DHFR

Functionⁱ

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 DHFR2.2 Publications

Catalytic activityⁱ

5,6,7,8-tetrahydrofolate + NADP⁺ = 7,8-dihydrofolate + NADPH.PROSITE-ProRule annotation7 Publications

Kineticsⁱ

K_M=
2.7 µM for dihydrofolate
3 Publications
Manual assertion based on experiment inⁱ
- Ref.9
  "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.
- Ref.20
  "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.
- Ref.24
  "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.
K_M=
4.0 µM for NADPH
3 Publications
Manual assertion based on experiment inⁱ
- Ref.9
  "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.
- Ref.20
  "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.
- Ref.24
  "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.

Pathwayⁱ: tetrahydrofolate biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate.
Proteins known to be involved in this subpathway in this organism are:

Dihydrofolate reductase 2, mitochondrial (DHFR2), Dihydrofolate reductase (DHFR)

This subpathway is part of the pathway tetrahydrofolate biosynthesis, which is itself part of Cofactor biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate, the pathway tetrahydrofolate biosynthesis and in Cofactor biosynthesis.

Sites

Feature key	Position(s)	DescriptionActions	Length
Binding siteⁱ	10	NADP; via amide nitrogen and carbonyl oxygen3 Publications	1
Binding siteⁱ	65	Substrate1 Publication	1
Binding siteⁱ	71	Substrate1 Publication	1

Regions

Feature key	Position(s)	DescriptionActions	Length
Nucleotide bindingⁱ	16 – 22	NADP3 Publications	7
Nucleotide bindingⁱ	55 – 57	NADP3 Publications	3
Nucleotide bindingⁱ	77 – 79	NADP3 Publications	3
Nucleotide bindingⁱ	117 – 124	NADP3 Publications	8

GO - Molecular functionⁱ

dihydrofolate reductase activity
Source: UniProtKB
Inferred from direct assayⁱ
- 12096917
- 21876184
drug binding
Source: UniProtKB
Inferred from direct assayⁱ
- 12096917
- 15039552
folate reductase activity Source: Reactome
folic acid binding
Source: BHF-UCL
Inferred from direct assayⁱ
- 2303423
methotrexate binding
Source: BHF-UCL
Inferred from direct assayⁱ
- 2303423
mRNA binding
Source: UniProtKB
Inferred from direct assayⁱ
- 21876184
NADP binding
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
NADPH binding
Source: BHF-UCL
Inferred from direct assayⁱ
- 2303423
sequence-specific mRNA binding
Source: CAFA
Inferred from direct assayⁱ
- 8490020
translation repressor activity, mRNA regulatory element binding
Source: CAFA
Inferred from direct assayⁱ
- 8490020

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

axon regeneration Source: BHF-UCL
dihydrofolate metabolic process
Source: BHF-UCL
Inferred from direct assayⁱ
- 2303423
- 23707606
folic acid metabolic process Source: BHF-UCL
negative regulation of translation
Source: CAFA
Inferred from direct assayⁱ
- 8490020
one-carbon metabolic process Source: UniProtKB-KW
oxidation-reduction process
Source: BHF-UCL
Inferred from direct assayⁱ
- 23707606
positive regulation of nitric-oxide synthase activity Source: BHF-UCL
regulation of removal of superoxide radicals Source: BHF-UCL
regulation of transcription involved in G1/S transition of mitotic cell cycle Source: Reactome
response to methotrexate Source: BHF-UCL
tetrahydrobiopterin biosynthetic process
Source: BHF-UCL
Inferred from mutant phenotypeⁱ
- 23707606
tetrahydrofolate biosynthetic process
Source: BHF-UCL
Inferred from direct assayⁱ
- 2303423
tetrahydrofolate metabolic process
Source: UniProtKB
Inferred from direct assayⁱ
- 12096917
- 21876184

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Oxidoreductase, RNA-binding
Biological process	Methotrexate resistance, One-carbon metabolism
Ligand	NADP

Enzyme and pathway databases

BioCycⁱ	MetaCyc:HS09699-MONOMER
BRENDAⁱ	1.5.1.3 2681
Reactomeⁱ	R-HSA-1474151 Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation R-HSA-196757 Metabolism of folate and pterines R-HSA-539107 Activation of E2F1 target genes at G1/S
SABIO-RKⁱ	P00374
SIGNORⁱ	P00374
UniPathwayⁱ	UPA00077;UER00158

Protein family/group databases

MoonProtⁱ	P00374

MoonProtⁱ

P00374

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Dihydrofolate reductase (EC:1.5.1.3)
Gene namesⁱ	Name:DHFR
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 5

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000228716.6
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:2861 DHFR
MIMⁱ	126060 gene
neXtProtⁱ	NX_P00374

Keywords - Cellular componentⁱ

Cytoplasm, Mitochondrion

Pathology & Biotechⁱ

Involvement in diseaseⁱ

Megaloblastic anemia due to dihydrofolate reductase deficiency (DHFRD)2 Publications

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionAn 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.

Mutagenesis

Feature key	Position(s)	DescriptionActions	Length
Mutagenesisⁱ	23	L → F, W or Y: Decreases affinity for NADP and dihydrofolate over 10-fold. 2 Publications	1
Mutagenesisⁱ	23	L → R: Strongly decreased affinity for methotrexate. Decreases catalytic rate constant 200-fold. Decreases affinity for NADP and dihydrofolate over 10-fold. 2 Publications	1
Mutagenesisⁱ	32	F → R: Reduces catalytic rate 5-fold. Reduces affinity for dihydrofolate 9-fold; when associated with E-36. 1 Publication	1
Mutagenesisⁱ	36	Q → E: Reduces catalytic rate 2-fold. Reduces affinity for dihydrofolate 9-fold; when associated with R-32. 3 Publications	1
Mutagenesisⁱ	36	Q → K: Increases affinity for dihydrofolate about 3-fold. Reduces affinity for NADPH about 3-fold. 3 Publications	1
Mutagenesisⁱ	36	Q → S: Increases affinity for dihydrofolate about 2-fold. No effect on affinity for NADPH. 3 Publications	1
Mutagenesisⁱ	65	N → F: Increases affinity for dihydrofolate about 3-fold. No effect on affinity for NADPH. 2 Publications	1
Mutagenesisⁱ	65	N → S: Increases affinity for dihydrofolate about 15-fold. No effect on affinity for NADPH. 2 Publications	1

Keywords - Diseaseⁱ

Disease mutation

Organism-specific databases

DisGeNET More...DisGeNETⁱ	1719
MalaCards human disease database More...MalaCardsⁱ	DHFR
MIMⁱ	613839 phenotype
Open Targets More...OpenTargetsⁱ	ENSG00000228716
Orphanetⁱ	319651 Constitutional megaloblastic anemia with severe neurologic disease
PharmGKBⁱ	PA143

Chemistry databases

ChEMBLⁱ	CHEMBL202
Drug and drug target database More...DrugBankⁱ	DB03461 2'-Monophosphoadenosine 5'-Diphosphoribose DB08878 Aminopterin DB03886 Biopterin DB00798 Gentamicin DB00563 Methotrexate DB00157 NADH DB00642 Pemetrexed DB06813 Pralatrexate DB01131 Proguanil DB00205 Pyrimethamine DB03351 Sri-9439 DB03060 Sri-9662 DB00440 Trimethoprim DB01157 Trimetrexate
IUPHAR/BPS Guide to PHARMACOLOGY More...GuidetoPHARMACOLOGYⁱ	2603

Polymorphism and mutation databases

BioMutaⁱ	DHFR
DMDMⁱ	118992

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000186362	1 – 187	Dihydrofolate reductaseAdd BLAST		187

Proteomic databases

EPDⁱ	P00374
MaxQB - The MaxQuant DataBase More...MaxQBⁱ	P00374
PaxDbⁱ	P00374
PeptideAtlas More...PeptideAtlasⁱ	P00374
PRIDEⁱ	P00374
ProteomicsDBⁱ	51237

2D gel databases

UCD-2DPAGEⁱ	P00374

UCD-2DPAGEⁱ

P00374

PTM databases

iPTMnetⁱ	P00374
PhosphoSitePlusⁱ	P00374
SwissPalmⁱ	P00374

Expressionⁱ

Tissue specificityⁱ

Gene expression databases

Bgeeⁱ	ENSG00000228716 Expressed in 232 organ(s), highest expression level in buccal mucosa cell
CleanExⁱ	HS_DHFR
ExpressionAtlasⁱ	P00374 baseline and differential
Genevisibleⁱ	P00374 HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	CAB037129 HPA051465

HPAⁱ

CAB037129
HPA051465

Interactionⁱ

Subunit structureⁱ

Homodimer.7 Publications

Protein-protein interaction databases

BioGridⁱ	108065, 16 interactors
IntActⁱ	P00374, 5 interactors
Molecular INTeraction database More...MINTⁱ	P00374
STRINGⁱ	9606.ENSP00000396308

Chemistry databases

BindingDBⁱ

P00374

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Beta strandⁱ	5 – 11	Combined sources	7
Beta strandⁱ	16 – 19	Combined sources	4
Beta strandⁱ	24 – 26	Combined sources	3
Helixⁱ	29 – 40	Combined sources	12
Beta strandⁱ	43 – 46	Combined sources	4
Beta strandⁱ	48 – 54	Combined sources	7
Helixⁱ	55 – 60	Combined sources	6
Helixⁱ	63 – 65	Combined sources	3
Beta strandⁱ	71 – 76	Combined sources	6
Beta strandⁱ	88 – 93	Combined sources	6
Helixⁱ	94 – 101	Combined sources	8
Turnⁱ	104 – 109	Combined sources	6
Beta strandⁱ	110 – 115	Combined sources	6
Helixⁱ	119 – 126	Combined sources	8
Beta strandⁱ	128 – 130	Combined sources	3
Beta strandⁱ	132 – 141	Combined sources	10
Beta strandⁱ	146 – 148	Combined sources	3
Turnⁱ	154 – 156	Combined sources	3
Beta strandⁱ	157 – 159	Combined sources	3
Beta strandⁱ	161 – 163	Combined sources	3
Beta strandⁱ	171 – 173	Combined sources	3
Beta strandⁱ	176 – 185	Combined sources	10

Show more details

3D structure databases

ProteinModelPortalⁱ	P00374
SMRⁱ	P00374
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Miscellaneous databases

EvolutionaryTraceⁱ	P00374

EvolutionaryTraceⁱ

P00374

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Domainⁱ	4 – 185	DHFRPROSITE-ProRule annotationAdd BLAST		182

Region

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Regionⁱ	31 – 36	Substrate binding1 Publication		6

Sequence similaritiesⁱ

Belongs to the dihydrofolate reductase family.Curated

Phylogenomic databases

eggNOGⁱ	KOG1324 Eukaryota COG0262 LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00390000010283
HOGENOMⁱ	HOG000040235
HOVERGENⁱ	HBG000773
InParanoidⁱ	P00374
KEGG Orthology (KO) More...KOⁱ	K00287
OMAⁱ	RDNQLPW
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G0PRK
PhylomeDBⁱ	P00374
TreeFamⁱ	TF317636

Family and domain databases

Conserved Domains Database More...CDDⁱ	cd00209 DHFR, 1 hit
Gene3Dⁱ	3.40.430.10, 1 hit
InterProⁱ	View protein in InterPro IPR024072 DHFR-like_dom_sf IPR017925 DHFR_CS IPR001796 DHFR_dom
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00186 DHFR_1, 1 hit
SUPFAMⁱ	SSF53597 SSF53597, 1 hit
PROSITEⁱ	View protein in PROSITE PS00075 DHFR_1, 1 hit PS51330 DHFR_2, 1 hit

Sequences (2+)ⁱ

Sequence statusⁱ: Complete.

This entry describes 2 isoformsⁱ produced by alternative splicing. Align Add to basket

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show all Align All

Isoform 1 (identifier: P00374-1) [UniParc]FASTA Add to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL 
        60         70         80         90        100
VIMGKKTWFS IPEKNRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKL 
       110        120        130        140        150
TEQPELANKV DMVWIVGGSS VYKEAMNHPG HLKLFVTRIM QDFESDTFFP 
       160        170        180 
EIDLEKYKLL PEYPGVLSDV QEEKGIKYKF EVYEKND

Length:187

Mass (Da):21,453

Last modified:January 23, 2007 - v2

Checksum:ⁱEBDF3D1EC73E1566

GO

Isoform 2 (identifier: P00374-2) [UniParc]FASTA Add to basket

The sequence of this isoform differs from the canonical sequence as follows:
1-52: Missing.

« Hide

        10         20         30         40         50
MGKKTWFSIP EKNRPLKGRI NLVLSRELKE PPQGAHFLSR SLDDALKLTE 
        60         70         80         90        100
QPELANKVDM VWIVGGSSVY KEAMNHPGHL KLFVTRIMQD FESDTFFPEI 
       110        120        130 
DLEKYKLLPE YPGVLSDVQE EKGIKYKFEV YEKND

Note: No experimental confirmation available.

Show »

Length:135

Mass (Da):15,672

Checksum:ⁱ92704AAABEE1EF40

GO

Computationally mapped potential isoform sequencesⁱ

There is 1 potential isoform mapped to this entry.BLAST Align Show all Add to basket

	Entry	Entry name		Protein names	Gene names	Length	Annotation

	B4DM58	B4DM58_HUMAN		Dihydrofolate reductase Dihydrofolate reductase (cDNA FLJ51500, highly similar to Dihydrofolate reductase)	DHFR	129	Annotation score:

Experimental Info

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Sequence conflictⁱ	113	V → L in AAH70280 (PubMed:15489334).Curated		1

Natural variant

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Natural variantⁱVAR_065818	80	L → F in DHFRD. 1 PublicationCorresponds to variant dbSNP:rs387906619EnsemblClinVar.		1
Natural variantⁱVAR_065819	153	D → V in DHFRD. 1 PublicationCorresponds to variant dbSNP:rs121913223EnsemblClinVar.		1

Alternative sequence

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Alternative sequenceⁱVSP_056352	1 – 52	Missing in isoform 2. 1 PublicationAdd BLAST		52

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	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 AK293146 mRNA Translation: BAG56693.1 AC008434 Genomic DNA No translation available. AC010270 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
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS47240.1 [P00374-1] CCDS78028.1 [P00374-2]
PIRⁱ	A22551 RDHUD
NCBI Reference Sequences More...RefSeqⁱ	NP_000782.1, NM_000791.3 [P00374-1] NP_001277283.1, NM_001290354.1 [P00374-2]
UniGeneⁱ	Hs.592364 Hs.648635

Genome annotation databases

Ensemblⁱ	ENST00000439211; ENSP00000396308; ENSG00000228716 [P00374-1] ENST00000504396; ENSP00000421334; ENSG00000228716 [P00374-2] ENST00000505337; ENSP00000426474; ENSG00000228716 [P00374-1]
GeneIDⁱ	1719
KEGGⁱ	hsa:1719
UCSC genome browser More...UCSCⁱ	uc003kgy.2 human [P00374-1]

Keywords - Coding sequence diversityⁱ

Alternative splicing

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
P00374	Dihydrofolate reductase, isoform CRA_a		HUMAN		262	UniRef100_P00374
Trimethoprim resistant protein		ECO57		187
Trimethoprim resistant protein		SHISS		187
Dihydrofolate reductase		HUMAN		187
UPI0000110FCE		HUMAN		186
P00374-2	Dihydrofolate reductase/Cytidine and deoxycytidylate deaminase zinc-binding region/Uracil phosphoribosyltransferase, putative		PLABE		559	UniRef100_A0A1D3PVI6
Fur1p		YEASO		142
Fcy1p		YEASA		153

Protein	Similar proteins		Species	Score	Length	Source
P00374	Dihydrofolate reductase, isoform CRA_a		HUMAN		262	UniRef90_P00374
Trimethoprim resistant protein		ECO57		187
Trimethoprim resistant protein		SHISS		187
Dihydrofolate reductase		MACMU		187
Dihydrofolate reductase		GORGO		187
+23
P00374-2	Dihydrofolate reductase/Cytidine and deoxycytidylate deaminase zinc-binding region/Uracil phosphoribosyltransferase, putative		PLABE		559	UniRef90_A0A1D3PVI6
Fur1p		YEASO		142
Fcy1p		YEASA		153

Protein	Similar proteins		Species	Score	Length	Source
P00374	Dihydrofolate reductase, isoform CRA_a		HUMAN		262	UniRef50_P00374
Trimethoprim resistant protein		ECO57		187
Trimethoprim resistant protein		SHISS		187
Dihydrofolate reductase		CHLSB		187
Uncharacterized protein		MACNE		187
+29
P00374-2	Dihydrofolate reductase/Cytidine and deoxycytidylate deaminase zinc-binding region/Uracil phosphoribosyltransferase, putative		PLABE		559	UniRef50_A0A1D3PVI6
Fur1p		YEASO		142
Fcy1p		YEASA		153

Cross-referencesⁱ

Web resourcesⁱ

Wikipedia

Dihydrofolate reductase entry

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	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 AK293146 mRNA Translation: BAG56693.1 AC008434 Genomic DNA No translation available. AC010270 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
CCDSⁱ	CCDS47240.1 [P00374-1] CCDS78028.1 [P00374-2]
PIRⁱ	A22551 RDHUD
RefSeqⁱ	NP_000782.1, NM_000791.3 [P00374-1] NP_001277283.1, NM_001290354.1 [P00374-2]
UniGeneⁱ	Hs.592364 Hs.648635

3D structure databases

Select the link destinations: Protein Data Bank Europe More...PDBeⁱ Protein Data Bank RCSB More...RCSB PDBⁱ Protein Data Bank Japan More...PDBjⁱ Links Updated	PDB 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	2-187	[»]
	1DLS	X-ray	2.30	A	2-187	[»]
	1DRF	X-ray	2.00	A	2-187	[»]
	1HFP	X-ray	2.10	A	2-187	[»]
	1HFQ	X-ray	2.10	A	2-187	[»]
	1HFR	X-ray	2.10	A	2-187	[»]
	1KMS	X-ray	1.09	A	2-187	[»]
	1KMV	X-ray	1.05	A	2-187	[»]
	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	2-187	[»]
	1PD9	X-ray	2.20	A	2-187	[»]
	1PDB	X-ray	2.20	A	2-187	[»]
	1S3U	X-ray	2.50	A	2-187	[»]
	1S3V	X-ray	1.80	A	2-187	[»]
	1S3W	X-ray	1.90	A	2-187	[»]
	1U71	X-ray	2.20	A	2-187	[»]
	1U72	X-ray	1.90	A	2-187	[»]
	1YHO	NMR	-	A	2-187	[»]
	2C2S	X-ray	1.40	A/B	2-187	[»]
	2C2T	X-ray	1.50	A/B	2-187	[»]
	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	[»]
	4G95	X-ray	1.35	A	2-187	[»]
	4KAK	X-ray	1.80	A/B	2-187	[»]
	4KBN	X-ray	1.84	A/B	2-187	[»]
	4KD7	X-ray	2.72	A/B	2-187	[»]
	4KEB	X-ray	1.45	A/B	2-187	[»]
	4KFJ	X-ray	1.76	A/B	2-187	[»]
	4M6J	X-ray	1.20	A	1-187	[»]
	4M6K	X-ray	1.40	A	1-187	[»]
	4M6L	X-ray	1.70	A	1-187	[»]
4QHV	X-ray	1.61	A	2-187	[»]
4QJC	X-ray	1.62	A	2-187	[»]
5HPB	X-ray	1.65	A	2-187	[»]
5HQY	X-ray	1.46	A	2-187	[»]
5HQZ	X-ray	1.46	A	2-187	[»]
5HSR	X-ray	1.21	A	2-187	[»]
5HSU	X-ray	1.46	A	2-187	[»]
5HT4	X-ray	1.60	A	2-187	[»]
5HT5	X-ray	1.90	A	2-187	[»]
5HUI	X-ray	1.46	A	2-187	[»]
5HVB	X-ray	1.60	A	2-187	[»]
5HVE	X-ray	1.46	A	2-187	[»]
6DAV	X-ray	1.55	A/B	1-187	[»]
6DE4	X-ray	2.41	A/B	2-187	[»]
ProteinModelPortalⁱ	P00374
SMRⁱ	P00374
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	108065, 16 interactors
IntActⁱ	P00374, 5 interactors
MINTⁱ	P00374
STRINGⁱ	9606.ENSP00000396308

Chemistry databases

BindingDBⁱ	P00374
ChEMBLⁱ	CHEMBL202
DrugBankⁱ	DB03461 2'-Monophosphoadenosine 5'-Diphosphoribose DB08878 Aminopterin DB03886 Biopterin DB00798 Gentamicin DB00563 Methotrexate DB00157 NADH DB00642 Pemetrexed DB06813 Pralatrexate DB01131 Proguanil DB00205 Pyrimethamine DB03351 Sri-9439 DB03060 Sri-9662 DB00440 Trimethoprim DB01157 Trimetrexate
GuidetoPHARMACOLOGYⁱ	2603

Protein family/group databases

MoonProtⁱ	P00374

MoonProtⁱ

P00374

PTM databases

iPTMnetⁱ	P00374
PhosphoSitePlusⁱ	P00374
SwissPalmⁱ	P00374

Polymorphism and mutation databases

BioMutaⁱ	DHFR
DMDMⁱ	118992

2D gel databases

UCD-2DPAGEⁱ	P00374

UCD-2DPAGEⁱ

P00374

Proteomic databases

EPDⁱ	P00374
MaxQBⁱ	P00374
PaxDbⁱ	P00374
PeptideAtlasⁱ	P00374
PRIDEⁱ	P00374
ProteomicsDBⁱ	51237

Protocols and materials databases

The DNASU plasmid repository More...DNASUⁱ	1719
Structural Biology Knowledgebase	Search...

Genome annotation databases

Ensemblⁱ	ENST00000439211; ENSP00000396308; ENSG00000228716 [P00374-1] ENST00000504396; ENSP00000421334; ENSG00000228716 [P00374-2] ENST00000505337; ENSP00000426474; ENSG00000228716 [P00374-1]
GeneIDⁱ	1719
KEGGⁱ	hsa:1719
UCSCⁱ	uc003kgy.2 human [P00374-1]

Organism-specific databases

CTDⁱ	1719
DisGeNETⁱ	1719
EuPathDBⁱ	HostDB:ENSG00000228716.6
GeneCardsⁱ	DHFR
HGNCⁱ	HGNC:2861 DHFR
HPAⁱ	CAB037129 HPA051465
MalaCardsⁱ	DHFR
MIMⁱ	126060 gene 613839 phenotype
neXtProtⁱ	NX_P00374
OpenTargetsⁱ	ENSG00000228716
Orphanetⁱ	319651 Constitutional megaloblastic anemia with severe neurologic disease
PharmGKBⁱ	PA143
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	KOG1324 Eukaryota COG0262 LUCA
GeneTreeⁱ	ENSGT00390000010283
HOGENOMⁱ	HOG000040235
HOVERGENⁱ	HBG000773
InParanoidⁱ	P00374
KOⁱ	K00287
OMAⁱ	RDNQLPW
OrthoDBⁱ	EOG091G0PRK
PhylomeDBⁱ	P00374
TreeFamⁱ	TF317636

Enzyme and pathway databases

UniPathwayⁱ	UPA00077;UER00158
BioCycⁱ	MetaCyc:HS09699-MONOMER
BRENDAⁱ	1.5.1.3 2681
Reactomeⁱ	R-HSA-1474151 Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation R-HSA-196757 Metabolism of folate and pterines R-HSA-539107 Activation of E2F1 target genes at G1/S
SABIO-RKⁱ	P00374
SIGNORⁱ	P00374

Miscellaneous databases

ChiTaRSⁱ	DHFR human
EvolutionaryTraceⁱ	P00374
GeneWikiⁱ	Dihydrofolate_reductase
GenomeRNAiⁱ	1719
Protein Ontology More...PROⁱ	PR:P00374
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000228716 Expressed in 232 organ(s), highest expression level in buccal mucosa cell
CleanExⁱ	HS_DHFR
ExpressionAtlasⁱ	P00374 baseline and differential
Genevisibleⁱ	P00374 HS

Family and domain databases

CDDⁱ	cd00209 DHFR, 1 hit
Gene3Dⁱ	3.40.430.10, 1 hit
InterProⁱ	View protein in InterPro IPR024072 DHFR-like_dom_sf IPR017925 DHFR_CS IPR001796 DHFR_dom
Pfamⁱ	View protein in Pfam PF00186 DHFR_1, 1 hit
SUPFAMⁱ	SSF53597 SSF53597, 1 hit
PROSITEⁱ	View protein in PROSITE PS00075 DHFR_1, 1 hit PS51330 DHFR_2, 1 hit
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	DYR_HUMAN
Accessionⁱ	P00374Primary (citable) accession number: P00374 Secondary accession number(s): B4DDD2, Q14130, Q6IRW8
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
	Last sequence update:	January 23, 2007
	Last modified:	November 7, 2018
	This is version 204 of the entry and version 2 of the sequence. See complete history.
Entry statusⁱ	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.

Miscellaneousⁱ

Keywords - Technical termⁱ

3D-structure, Complete proteome, Reference proteome

Documents

SIMILARITY comments
Index of protein domains and families
Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations
Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations
MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
PATHWAY comments
Index of metabolic and biosynthesis pathways
PDB cross-references
Index of Protein Data Bank (PDB) cross-references
Human chromosome 5
Human chromosome 5: entries, gene names and cross-references to MIM

UniProtKB

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UniRef

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Supporting data

UniProtKB - P00374 (DYR_HUMAN)

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Dihydrofolate reductase

Select a section on the left to see content.

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

<p>This subsection of the ‘Function’ section describes biophysical and chemical properties, such as maximal absorption, kinetic parameters, pH dependence, redox potentials and temperature dependence.<p><a href='/help/biophysicochemical_properties' target='_top'>More...</a></p>Kineticsi

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section describes the metabolic pathway(s) associated with a protein.<p><a href='/help/pathway' target='_top'>More...</a></p>Pathwayi: tetrahydrofolate biosynthesis

Sites

Regions

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

Protein family/group databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Mitochondrion

Other locations

Cytosol

Mitochondrion

Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

Keywords - Diseasei

Organism-specific databases

Chemistry databases

Polymorphism and mutation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Proteomic databases

2D gel databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Organism-specific databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

Protein-protein interaction databases

Chemistry databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

3D structure databases

Miscellaneous databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Region

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Phylogenomic databases

Family and domain databases

Experimental Info

Natural variant

Alternative sequence

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross_references_section">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

Sequence databases

3D structure databases

Protein-protein interaction databases

Chemistry databases

Protein family/group databases

PTM databases

Polymorphism and mutation databases

2D gel databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Your basket is currently empty. ⁱ

Functionⁱ

Kineticsⁱ

Pathwayⁱ: tetrahydrofolate biosynthesis

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

Keywords - Diseaseⁱ

PTM / Processingⁱ

Expressionⁱ

Interactionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Web resourcesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ