
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P00374"
FT BINDING 70
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:1510919"
FT BINDING 76..78
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:1510919,
FT ECO:0007744|PDB:1DR1"
FT BINDING 116..123
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000305|PubMed:1510919"
FT CONFLICT 141
FT /note="E -> Q (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 3..10
FT /evidence="ECO:0007829|PDB:8DFR"
FT STRAND 15..18
FT /evidence="ECO:0007829|PDB:8DFR"
FT STRAND 23..25
FT /evidence="ECO:0007829|PDB:1DR4"
FT HELIX 28..39
FT /evidence="ECO:0007829|PDB:8DFR"
FT STRAND 47..53
FT /evidence="ECO:0007829|PDB:8DFR"
FT HELIX 54..59
FT /evidence="ECO:0007829|PDB:8DFR"
FT HELIX 62..64
FT /evidence="ECO:0007829|PDB:8DFR"
FT STRAND 70..75
FT /evidence="ECO:0007829|PDB:8DFR"
FT STRAND 87..92
FT /evidence="ECO:0007829|PDB:8DFR"
FT HELIX 93..101
FT /evidence="ECO:0007829|PDB:8DFR"
FT HELIX 103..106
FT /evidence="ECO:0007829|PDB:8DFR"
FT STRAND 109..114
FT /evidence="ECO:0007829|PDB:8DFR"
FT HELIX 118..126
FT /evidence="ECO:0007829|PDB:8DFR"
FT STRAND 127..140
FT /evidence="ECO:0007829|PDB:8DFR"
FT STRAND 145..147
FT /evidence="ECO:0007829|PDB:8DFR"
FT TURN 153..155
FT /evidence="ECO:0007829|PDB:8DFR"
FT STRAND 156..158
FT /evidence="ECO:0007829|PDB:8DFR"
FT STRAND 170..172
FT /evidence="ECO:0007829|PDB:8DFR"
FT STRAND 175..184
FT /evidence="ECO:0007829|PDB:8DFR"
SQ SEQUENCE 189 AA; 21650 MW; BC5F50C94BCA3EDA CRC64;
VRSLNSIVAV CQNMGIGKDG NLPWPPLRNE YKYFQRMTST SHVEGKQNAV IMGKKTWFSI
PEKNRPLKDR INIVLSRELK EAPKGAHYLS KSLDDALALL DSPELKSKVD MVWIVGGTAV
YKAAMEKPIN HRLFVTRILH EFESDTFFPE IDYKDFKLLT EYPGVPADIQ EEDGIQYKFE
VYQKSVLAQ
