P00374 (DYR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Dihydrofolate reductase
EC=1.5.1.3

Gene names

Name:

DHFR

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	187 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 process	Methotrexate resistance One-carbon metabolism
Disease	Disease mutation
Ligand	NADP RNA-binding
Molecular function	Oxidoreductase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	folic acid metabolic process Traceable author statement. Source: Reactome glycine biosynthetic process Non-traceable author statement. Source: UniProtKB nitric oxide metabolic process Traceable author statement. Source: Reactome nucleotide biosynthetic process Non-traceable author statement. Source: UniProtKB 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 phase of mitotic cell cycle Traceable author statement. Source: Reactome response to methotrexate Inferred from electronic annotation. Source: UniProtKB-KW tetrahydrofolate biosynthetic process Inferred from electronic annotation. Source: UniProtKB-UniPathway tetrahydrofolate metabolic process Inferred from direct assay Ref.16Ref.8. Source: UniProtKB
Cellular_component	cytosol Traceable author statement. Source: Reactome nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	NADP 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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 187

186

Dihydrofolate reductase

PRO_0000186362

Regions

Domain

4 – 185

182

DHFR

Nucleotide binding

16 – 22

7

NADP

Nucleotide binding

55 – 57

3

NADP

Nucleotide binding

77 – 79

3

NADP

Nucleotide binding

117 – 124

8

NADP

Region

31 – 36

6

Substrate binding

Sites

Binding site

10

1

NADP; via amide nitrogen and carbonyl oxygen

Binding site

65

1

Substrate

Binding site

71

1

Substrate

Natural variations

Natural variant

80

1

L → F in DHFRD. Ref.6

VAR_065818

Natural variant

153

1

D → V in DHFRD. Ref.26

VAR_065819

Experimental info

Mutagenesis

23

1

L → F, W or Y: Decreases affinity for NADP and dihydrofolate over 10-fold. Ref.13 Ref.20

Mutagenesis

23

1

L → 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

Mutagenesis

32

1

F → R: Reduces catalytic rate 5-fold. Reduces affinity for dihydrofolate 9-fold; when associated with E-36. Ref.24

Mutagenesis

36

1

Q → E: Reduces catalytic rate 2-fold. Reduces affinity for dihydrofolate 9-fold; when associated with R-32. Ref.19 Ref.23 Ref.24

Mutagenesis

36

1

Q → K: Increases affinity for dihydrofolate about 3-fold. Reduces affinity for NADPH about 3-fold. Ref.19 Ref.23 Ref.24

Mutagenesis

36

1

Q → S: Increases affinity for dihydrofolate about 2-fold. No effect on affinity for NADPH. Ref.19 Ref.23 Ref.24

Mutagenesis

65

1

N → F: Increases affinity for dihydrofolate about 3-fold. No effect on affinity for NADPH. Ref.19 Ref.23

Mutagenesis

65

1

N → S: Increases affinity for dihydrofolate about 15-fold. No effect on affinity for NADPH. Ref.19 Ref.23

Sequence conflict

113

1

V → L in AAH70280. Ref.5

Secondary structure

1

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187

Helix Strand Turn

Details...

Beta strand

5 – 11

7

Beta strand

16 – 19

4

Beta strand

24 – 26

3

Helix

29 – 40

12

Beta strand

43 – 46

4

Beta strand

48 – 54

7

Helix

55 – 60

6

Helix

63 – 65

3

Beta strand

71 – 76

6

Beta strand

88 – 93

6

Helix

94 – 101

8

Turn

104 – 109

6

Beta strand

110 – 115

6

Helix

119 – 126

8

Beta strand

128 – 130

3

Beta strand

132 – 141

10

Beta strand

146 – 148

3

Turn

154 – 156

3

Beta strand

157 – 159

3

Beta strand

161 – 163

3

Beta strand

171 – 173

3

Beta strand

176 – 185

10

Sequences

	Sequence		Length	Mass (Da)
	P00374 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: EBDF3D1EC73E1566	FASTA	187	21,453
	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

References

	« Hide 'large scale' referencesShow '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. , 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 , K01612, K01613, J00138, K01614 Genomic DNA. Translation: AAA58484.1.
X00855 , 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.

IPI

IPI00030357.

PIR

RDHUD. A22551.

RefSeq

NP_000782.1. NM_000791.3.

UniGene

Hs.592364.
Hs.648635.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BOZ	X-ray	2.10	A	2-187	[»]
1DHF	X-ray	2.30	A/B	2-187	[»]
1DLR	X-ray	2.30	A	2-186	[»]
1DLS	X-ray	2.30	A	2-186	[»]
1DRF	X-ray	2.00	A	2-187	[»]
1HFP	X-ray	2.10	A	2-186	[»]
1HFQ	X-ray	2.10	A	2-186	[»]
1HFR	X-ray	2.10	A	2-186	[»]
1KMS	X-ray	1.09	A	2-186	[»]
1KMV	X-ray	1.05	A	2-186	[»]
1MVS	X-ray	1.90	A	1-187	[»]
1MVT	X-ray	1.80	A	1-187	[»]
1OHJ	X-ray	2.50	A	2-187	[»]
1OHK	X-ray	2.50	A	2-187	[»]
1PD8	X-ray	2.10	A	2-186	[»]
1PD9	X-ray	2.20	A	2-186	[»]
1PDB	X-ray	2.20	A	2-186	[»]
1S3U	X-ray	2.50	A	2-186	[»]
1S3V	X-ray	1.80	A	2-186	[»]
1S3W	X-ray	1.90	A	2-186	[»]
1U71	X-ray	2.20	A	2-186	[»]
1U72	X-ray	1.90	A	2-186	[»]
1YHO	NMR	-	A	2-186	[»]
2C2S	X-ray	1.40	A/B	2-186	[»]
2C2T	X-ray	1.50	A/B	2-186	[»]
2DHF	X-ray	2.30	A/B	2-187	[»]
2W3A	X-ray	1.50	A/B	1-187	[»]
2W3B	X-ray	1.27	A/B	1-187	[»]
2W3M	X-ray	1.60	A/B	1-187	[»]
3EIG	X-ray	1.70	A	2-187	[»]
3F8Y	X-ray	1.45	A	1-187	[»]
3F8Z	X-ray	2.01	A	1-187	[»]
3F91	X-ray	1.90	A	1-187	[»]
3FS6	X-ray	1.23	A	1-187	[»]
3GHC	X-ray	1.30	A	2-187	[»]
3GHV	X-ray	1.30	A	2-187	[»]
3GHW	X-ray	1.24	A	2-187	[»]
3GI2	X-ray	1.53	A	1-187	[»]
3GYF	X-ray	1.70	A	1-187	[»]
3L3R	X-ray	2.00	A	2-187	[»]
3N0H	X-ray	1.92	A	2-187	[»]
3NTZ	X-ray	1.35	A	2-187	[»]
3NU0	X-ray	1.35	A	2-187	[»]
3NXO	X-ray	1.35	A	2-187	[»]
3NXR	X-ray	1.35	A	2-187	[»]
3NXT	X-ray	1.70	A	2-187	[»]
3NXV	X-ray	1.90	A	2-187	[»]
3NXX	X-ray	1.35	A	2-187	[»]
3NXY	X-ray	1.90	A	2-187	[»]
3NZD	X-ray	1.80	A	2-187	[»]
3OAF	X-ray	1.70	A	2-187	[»]
3S3V	X-ray	1.53	A	2-187	[»]
3S7A	X-ray	1.80	A	2-187	[»]
4DDR	X-ray	2.05	A	2-187	[»]

ProteinModelPortal

P00374.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000396308.

PTM databases

PhosphoSite

P00374.

Polymorphism databases

DMDM

118992.

2D gel databases

UCD-2DPAGE

P00374.

Proteomic databases

PaxDb

P00374.

PRIDE

P00374.

Protocols and materials databases

DNASU

1719.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000439211; ENSP00000396308; ENSG00000228716.
ENST00000505337; ENSP00000426474; ENSG00000228716.

GeneID

1719.

KEGG

hsa:1719.

UCSC

uc003kgy.1. human.

Organism-specific databases

CTD

1719.

GeneCards

GC05M079922.

HGNC

HGNC:2861. DHFR.

HPA

CAB037129.
HPA051465.

MIM

126060. gene.
613839. phenotype.

neXtProt

NX_P00374.

Orphanet

35858. Grasbeck-Imerslund disease.

PharmGKB

PA143.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0262.

HOGENOM

HOG000040235.

HOVERGEN

HBG000773.

InParanoid

P00374.

KO

K00287.

OMA

MVGSLNC.

OrthoDB

EOG4QJRPF.

PhylomeDB

P00374.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.
REACT_115566. Cell Cycle.

SABIO-RK

P00374.

UniPathway

UPA00077; UER00158.

Gene expression databases

ArrayExpress

P00374.

Bgee

P00374.

CleanEx

HS_DHFR.

Genevestigator

P00374.

GermOnline

ENSG00000188985. Homo sapiens.

Family and domain databases

Gene3D

3.40.430.10. 1 hit.

InterPro

IPR012259. DHFR.
IPR024072. DHFR-like_dom.
IPR017925. DHFR_CS.
IPR001796. DHFR_dom.
[Graphical view]

Pfam

PF00186. DHFR_1. 1 hit.
[Graphical view]

PRINTS

PR00070. DHFR.

SUPFAM

SSF53597. SSF53597. 1 hit.

PROSITE

PS00075. DHFR_1. 1 hit.
PS51330. DHFR_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P00374.

ChEMBL

CHEMBL202.

ChiTaRS

DHFR. human.

DrugBank

DB00250. Dapsone.
DB01093. Dimethyl sulfoxide.
DB00555. Lamotrigine.
DB00563. Methotrexate.
DB00157. NADH.
DB00642. Pemetrexed.
DB01131. Proguanil.
DB00205. Pyrimethamine.
DB00440. Trimethoprim.
DB01157. Trimetrexate.

EvolutionaryTrace

P00374.

GenomeRNAi

1719.

NextBio

6964.

SOURCE

Search...

Entry information

Entry name

DYR_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 152 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.