Protein:DHFR |
Protein Summary |
 Gene summary |
| Gene name: DHFR | ASpdb.0 ID: 1719 | Gene | Gene symbol | DHFR | Gene ID | 1719 |
| Gene name | dihydrofolate reductase |
| Synonyms | DHFR1|DHFRP1|DYR |
| Cytomap | 5q14.1 |
| Type of gene | protein-coding |
| Description | dihydrofolate reductase |
| Modification date | 20240305 |
| UniProtAcc | P00374 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | DHFR | GO:0000900 | mRNA regulatory element binding translation repressor activity | 8490020 |
| Gene | DHFR | GO:0003729 | mRNA binding | 21876184 |
| Gene | DHFR | GO:0004146 | dihydrofolate reductase activity | 2303423|12096917|21876184|23707606 |
| Gene | DHFR | GO:0005542 | folic acid binding | 2303423 |
| Gene | DHFR | GO:0005739 | mitochondrion | - |
| Gene | DHFR | GO:0017148 | negative regulation of translation | 8490020 |
| Gene | DHFR | GO:0046452 | dihydrofolate metabolic process | 2303423|23707606 |
| Gene | DHFR | GO:0046653 | tetrahydrofolate metabolic process | 12096917|21876184 |
| Gene | DHFR | GO:0046654 | tetrahydrofolate biosynthetic process | 2303423 |
| Gene | DHFR | GO:0070402 | NADPH binding | 2303423 |
| Gene | DHFR | GO:1990825 | sequence-specific mRNA binding | 8490020 |
AS Summary |
| Information of the canonical protein with experimentally identified structure from PDB (2023). |
| UniProt Acc | File name | PDB ID | Method | Resolution | Chain | Start | End |
| P00374-1 | P00374-1_1kmv_A.pdb | 1KMV | X-ray | 1.05 | A | 2 | 187 |
| ASpdb's canonical and alternatively spliced isoform information. |
| accession_id | gene_name | canonical_id | alternative_id | canonical_length | alternative_length | canonical_start | canonical_end | type | originalSEQ | variationSEQ | alternative_start | alternative_end |
| P00374 | DHFR | P00374-1 | P00374-2 | 187 | 135 | 1 | 52 | Deletion | none | none | 0 | 0 |
| Multiple sequence alignment of our canonical and alternatively spliced DHFR |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of DHFR |
| UniProt-id | ENSG | ENST | ENSP |
| P00374-1 | ENSG00000228716.7 | ENST00000439211.7 | ENSP00000396308.2 |
| P00374-1 | ENSG00000228716.7 | ENST00000505337.5 | ENSP00000426474.1 |
| P00374-2 | ENSG00000228716.7 | ENST00000504396.1 | ENSP00000421334.1 |
| UniProt-id | NM ID | NP ID |
| P00374-1 | NM_000791.3 | NP_000782.1 |
| P00374-2 | NM_001290354.1 | NP_001277283.1 |
| Amino acid sequences of our canonical and alternatively spliced DHFR |
| accession_id | Protein sequence |
| P00374-1 | MVGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQRMTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVLSRELKEPPQGAHFL SRSLDDALKLTEQPELANKVDMVWIVGGSSVYKEAMNHPGHLKLFVTRIMQDFESDTFFPEIDLEKYKLLPEYPGVLSDVQEEKGIKYKF |
| P00374-2 | MGKKTWFSIPEKNRPLKGRINLVLSRELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVWIVGGSSVYKEAMNHPGHLKLFVTRIMQD |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| DHFR (go to UniProt):P00374 |
| Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| P00374 | Domain | 4 | 185 | Note=DHFR;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00660 | Type=Deletion;Start=1;End=52 |
Gene Isoform Structures and Expression Levels for DHFR |
| Gene structures of our canonical and alternative spliced genes of DHFR * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Expression levels of gene isoforms across GTEx. |
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| Expression levels of gene isoforms across TCGA. |
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Protein Structures |
| PDB and CIF files of the predicted protein structures * Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| 3D view using mol* of P00374-1 |
| 3D view using mol* of P00374-2 |
pLDDT Score Distribution |
| pLDDT score distribution of the predicted protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
| pLDDT distribution across the protein length of P00374-1 |
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| pLDDT distribution across the protein length of P00374-2 |
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Ramachandran Plot of Protein Structures |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide. |
| Ramachandran plot of P00374-1 |
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Potential Active Site Information |
| The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite. |
| UniProt-id | Site score | Size | D score | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| P00374-1 | 1.052 | 250 | 1.047 | 681.541 | 0.437 | 0.775 | 0.999 | 0.679 | 1.097 | 0.618 | 0.75 | 8,9,10,17,18,19,20,21,22,23,25,27,28,29,31,32,34,3 5,36,54,55,56,57,60,61,62,65,68,71,76,77,78,79,92, 93,116,117,118,119,120,121,122,124,137,146,147 |
| P00374-2 | 1.082 | 163 | 1.113 | 200.312 | 0.309 | 0.782 | 1.009 | 1.264 | 0.908 | 1.392 | 0.298 | 1,16,19,20,21,22,24,42,45,46,49,54,57,58,59,60,61, 62,63,64,69 |
Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
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| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of P00374-1_P00374-1_1kmv_A.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P00374-1_1kmv_A_P00374-2.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P00374-1_P00374-2.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P00374-1_vs_P00374-2.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P00374-1_vs_P00374-2.png |
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Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to DHFR |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P00374 | DHFR | DB08234 | 5-[3-(2,5-dimethoxyphenyl)prop-1-yn-1-yl]-6-ethylpyrimidine-2,4-diamine | experimental | |
| P00374 | DHFR | DB01131 | Proguanil | approved | inhibitor |
| P00374 | DHFR | DB00798 | Gentamicin | approved, vet_approved | |
| P00374 | DHFR | DB07140 | 5-[(3R)-3-(5-methoxybiphenyl-3-yl)but-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine | experimental | |
| P00374 | DHFR | DB00205 | Pyrimethamine | approved, investigational, vet_approved | inhibitor |
| P00374 | DHFR | DB07142 | 5-[(3R)-3-(5-methoxy-3',5'-dimethylbiphenyl-3-yl)but-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine | experimental | |
| P00374 | DHFR | DB08406 | [N-(2,4-DIAMINOPTERIDIN-6-YL)-METHYL]-DIBENZ[B,F]AZEPINE | experimental | |
| P00374 | DHFR | DB07144 | 5-[(3R)-3-(5-methoxy-2',6'-dimethylbiphenyl-3-yl)but-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine | experimental | |
| P00374 | DHFR | DB08642 | (2R,6S)-6-{[methyl(3,4,5-trimethoxyphenyl)amino]methyl}-1,2,5,6,7,8-hexahydroquinazoline-2,4-diamine | experimental | |
| P00374 | DHFR | DB00642 | Pemetrexed | approved, investigational | inhibitor |
| P00374 | DHFR | DB08448 | (4aS)-5-[(2,4-diaminopteridin-6-yl)methyl]-4a,5-dihydro-2H-dibenzo[b,f]azepin-8-ol | experimental | |
| P00374 | DHFR | DB00563 | Methotrexate | approved | inhibitor |
| P00374 | DHFR | DB02919 | 2,4-Diamino-6-[N-(3',4',5'-Trimethoxybenzyl)-N-Methylamino]Pyrido[2,3-D]Pyrimidine | experimental | |
| P00374 | DHFR | DB07141 | 5-[(3R)-3-(5-methoxy-4'-methylbiphenyl-3-yl)but-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine | experimental | |
| P00374 | DHFR | DB06813 | Pralatrexate | approved, investigational | substrate, inhibitor |
| P00374 | DHFR | DB02583 | N6-(2,5-Dimethoxy-Benzyl)-N6-Methyl-Pyrido[2,3-D]Pyrimidine-2,4,6-Triamine | experimental | |
| P00374 | DHFR | DB02559 | 6-(Octahydro-1h-Indol-1-Ylmethyl)Decahydroquinazoline-2,4-Diamine | experimental | |
| P00374 | DHFR | DB03987 | 2,4-Diamino-6-[N-(3',5'-Dimethoxybenzyl)-N-Methylamino]Pyrido[2,3-D]Pyrimidine | experimental | |
| P00374 | DHFR | DB03351 | Sri-9439 | experimental | |
| P00374 | DHFR | DB03886 | Biopterin | experimental | |
| P00374 | DHFR | DB02427 | 2,4-Diamino-6-[N-(2',5'-Dimethoxybenzyl)-N-Methylamino]Quinazoline | experimental | |
| P00374 | DHFR | DB03125 | 2,4-Diamino-5-(3,4,5-Trimethoxy-Benzyl)-Pyrimidin-1-Ium | experimental | |
| P00374 | DHFR | DB03695 | Piritrexim | investigational | |
| P00374 | DHFR | DB01157 | Trimetrexate | approved, investigational | inhibitor |
| P00374 | DHFR | DB02104 | 2,4-Diamino-5-Methyl-6-[(3,4,5-Trimethoxy-N-Methylanilino)Methyl]Pyrido[2,3-D]Pyrimidine | experimental | |
| P00374 | DHFR | DB06358 | Iclaprim | investigational | |
| P00374 | DHFR | DB00157 | NADH | approved, nutraceutical | |
| P00374 | DHFR | DB03060 | Sri-9662 | experimental | |
| P00374 | DHFR | DB03461 | Nicotinamide adenine dinucleotide phosphate | experimental |
Related Diseases to DHFR |
| Previous studies relating to the alternative splicing of DHFR and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
Clinically important variants in DHFR |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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