Details for: DHFR

Gene ID: 1719

Symbol: DHFR

Ensembl ID: ENSG00000228716

Description: dihydrofolate reductase

Associated with

Cells (max top 100)

(Marker Score score is uniquely calculated using our advanced thresholding algorithms to reveal cell-specific gene markers)

  • Cell Name: erythroid progenitor cell (CL0000038)
    Fold Change: 1.9
    Marker Score: 1977
  • Cell Name: proerythroblast (CL0000547)
    Fold Change: 1.68
    Marker Score: 1141
  • Cell Name: large pre-B-II cell (CL0000957)
    Fold Change: 1.64
    Marker Score: 4447
  • Cell Name: migratory enteric neural crest cell (CL0002607)
    Fold Change: 1.58
    Marker Score: 1488
  • Cell Name: renal principal cell (CL0005009)
    Fold Change: 1.5
    Marker Score: 1153
  • Cell Name: primitive red blood cell (CL0002355)
    Fold Change: 1.48
    Marker Score: 1112
  • Cell Name: epithelial cell of prostate (CL0002231)
    Fold Change: 1.48
    Marker Score: 1026
  • Cell Name: tonsil germinal center B cell (CL2000006)
    Fold Change: 1.47
    Marker Score: 4349
  • Cell Name: mural cell (CL0008034)
    Fold Change: 1.46
    Marker Score: 168039
  • Cell Name: kidney interstitial fibroblast (CL1000692)
    Fold Change: 1.43
    Marker Score: 2748
  • Cell Name: renal alpha-intercalated cell (CL0005011)
    Fold Change: 1.4
    Marker Score: 735
  • Cell Name: renal interstitial pericyte (CL1001318)
    Fold Change: 1.38
    Marker Score: 1318
  • Cell Name: neural crest cell (CL0011012)
    Fold Change: 1.32
    Marker Score: 1409
  • Cell Name: hepatic stellate cell (CL0000632)
    Fold Change: 1.26
    Marker Score: 474
  • Cell Name: fraction A pre-pro B cell (CL0002045)
    Fold Change: 1.25
    Marker Score: 1256
  • Cell Name: smooth muscle cell of prostate (CL1000487)
    Fold Change: 1.19
    Marker Score: 302.5
  • Cell Name: kidney loop of Henle thin descending limb epithelial cell (CL1001111)
    Fold Change: 1.15
    Marker Score: 1237
  • Cell Name: oogonial cell (CL0000024)
    Fold Change: 1.1
    Marker Score: 1578.5
  • Cell Name: midzonal region hepatocyte (CL0019028)
    Fold Change: 1.1
    Marker Score: 4726
  • Cell Name: parietal epithelial cell (CL1000452)
    Fold Change: 1.08
    Marker Score: 392
  • Cell Name: promyelocyte (CL0000836)
    Fold Change: 1.04
    Marker Score: 512
  • Cell Name: papillary tips cell (CL1000597)
    Fold Change: 1.03
    Marker Score: 208
  • Cell Name: primordial germ cell (CL0000670)
    Fold Change: 1.02
    Marker Score: 1284
  • Cell Name: Unknown (CL0000548)
    Fold Change: 1.01
    Marker Score: 737
  • Cell Name: cerebral cortex GABAergic interneuron (CL0010011)
    Fold Change: 1
    Marker Score: 71745
  • Cell Name: forebrain radial glial cell (CL0013000)
    Fold Change: 1
    Marker Score: 47970
  • Cell Name: epithelial cell of proximal tubule (CL0002306)
    Fold Change: 1
    Marker Score: 3537
  • Cell Name: periportal region hepatocyte (CL0019026)
    Fold Change: 0.98
    Marker Score: 5274.5
  • Cell Name: absorptive cell (CL0000212)
    Fold Change: 0.98
    Marker Score: 30399
  • Cell Name: kidney epithelial cell (CL0002518)
    Fold Change: 0.97
    Marker Score: 1030
  • Cell Name: mature microglial cell (CL0002629)
    Fold Change: 0.96
    Marker Score: 347
  • Cell Name: early lymphoid progenitor (CL0000936)
    Fold Change: 0.96
    Marker Score: 469
  • Cell Name: neuroblast (sensu Vertebrata) (CL0000031)
    Fold Change: 0.96
    Marker Score: 600
  • Cell Name: tuft cell of colon (CL0009041)
    Fold Change: 0.95
    Marker Score: 490
  • Cell Name: podocyte (CL0000653)
    Fold Change: 0.95
    Marker Score: 351
  • Cell Name: intestinal crypt stem cell of colon (CL0009043)
    Fold Change: 0.95
    Marker Score: 2405
  • Cell Name: plasmablast (CL0000980)
    Fold Change: 0.94
    Marker Score: 1256
  • Cell Name: pro-T cell (CL0000827)
    Fold Change: 0.94
    Marker Score: 3862
  • Cell Name: BEST4+ intestinal epithelial cell, human (CL4030026)
    Fold Change: 0.94
    Marker Score: 444.5
  • Cell Name: endothelial cell of vascular tree (CL0002139)
    Fold Change: 0.94
    Marker Score: 1362
  • Cell Name: transit amplifying cell (CL0009010)
    Fold Change: 0.92
    Marker Score: 5264
  • Cell Name: epithelial cell of nephron (CL1000449)
    Fold Change: 0.92
    Marker Score: 1914
  • Cell Name: abnormal cell (CL0001061)
    Fold Change: 0.91
    Marker Score: 2717
  • Cell Name: kidney connecting tubule epithelial cell (CL1000768)
    Fold Change: 0.9
    Marker Score: 1276
  • Cell Name: mature astrocyte (CL0002627)
    Fold Change: 0.9
    Marker Score: 593
  • Cell Name: centrilobular region hepatocyte (CL0019029)
    Fold Change: 0.9
    Marker Score: 5786.5
  • Cell Name: stem cell (CL0000034)
    Fold Change: 0.88
    Marker Score: 2084
  • Cell Name: neoplastic cell (CL0001063)
    Fold Change: 0.87
    Marker Score: 5294
  • Cell Name: epithelial cell of small intestine (CL0002254)
    Fold Change: 0.87
    Marker Score: 313
  • Cell Name: cholangiocyte (CL1000488)
    Fold Change: 0.87
    Marker Score: 324
  • Cell Name: late promyelocyte (CL0002151)
    Fold Change: 0.86
    Marker Score: 216
  • Cell Name: mesenchymal cell (CL0008019)
    Fold Change: 0.85
    Marker Score: 1437
  • Cell Name: fetal cardiomyocyte (CL0002495)
    Fold Change: 0.83
    Marker Score: 274
  • Cell Name: Kupffer cell (CL0000091)
    Fold Change: 0.81
    Marker Score: 810
  • Cell Name: early T lineage precursor (CL0002425)
    Fold Change: 0.8
    Marker Score: 611
  • Cell Name: osteoclast (CL0000092)
    Fold Change: 0.79
    Marker Score: 395
  • Cell Name: small intestine goblet cell (CL1000495)
    Fold Change: 0.79
    Marker Score: 315
  • Cell Name: intestinal epithelial cell (CL0002563)
    Fold Change: 0.78
    Marker Score: 1268
  • Cell Name: L5 extratelencephalic projecting glutamatergic cortical neuron (CL4023041)
    Fold Change: 0.77
    Marker Score: 1183
  • Cell Name: endothelial cell of pericentral hepatic sinusoid (CL0019022)
    Fold Change: 0.76
    Marker Score: 817
  • Cell Name: enteric smooth muscle cell (CL0002504)
    Fold Change: 0.75
    Marker Score: 1762
  • Cell Name: Cajal-Retzius cell (CL0000695)
    Fold Change: 0.74
    Marker Score: 382
  • Cell Name: erythroblast (CL0000765)
    Fold Change: 0.73
    Marker Score: 458
  • Cell Name: placental villous trophoblast (CL2000060)
    Fold Change: 0.71
    Marker Score: 2808
  • Cell Name: brush cell (CL0002204)
    Fold Change: 0.7
    Marker Score: 637
  • Cell Name: enterocyte of epithelium of small intestine (CL1000334)
    Fold Change: 0.69
    Marker Score: 2875
  • Cell Name: neutrophil progenitor cell (CL0000834)
    Fold Change: 0.68
    Marker Score: 174
  • Cell Name: mesothelial cell (CL0000077)
    Fold Change: 0.68
    Marker Score: 272
  • Cell Name: ovarian surface epithelial cell (CL2000064)
    Fold Change: 0.67
    Marker Score: 1826
  • Cell Name: radial glial cell (CL0000681)
    Fold Change: 0.66
    Marker Score: 245
  • Cell Name: L6b glutamatergic cortical neuron (CL4023038)
    Fold Change: 0.65
    Marker Score: 5602
  • Cell Name: transit amplifying cell of small intestine (CL0009012)
    Fold Change: 0.65
    Marker Score: 270
  • Cell Name: choroid plexus epithelial cell (CL0000706)
    Fold Change: 0.65
    Marker Score: 597
  • Cell Name: epicardial adipocyte (CL1000309)
    Fold Change: 0.65
    Marker Score: 314
  • Cell Name: intestinal crypt stem cell (CL0002250)
    Fold Change: 0.65
    Marker Score: 243
  • Cell Name: kidney distal convoluted tubule epithelial cell (CL1000849)
    Fold Change: 0.64
    Marker Score: 682
  • Cell Name: Hofbauer cell (CL3000001)
    Fold Change: 0.64
    Marker Score: 353
  • Cell Name: lactocyte (CL0002325)
    Fold Change: 0.63
    Marker Score: 10186
  • Cell Name: type EC enteroendocrine cell (CL0000577)
    Fold Change: 0.63
    Marker Score: 596
  • Cell Name: B cell (CL0000236)
    Fold Change: 0.63
    Marker Score: 600
  • Cell Name: multi-ciliated epithelial cell (CL0005012)
    Fold Change: 0.63
    Marker Score: 1197
  • Cell Name: secretory cell (CL0000151)
    Fold Change: 0.62
    Marker Score: 1140
  • Cell Name: renal beta-intercalated cell (CL0002201)
    Fold Change: 0.62
    Marker Score: 195
  • Cell Name: kidney proximal straight tubule epithelial cell (CL1000839)
    Fold Change: 0.61
    Marker Score: 1432
  • Cell Name: common myeloid progenitor (CL0000049)
    Fold Change: 0.61
    Marker Score: 161
  • Cell Name: enterocyte (CL0000584)
    Fold Change: 0.61
    Marker Score: 2913
  • Cell Name: common lymphoid progenitor (CL0000051)
    Fold Change: 0.6
    Marker Score: 412
  • Cell Name: myeloid cell (CL0000763)
    Fold Change: 0.6
    Marker Score: 958
  • Cell Name: hepatocyte (CL0000182)
    Fold Change: 0.6
    Marker Score: 407
  • Cell Name: transit amplifying cell of colon (CL0009011)
    Fold Change: 0.59
    Marker Score: 272
  • Cell Name: early pro-B cell (CL0002046)
    Fold Change: 0.59
    Marker Score: 5984.5
  • Cell Name: thymocyte (CL0000893)
    Fold Change: 0.59
    Marker Score: 618
  • Cell Name: pre-conventional dendritic cell (CL0002010)
    Fold Change: 0.58
    Marker Score: 172
  • Cell Name: precursor B cell (CL0000817)
    Fold Change: 0.57
    Marker Score: 380
  • Cell Name: endothelial cell of periportal hepatic sinusoid (CL0019021)
    Fold Change: 0.56
    Marker Score: 155
  • Cell Name: lymphocyte (CL0000542)
    Fold Change: 0.56
    Marker Score: 283
  • Cell Name: enteric neuron (CL0007011)
    Fold Change: 0.56
    Marker Score: 296
  • Cell Name: intestinal enteroendocrine cell (CL1001516)
    Fold Change: 0.55
    Marker Score: 442
  • Cell Name: erythroid lineage cell (CL0000764)
    Fold Change: 0.55
    Marker Score: 276
  • Cell Name: hematopoietic multipotent progenitor cell (CL0000837)
    Fold Change: 0.54
    Marker Score: 266

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Other Information

**Key characteristics:** * It is a multi-functional enzyme with activity in DNA and RNA synthesis, as well as in folate and cofactor metabolism. * It is highly expressed in cells of the hematopoietic and epithelial lineages. * It is a key regulator of cell cycle progression, being upregulated in proliferating cells and downregulated in apoptotic cells. **Pathways and functions:** * **Folate synthesis:** DHFR is responsible for the synthesis of tetrahydrofolate (thf), which is a precursor to DNA, RNA, and protein synthesis. * **Folate and cofactor metabolism:** DHFR is involved in the recycling of folate and maintenance of its pools. * **Cell cycle regulation:** DHFR is critical for the G1/S transition in the cell cycle, where it promotes the progression of cells from the G1 phase to the S phase. * **Mitotic checkpoint:** DHFR is also involved in the regulation of the mitotic checkpoint, where it prevents cell cycle progression in the absence of growth factors. **Clinical significance:** * Mutations in DHFR have been linked to several human diseases, including megaloblastic anemia, a condition characterized by low blood cell counts. * DHFR inhibitors are being investigated as potential therapeutics for cancer and other diseases that are characterized by folate deficiency. **Additional information:** * DHFR is a highly conserved protein with important functions in humans. * It is a well-studied target for cancer therapy. * DHFR inhibitors have been shown to be effective in treating cancer in vitro and in animal models.

Genular Protein ID: 4053884756

Symbol: DYR_HUMAN

Name: Dihydrofolate reductase

UniProtKB Accession Codes:

P00374 B4DDD2 Q14130 Q6IRW8

Database IDs:

AGR 2 AlphaFoldDB 1 Antibodypedia 1 BMRB 1 BRENDA 1 Bgee 1 BindingDB 1 BioCyc 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CTD 1 ChEBI 10 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 32 DrugCentral 1 EC 2 EMBL 19 EPD 1 Ensembl 3 EvolutionaryTrace 1 ExpressionAtlas 1 GO 21 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 Genevisible 1 GenomeRNAi 1 GuidetoPHARMACOLOGY 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 MaxQB 1 MoonProt 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PDB 94 PDBsum 88 PIR 1 PRINTS 1 PRO 1 PROSITE 2 PROSITE-ProRule 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 Reactome 3 RefSeq 2 Rhea 1 SABIO-RK 1 SIGNOR 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCD-2DPAGE 1 UCSC 1 UniPathway 1 UniProtKB 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 6323448

Title: The functional human dihydrofolate reductase gene.

PubMed ID: 6323448

DOI: 10.1016/s0021-9258(17)43186-3

PubMed ID: 6687716

Title: The nucleotide sequence of the cDNA coding for the human dihydrofolic acid reductase.

PubMed ID: 6687716

DOI: 10.1016/0378-1119(83)90147-6

PubMed ID: 6235374

Title: 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.

PubMed ID: 6235374

DOI: 10.1016/0022-2836(84)90419-4

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15372022

Title: The DNA sequence and comparative analysis of human chromosome 5.

PubMed ID: 15372022

DOI: 10.1038/nature02919

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 21310276

Title: Identification and characterization of an inborn error of metabolism caused by dihydrofolate reductase deficiency.

PubMed ID: 21310276

DOI: 10.1016/j.ajhg.2011.01.004

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 21876184

Title: The former annotated human pseudogene dihydrofolate reductase-like 1 (DHFRL1) is expressed and functional.

PubMed ID: 21876184

DOI: 10.1073/pnas.1103605108

PubMed ID: 21876188

Title: Identification of a de novo thymidylate biosynthesis pathway in mammalian mitochondria.

PubMed ID: 21876188

DOI: 10.1073/pnas.1103623108

PubMed ID: 3383852

Title: Crystal structure of human dihydrofolate reductase complexed with folate.

PubMed ID: 3383852

DOI: 10.1111/j.1432-1033.1988.tb14108.x

PubMed ID: 2248959

Title: Crystal structures of recombinant human dihydrofolate reductase complexed with folate and 5-deazafolate.

PubMed ID: 2248959

DOI: 10.1021/bi00492a021

PubMed ID: 1731871

Title: Sequence-specific 1H and 15N resonance assignments for human dihydrofolate reductase in solution.

PubMed ID: 1731871

DOI: 10.1021/bi00116a031

PubMed ID: 7890613

Title: Methotrexate-resistant variants of human dihydrofolate reductase with substitutions of leucine 22. Kinetics, crystallography, and potential as selectable markers.

PubMed ID: 7890613

DOI: 10.1074/jbc.270.10.5057

PubMed ID: 9374868

Title: 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.

PubMed ID: 9374868

DOI: 10.1021/bi971711l

PubMed ID: 9719595

Title: 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.

PubMed ID: 9719595

DOI: 10.1021/jm980081y

PubMed ID: 12096917

Title: Atomic structures of human dihydrofolate reductase complexed with NADPH and two lipophilic antifolates at 1.09 A and 1.05 A resolution.

PubMed ID: 12096917

DOI: 10.1016/s0022-2836(02)00469-2

PubMed ID: 12657784

Title: Analysis of two polymorphic forms of a pyrido[2,3-d]pyrimidine N9-C10 reversed-bridge antifolate binary complex with human dihydrofolate reductase.

PubMed ID: 12657784

DOI: 10.1107/s0907444903001951

PubMed ID: 12925791

Title: Analysis of three crystal structure determinations of a 5-methyl-6-N-methylanilino pyridopyrimidine antifolate complex with human dihydrofolate reductase.

PubMed ID: 12925791

DOI: 10.1107/s0907444903014963

PubMed ID: 15039552

Title: Structure determination of tetrahydroquinazoline antifolates in complex with human and Pneumocystis carinii dihydrofolate reductase: correlations between enzyme selectivity and stereochemistry.

PubMed ID: 15039552

DOI: 10.1107/s0907444904002094

PubMed ID: 15681865

Title: 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.

PubMed ID: 15681865

DOI: 10.1107/s0907444904030422

PubMed ID: 16222560

Title: Solution structure of human dihydrofolate reductase in its complex with trimethoprim and NADPH.

PubMed ID: 16222560

DOI: 10.1007/s10858-005-1475-z

PubMed ID: 17569517

Title: Novel boron-containing, nonclassical antifolates: synthesis and preliminary biological and structural evaluation.

PubMed ID: 17569517

DOI: 10.1021/jm0701977

PubMed ID: 19196009

Title: Correlations of inhibitor kinetics for Pneumocystis jirovecii and human dihydrofolate reductase with structural data for human active site mutant enzyme complexes.

PubMed ID: 19196009

DOI: 10.1021/bi801960h

PubMed ID: 19478082

Title: Multiple conformers in active site of human dihydrofolate reductase F31R/Q35E double mutant suggest structural basis for methotrexate resistance.

PubMed ID: 19478082

DOI: 10.1074/jbc.m109.018010

PubMed ID: 19719239

Title: 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.

PubMed ID: 19719239

DOI: 10.1021/jm900490a

PubMed ID: 21310277

Title: Dihydrofolate reductase deficiency due to a homozygous DHFR mutation causes megaloblastic anemia and cerebral folate deficiency leading to severe neurologic disease.

PubMed ID: 21310277

DOI: 10.1016/j.ajhg.2011.01.007

Sequence Information:

  • Length: 187
  • Mass: 21453
  • Checksum: EBDF3D1EC73E1566
  • Sequence:
    • MVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMGKKTWFS 
IPEKNRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKL TEQPELANKV DMVWIVGGSS 
VYKEAMNHPG HLKLFVTRIM QDFESDTFFP EIDLEKYKLL PEYPGVLSDV QEEKGIKYKF 
EVYEKND

Genular Protein ID: 3716210371

Symbol: B4DM58_HUMAN

Name: N/A

UniProtKB Accession Codes:

B4DM58

Database IDs:

ARBA 6 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CDD 1 CTD 1 ChiTaRS 1 DNASU 1 EMBL 4 EPD 1 Ensembl 2 GO 7 Gene3D 1 GeneTree 1 GenomeRNAi 1 HGNC 1 InterPro 4 MassIVE 1 MaxQB 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PRINTS 1 PROSITE 3 Pfam 1 Proteomes 2 ProteomicsDB 1 RefSeq 1 RuleBase 1 SUPFAM 1 UCSC 1 UniPathway 1 VEuPathDB 1

Citations:

PubMed ID: 15372022

Title: The DNA sequence and comparative analysis of human chromosome 5.

PubMed ID: 15372022

DOI: 10.1038/nature02919

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

Sequence Information:

  • Length: 129
  • Mass: 14500
  • Checksum: A86D545B3347CB61
  • Sequence:
    • MVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMGKKTWFS 
IPEKNRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKL TEQPELANKV DMVWIVGGSS 
VYKIPRCSL

Database document:

This is a preview of the gene's schema. Only a few entries are kept for 'singleCellExpressions,' 'mRNAExpressions,' and other large data arrays for visualization purposes. For the full schema, download it here.