DYR_DROME
ID DYR_DROME Reviewed; 182 AA.
AC P17719; A4V302; Q9VEU4;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 3.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Dihydrofolate reductase;
DE EC=1.5.1.3;
GN Name=Dhfr; ORFNames=CG14887;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE, AND PROTEIN SEQUENCE OF 155-176.
RC STRAIN=Canton-S;
RX PubMed=8195153; DOI=10.1016/s0021-9258(17)36589-4;
RA Hao H., Tyshenko M.G., Walker V.K.;
RT "Dihydrofolate reductase of Drosophila. Cloning and expression of a gene
RT with a rare transcript.";
RL J. Biol. Chem. 269:15179-15185(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [4]
RP PROTEIN SEQUENCE OF 1-23.
RC STRAIN=Canton-S;
RX PubMed=2116172; DOI=10.1016/0167-4838(90)90258-h;
RA Rancourt S.L., Walker V.K.;
RT "The purification of dihydrofolate reductase from Drosophila
RT melanogaster.";
RL Biochim. Biophys. Acta 1039:261-268(1990).
RN [5]
RP INTERACTION WITH VG, AND INVOLVEMENT IN DNA REPLICATION.
RX PubMed=14526388; DOI=10.1038/sj.cdd.4401321;
RA Delanoue R., Legent K., Godefroy N., Flagiello D., Dutriaux A., Vaudin P.,
RA Becker J.L., Silber J.;
RT "The Drosophila wing differentiation factor vestigial-scalloped is required
RT for cell proliferation and cell survival at the dorso-ventral boundary of
RT the wing imaginal disc.";
RL Cell Death Differ. 11:110-122(2004).
CC -!- FUNCTION: By interacting with vestigial (vg), may control genes
CC involved in DNA replication.
CC -!- FUNCTION: Key enzyme in folate metabolism. Catalyzes an essential
CC reaction for de novo glycine and purine synthesis, and for DNA
CC precursor synthesis (By similarity). {ECO:0000250}.
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 -!- SUBUNIT: Monomer. Interacts with vg. {ECO:0000269|PubMed:14526388}.
CC -!- SIMILARITY: Belongs to the dihydrofolate reductase family.
CC {ECO:0000305}.
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DR EMBL; U06861; AAA19051.1; -; Unassigned_DNA.
DR EMBL; AE014297; AAF55324.1; -; Genomic_DNA.
DR EMBL; AE014297; ABI31175.1; -; Genomic_DNA.
DR PIR; A53803; A53803.
DR PIR; S10759; A33105.
DR RefSeq; NP_001036720.1; NM_001043255.2.
DR RefSeq; NP_732147.1; NM_169721.2.
DR AlphaFoldDB; P17719; -.
DR SMR; P17719; -.
DR BioGRID; 67048; 3.
DR DIP; DIP-20310N; -.
DR IntAct; P17719; 1.
DR STRING; 7227.FBpp0110210; -.
DR PaxDb; P17719; -.
DR PRIDE; P17719; -.
DR DNASU; 42003; -.
DR EnsemblMetazoa; FBtr0083295; FBpp0082746; FBgn0004087.
DR EnsemblMetazoa; FBtr0110910; FBpp0110210; FBgn0004087.
DR GeneID; 42003; -.
DR KEGG; dme:Dmel_CG14887; -.
DR UCSC; CG14887-RB; d. melanogaster.
DR CTD; 1719; -.
DR FlyBase; FBgn0004087; Dhfr.
DR VEuPathDB; VectorBase:FBgn0004087; -.
DR eggNOG; KOG1324; Eukaryota.
DR GeneTree; ENSGT00940000168797; -.
DR HOGENOM; CLU_043966_2_3_1; -.
DR InParanoid; P17719; -.
DR OMA; RDNQLPW; -.
DR OrthoDB; 1489621at2759; -.
DR PhylomeDB; P17719; -.
DR BRENDA; 1.5.1.3; 1994.
DR Reactome; R-DME-196757; Metabolism of folate and pterines.
DR UniPathway; UPA00077; UER00158.
DR BioGRID-ORCS; 42003; 1 hit in 3 CRISPR screens.
DR GenomeRNAi; 42003; -.
DR PRO; PR:P17719; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0004087; Expressed in adult abdomen and 24 other tissues.
DR ExpressionAtlas; P17719; baseline and differential.
DR Genevisible; P17719; DM.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0004146; F:dihydrofolate reductase activity; IDA:FlyBase.
DR GO; GO:0050661; F:NADP binding; IBA:GO_Central.
DR GO; GO:0046452; P:dihydrofolate metabolic process; IBA:GO_Central.
DR GO; GO:0006260; P:DNA replication; IEA:UniProtKB-KW.
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:0046654; P:tetrahydrofolate biosynthetic process; IBA:GO_Central.
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 Direct protein sequencing; DNA replication; NADP; One-carbon metabolism;
KW Oxidoreductase; Reference proteome.
FT CHAIN 1..182
FT /note="Dihydrofolate reductase"
FT /id="PRO_0000186370"
FT DOMAIN 3..180
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"
FT BINDING 15..21
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 29..34
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 53..55
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 69
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 75..77
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 113..120
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT CONFLICT 3
FT /note="R -> T (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 11
FT /note="C -> S (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 134
FT /note="K -> Q (in Ref. 1; AAA19051)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 182 AA; 20775 MW; D2C9198F1D2CE430 CRC64;
MLRFNLIVAV CENFGIGIRG DLPWRIKSEL KYFSRTTKRT SDPTKQNAVV MGRKTYFGVP
ESKRPLPDRL NIVLSTTLQE SDLPKGVLLC PNLETAMKIL EEQNEVENIW IVGGSGVYEE
AMASPRCHRL YITKIMQKFD CDTFFPAIPD SFREVAPDSD MPLGVQEENG IKFEYKILEK
HS
