Reviewed, UniProtKB/Swiss-Prot P17719 (DYR_DROME)

Names and origin

Protein names

Recommended name:
    Dihydrofolate reductase
    EC=1.5.1.3

Gene names

Name:	Dhfr
ORF Names:	CG14887

Organism

Drosophila melanogaster (Fruit fly) [Complete proteome]

Taxonomic identifier

7227 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Arthropoda › Hexapoda › Insecta › Pterygota › Neoptera › Endopterygota › Diptera › Brachycera › Muscomorpha › Ephydroidea › Drosophilidae › Drosophila › Sophophora

Protein attributes

Sequence length	182 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	By interacting with vestigial (vg), may control genes involved in DNA replication.
Catalytic activity	5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH.
Pathway	Cofactor biosynthesis; tetrahydrofolate biosynthesis; 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate: step 1/1.
Subunit structure	Monomer. Interacts with vg. Ref.5
Miscellaneous	The reaction catalyzed by this enzyme represents an essential step for de novo glycine and purine synthesis, DNA precursor synthesis, and for the conversion of dUMP to dTMP.
Sequence similarities	Belongs to the dihydrofolate reductase family. Contains 1 DHFR (dihydrofolate reductase) domain.

Ontologies

Keywords
Biological process	DNA replication One-carbon metabolism
Ligand	NADP
Molecular function	Oxidoreductase
Technical term	Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	DNA replication Inferred from electronic annotation. Source: UniProtKB-KW glycine biosynthetic process Inferred from electronic annotation. Source: InterPro nucleotide biosynthetic process Inferred from electronic annotation. Source: InterPro one-carbon metabolic process Inferred from electronic annotation. Source: UniProtKB-KW oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	NADP or NADPH binding Inferred from electronic annotation. Source: InterPro dihydrofolate reductase activity Ref.4 Inferred from direct assay. Source: FlyBase protein binding Ref.5 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
	Q9VNA3	1	EBI-152625,EBI-136908

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 182	182	Dihydrofolate reductase		PRO_0000186370
Regions
	Domain	3 – 180	178	DHFR
Experimental info
	Sequence conflict	3	1	R → T AA sequence Ref.4
	Sequence conflict	11	1	C → S AA sequence Ref.4
	Sequence conflict	134	1	K → Q in AAA19051. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P17719-1 [UniParc]. Last modified June 1, 2001. Version 3. Checksum: D2C9198F1D2CE430	FASTA	182	20,775
	10 20 30 40 50 60 MLRFNLIVAV CENFGIGIRG DLPWRIKSEL KYFSRTTKRT SDPTKQNAVV MGRKTYFGVP 70 80 90 100 110 120 ESKRPLPDRL NIVLSTTLQE SDLPKGVLLC PNLETAMKIL EEQNEVENIW IVGGSGVYEE 130 140 150 160 170 180 AMASPRCHRL YITKIMQKFD CDTFFPAIPD SFREVAPDSD MPLGVQEENG IKFEYKILEK HS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Dihydrofolate reductase of Drosophila. Cloning and expression of a gene with a rare transcript." Hao H., Tyshenko M.G., Walker V.K. J. Biol. Chem. 269:15179-15185(1994) [PubMed: 8195153] [Abstract] Cited for: NUCLEOTIDE SEQUENCE, PROTEIN SEQUENCE OF 155-176. Strain: Canton-S.
[2]	"The genome sequence of Drosophila melanogaster." Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., Sutton G.G., Wortman J.R., Yandell M.D. , Zhang Q., Chen L.X., Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C. Science 287:2185-2195(2000) [PubMed: 10731132] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Berkeley.
[3]	"Annotation of the Drosophila melanogaster euchromatic genome: a systematic review." Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., Bettencourt B.R., Celniker S.E., de Grey A.D.N.J. , Drysdale R.A., Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E. Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002) [PubMed: 12537572] [Abstract] Cited for: GENOME REANNOTATION.
[4]	"The purification of dihydrofolate reductase from Drosophila melanogaster." Rancourt S.L., Walker V.K. Biochim. Biophys. Acta 1039:261-268(1990) [PubMed: 2116172] [Abstract] Cited for: PROTEIN SEQUENCE OF 1-23. Strain: Canton-S.
[5]	"The Drosophila wing differentiation factor vestigial-scalloped is required for cell proliferation and cell survival at the dorso-ventral boundary of the wing imaginal disc." Delanoue R., Legent K., Godefroy N., Flagiello D., Dutriaux A., Vaudin P., Becker J.L., Silber J. Cell Death Differ. 11:110-122(2004) [PubMed: 14526388] [Abstract] Cited for: INTERACTION WITH VG, INVOLVEMENT IN DNA REPLICATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	U06861 Unassigned DNA. Translation: AAA19051.1. AE014297 Genomic DNA. Translation: AAF55324.1.
PIR	A53803. A33105. S10759.
RefSeq	NP_001036720.1. NP_732147.1.
UniGene	Dm.8025
3D structure databases
HSSP	HSSP built from PDB template 1KMV based on UniProtKB P00374.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP:20310N.
IntAct	P17719. 3 interactions.
STRING	P17719.
Genome annotation databases
Ensembl	FBtr0110910; FBpp0110210; FBgn0004087; Drosophila melanogaster. [Genome view]
GeneID	42003.
KEGG	dme:Dmel_CG14887.
NMPDR	fig|7227.3.peg.13160.
Organism-specific databases
CTD	42003.
FlyBase	FBgn0004087. Dhfr.
Phylogenomic databases
HOGENOM	P17719.
OMA	PLNCIVA.
Enzyme and pathway databases
BioCyc	DMEL-XXX-02:DMEL-XXX-02-011944-MON.
BRENDA	1.5.1.3. 48.
Gene expression databases
GermOnline	CG14887. Drosophila melanogaster.
Family and domain databases
InterPro	IPR012259. DHFR. IPR001796. DHFR_reg. IPR017925. Dihydrofolate_reductase_CS. [Graphical view]
PANTHER	PTHR11549:SF1. DHFR. 1 hit.
Pfam	PF00186. DHFR_1. 1 hit. [Graphical view]
PRINTS	PR00070. DHFR.
PROSITE	PS00075. DHFR_1. 1 hit. PS51330. DHFR_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	826685.

Entry information

Entry name

DYR_DROME

Accession

Primary (citable) accession number: P17719
Secondary accession number(s): Q9VEU4

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
Last sequence update:	June 1, 2001
Last modified:	November 3, 2009
This is version 85 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Drosophila annotation project