UniProtKB - P00374 (DYR_HUMAN)
Protein
Dihydrofolate reductase
Gene
DHFR
Organism
Homo sapiens (Human)
Status
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
- (6S)-5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + H+ + NADPHPROSITE-ProRule annotation7 PublicationsEC:1.5.1.3PROSITE-ProRule annotation7 Publications
Kineticsi
- KM=2.7 µM for dihydrofolate3 Publications
- KM=4.0 µM for NADPH3 Publications
: tetrahydrofolate biosynthesis Pathwayi
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 (DHFR), Dihydrofolate reductase (DYR), Dihydrofolate reductase 2, mitochondrial (DHFR2), Dihydrofolate reductase (DHFR), Dihydrofolate reductase (DHFR)
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 | Graphical view | 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 | Graphical view | 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
- drug binding Source: UniProtKB
- folic acid binding Source: BHF-UCL
- methotrexate binding Source: BHF-UCL
- mRNA binding Source: UniProtKB
- NADP binding Source: GO_Central
- NADPH binding Source: BHF-UCL
- sequence-specific mRNA binding Source: CAFA
- translation repressor activity, mRNA regulatory element binding Source: CAFA
GO - Biological processi
- axon regeneration Source: BHF-UCL
- dihydrofolate metabolic process Source: BHF-UCL
- folic acid metabolic process Source: BHF-UCL
- glycine biosynthetic process Source: InterPro
- negative regulation of translation Source: CAFA
- one-carbon metabolic process Source: UniProtKB-KW
- 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
- tetrahydrofolate biosynthetic process Source: BHF-UCL
- tetrahydrofolate metabolic process Source: UniProtKB
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 |
PathwayCommonsi | P00374 |
Reactomei | R-HSA-1474151, Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation R-HSA-196757, Metabolism of folate and pterines R-HSA-69205, G1/S-Specific Transcription |
SABIO-RKi | P00374 |
SIGNORi | P00374 |
UniPathwayi | UPA00077;UER00158 |
Protein family/group databases
MoonProti | P00374 |
Names & Taxonomyi
Protein namesi | |
Gene namesi | Name:DHFR |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:2861, DHFR |
MIMi | 126060, gene |
neXtProti | NX_P00374 |
VEuPathDBi | HostDB:ENSG00000228716.6 |
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm By similarity
Mitochondrion
- Mitochondrion By similarity
Cytosol
- cytosol Source: Reactome
Mitochondrion
- mitochondrion Source: HPA
Keywords - Cellular componenti
Cytoplasm, MitochondrionPathology & Biotechi
Involvement in diseasei
Megaloblastic anemia due to dihydrofolate reductase deficiency (DHFRD)2 Publications
The disease is caused by variants 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.
Related information in OMIMFeature 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 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | 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 variantOrganism-specific databases
DisGeNETi | 1719 |
MalaCardsi | DHFR |
MIMi | 613839, phenotype |
OpenTargetsi | ENSG00000228716 |
Orphaneti | 319651, Constitutional megaloblastic anemia with severe neurologic disease |
PharmGKBi | PA143 |
Miscellaneous databases
Pharosi | P00374, Tclin |
Chemistry databases
ChEMBLi | CHEMBL202 |
DrugBanki | DB08642, (2R,6S)-6-{[methyl(3,4,5-trimethoxyphenyl)amino]methyl}-1,2,5,6,7,8-hexahydroquinazoline-2,4-diamine DB08448, (4aS)-5-[(2,4-diaminopteridin-6-yl)methyl]-4a,5-dihydro-2H-dibenzo[b,f]azepin-8-ol DB03125, 2,4-Diamino-5-(3,4,5-Trimethoxy-Benzyl)-Pyrimidin-1-Ium DB02104, 2,4-Diamino-5-Methyl-6-[(3,4,5-Trimethoxy-N-Methylanilino)Methyl]Pyrido[2,3-D]Pyrimidine DB02427, 2,4-Diamino-6-[N-(2',5'-Dimethoxybenzyl)-N-Methylamino]Quinazoline DB02919, 2,4-Diamino-6-[N-(3',4',5'-Trimethoxybenzyl)-N-Methylamino]Pyrido[2,3-D]Pyrimidine DB03987, 2,4-Diamino-6-[N-(3',5'-Dimethoxybenzyl)-N-Methylamino]Pyrido[2,3-D]Pyrimidine DB07144, 5-[(3R)-3-(5-methoxy-2',6'-dimethylbiphenyl-3-yl)but-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine DB07142, 5-[(3R)-3-(5-methoxy-3',5'-dimethylbiphenyl-3-yl)but-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine DB07141, 5-[(3R)-3-(5-methoxy-4'-methylbiphenyl-3-yl)but-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine DB07140, 5-[(3R)-3-(5-methoxybiphenyl-3-yl)but-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine DB08234, 5-[3-(2,5-dimethoxyphenyl)prop-1-yn-1-yl]-6-ethylpyrimidine-2,4-diamine DB02559, 6-(Octahydro-1h-Indol-1-Ylmethyl)Decahydroquinazoline-2,4-Diamine DB08406, [N-(2,4-DIAMINOPTERIDIN-6-YL)-METHYL]-DIBENZ[B,F]AZEPINE DB08878, Aminopterin DB03886, Biopterin DB00158, Folic acid DB00798, Gentamicin DB06358, Iclaprim DB00555, Lamotrigine DB00563, Methotrexate DB02583, N6-(2,5-Dimethoxy-Benzyl)-N6-Methyl-Pyrido[2,3-D]Pyrimidine-2,4,6-Triamine DB00157, NADH DB03461, Nicotinamide adenine dinucleotide phosphate DB00642, Pemetrexed DB03695, Piritrexim DB06813, Pralatrexate DB01131, Proguanil DB00205, Pyrimethamine DB03351, Sri-9439 DB03060, Sri-9662 DB01157, Trimetrexate |
DrugCentrali | P00374 |
GuidetoPHARMACOLOGYi | 2603 |
Genetic variation 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 |
jPOSTi | P00374 |
MassIVEi | P00374 |
MaxQBi | P00374 |
PaxDbi | P00374 |
PeptideAtlasi | P00374 |
PRIDEi | P00374 |
ProteomicsDBi | 3847 51237 [P00374-1] |
2D gel databases
UCD-2DPAGEi | P00374 |
PTM databases
iPTMneti | P00374 |
PhosphoSitePlusi | P00374 |
SwissPalmi | P00374 |
Expressioni
Tissue specificityi
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.1 Publication
Gene expression databases
Bgeei | ENSG00000228716, Expressed in buccal mucosa cell and 247 other tissues |
ExpressionAtlasi | P00374, baseline and differential |
Genevisiblei | P00374, HS |
Organism-specific databases
HPAi | ENSG00000228716, Low tissue specificity |
Interactioni
Subunit structurei
Homodimer.
7 PublicationsProtein-protein interaction databases
BioGRIDi | 108065, 33 interactors |
IntActi | P00374, 9 interactors |
MINTi | P00374 |
STRINGi | 9606.ENSP00000396308 |
Chemistry databases
BindingDBi | P00374 |
Miscellaneous databases
RNActi | P00374, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
BMRBi | P00374 |
SMRi | P00374 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
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 |
GeneTreei | ENSGT00390000010283 |
HOGENOMi | CLU_043966_2_3_1 |
InParanoidi | P00374 |
OMAi | RDNQLPW |
PhylomeDBi | P00374 |
TreeFami | TF317636 |
Family and domain databases
CDDi | cd00209, DHFR, 1 hit |
Gene3Di | 3.40.430.10, 1 hit |
InterProi | View protein in InterPro IPR012259, DHFR IPR024072, DHFR-like_dom_sf IPR017925, DHFR_CS IPR001796, DHFR_dom |
PANTHERi | PTHR48069, PTHR48069, 1 hit |
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 |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
Isoform 1 (identifier: P00374-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketB4DM58 | B4DM58_HUMAN | 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 |
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] |
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] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
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] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi 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 | [»] | |
6A7C | X-ray | 2.06 | A | 2-187 | [»] | |
6A7E | X-ray | 1.85 | A | 2-187 | [»] | |
6DAV | X-ray | 1.55 | A/B | 1-187 | [»] | |
6DE4 | X-ray | 2.41 | A/B | 2-187 | [»] | |
6VCJ | X-ray | 2.34 | A/B/C/D | 1-187 | [»] | |
BMRBi | P00374 | |||||
SMRi | P00374 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 108065, 33 interactors |
IntActi | P00374, 9 interactors |
MINTi | P00374 |
STRINGi | 9606.ENSP00000396308 |
Chemistry databases
BindingDBi | P00374 |
ChEMBLi | CHEMBL202 |
DrugBanki | DB08642, (2R,6S)-6-{[methyl(3,4,5-trimethoxyphenyl)amino]methyl}-1,2,5,6,7,8-hexahydroquinazoline-2,4-diamine DB08448, (4aS)-5-[(2,4-diaminopteridin-6-yl)methyl]-4a,5-dihydro-2H-dibenzo[b,f]azepin-8-ol DB03125, 2,4-Diamino-5-(3,4,5-Trimethoxy-Benzyl)-Pyrimidin-1-Ium DB02104, 2,4-Diamino-5-Methyl-6-[(3,4,5-Trimethoxy-N-Methylanilino)Methyl]Pyrido[2,3-D]Pyrimidine DB02427, 2,4-Diamino-6-[N-(2',5'-Dimethoxybenzyl)-N-Methylamino]Quinazoline DB02919, 2,4-Diamino-6-[N-(3',4',5'-Trimethoxybenzyl)-N-Methylamino]Pyrido[2,3-D]Pyrimidine DB03987, 2,4-Diamino-6-[N-(3',5'-Dimethoxybenzyl)-N-Methylamino]Pyrido[2,3-D]Pyrimidine DB07144, 5-[(3R)-3-(5-methoxy-2',6'-dimethylbiphenyl-3-yl)but-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine DB07142, 5-[(3R)-3-(5-methoxy-3',5'-dimethylbiphenyl-3-yl)but-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine DB07141, 5-[(3R)-3-(5-methoxy-4'-methylbiphenyl-3-yl)but-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine DB07140, 5-[(3R)-3-(5-methoxybiphenyl-3-yl)but-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine DB08234, 5-[3-(2,5-dimethoxyphenyl)prop-1-yn-1-yl]-6-ethylpyrimidine-2,4-diamine DB02559, 6-(Octahydro-1h-Indol-1-Ylmethyl)Decahydroquinazoline-2,4-Diamine DB08406, [N-(2,4-DIAMINOPTERIDIN-6-YL)-METHYL]-DIBENZ[B,F]AZEPINE DB08878, Aminopterin DB03886, Biopterin DB00158, Folic acid DB00798, Gentamicin DB06358, Iclaprim DB00555, Lamotrigine DB00563, Methotrexate DB02583, N6-(2,5-Dimethoxy-Benzyl)-N6-Methyl-Pyrido[2,3-D]Pyrimidine-2,4,6-Triamine DB00157, NADH DB03461, Nicotinamide adenine dinucleotide phosphate DB00642, Pemetrexed DB03695, Piritrexim DB06813, Pralatrexate DB01131, Proguanil DB00205, Pyrimethamine DB03351, Sri-9439 DB03060, Sri-9662 DB01157, Trimetrexate |
DrugCentrali | P00374 |
GuidetoPHARMACOLOGYi | 2603 |
Protein family/group databases
MoonProti | P00374 |
PTM databases
iPTMneti | P00374 |
PhosphoSitePlusi | P00374 |
SwissPalmi | P00374 |
Genetic variation databases
BioMutai | DHFR |
DMDMi | 118992 |
2D gel databases
UCD-2DPAGEi | P00374 |
Proteomic databases
EPDi | P00374 |
jPOSTi | P00374 |
MassIVEi | P00374 |
MaxQBi | P00374 |
PaxDbi | P00374 |
PeptideAtlasi | P00374 |
PRIDEi | P00374 |
ProteomicsDBi | 3847 51237 [P00374-1] |
Protocols and materials databases
Antibodypediai | 24646, 299 antibodies |
DNASUi | 1719 |
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 |
GeneCardsi | DHFR |
HGNCi | HGNC:2861, DHFR |
HPAi | ENSG00000228716, Low tissue specificity |
MalaCardsi | DHFR |
MIMi | 126060, gene 613839, phenotype |
neXtProti | NX_P00374 |
OpenTargetsi | ENSG00000228716 |
Orphaneti | 319651, Constitutional megaloblastic anemia with severe neurologic disease |
PharmGKBi | PA143 |
VEuPathDBi | HostDB:ENSG00000228716.6 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1324, Eukaryota |
GeneTreei | ENSGT00390000010283 |
HOGENOMi | CLU_043966_2_3_1 |
InParanoidi | P00374 |
OMAi | RDNQLPW |
PhylomeDBi | P00374 |
TreeFami | TF317636 |
Enzyme and pathway databases
UniPathwayi | UPA00077;UER00158 |
BioCyci | MetaCyc:HS09699-MONOMER |
BRENDAi | 1.5.1.3, 2681 |
PathwayCommonsi | P00374 |
Reactomei | R-HSA-1474151, Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation R-HSA-196757, Metabolism of folate and pterines R-HSA-69205, G1/S-Specific Transcription |
SABIO-RKi | P00374 |
SIGNORi | P00374 |
Miscellaneous databases
BioGRID-ORCSi | 1719, 565 hits in 1001 CRISPR screens |
ChiTaRSi | DHFR, human |
EvolutionaryTracei | P00374 |
GeneWikii | Dihydrofolate_reductase |
GenomeRNAii | 1719 |
Pharosi | P00374, Tclin |
PROi | PR:P00374 |
RNActi | P00374, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000228716, Expressed in buccal mucosa cell and 247 other tissues |
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 IPR012259, DHFR IPR024072, DHFR-like_dom_sf IPR017925, DHFR_CS IPR001796, DHFR_dom |
PANTHERi | PTHR48069, PTHR48069, 1 hit |
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... |
MobiDBi | 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: | April 7, 2021 | |
This is version 220 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, Reference proteomeDocuments
- Human chromosome 5
Human chromosome 5: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - 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 - SIMILARITY comments
Index of protein domains and families