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

(6S)-5,6,7,8-tetrahydrofolate
Search proteins in UniProtKB for this molecule.
Search chemical reactions in Rhea for this molecule.
See the description of this molecule in ChEBI.
+
NADP⁺
Search proteins in UniProtKB for this molecule.
Search chemical reactions in Rhea for this molecule.
See the description of this molecule in ChEBI.
=
7,8-dihydrofolate
Search proteins in UniProtKB for this molecule.
Search chemical reactions in Rhea for this molecule.
See the description of this molecule in ChEBI.
+
H⁺
Search proteins in UniProtKB for this molecule.
Search chemical reactions in Rhea for this molecule.
See the description of this molecule in ChEBI.
+
NADPH
Search proteins in UniProtKB for this molecule.
Search chemical reactions in Rhea for this molecule.
See the description of this molecule in ChEBI.
PROSITE-ProRule annotation
Manual assertion according to rulesⁱ
- PROSITE-ProRule:PRU00660
7 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.16
  "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.
- Ref.17
  "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.
- 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.23
  "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.
- 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.
- Ref.25
  "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.
EC:
1.5.1.3
- Search proteins in UniProtKB for this EC number.
- See the description of this EC number in ENZYME.
- Search reactions for this EC number in Rhea.
PROSITE-ProRule annotation
Manual assertion according to rulesⁱ
- PROSITE-ProRule:PRU00660
7 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.16
  "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.
- Ref.17
  "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.
- 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.23
  "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.
- 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.
- Ref.25
  "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.
Source:
Rhea
Search for this reaction in UniProtKB.
See the description of this reaction in Rhea.
. Show »« Hide
(6S)-5,6,7,8-tetrahydrofolate
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NADP⁺
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=
7,8-dihydrofolate
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H⁺
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NADPH

Kineticsⁱ

Pathwayⁱ: tetrahydrofolate biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate. 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

Complete GO annotation on QuickGO ...

GO - Biological processⁱ

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
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

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

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

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 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 OMIM

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

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 variant

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

Miscellaneous databases

Pharosⁱ	P00374, Tclin

Pharosⁱ

P00374, Tclin

Chemistry databases

ChEMBLⁱ	CHEMBL202
Drug and drug target database More...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
DrugCentral More...DrugCentralⁱ	P00374
IUPHAR/BPS Guide to PHARMACOLOGY More...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
MaxQB - The MaxQuant DataBase More...MaxQBⁱ	P00374
PaxDbⁱ	P00374
PeptideAtlas More...PeptideAtlasⁱ	P00374
PRIDEⁱ	P00374
ProteomicsDBⁱ	3847 51237 [P00374-1]

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 buccal mucosa cell and 248 other tissues
ExpressionAtlasⁱ	P00374, baseline and differential
Genevisibleⁱ	P00374, HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	ENSG00000228716, Low tissue specificity

HPAⁱ

ENSG00000228716, Low tissue specificity

Interactionⁱ

Subunit structureⁱ

Homodimer.

7 Publications

Protein-protein interaction databases

BioGRIDⁱ	108065, 34 interactors
IntActⁱ	P00374, 9 interactors
STRINGⁱ	9606.ENSP00000396308

Chemistry databases

BindingDBⁱ

P00374

Miscellaneous databases

RNActⁱ	P00374, protein

RNActⁱ

P00374, protein

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

BMRBⁱ	P00374
SMRⁱ	P00374
ModBaseⁱ	Search...
PDBe-KBⁱ	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
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00390000010283
HOGENOMⁱ	CLU_043966_2_3_1
InParanoidⁱ	P00374
OMAⁱ	RDNQLPW
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 IPR012259, DHFR IPR024072, DHFR-like_dom_sf IPR017925, DHFR_CS IPR001796, DHFR_dom
PANTHERⁱ	PTHR48069, PTHR48069, 1 hit
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 canonicalⁱ 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

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, EC 1.5.1.3	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 K01614 Genomic DNA Translation: AAA58484.1 X00855 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]

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		HUMAN		262	UniRef100_P00374
Dihydrofolate reductase		SHISS		187
Dihydrofolate reductase		ECO57		187
Dihydrofolate reductase		HUMAN		187
+1
P00374-2	Bifunctional dihydrofolate reductase-thymidylate synthase		PLABE		559	UniRef100_A0A1D3PVI6

Protein	Similar proteins		Species	Score	Length	Source
P00374	Dihydrofolate reductase		HUMAN		262	UniRef90_P00374
Dihydrofolate reductase		SHISS		187
Dihydrofolate reductase		ECO57		187
Dihydrofolate reductase		MACMU		187
Dihydrofolate reductase		CHLSB		187
+28
P00374-2	Bifunctional dihydrofolate reductase-thymidylate synthase		PLABE		559	UniRef90_A0A1D3PVI6

Protein	Similar proteins		Species	Score	Length	Source
P00374	Viral dihydrofolate reductase		SHV24		186	UniRef50_P00374
Viral dihydrofolate reductase		SHV2C		213
Dihydrofolate reductase		MESAU		187
Dihydrofolate reductase		RAT		187
Dihydrofolate reductase		PIG		186
+422
P00374-2	Bifunctional dihydrofolate reductase-thymidylate synthase		PLABE		559	UniRef50_A0A1D3PVI6

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 K01614 Genomic DNA Translation: AAA58484.1 X00855 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: 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	[»]
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	[»]
7ESE	X-ray	1.85	A	1-187	[»]
BMRBⁱ	P00374
SMRⁱ	P00374
ModBaseⁱ	Search...
PDBe-KBⁱ	Search...

Protein-protein interaction databases

BioGRIDⁱ	108065, 34 interactors
IntActⁱ	P00374, 9 interactors
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

MoonProtⁱ

P00374

PTM databases

iPTMnetⁱ	P00374
PhosphoSitePlusⁱ	P00374
SwissPalmⁱ	P00374

Genetic variation databases

BioMutaⁱ	DHFR
DMDMⁱ	118992

2D gel databases

UCD-2DPAGEⁱ	P00374

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, 306 antibodies
The DNASU plasmid repository More...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
GenAtlas: human gene database More...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, 572 hits in 1025 CRISPR screens
ChiTaRSⁱ	DHFR, human
EvolutionaryTraceⁱ	P00374
GeneWikiⁱ	Dihydrofolate_reductase
GenomeRNAiⁱ	1719
Pharosⁱ	P00374, Tclin
Protein Ontology More...PROⁱ	PR:P00374
RNActⁱ	P00374, protein
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000228716, Expressed in buccal mucosa cell and 248 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
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:	September 29, 2021
	This is version 222 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 proteome

Documents

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

UniProtKB

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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 <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<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

Cytoplasm and Cytosol

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

Miscellaneous databases

Chemistry databases

Genetic variation 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

Miscellaneous 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

Genetic variation databases

2D gel databases

Proteomic databases

Protocols and materials databases

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Organism-specific databases

Phylogenomic databases

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Functionⁱ

Catalytic activityⁱ

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