DHFR2

Functionⁱ

Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Required to prevent uracil accumulation in mtDNA. Binds its own mRNA and that of DHFR.2 Publications

Miscellaneous

Humans have acquired two dihydrofolate reductase enzymes during their evolution, DHFR and DHFR2. In contrast to human, mice and brown rats have just one.1 Publication

Catalytic activityⁱ

5,6,7,8-tetrahydrofolate + NADP⁺ = 7,8-dihydrofolate + NADPH.PROSITE-ProRule annotation1 Publication

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.
Proteins known to be involved in this subpathway in this organism are:

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

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

Sites

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Binding siteⁱ	10	NADP; via amide nitrogen and carbonyl oxygenBy similarity		1
Binding siteⁱ	71	SubstrateBy similarity		1

Regions

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

GO - Molecular functionⁱ

dihydrofolate reductase activity
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 21876188
mRNA binding
Source: UniProtKB
Inferred from direct assayⁱ
- 21876184
NADP binding
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

dihydrofolate metabolic process
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
folic acid metabolic process
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
one-carbon metabolic process Source: UniProtKB-KW
tetrahydrofolate biosynthetic process
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
tetrahydrofolate metabolic process
Source: UniProtKB
Inferred from direct assayⁱ
- 21876184
thymidine biosynthetic process
Source: UniProtKB
Inferred from direct assayⁱ
- 21876188

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Oxidoreductase
Biological process	One-carbon metabolism
Ligand	NADP

Enzyme and pathway databases

BioCycⁱ	MetaCyc:ENSG00000178700-MONOMER
Reactomeⁱ	R-HSA-196757 Metabolism of folate and pterines
UniPathwayⁱ	UPA00077;UER00158

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Dihydrofolate reductase 2, mitochondrial Alternative name(s): Dihydrofolate reductase, mitochondrial (EC:1.5.1.3) Dihydrofolate reductase-like protein 1
Gene namesⁱ	Name:DHFR2Imported Synonyms:DHFRL1, DHFRP4
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 3

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000178700.7
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:27309 DHFR2
MIMⁱ	616588 gene
neXtProtⁱ	NX_Q86XF0

Keywords - Cellular componentⁱ

Membrane, Mitochondrion, Mitochondrion inner membrane

Pathology & Biotechⁱ

Organism-specific databases

DisGeNET More...DisGeNETⁱ	200895
Open Targets More...OpenTargetsⁱ	ENSG00000178700
PharmGKBⁱ	PA134889916

Polymorphism and mutation databases

BioMutaⁱ	DHFRL1
DMDMⁱ	74727819

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000186368	1 – 187	Dihydrofolate reductase 2, mitochondrialAdd BLAST		187

Proteomic databases

EPDⁱ	Q86XF0
MaxQB - The MaxQuant DataBase More...MaxQBⁱ	Q86XF0
PaxDbⁱ	Q86XF0
PeptideAtlas More...PeptideAtlasⁱ	Q86XF0
PRIDEⁱ	Q86XF0
ProteomicsDBⁱ	70273
TopDownProteomicsⁱ	Q86XF0

PTM databases

iPTMnetⁱ	Q86XF0
PhosphoSitePlusⁱ	Q86XF0

Expressionⁱ

Tissue specificityⁱ

Expressed in numerous cell lines.1 Publication

Gene expression databases

Bgeeⁱ	ENSG00000178700 Expressed in 208 organ(s), highest expression level in buccal mucosa cell
ExpressionAtlasⁱ	Q86XF0 baseline and differential
Genevisibleⁱ	Q86XF0 HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	HPA051465

HPAⁱ

HPA051465

Interactionⁱ

Protein-protein interaction databases

BioGridⁱ	128354, 61 interactors
IntActⁱ	Q86XF0, 2 interactors
STRINGⁱ	9606.ENSP00000319170

Structureⁱ

3D structure databases

ProteinModelPortalⁱ	Q86XF0
SMRⁱ	Q86XF0
ModBaseⁱ	Search...
MobiDBⁱ	Search...

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 bindingBy similarity		6

Sequence similaritiesⁱ

Belongs to the dihydrofolate reductase family.Curated

Phylogenomic databases

eggNOGⁱ	KOG1324 Eukaryota COG0262 LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00390000010283
HOGENOMⁱ	HOG000040235
HOVERGENⁱ	HBG000773
InParanoidⁱ	Q86XF0
KEGG Orthology (KO) More...KOⁱ	K00287
OMAⁱ	QYEFQMW
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G0PRK
PhylomeDBⁱ	Q86XF0
TreeFamⁱ	TF317636

Family and domain databases

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

Sequence (1+)ⁱ

Sequence statusⁱ: Complete.

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

Q86XF0-1 [UniParc]FASTA Add to basket

« Hide

        10         20         30         40         50
MFLLLNCIVA VSQNMGIGKN GDLPRPPLRN EFRYFQRMTT TSSVEGKQNL 
        60         70         80         90        100
VIMGRKTWFS IPEKNRPLKD RINLVLSREL KEPPQGAHFL ARSLDDALKL 
       110        120        130        140        150
TERPELANKV DMIWIVGGSS VYKEAMNHLG HLKLFVTRIM QDFESDTFFS 
       160        170        180 
EIDLEKYKLL PEYPGVLSDV QEGKHIKYKF EVCEKDD

Length:187

Mass (Da):21,620

Last modified:June 1, 2003 - v1

Checksum:ⁱBA6548FB0F576FF7

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

	C9JJ68	C9JJ68_HUMAN		Dihydrofolate reductase 2, mitochon... Dihydrofolate reductase 2, mitochondrial	DHFR2	114	Annotation score:

Natural variant

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Natural variantⁱVAR_061135	166	V → I1 PublicationCorresponds to variant dbSNP:rs17855824Ensembl.		1

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	AL832912 mRNA Translation: CAH10617.1 AC130896 Genomic DNA No translation available. CH471052 Genomic DNA Translation: EAW79895.1 CH471052 Genomic DNA Translation: EAW79896.1 BC045541 mRNA Translation: AAH45541.1 BC063379 mRNA Translation: AAH63379.1
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS2926.1
NCBI Reference Sequences More...RefSeqⁱ	NP_001182572.1, NM_001195643.1 NP_789785.1, NM_176815.4 XP_011510839.1, XM_011512537.2
UniGeneⁱ	Hs.718516

Genome annotation databases

Ensemblⁱ	ENST00000314636; ENSP00000319170; ENSG00000178700 ENST00000394221; ENSP00000377768; ENSG00000178700 ENST00000461173; ENSP00000418415; ENSG00000178700 ENST00000619045; ENSP00000480823; ENSG00000178700
GeneIDⁱ	200895
KEGGⁱ	hsa:200895
UCSC genome browser More...UCSCⁱ	uc003dri.3 human

Keywords - Coding sequence diversityⁱ

Polymorphism

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
Q86XF0	Dihydrofolate reductase 2, mitochondrial (Fragment)		HUMAN		114	UniRef100_Q86XF0

Protein	Similar proteins		Species	Score	Length	Source
Q86XF0	Dihydrofolate reductase 2, mitochondrial (Fragment)		HUMAN		114	UniRef90_Q86XF0
dihydrofolate reductase isoform X1		Florida manatee		189
Uncharacterized protein		COLAP		187
Uncharacterized protein		MANLE		187
Uncharacterized protein (Fragment)		MACFA		187
+80

Protein	Similar proteins		Species	Score	Length	Source
Q86XF0	Dihydrofolate reductase	)	MOUSE		187	UniRef50_P00375
Dihydrofolate reductase		RAT		187
Dihydrofolate reductase	)	CHICK		189
Dihydrofolate reductase		BOVIN		187
Dihydrofolate reductase		PIG		186
+420

Cross-referencesⁱ

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	AL832912 mRNA Translation: CAH10617.1 AC130896 Genomic DNA No translation available. CH471052 Genomic DNA Translation: EAW79895.1 CH471052 Genomic DNA Translation: EAW79896.1 BC045541 mRNA Translation: AAH45541.1 BC063379 mRNA Translation: AAH63379.1
CCDSⁱ	CCDS2926.1
RefSeqⁱ	NP_001182572.1, NM_001195643.1 NP_789785.1, NM_176815.4 XP_011510839.1, XM_011512537.2
UniGeneⁱ	Hs.718516

3D structure databases

ProteinModelPortalⁱ	Q86XF0
SMRⁱ	Q86XF0
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	128354, 61 interactors
IntActⁱ	Q86XF0, 2 interactors
STRINGⁱ	9606.ENSP00000319170

PTM databases

iPTMnetⁱ	Q86XF0
PhosphoSitePlusⁱ	Q86XF0

Polymorphism and mutation databases

BioMutaⁱ	DHFRL1
DMDMⁱ	74727819

Proteomic databases

EPDⁱ	Q86XF0
MaxQBⁱ	Q86XF0
PaxDbⁱ	Q86XF0
PeptideAtlasⁱ	Q86XF0
PRIDEⁱ	Q86XF0
ProteomicsDBⁱ	70273
TopDownProteomicsⁱ	Q86XF0

Protocols and materials databases

The DNASU plasmid repository More...DNASUⁱ	200895
Structural Biology Knowledgebase	Search...

Genome annotation databases

Ensemblⁱ	ENST00000314636; ENSP00000319170; ENSG00000178700 ENST00000394221; ENSP00000377768; ENSG00000178700 ENST00000461173; ENSP00000418415; ENSG00000178700 ENST00000619045; ENSP00000480823; ENSG00000178700
GeneIDⁱ	200895
KEGGⁱ	hsa:200895
UCSCⁱ	uc003dri.3 human

Organism-specific databases

CTDⁱ	200895
DisGeNETⁱ	200895
EuPathDBⁱ	HostDB:ENSG00000178700.7
GeneCardsⁱ	DHFR2
HGNCⁱ	HGNC:27309 DHFR2
HPAⁱ	HPA051465
MIMⁱ	616588 gene
neXtProtⁱ	NX_Q86XF0
OpenTargetsⁱ	ENSG00000178700
PharmGKBⁱ	PA134889916
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	KOG1324 Eukaryota COG0262 LUCA
GeneTreeⁱ	ENSGT00390000010283
HOGENOMⁱ	HOG000040235
HOVERGENⁱ	HBG000773
InParanoidⁱ	Q86XF0
KOⁱ	K00287
OMAⁱ	QYEFQMW
OrthoDBⁱ	EOG091G0PRK
PhylomeDBⁱ	Q86XF0
TreeFamⁱ	TF317636

Enzyme and pathway databases

UniPathwayⁱ	UPA00077;UER00158
BioCycⁱ	MetaCyc:ENSG00000178700-MONOMER
Reactomeⁱ	R-HSA-196757 Metabolism of folate and pterines

Miscellaneous databases

ChiTaRSⁱ	DHFR2 human
GenomeRNAiⁱ	200895
Protein Ontology More...PROⁱ	PR:Q86XF0
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000178700 Expressed in 208 organ(s), highest expression level in buccal mucosa cell
ExpressionAtlasⁱ	Q86XF0 baseline and differential
Genevisibleⁱ	Q86XF0 HS

Family and domain databases

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

Entry informationⁱ

Entry nameⁱ	DYR2_HUMAN
Accessionⁱ	Q86XF0Primary (citable) accession number: Q86XF0 Secondary accession number(s): D3DN30, Q6P4I9
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	December 20, 2005
	Last sequence update:	June 1, 2003
	Last modified:	November 7, 2018
	This is version 123 of the entry and version 1 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

Complete proteome, Reference proteome

Documents

SIMILARITY comments
Index of protein domains and families
Human chromosome 3
Human chromosome 3: entries, gene names and cross-references to MIM
Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations
Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations
MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
PATHWAY comments
Index of metabolic and biosynthesis pathways

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UniProtKB - Q86XF0 (DYR2_HUMAN)

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Dihydrofolate reductase 2, mitochondrial

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

Miscellaneous

<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

<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

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

Organism-specific databases

Polymorphism and mutation databases

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

Molecule processing

Proteomic databases

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

<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

3D structure 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

Natural variant

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

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Polymorphism and mutation databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

Documents

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Functionⁱ

Kineticsⁱ

Pathwayⁱ: tetrahydrofolate biosynthesis

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Expressionⁱ

Interactionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ