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P00374 (DYR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 163. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Dihydrofolate reductase

EC=1.5.1.3
Gene names
Name:DHFR
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length187 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its own mRNA and that of DHFRL1. Ref.9 Ref.16

Catalytic activity

5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH. Ref.8 Ref.15 Ref.16 Ref.19 Ref.22 Ref.23 Ref.24

Pathway

Cofactor biosynthesis; tetrahydrofolate biosynthesis; 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate: step 1/1.

Subunit structure

Homodimer. Ref.11

Tissue specificity

Widely expressed in fetal and adult tissues, including throughout the fetal and adult brains and whole blood. Expression is higher in the adult brain than in the fetal brain. Ref.6

Involvement in disease

Megaloblastic anemia due to dihydrofolate reductase deficiency (DHFRD) [MIM:613839]: An inborn error of metabolism, characterized by megaloblastic anemia and/or pancytopenia, severe cerebral folate deficiency, and cerebral tetrahydrobiopterin deficiency. Clinical features include variable neurologic symptoms, ranging from severe developmental delay and generalized seizures in infancy, to childhood absence epilepsy with learning difficulties, to lack of symptoms.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 Ref.26

Sequence similarities

Belongs to the dihydrofolate reductase family.

Contains 1 DHFR (dihydrofolate reductase) domain.

Biophysicochemical properties

Kinetic parameters:

KM=2.7 µM for dihydrofolate Ref.8 Ref.19 Ref.23

KM=4.0 µM for NADPH

Ontologies

Keywords
   Biological processMethotrexate resistance
One-carbon metabolism
   DiseaseDisease mutation
   LigandNADP
RNA-binding
   Molecular functionOxidoreductase
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG1/S transition of mitotic cell cycle

Traceable author statement. Source: Reactome

folic acid metabolic process

Traceable author statement. Source: Reactome

glycine biosynthetic process

Inferred from electronic annotation. Source: InterPro

mitotic cell cycle

Traceable author statement. Source: Reactome

nitric oxide metabolic process

Traceable author statement. Source: Reactome

nucleotide biosynthetic process

Inferred from electronic annotation. Source: InterPro

one-carbon metabolic process

Inferred from electronic annotation. Source: UniProtKB-KW

regulation of nitric-oxide synthase activity

Traceable author statement. Source: Reactome

regulation of transcription involved in G1/S transition of mitotic cell cycle

Traceable author statement. Source: Reactome

response to methotrexate

Inferred from electronic annotation. Source: UniProtKB-KW

small molecule metabolic process

Traceable author statement. Source: Reactome

tetrahydrofolate biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-UniPathway

tetrahydrofolate metabolic process

Inferred from direct assay Ref.16Ref.8. Source: UniProtKB

vitamin metabolic process

Traceable author statement. Source: Reactome

water-soluble vitamin metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

nucleoplasm

Traceable author statement. Source: Reactome

   Molecular_functionNADP binding

Inferred from electronic annotation. Source: InterPro

dihydrofolate reductase activity

Inferred from direct assay Ref.16Ref.8. Source: UniProtKB

drug binding

Inferred from direct assay Ref.16Ref.19. Source: UniProtKB

mRNA binding

Inferred from direct assay Ref.8. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 187186Dihydrofolate reductase
PRO_0000186362

Regions

Domain4 – 185182DHFR
Nucleotide binding16 – 227NADP
Nucleotide binding55 – 573NADP
Nucleotide binding77 – 793NADP
Nucleotide binding117 – 1248NADP
Region31 – 366Substrate binding

Sites

Binding site101NADP; via amide nitrogen and carbonyl oxygen
Binding site651Substrate
Binding site711Substrate

Natural variations

Natural variant801L → F in DHFRD. Ref.6
VAR_065818
Natural variant1531D → V in DHFRD. Ref.26
VAR_065819

Experimental info

Mutagenesis231L → F, W or Y: Decreases affinity for NADP and dihydrofolate over 10-fold. Ref.13 Ref.20
Mutagenesis231L → R: Strongly decreased affinity for methotrexate. Decreases catalytic rate constant 200-fold. Decreases affinity for NADP and dihydrofolate over 10-fold. Ref.13 Ref.20
Mutagenesis321F → R: Reduces catalytic rate 5-fold. Reduces affinity for dihydrofolate 9-fold; when associated with E-36. Ref.24
Mutagenesis361Q → E: Reduces catalytic rate 2-fold. Reduces affinity for dihydrofolate 9-fold; when associated with R-32. Ref.19 Ref.23 Ref.24
Mutagenesis361Q → K: Increases affinity for dihydrofolate about 3-fold. Reduces affinity for NADPH about 3-fold. Ref.19 Ref.23 Ref.24
Mutagenesis361Q → S: Increases affinity for dihydrofolate about 2-fold. No effect on affinity for NADPH. Ref.19 Ref.23 Ref.24
Mutagenesis651N → F: Increases affinity for dihydrofolate about 3-fold. No effect on affinity for NADPH. Ref.19 Ref.23
Mutagenesis651N → S: Increases affinity for dihydrofolate about 15-fold. No effect on affinity for NADPH. Ref.19 Ref.23
Sequence conflict1131V → L in AAH70280. Ref.5

Secondary structure

......................................... 187
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P00374 [UniParc].

Last modified January 23, 2007. Version 2.
Checksum: EBDF3D1EC73E1566

FASTA18721,453
        10         20         30         40         50         60 
MVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMGKKTWFS 

        70         80         90        100        110        120 
IPEKNRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKL TEQPELANKV DMVWIVGGSS 

       130        140        150        160        170        180 
VYKEAMNHPG HLKLFVTRIM QDFESDTFFP EIDLEKYKLL PEYPGVLSDV QEEKGIKYKF 


EVYEKND 

« Hide

References

« Hide 'large scale' references
[1]"The functional human dihydrofolate reductase gene."
Chen M.-J., Shimada T., Moulton A.D., Cline A., Humphries R.K., Maizel J., Nienhuis A.W.
J. Biol. Chem. 259:3933-3943(1984) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"The nucleotide sequence of the cDNA coding for the human dihydrofolic acid reductase."
Masters J.N., Attardi G.
Gene 21:59-63(1983) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Human dihydrofolate reductase gene organization. Extensive conservation of the G + C-rich 5' non-coding sequence and strong intron size divergence from homologous mammalian genes."
Yang J.K., Masters J.N., Attardi G.
J. Mol. Biol. 176:169-187(1984) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"The DNA sequence and comparative analysis of human chromosome 5."
Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. expand/collapse author list , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Eye.
[6]"Identification and characterization of an inborn error of metabolism caused by dihydrofolate reductase deficiency."
Banka S., Blom H.J., Walter J., Aziz M., Urquhart J., Clouthier C.M., Rice G.I., de Brouwer A.P., Hilton E., Vassallo G., Will A., Smith D.E., Smulders Y.M., Wevers R.A., Steinfeld R., Heales S., Crow Y.J., Pelletier J.N., Jones S., Newman W.G.
Am. J. Hum. Genet. 88:216-225(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, VARIANT DHFRD PHE-80.
[7]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]"The former annotated human pseudogene dihydrofolate reductase-like 1 (DHFRL1) is expressed and functional."
McEntee G., Minguzzi S., O'Brien K., Ben Larbi N., Loscher C., O'Fagain C., Parle-McDermott A.
Proc. Natl. Acad. Sci. U.S.A. 108:15157-15162(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, RNA-BINDING, BIOPHYSICOCHEMICAL PROPERTIES.
[9]"Identification of a de novo thymidylate biosynthesis pathway in mammalian mitochondria."
Anderson D.D., Quintero C.M., Stover P.J.
Proc. Natl. Acad. Sci. U.S.A. 108:15163-15168(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[10]"Crystal structure of human dihydrofolate reductase complexed with folate."
Oefner C., D'Arcy A., Winkler F.K.
Eur. J. Biochem. 174:377-385(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH FOLATE.
[11]"Crystal structures of recombinant human dihydrofolate reductase complexed with folate and 5-deazafolate."
Davies J.F., Delcamp T.J., Prendergast N.J., Ashford V.A., Freisheim J.H., Kraut J.
Biochemistry 29:9467-9479(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEXES WITH FOLATE AND 5-DEAZAFOLATE, SUBUNIT.
[12]"Sequence-specific 1H and 15N resonance assignments for human dihydrofolate reductase in solution."
Stockman B.J., Nirmala N.R., Wagner G., Delcamp T.J., Deyarman M.T., Freisheim J.H.
Biochemistry 31:218-229(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR.
[13]"Methotrexate-resistant variants of human dihydrofolate reductase with substitutions of leucine 22. Kinetics, crystallography, and potential as selectable markers."
Lewis W.S., Cody V., Galitsky N., Luft J.R., Pangborn W., Chunduru S.K., Spencer H.T., Appleman J.R., Blakley R.L.
J. Biol. Chem. 270:5057-5064(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEXES WITH NADPH; PIRITREXIM AND METOTHREXATE, MUTAGENESIS OF LEU-23.
[14]"Comparison of two independent crystal structures of human dihydrofolate reductase ternary complexes reduced with nicotinamide adenine dinucleotide phosphate and the very tight-binding inhibitor PT523."
Cody V., Galitsky N., Luft J.R., Pangborn W., Blakley R.L., Gangjee A.
Biochemistry 36:13897-13903(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
[15]"Structure-based design and synthesis of lipophilic 2,4-diamino-6-substituted quinazolines and their evaluation as inhibitors of dihydrofolate reductases and potential antitumor agents."
Gangjee A., Vidwans A.P., Vasudevan A., Queener S.F., Kisliuk R.L., Cody V., Li R., Galitsky N., Luft J.R., Pangborn W.
J. Med. Chem. 41:3426-3434(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEXES WITH NADPH AND QUINAZOLINE INHIBITORS, CATALYTIC ACTIVITY.
[16]"Atomic structures of human dihydrofolate reductase complexed with NADPH and two lipophilic antifolates at 1.09 A and 1.05 A resolution."
Klon A.E., Heroux A., Ross L.J., Pathak V., Johnson C.A., Piper J.R., Borhani D.W.
J. Mol. Biol. 320:677-693(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.05 ANGSTROMS) IN COMPLEXES WITH NADP AND THE SYNTHETIC INHIBITORS SRI-9439 AND SRI-9662, FUNCTION, CATALYTIC ACTIVITY.
[17]"Analysis of two polymorphic forms of a pyrido[2,3-d]pyrimidine N9-C10 reversed-bridge antifolate binary complex with human dihydrofolate reductase."
Cody V., Galitsky N., Luft J.R., Pangborn W., Gangjee A.
Acta Crystallogr. D 59:654-661(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COMPLEX WITH INHIBITOR.
[18]"Analysis of three crystal structure determinations of a 5-methyl-6-N-methylanilino pyridopyrimidine antifolate complex with human dihydrofolate reductase."
Cody V., Luft J.R., Pangborn W., Gangjee A.
Acta Crystallogr. D 59:1603-1609(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH INHIBITOR.
[19]"Structure determination of tetrahydroquinazoline antifolates in complex with human and Pneumocystis carinii dihydrofolate reductase: correlations between enzyme selectivity and stereochemistry."
Cody V., Luft J.R., Pangborn W., Gangjee A., Queener S.F.
Acta Crystallogr. D 60:646-655(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COMPLEX WITH NADPH AND INHIBITOR, MUTAGENESIS OF GLN-36 AND ASN-65, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES.
[20]"Understanding the role of Leu22 variants in methotrexate resistance: comparison of wild-type and Leu22Arg variant mouse and human dihydrofolate reductase ternary crystal complexes with methotrexate and NADPH."
Cody V., Luft J.R., Pangborn W.
Acta Crystallogr. D 61:147-155(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEXES WITH NADP AND METHOTREXATE, MUTAGENESIS OF LEU-23.
[21]"Solution structure of human dihydrofolate reductase in its complex with trimethoprim and NADPH."
Kovalevskaya N.V., Smurnyy Y.D., Polshakov V.I., Birdsall B., Bradbury A.F., Frenkiel T., Feeney J.
J. Biomol. NMR 33:69-72(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR IN COMPLEX WITH TRIMETHOPRIM AND NADPH.
[22]"Novel boron-containing, nonclassical antifolates: synthesis and preliminary biological and structural evaluation."
Reynolds R.C., Campbell S.R., Fairchild R.G., Kisliuk R.L., Micca P.L., Queener S.F., Riordan J.M., Sedwick W.D., Waud W.R., Leung A.K., Dixon R.W., Suling W.J., Borhani D.W.
J. Med. Chem. 50:3283-3289(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.40 ANGSTROMS) IN COMPLEXES WITH NADP AND BORON-CONTAINING INHIBITORS, CATALYTIC ACTIVITY.
[23]"Correlations of inhibitor kinetics for Pneumocystis jirovecii and human dihydrofolate reductase with structural data for human active site mutant enzyme complexes."
Cody V., Pace J., Makin J., Piraino J., Queener S.F., Rosowsky A.
Biochemistry 48:1702-1711(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.23 ANGSTROMS) IN COMPLEXES WITH NADP AND THE SYNTHETIC INHIBITOR PY957, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF GLN-36 AND ASN-65.
[24]"Multiple conformers in active site of human dihydrofolate reductase F31R/Q35E double mutant suggest structural basis for methotrexate resistance."
Volpato J.P., Yachnin B.J., Blanchet J., Guerrero V., Poulin L., Fossati E., Berghuis A.M., Pelletier J.N.
J. Biol. Chem. 284:20079-20089(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF MUTANT ARG-32/GLU-36 IN COMPLEX WITH METHOTREXATE AND NADP, MUTAGENESIS OF PHE-32 AND GLN-36, CATALYTIC ACTIVITY.
[25]"Design, synthesis, and X-ray crystal structure of classical and nonclassical 2-amino-4-oxo-5-substituted-6-ethylthieno[2,3-d]pyrimidines as dual thymidylate synthase and dihydrofolate reductase inhibitors and as potential antitumor agents."
Gangjee A., Li W., Kisliuk R.L., Cody V., Pace J., Piraino J., Makin J.
J. Med. Chem. 52:4892-4902(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.24 ANGSTROMS) OF 1-187.
[26]"Dihydrofolate reductase deficiency due to a homozygous DHFR mutation causes megaloblastic anemia and cerebral folate deficiency leading to severe neurologic disease."
Cario H., Smith D.E., Blom H., Blau N., Bode H., Holzmann K., Pannicke U., Hopfner K.P., Rump E.M., Ayric Z., Kohne E., Debatin K.M., Smulders Y., Schwarz K.
Am. J. Hum. Genet. 88:226-231(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT DHFRD VAL-153.
+Additional computationally mapped references.

Web resources

Wikipedia

Dihydrofolate reductase entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J00140 mRNA. Translation: AAA58485.1.
V00507 mRNA. Translation: CAA23765.1.
J00139 expand/collapse EMBL AC list , K01612, K01613, J00138, K01614 Genomic DNA. Translation: AAA58484.1.
X00855 expand/collapse EMBL AC list , X00856, X00857, X00858, X00859 Genomic DNA. Translation: CAA25409.1.
AC008434 Genomic DNA. No translation available.
BC000192 mRNA. Translation: AAH00192.1.
BC003584 mRNA. Translation: AAH03584.2.
BC070280 mRNA. Translation: AAH70280.1.
BC071996 mRNA. Translation: AAH71996.1.
CCDSCCDS47240.1.
PIRRDHUD. A22551.
RefSeqNP_000782.1. NM_000791.3.
UniGeneHs.592364.
Hs.648635.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1BOZX-ray2.10A2-187[»]
1DHFX-ray2.30A/B2-187[»]
1DLRX-ray2.30A2-187[»]
1DLSX-ray2.30A2-187[»]
1DRFX-ray2.00A2-187[»]
1HFPX-ray2.10A2-187[»]
1HFQX-ray2.10A2-187[»]
1HFRX-ray2.10A2-187[»]
1KMSX-ray1.09A2-187[»]
1KMVX-ray1.05A2-187[»]
1MVSX-ray1.90A1-187[»]
1MVTX-ray1.80A1-187[»]
1OHJX-ray2.50A2-187[»]
1OHKX-ray2.50A2-187[»]
1PD8X-ray2.10A2-187[»]
1PD9X-ray2.20A2-187[»]
1PDBX-ray2.20A2-187[»]
1S3UX-ray2.50A2-187[»]
1S3VX-ray1.80A2-187[»]
1S3WX-ray1.90A2-187[»]
1U71X-ray2.20A2-187[»]
1U72X-ray1.90A2-187[»]
1YHONMR-A2-187[»]
2C2SX-ray1.40A/B2-187[»]
2C2TX-ray1.50A/B2-187[»]
2DHFX-ray2.30A/B2-187[»]
2W3AX-ray1.50A/B1-187[»]
2W3BX-ray1.27A/B1-187[»]
2W3MX-ray1.60A/B1-187[»]
3EIGX-ray1.70A2-187[»]
3F8YX-ray1.45A1-187[»]
3F8ZX-ray2.01A1-187[»]
3F91X-ray1.90A1-187[»]
3FS6X-ray1.23A1-187[»]
3GHCX-ray1.30A2-187[»]
3GHVX-ray1.30A2-187[»]
3GHWX-ray1.24A2-187[»]
3GI2X-ray1.53A1-187[»]
3GYFX-ray1.70A1-187[»]
3L3RX-ray2.00A2-187[»]
3N0HX-ray1.92A2-187[»]
3NTZX-ray1.35A2-187[»]
3NU0X-ray1.35A2-187[»]
3NXOX-ray1.35A2-187[»]
3NXRX-ray1.35A2-187[»]
3NXTX-ray1.70A2-187[»]
3NXVX-ray1.90A2-187[»]
3NXXX-ray1.35A2-187[»]
3NXYX-ray1.90A2-187[»]
3NZDX-ray1.80A2-187[»]
3OAFX-ray1.70A2-187[»]
3S3VX-ray1.53A2-187[»]
3S7AX-ray1.80A2-187[»]
4DDRX-ray2.05A2-187[»]
4G95X-ray1.35A2-187[»]
4KAKX-ray1.80A/B2-187[»]
4KBNX-ray1.84A/B2-187[»]
4KD7X-ray2.72A/B2-187[»]
4KEBX-ray1.45A/B2-187[»]
4KFJX-ray1.76A/B2-187[»]
4M6JX-ray1.20A1-187[»]
4M6KX-ray1.40A1-187[»]
4M6LX-ray1.70A1-187[»]
ProteinModelPortalP00374.
SMRP00374. Positions 2-186.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108065. 8 interactions.
MINTMINT-5002355.
STRING9606.ENSP00000396308.

Chemistry

BindingDBP00374.
ChEMBLCHEMBL202.
DrugBankDB00250. Dapsone.
DB01093. Dimethyl sulfoxide.
DB00555. Lamotrigine.
DB00563. Methotrexate.
DB00157. NADH.
DB00642. Pemetrexed.
DB01131. Proguanil.
DB00205. Pyrimethamine.
DB00440. Trimethoprim.
DB01157. Trimetrexate.
GuidetoPHARMACOLOGY2603.

PTM databases

PhosphoSiteP00374.

Polymorphism databases

DMDM118992.

2D gel databases

UCD-2DPAGEP00374.

Proteomic databases

MaxQBP00374.
PaxDbP00374.
PRIDEP00374.

Protocols and materials databases

DNASU1719.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000439211; ENSP00000396308; ENSG00000228716.
ENST00000505337; ENSP00000426474; ENSG00000228716.
GeneID1719.
KEGGhsa:1719.
UCSCuc003kgy.1. human.

Organism-specific databases

CTD1719.
GeneCardsGC05M079922.
HGNCHGNC:2861. DHFR.
HPACAB037129.
HPA051465.
MIM126060. gene.
613839. phenotype.
neXtProtNX_P00374.
Orphanet319651. Constitutional megaloblastic anemia with severe neurologic disease.
PharmGKBPA143.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0262.
HOGENOMHOG000040235.
HOVERGENHBG000773.
InParanoidP00374.
KOK00287.
OMALPWHPIR.
OrthoDBEOG7V1FS3.
PhylomeDBP00374.
TreeFamTF317636.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
REACT_115566. Cell Cycle.
REACT_116125. Disease.
SABIO-RKP00374.
UniPathwayUPA00077; UER00158.

Gene expression databases

ArrayExpressP00374.
BgeeP00374.
CleanExHS_DHFR.
GenevestigatorP00374.

Family and domain databases

Gene3D3.40.430.10. 1 hit.
InterProIPR012259. DHFR.
IPR024072. DHFR-like_dom.
IPR017925. DHFR_CS.
IPR001796. DHFR_dom.
[Graphical view]
PfamPF00186. DHFR_1. 1 hit.
[Graphical view]
PRINTSPR00070. DHFR.
SUPFAMSSF53597. SSF53597. 1 hit.
PROSITEPS00075. DHFR_1. 1 hit.
PS51330. DHFR_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSDHFR. human.
EvolutionaryTraceP00374.
GeneWikiDihydrofolate_reductase.
GenomeRNAi1719.
NextBio6964.
PROP00374.
SOURCESearch...

Entry information

Entry nameDYR_HUMAN
AccessionPrimary (citable) accession number: P00374
Secondary accession number(s): Q14130, Q6IRW8
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 163 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM